New Journal of Chemistry January 2009a

Volume 33 | Number 1 | 2009
A new journal from RSC Publishing

launching in 2009
New Journal of Chemistry An international journal of the chemical sciences
www.rsc.org/njc Volume 33 | Number 1 | January 2009 | Pages 1–212
NJC
060877
Metallomics
Integrated biometal science
This timely new journal will cover the research fields related to metals in
Metallomics
Number 1 | 2008
biological, environmental and clinical systems and is expected to be the core

publication for the emerging metallomics community. The journal will be
www.rsc.org/metallomics Volume 1 | Number 1 | January 2009 | Pages 1–100 supported by an international Editorial Board, chaired by Professor Joseph A.
Metallomics
Caruso of the University of Cincinnati/Agilent Technologies Metallomics Center of

the Americas.
Metallomics will publish six issues in the first year, increasing to 12 issues in 2010.
The journal will contain a full mix of research articles including Communications,
Reviews, Full papers, and Editorials. From launch, the latest issue will be freely
available online to all readers. Free institutional access to previous issues
throughout 2009 and 2010 will be available following a simple registration process.
ISSN 1756-5901
Contact the editor, Niamh O’Connor, at metallomics@rsc.org for further
information or visit the website.
Pages 1–100
1754-5692(2008)1:1;1-6
1756-5901(2009) 1:1;l-m
Submit your work now!

Pages 1–212
www.rsc.org/metallomics
Supporting the
ISSN 1144-0546
PAPER
Registered Charity Number 207890 T. Yong-Jin Han et al.
The solubility and recrystallization of
1,3,5-triamino-2,4,6-trinitrobenzene
in a 3-ethyl-1-methylimidazolium
acetate–DMSO co-solvent system 1144-0546(2009)33:1;1-2
launching in 2009
Integrative Biology
Quantitative biosciences from nano to macro
Integrative Biology provides a unique venue for elucidating biological

processes, mechanisms and phenomena through quantitative enabling
Integrative Biology technologies at the convergence of biology with physics, chemistry,
www.rsc.org/ibiology Volume 1 | Number 1 | January 2009 | Pages 1–140 engineering, imaging and informatics.
Journal of Materials Chemistry

With 12 issues published annually, Integrative Biology will contain a
mix of research articles including Full papers, Reviews (Tutorial & Critical),
and Perspectives. It will be supported by an international Editorial Board,
chaired by Distinguished Scientist Dr Mina J Bissell of Lawrence Berkeley
National Laboratory.
The current issue of Integrative Biology will be freely available to all
readers via the website. Free institutional online access to all 2009 and
ISSN 1757-9694
2010 content of the journal will be available following registration at
Pages 1–140
1757-9694(2009) 1:1;1
0959-9428(2008)18:1;1-J
www.rsc.org/ibiology_registration
Contact the Editor, Harp Minhas, at ibiology@rsc.org or visit the website for more details.
060858
ISSN 1144-0546
www.rsc.org/ibiology
Registered Charity Number 207890
PAPER
Rudi van Eldik et al.
Metal ion-catalyzed oxidative degradation of Orange II by H2O2.
High catalytic activity of simple manganese salts
NJC
New Journal of Chemistry. An international journal for the chemical sciences
www.rsc.org/njc
RSC Publishing is a not-for-profit publisher and a division of the Royal Society of Chemistry. Any surplus made is used to support charitable
activities aimed at advancing the chemical sciences. Full details are available from www.rsc.org
IN THIS ISSUE
ISSN 1144–0546 CODEN NJCHES 33(1) 1–212 (2009)
Cover Inside Cover

See T. Yong-Jin Han et al., See Rudi van Eldik et al.,
pp. 50–56. pp. 34–49.
A very strong inter- and intra- Organic dyes from industrial
molecular hydrogen bonding waste water effluents can cause
solid, 1,3,5-triamino-2,4,6- large scale pollution of natural
trinitrobenzene, can be dissolved rivers. Simple metal ions catalyze
and recrystallized in a 3-ethyl-1- the oxidative degradation of such
methylimidazolium acetate–DMSO dyes and rapidly clean the
co-solvent system. Image polluted water. Image
reproduced with the permission of reproduced with permission of
Lawrence Livermore National Erika Ember, Sabine Rothbart,
Laboratory and T. Yong-Jin Han, Ralph Puchta and Rudi van Eldik
Philip F. Pagoria, Alexander E. Gash, from New J. Chem., 2009, 33, 34.
Amitesh Maiti, Christine A. Orme,
Alexander R. Mitchell and Laurence
E. Fried from New J. Chem., 2009,
33, 50.
CHEMICAL SCIENCE
C1
Drawing together research highlights and news from all RSC
publications, Chemical Science provides a ‘snapshot’ of the
latest developments across the chemical sciences, showcasing
newsworthy articles and significant scientific advances.
EDITORIAL
17
Changes ahead for NJC in 2009
Denise Parent and Sarah Ruthven highlight the changes

to NJC for the year ahead, together with the latest news
from the RSC.
This journal is
c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009 New J. Chem., 2009, 33, 3–16 | 3
EDITORIAL STAFF
Editor (RSC)
NJC
Sarah Ruthven New Journal of Chemistry
Editor (CNRS) An international journal for the chemical sciences
Denise Parent
Assistant editors www.rsc.org/njc
Marie Cote (CNRS) The New Journal of Chemistry is a broad-based primary journal encompassing all branches
Sarah Dixon (RSC)
of the chemical sciences. Published monthly, it contains full research articles, letters, opinions
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LETTERS
19
Evidence of crystalline/glassy intermediates in bismuth
phosphates
Marie Colmont,* Laurent Delevoye and Olivier Mentré
The wide NMR chemical shift range of 17O provides a
profitable source of information about partially ordered
materials. In addition, original phosphorous/oxygen
through-bond correlation experiments have allowed the
unambiguous assignment of the 17O resonances.
23
A supramolecular sensing system for AgI at nanomolar
levels by the formation of a luminescent
AgI– TbIII–thiacalix[4]arene ternary complex
Nobuhiko Iki,* Munehiro Ohta, Teppei Tanaka,

Takayuki Horiuchi and Hitoshi Hoshino
The first example of the detection of AgI ions using
supramolecular chemistry is demonstrated, in which two
thiacalix[4]arene ligands are linked by analyte AgI ions and
then coordinate to TbIII ions to form a luminescent ternary
complex, AgI2 TbIII2 TCAS2, enabling the detection of AgI at
concentrations as low as 3.2 10 9 M.
PAPERS
26
Ionic liquids with dual biological function: sweet
and anti-microbial, hydrophobic quaternary
ammonium-based salts
Whitney L. Hough-Troutman, Marcin Smiglak,
Scott Griffin, W. Matthew Reichert, Ilona Mirska,
Jadwiga Jodynis-Liebert, Teresa Adamska, Jan Nawrot,
Monika Stasiewicz, Robin D. Rogers* and Juliusz Pernak*
Newly synthesized dual function ionic liquids combine both
anti-microbial and sweetener properties into one compound.
34
Metal ion-catalyzed oxidative degradation of Orange II
by H2O2. High catalytic activity of simple manganese
salts
Erika Ember, Sabine Rothbart, Ralph Puchta and

Rudi van Eldik*
In an effort to develop new routes for the clean oxidation
of non-biodegradable organic dyes, a detailed study of some
environmentally friendly Mn(II) salts that form very efficient
in situ catalysts for the activation of H2O2 in the oxidation of
substrates such as Orange II under mild reaction conditions,
was performed.
This journal is
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PAPERS
50
The solubility and recrystallization of 1,3,5-triamino-2,4,6-
trinitrobenzene in a 3-ethyl-1-methylimidazolium
acetate–DMSO co-solvent system
T. Yong-Jin Han,* Philip F. Pagoria, Alexander E. Gash,
Amitesh Maiti, Christine A. Orme, Alexander R. Mitchell
and Laurence E. Fried
A highly hydrogen-bonded solid, 1,3,5-triamino-2,4,6-
trinitrobenzene (TATB), was dissolved and recrystallized
in various IL systems. Dissolution of TATB in EMImOAc
occurred by forming a very stable s-complex.
57
Supramolecular synthesis of some molecular adducts
of 4,40 -bipyridine N,N0 -dioxide
Kapildev K. Arora, Mayura S. Talwelkar and

V. R. Pedireddi*
4,4’-Bipyridine N,N0 -dioxide has yielded different types of
supramolecular assemblies from simple stacked sheet structures
to pseudorotaxane and stair-case type structures depending
upon its interaction with the co-crystallizing agents used in the
supramolecular synthesis.
64
Synthesis and characterisation of bulky guanidines and
phosphaguanidines: precursors for low oxidation state
metallacycles
Guoxia Jin, Cameron Jones,* Peter C. Junk,
Kai-Alexander Lippert, Richard P. Rose and
Andreas Stasch
Reactions of alkali metal amides or phosphides with the bulky
carbodiimide, ArNQCQNAr (Ar = C6H3Pri2-2,6), followed
by aqueous work-ups, have yielded several guanidines, a
bifunctional guanidine and two phosphaguanidines (e.g. see
picture).
76
The hydrogen bond acidity and other descriptors
for oximes
Michael H. Abraham,* Javier Gil-Lostes,

J. Enrique Cometto-Muňiz, William S. Cain,
Colin F. Poole, Sanka N. Atapattu, Raymond J. Abraham
and Paul Leonard
The hydrogen bond acidity of cyclohexanone oxime and
acetone oxime are 0.33 and 0.37, respectively; this places
oximes as about the same hydrogen bond acidity as alcohols.
This journal is
Make an impact
Chemical Communications
www.rsc.org/chemcomm Number 39 | 21 October 2007 | Pages 3969 – 4060
ISSN 1359-7345 FEATURE ARTICLES

COMMUNICATION Yoshinori Yamanoi and Hiroshi Nishihara
Takahiko Kojima et al. Assembly of nanosize metallic particles
A discrete conglomerate of a and molecular wires on electrode surfaces
distorted Mo(V)-porphyrin with a DonnaG.Blackmond and Martin Klussmann
directly coordinated Keggin-type Assessing phase behavior models for the
polyoxometalate evolution of homochirality 1359-7345(2007)39;1-Y
Introducing Professor Mike Doyle
Associate Editor for Organic Chemistry

Michael P. (Mike) Doyle is Professor and Chair of the Department of Chemistry
and Biochemistry at the University of Maryland, College Park. He has been the
recipient of numerous awards, including the George C. Pimentel Award for
Chemical Education in 2002 and the Arthur C. Cope Scholar Award in 2006. He
has written or coauthored ten books, including Basic Organic Stereochemistry, 20
book chapters, and he is the co-author of more than 270 journal publications. The
inventor of chiral dirhodium carboxamidate catalysts known as “Doyle catalysts,”
his research is focused on applications with metal carbene transformations,
Lewis acid catalyzed reactions, and selective catalytic oxidations.
“ChemComm is an outstanding forum
for the communication of significant
research in the chemical sciences, and
Submit your work to ChemComm I am honoured to be a member of
the editorial family. I continue to be
Professor Doyle will be delighted to receive submissions from North amazed with the breadth of exciting
America in the field of organic chemistry. Submissions to ChemComm chemistry that is being submitted
are welcomed via ReSourCe, our homepage for authors and referees. to ChemComm and the high level
of professionalism that is found at
ChemComm.”
020878
www.rsc.org/chemcomm
PAPERS
82
Electrochemical methodology for determination
of imidazolium ionic liquids (solids at room temperature)
properties: influence of the temperature
M. P. Stracke, M. V. Migliorini, E. Lissner,
H. S. Schrekker, D. Back, E. S. Lang, J. Dupont* and
R. S. Gonçalves*
Electrochemical impedance spectroscopy for determination
of imidazolium ionic liquid physicochemical properties: the
influence of the temperature on the Nyquist diagrams.
88
A new family of biocompatible and stable magnetic
nanoparticles: silica cross-linked pluronic F127 micelles
loaded with iron oxides
Zhaoyang Liu,* Jun Ding and Junmin Xue*

A new family of magnetic nanoparticles, silica cross-linked
pluronic F127 micelles loaded with iron oxides having the
properties of high biocompatibility, physical and chemical
stability, high magnetism, and low-cost production, have been
synthesized.
93
Novel thiophene-conjugated indoline dyes for zinc oxide
solar cells
Takuya Dentani, Yasuhiro Kubota, Kazumasa Funabiki,

Jiye Jin, Tsukasa Yoshida, Hideki Minoura,
Hidetoshi Miura and Masaki Matsui*
The introduction of thiophene ring(s) into D131-type indoline
dyes improved cell performance due to their appropriate
energy levels and bathochromic shift in the UV-vis absorption
band on zinc oxide.
102
Gold imidazolium-based ionic liquids, efficient catalysts
for cycloisomerization of c-acetylenic carboxylic acids
Florentina Nea]u, Vasile I. Pârvulescu,
Véronique Michelet, Jean-Pierre Gênet,
Alexandre Goguet and Christopher Hardacre
Ionic liquid stabilized gold(III) chloride is shown to be a very
active catalyst in the cyclization of sterically hindered and
unhindered acetylenic carboxylic acid substrates even in the
absence of a base.
This journal is
Chemistry at Oxford:
A History from 1600 to 2005
A fascinating and unique history of the
Oxford Chemistry School!
● Discover how individuals have shaped the

school and made great achievements in
teaching and research
● Read about the seminal works of Robert Boyle,
Hinshelwood, Robinson and Hodgkin
● Discover how separate branches of chemistry
(organic, physical, inorganic and biological)
have evolved in Oxford
● Get to grips with the unusual character of
Oxford University and learn more about its
unique history.
This fantastic new book will appeal to all those interested in the history and present day style
of science, especially chemistry, education and research at Oxford as contrasted with that to
be found elsewhere.
10070
Hardback | 300 pages | ISBN 9780854041398 | 2008 | £54.95
www.rsc.org/books
PAPERS
107
Magnetically moveable bimetallic (nickel/silver)
nanoparticle/carbon nanotube composites for methanol
oxidation
Guan-Ping Jin,* Ronan Baron, Neil V. Rees, Lei Xiao and
Richard G. Compton*
The functionalization of carbon nanotubes with both AgNPs
and a minute fraction of NiNPs add to the electrocatalytic
properties of the AgNPs, the possibility to easily move them in
solution using a magnet. The bi-functionalized carbon
nanotubes are then easily recoverable after use.
112
Microwave-assisted facile synthesis of discotic liquid
crystalline symmetrical donor–acceptor–donor triads
Satyam Kumar Gupta, V. A. Raghunathan and

Sandeep Kumar*
The first examples of columnar phase forming
triphenylene-anthraquinone-based donor–acceptor–donor
triads were prepared and characterized by polarizing optical
microscopy, differential scanning calorimetry and
X-ray diffractometry.
119
Synthesis, crystal structures and luminescence properties
of lanthanide oxalatophosphonates with a
three-dimensional framework structure
Yanyu Zhu, Zhengang Sun,* Yan Zhao, Jing Zhang,
Xin Lu, Na Zhang, Lei Liu and Fei Tong
Six new three-dimensional (3D) lanthanide
oxalatophosphonates, [Ln(HL)(C2O4)0.5(H2O)2] H2O
(Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6);
H3L = H2O3PCH(OH)CO2H), have been synthesized and
structurally characterized. Compound 6 shows strong red
luminescence in the solid state at room temperature.
125
The annular tautomerism of the curcuminoid
NH-pyrazoles
Pilar Cornago,* Pilar Cabildo, Rosa M. Claramunt,

Latifa Bouissane, Elena Pinilla, M. Rosario Torres and
José Elguero
The structures of six NH-pyrazoles, derived from curcumin
and related b-diketones, have been established by
X-ray crystallography, and solid state 13C and 15N CPMAS
NMR spectroscopy.
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Registered Charity Number 207890 PERSPECTIVE
Zhaohua Dai and James W. Canary
Tailoring tripodal ligands for
zinc sensing 1144-0546(2007)31:10;1-8
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PAPERS
136
Neutral 5-nitrotetrazoles: easy initiation with low pollution
Thomas M. Klapötke,* Carles Miró Sabaté and

Jörg Stierstorfer
New synthesis, crystal structures and characterization of
neutral 5-nitro-2H-tetrazole, 1-methyl-5-nitrotetrazole and
2-methyl-5-nitrotetrazole are presented. These nitrogen-rich
compounds were tested to be highly energetic with increased
sensitivities towards impact, friction and electrical discharge.
148
Probing multivalency for the inhibition of an enzyme:
glycogen phosphorylase as a case study
Samy Cecioni, Oana-Andreea Argintaru, Tibor Docsa,

Pál Gergely, Jean-Pierre Praly and Sébastien Vidal*
The concept of multivalency was applied to the inhibition
of an enzyme (glycogen phosporylase). Trivalent inhibitors
were synthesized and displayed improved activities in
comparison to their monovalent counterparts.
157
The formation of silver nanofibres by liquid/liquid
interfacial reactions: mechanistic aspects
Kun Luo and Robert A. W. Dryfe*

Silver nano-fibres deposited by spontaneous reduction at the
water/organic interface.
164
The role of nucleophilic catalysis in chemistry and
stereochemistry of ribonucleoside H-phosphonate
condensation
Michal Sobkowski,* Jacek Stawinski and Adam Kraszewski
Reactions of ribonucleoside 30 -H-phosphonates with alcohols
proceed with high stereoselectivity towards the same
diastereomer irrespective of the presence or absence of
nucleophilic catalysts.
This journal is
PAPERS
171
Two polyaminophenolic fluorescent chemosensors for
H+ and Zn(II). Spectroscopic behaviour of free ligands
and of their dinuclear Zn(II) complexes
Gianluca Ambrosi, Cristina Battelli, Mauro Formica,
Vieri Fusi,* Luca Giorgi, Eleonora Macedi,
Mauro Micheloni,* Roberto Pontellini and Luca Prodi
UV-Vis and fluorescence properties of two polyamino-phenolic
ligands; design of new efficient fluorescent chemosensors for
H+ and Zn(II) ions.
181
Dynamic covalent self-assembled macrocycles prepared
from 2-formyl-aryl-boronic acids and 1,2-amino alcohols
Ewan Galbraith, Andrew M. Kelly, John S. Fossey,

Gabriele Kociok-Köhn, Matthew G. Davidson,
Steven D. Bull* and Tony D. James*
Reaction of 2-formyl-aryl-boronic acids with
1,2-amino alcohols results in dynamic covalent self assembly
to quantitatively afford tetracyclic macrocyclic Schiff base
boracycles containing bridging boron–oxygen–boron
functionality.
186
N-Inversion in 2-azabicyclopentane derivatives: model
simulations for a laser controlled molecular switch
Bastian Klaumünzer* and Dominik Kröner

Quantum model simulation of a N-inversion based laser
controlled molecular switch by IR-ladder-climbing or UV.
196
How does non-covalent Se?SeQO interaction stabilize
selenoxides at naphthalene 1,8-positions: structural and
theoretical investigations
Satoko Hayashi, Waro Nakanishi,* Atsushi Furuta,
Jozef Drabowicz, Takahiro Sasamori and Norihiro Tokitoh
Non-covalent G?SeQO 3c–4e interactions are demonstrated
to determine the fine structures of 8-G-1-[MeSe(O)]C10H6 and
operate to protect from racemization of the selenoxides: G of
SeMe acts more effectively than G of halogens.
14 | New J. Chem., 2009, 33, 3–16 This journal is

c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
PAPERS
207
Mechanistic aspects of nitrate ion reduction on silver
electrode: estimation of O–NO2 bond dissociation
energy using cyclic voltammetry
Mohsin Ahmad Bhat, Pravin Popinand Ingole,
Vijay Raman Chaudhari and Santosh Krishna Haram*
Cyclic voltammetric investigations for nitrate ion reduction
at silver electrode in alkaline medium, show that reaction
follows a concerted dissociative electron transfer mechanism,
with bond dissociation energy of O–NO2 bond of
ca. 48.4 kcal mol 1.
42nd IUPAC CONGRESS Chemistry Solutions

2–7 August 2009 | SECC | Glasgow | Scotland | UK
Call for abstracts Plenary speakers

This is your chance to take part in IUPAC 2009. Contributions Peter G Bruce, University of St Andrews
are invited for oral presentation by 16 January 2009 and poster Chris Dobson, University of Cambridge
abstracts are welcome until 5 June 2009. Ben L Feringa, University of Groningen
Sir Harold Kroto, Florida State University
Themes Klaus Müllen, Max-Planck Institute for Polymer Research
L Analysis & Detection Sir J Fraser Stoddart, Northwestern University
L Chemistry for Health Vivian W W Yam, The University of Hong Kong
L Communication & Education Richard N Zare, Stanford University
L Energy & Environment
L Industry & Innovation For a detailed list of symposia, keynote speakers and to submit
L Materials an abstract visit our website.
L Synthesis & Mechanisms
Sponsored by
www.iupac2009.org
This journal is
AUTHOR INDEX
Abraham, Michael H., 76 Funabiki, Kazumasa, 93 Kröner, Dominik, 186 Praly, Jean-Pierre, 148
Abraham, Raymond J., 76 Furuta, Atsushi, 196 Kubota, Yasuhiro, 93 Prodi, Luca, 171
Adamska, Teresa, 26 Fusi, Vieri, 171 Kumar, Sandeep, 112 Puchta, Ralph, 34
Ambrosi, Gianluca, 171 Galbraith, Ewan, 181 Lang, E. S., 82 Raghunathan, V. A., 112
Argintaru, Oana-Andreea, 148 Gash, Alexander E., 50 Leonard, Paul, 76 Rees, Neil V., 107
Arora, Kapildev K., 57 Gênet, Jean-Pierre, 102 Lippert, Kai-Alexander, 64 Reichert, W. Matthew, 26
Atapattu, Sanka N., 76 Gergely, Pál, 148 Lissner, E., 82 Rogers, Robin D., 26
Back, D., 82 Gil-Lostes, Javier, 76 Liu, Lei, 119 Rose, Richard P., 64
Baron, Ronan, 107 Giorgi, Luca, 171 Liu, Zhaoyang, 88 Rothbart, Sabine, 34
Battelli, Cristina, 171 Goguet, Alexandre, 102 Lu, Xin, 119 Sasamori, Takahiro, 196
Bhat, Mohsin Ahmad, 207 Gonçalves, R. S., 82 Luo, Kun, 157 Schrekker, H. S., 82
Bouissane, Latifa, 125 Griffin, Scott, 26 Macedi, Eleonora, 171 Smiglak, Marcin, 26
Bull, Steven D., 181 Gupta, Satyam Kumar, 112 Maiti, Amitesh, 50 Sobkowski, Michal, 164
Cabildo, Pilar, 125 Han, T. Yong-Jin, 50 Matsui, Masaki, 93 Stasch, Andreas, 64
Cain, William S., 76 Haram, Santosh Krishna, 207 Mentré, Olivier, 19 Stasiewicz, Monika, 26
Cecioni, Samy, 148 Hardacre, Christopher, 102 Michelet, Véronique, 102 Stawinski, Jacek, 164
Chaudhari, Vijay Raman, 207 Hayashi, Satoko, 196 Micheloni, Mauro, 171 Stierstorfer, Jörg, 136
Claramunt, Rosa M., 125 Horiuchi, Takayuki, 23 Migliorini, M. V., 82 Stracke, M. P., 82
Colmont, Marie, 19 Hoshino, Hitoshi, 23 Minoura, Hideki, 93 Sun, Zhengang, 119
Cometto-Muňiz, J. Enrique, 76 Hough-Troutman, Whitney Miró Sabaté, Carles, 136 Talwelkar, Mayura S., 57
Compton, Richard G., 107 L., 26 Mirska, Ilona, 26 Tanaka, Teppei, 23
Cornago, Pilar, 125 Iki, Nobuhiko, 23 Mitchell, Alexander R., 50 Tokitoh, Norihiro, 196
Davidson, Matthew G., 181 Ingole, Pravin Popinand, 207 Miura, Hidetoshi, 93 Tong, Fei, 119
Delevoye, Laurent, 19 James, Tony D., 181 Nakanishi, Waro, 196 Torres, M. Rosario, 125
Dentani, Takuya, 93 Jin, Guan-Ping, 107 Nawrot, Jan, 26 van Eldik, Rudi, 34
Ding, Jun, 88 Jin, Guoxia, 64 Nea]u, Florentina, 102 Vidal, Sébastien, 148
Docsa, Tibor, 148 Jin, Jiye, 93 Ohta, Munehiro, 23 Xiao, Lei, 107
Drabowicz, Jozef, 196 Jodynis-Liebert, Jadwiga, 26 Orme, Christine A., 50 Xue, Junmin, 88
Dryfe, Robert A. W., 157 Jones, Cameron, 64 Pagoria, Philip F., 50 Yoshida, Tsukasa, 93
Dupont, J., 82 Junk, Peter C., 64 Pârvulescu, Vasile I., 102 Zhang, Jing, 119
Elguero, José, 125 Kelly, Andrew M., 181 Pedireddi, V. R., 57 Zhang, Na, 119
Ember, Erika, 34 Klapötke, Thomas M., 136 Pernak, Juliusz, 26 Zhao, Yan, 119
Formica, Mauro, 171 Klaumünzer, Bastian, 186 Pinilla, Elena, 125 Zhu, Yanyu, 119
Fossey, John S., 181 Kociok-Köhn, Gabriele, 181 Pontellini, Roberto, 171
Fried, Laurence E., 50 Kraszewski, Adam, 164 Poole, Colin F., 76
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c the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
January 2009 / Volume 6 / Issue 1 / ISSN 1478-6524 / CSHCBM / www.rsc.org/chemicalscience
Chemical Science
Light-responsive azobenzene groups have brought polymers to life
Polymers strut their stuff under the spotlight
Chemists in Japan have created allows the film to act as a hinge joint
light-driven polymer films that and move flexibly. By controlling
walk like inchworms and move like the intensity of the light and the
robotic arms. position on the film where the light
The films, made by Tomiki is concentrated, the researchers can
Ikeda at the Tokyo Institute of make the film move as they chose.
Technology in Yokahama and ‘The polymers function with a
collaborators, contain a polymer minimum of moving parts which
which contracts when visible light minimises friction and surface
shines on it and expands again contact problems,’ says Ikeda. ‘One
under UV light. can envisage applications such as
The polymers respond to light direct light-to-mechanical energy
because they have azobenzene conversion, storage systems and in
groups – which contain N=N microfluidic devices.’
double bonds – incorporated into Graeme George, an expert in
them. Under visible light the N=N polymer science at Queensland
bonds have a cis conformation University of Technology,
which means the polymer is Brisbane, Australia, commends
bent. But when the light source is ‘the efficiency of the reversible
changed to UV the bonds become photo-processes.’ He adds that the
trans and the polymer flattens. time is ripe for further detailed
To make the polymer walk, polymer flattens, pushing the front Light can be used to studies of such systems to see if
the group incorporated it in a flat end forward. This continuous make the polymer film these photo driven polymers offer
laminated film with one pointed flattening–bending motion allows move like a robotic arm any challenge to their electroactive
end (at the back of the ‘worm’) the film to move forward like an counterparts.
and one flat end (at the front inchworm. Ruth Doherty
of the ‘worm’). As the polymer The robotic arm also requires
bends the pointed back end is clever lamination, but this time Reference
dragged forward then, when the the polymer layer and laminated T Ikeda et al, J. Mater. Chem., 2009, 19, 60
light source is changed to UV, the sections are alternated which (DOI: 10.01039/b815289f)
In this issue
Glowing report for explosive detection
Scientists are developing a new method to thwart terrorists
Crinkly tunnels aid gas storage

Trifluorolactate crystals may offer an alternative route to
hydrogen fuel cells
Porphyrins get energetic

This month’s Instant insight outlines recent advances in the
construction of interlocked molecules
Lighting a billion lives

Nobel peace prize winner Rajendra K Pachauri talks about
understanding climate change and giving light to humanity
A snapshot of the latest developments from across the chemical sciences

©The Royal Society of Chemistry 2009 Chem. Sci., 2009, 6, C1–C8 C1
CS.01.09.C1.indd 20 15/12/2008 15:00:16

Chemical Science
Research highlights
Capillary tubes offer cut price alternative to on-chip diagnostics
Cheaper than chips
French scientists have developed Defrancq.
a photochemical method for Once in place, the biomolecules
patterning biomolecules inside glass can bind cell proteins or antibodies
capillary tubes. The technique could present in biological fluids that are
lead to lab-on-capillary devices as flushed through the tube. These
cheaper alternatives to lab-on-a-chip protein and antibody biomarkers
medical diagnostics, they claim. can be used to identify disease
Eric Defrancq, at Joseph Fourier risk or progression or measure
University, Grenoble, and colleagues the effect of treatments. Different
say their lab-on-capillary vision biomolecules can be attached in
poses considerable challenges. the one tube, which permits multi-
‘Retaining the functionality and analyses to be performed in one
patterning of biomolecules in the experiment.
closed environment of a capillary ‘The challenge now is to use these
tube is difficult because there is no techniques to attach more complex
easy access to the inside surface,’ carbohydrates and proteins without
explains Defrancq. The exposed aminooxy groups Biomolecules can be losing the recognition properties
Defrancq overcame these then reacted with aldehyde groups patterned to the inside of of the immobilised biomolecule for
challenges by grafting patterns in the peptide and carbohydrate glass capillary tubes its target,’ says Defrancq. ‘It is only
of aminooxy groups masked with biomolecules, fixing them to the too easy to lose recognition during
photocleavable protecting groups to side of the tubes. ‘This method of the immobilisation process through
Reference
the inside surface of the capillaries. attaching molecules in patterns N Dendane et al, Lab Chip, either the chemistry or the methods
By shining light on the tubes, he allows us to position not just one 2008, 18, 2161 (DOI: 10.1039/ used.’
removed the protecting groups. biomolecule but many,’ explains b811786a) Janet Crombie
Why leaves turn red and orange during the autumn is not yet fully understood
Hints behind autumnal tints
Austrian scientists unravel the colourless, they were thought not to
secrets behind the dramatic colours contribute to the colours we see in
of autumn. autumn.
Bernhard Kräutler and colleagues These compounds were
at the University of Innsbruck, considered to be the final products
have shown for the first time that of chlorophyll breakdown, but
a yellow breakdown product of now Kräutler has shown that they
chlorophyll contributes to the may be oxidised to give a yellow-
colours of autumn. coloured compound. Using leaves
The change in autumn leaf colour from the Katsura Tree, a deciduous
is a phenomenon that affects the tree known for its beautiful autumn
normally green leaves of many leaves, they successfully detected
deciduous trees and shrubs. Every this yellow chlorophyll breakdown
year, for a few weeks in autumn, product, thus proving its existence.
a range of colours including The similarity in structure
intense yellows and reds shape the between bilirubin, a natural
landscape. So far, these colours have compound reported to help
been attributed to carotenoids and protect cells from damage, and this
flavonoids, explains Simone Moser, oxidised breakdown product may
a member of the research team. The suggest they too have important
colours are already present in the physiological properties. Moser says
leaf, but are not visible due to the The breakdown of chlorophyll Chlorophyll breakdown the team are interested in finding
predominant green of chlorophyll. is a process that was considered products may contribute out just what roles, if any, these
As autumn progresses chlorophyll an enigma until about 20 years to the colours of autumn compounds play in the plant.
disappears unmasking these ago, when the first non-green Sarah Corcoran
hidden colours. But this is not the chlorophyll breakdown product Reference
whole story, according to these was discovered, says Moser. As S Moser et al, Photochem. Photobiol. Sci., 2008,
researchers. these breakdown products were 7, 1577 (DOI: 10.1039/b813558d)
C2 Chem. Sci. , 2009, 6, C1–C8 ©The Royal Society of Chemistry 2009
CS.01.09.C2.indd 20 15/12/2008 15:04:15

Chemical Science
Scientists are developing a new method to thwart terrorists

Glowing report for explosive detection
Israeli scientists have developed a
sensitive method for detecting TATP
– an explosive popular with terrorists.
Triacetone triperoxide, or TATP,
is an explosive that has been used
by suicide bombers in Israel since
the 1980s. It was also employed by
the thwarted British ‘shoe bomber’
Richard Reid in December 2001 and
is alleged to have been used in the
London bombings of July 2005.
The explosive’s ingredients are
common chemicals and the material
does not contain nitrogen so can
pass through many scanners for
nitrogenous explosives. Detection
methods have been developed for
TATP in the past, but now Eran Sella a reporter group which fluoresces The dendrimer breaks explosive and, because one molecule
and Doron Shabat from Tel-Aviv at 510 nanometres when released down, and fluoresces, of hydrogen peroxide causes
University have designed a method from the polymer structure. The when exposed to each dendrimer to release three
that detects the explosive without any trigger for the dendrimer breakdown hydrogen peroxide fluorescent reporter molecules, a
sample pretreatment, and also simply is hydrogen peroxide, one of the readable detection signal can be
amplifies the resulting fluorescent natural decomposition products of obtained for TATP present on the
signal. The scientists say that samples the explosive. microgram scale.
could be collected in the real-world Most colour-producing tests Using more highly branched
using a swab or by vacuum. for TATP require the explosive to polymers each containing more
Their method uses a type be pretreated with acid, say the fluorescently-tagged building blocks
of dendrimer (a repeatedly scientists, so that it decomposes to ‘will significantly increase the
branched tree-like polymer) that produce large amounts of hydrogen detection sensitivity’, says Shabat.
spontaneously breaks down into its peroxide. But this new method is ‘The main challenge’, he says, ‘will
separate building blocks following a sensitive enough to detect the tiny be to selectively identify TATP in the
Reference
single trigger event. The dendrimer amounts of hydrogen peroxide E Sella and D Shabat, Chem. presence of other “powders” that
was designed to consist of three generated by the small degree Commun., 2008, 5701 (DOI: contain oxidative species’.
building blocks that each contains of natural decomposition of the 10.1039/b814855d) Freya Mearns
An European Union ban has reduced levels of the marine pollutant tributyltin
The tale of the snail
Gender-switching in mud snails has of Aveiro, Portugal, and colleagues years, albeit at a slow rate,’ says
decreased following a European measured the penis lengths in Simon Apte, the leader of the centre
Union ban on tributyltin (TBT) in the female snails to determine of environmental contaminants
ship hull paint. TBT pollution levels. ‘The main research at the CSIRO in Sydney,
TBT is an antifouling agent motivation to conduct this work was Australia.
that was used in paint to prevent to find if the legislation implemented Although TBT levels are
organisms from growing on the by the EU was effective,’ says Rato. decreasing, they are still high, Rato
hulls of ships. Unfortunately, it was They found a decrease in the levels comments. ‘Further monitoring
found that once it enters the water of imposex, and therefore a decrease surveys should be carried out in
it has a toxic effect on other marine in the levels of TBT, with hotspots order to determine whether these
organisms. By 2003, the use of these being found within harbours that EU measures are sufficient to reduce
paints was banned by the EU. contain marinas and commercial environmental TBT to a safe level,’
In the mud snails Nassarius fishing ports. From these results the he adds.
reticulatus TBT was found to cause group concluded that the regulation Rebecca Brodie
the imposex condition, where has had a favourable impact on
females develop male sexual pollution levels. Reference
characteristics such as a penis. Tributyltin causes ‘The data show that some recovery M Rato et al, J. Environ. Monit., 2009,
Milene Rato from the University imposex in female snails has occurred over the last five DOI:10.1039/b810188d
CS.01.09.C3.indd 30 15/12/2008 15:07:51

Chemical Science
Trifluorolactate crystals may offer an alternative route to hydrogen fuel cells

Crinkly tunnels aid gas storage
Japanese scientists have found a
new way to store gases based on
restraining gas molecules within
narrow tunnels.
Gas storage in microporous
materials generally relies on
physisorption – involving weak
Van der Waals interactions – to fill
the micropores with gas, explains
Toshimasa Katagiri, from Okayama
University, who led the research
team. Their new storage method
involves physically restraining the
gas within narrow tunnels (less than
one nanometre diameter) running gas molecules within the tunnel. Trifluorolactate crystals example, can be altered by changing
through nanoporous trifluorolactate ‘The unique adsorption–desorption can be adapted to store the length of the organic chain in the
crystals. properties of these materials are different gases trifluorolactates.
Katagiri and the team suggest very inspiring as they show the ‘We are now trying to grow a
that their new tunnel system may be great potential of engineered hybrid perfect single crystal with tunnels.
useful for storing gaseous molecules systems where hydrocarbon and They could act as true molecular
with weak physisorption, such as fluorocarbon domains alternate,’ sieves for separating gaseous
hydrogen, and could have fuel cell comments Giuseppe Resnati, molecules by their size, at room
applications. an expert in nanostructured temperature. Such a system would be
The internal tunnel surface materials at the Polytechnic of Milan, a key technology for the realisation
is serrated, thanks to the Italy. of a hydrogen fuel cell vehicle with
trifluoromethyl groups protruding The tunnel properties can be Reference
a methanol reforming system,’ says
into the tunnel cavity. These optimised to improve storage of a T Katagiri et al, CrystEngComm, Katagiri.
protrusions physically restrain the specific gas. Tunnel diameter, for 2009, DOI: 10.1039/b814508c Russell Johnson
A change of solvent found to dramatically improve important organic reactions

Fluorination gets a good reaction
European chemists have found that In particular, he reports that it is
using fluorinated solvents in olefin ‘possible to increase the metathesis
metathesis reactions substantially reaction yield by up to 18 times
improves the product yields by changing the solvent from 1,2-
obtained. dichloroethane to perfluorotoluene.’
The metathesis reactions of Jie Wu, professor of chemistry
alkenes (olefins) form a vital part at Fudan University, Shanghai,
of the armoury of transformations China, adds: ‘This is an excellent
available to synthetic organic improvement in metathesis
chemists. They provide a way of reactions, which will find
breaking and remaking carbon- applications in the synthesis of
carbon double bonds – allowing the advanced natural and biologically
substituent groups to be swapped active compounds.’
– and are usually catalysed by Grela says that uncovering the
transition metal complexes. nature of this effect and improving
Commercially available catalysts, the recycling efficiency of the
such as Grubbs’, remain popular valuable catalysts – to satisfy the
among chemists but are often guidelines of green chemistry – are
ineffective in more difficult reactions the next steps in his work.
like the multi-step total synthesis Poland, and colleagues have found Fluorinated solvents David Parker
of natural products and biologically that the yields of reactions using improve yields by up to
active molecules. these catalysts can be dramatically 18 times Reference
Karol Grela, from the Polish improved by using fluorinated C Samojłowicz et al, Chem. Commun., 2008,
Academy of Science, Warsaw, aromatic hydrocarbon solvents. 6282 (DOI: 10.1039/b816567j)
C4 Chem. Sci. , 2009, 6, C1–C8 ©The Royal Society of Chemistry 2009
CS.01.09.C4.indd 20 15/12/2008 15:15:33

Chemical Science
Instant insight
Porphyrins get energetic
Jonathan Faiz, Valérie Heitz and Jean-Pierre Sauvage, University of Strasbourg,
France, outline recent advances in the construction of interlocked molecules
inspired by photosynthesis
Artificially recreating photosynthesis

– in the quest to find environmentally
friendly and renewable energy
sources – is a hot topic across many
scientific disciplines. It is now
known that porphyrin-like units are
key features of the reaction centre
where photosynthesis occurs, and
synthetically reproducing these
molecules has become a very active
research area.
Porphyrins are planar and highly
conjugated cyclic molecules that can
complex a variety of metals. They
are found in many natural systems,
including blood (as hemoglobin in
their iron-complexed forms) and in
the photosynthetic reaction centre
(as magnesium-complexed chlorins, sketched on paper, the construction A transition metal ion route has given access to a wide
chlorophylls – which are structurally of catenanes or rotaxanes is not can hold together the variety of architectures in which
very similar to porphyrins). trivial. This is because attractive components needed to electron transfer can occur between
The electrochemical and forces are needed to hold the make a catenane porphyrins and, for example,
photoactive properties of porphyrins components together, to template fullerenes and electron-deficient
make them ideal for performing the reaction, before either the rings aromatic macrocycles.
energy and electron transfer in a are closed (in the case of catenanes) Rotaxanes have also been made
similar fashion to photosynthesis. or the stoppers are attached with a manganese porphyrin ring
Importantly their ability to form (rotaxanes). that has an olefin-containing
noncovalent interactions, with a One construction method is the backbone threaded through it. The
metal centre, can be exploited to form use of transition-metal templates, ring can zip along the backbone
mechanically interlocked systems where the various components and catalyse the oxidation of the
– such as catenanes and rotaxanes of the macrocycle contain 1,10- olefins in the backbone to epoxides
– that incorporate porphyrins in their phenanthroline units that can – demonstrating the sheer breadth
structure. coordinate to copper(i) ions of application of these porphyrin-
One of the most remarkable – holding the components in place. containing systems.
features of catenanes (two or several The rotaxanes and catenanes then Mechanically interlocked
interlocked rings) and rotaxanes form around the metal ion, that is porphyrin-containing architectures
(two-component assemblies removed once the macrocycle is are important synthetic analogues
consisting of a central thread constructed. This method has been of natural systems as they contain
encapsulated by a ring and stoppered used to make a comprehensive subunits held at predetermined
by two bulky units on each end of the range of rotaxanes, with porphyrin distances and geometries – but not
thread to stop the ring slipping off ) stoppers, and catenanes, containing through conventional covalent
is their high flexibility, meaning they porphyrins rings. bonds. In this way, just like natural
can undergo a very large number of Other templating methods systems, any intercomponent process
different motions. These movements for rotaxanes include the use of that occurs between subunits takes
are important in photosynthesis as hydrogen-bonding or π-stacking place through the shortest pathways,
they facilitate electron transfer. The interactions to either form a such as through hydrogen bonds or
motions occur both naturally due to macrocycle around a thread already solvent.
the molecules inherent energy (when bearing stoppers or to hold the
all the components are not or only macrocycle around the thread Read Jean-Pierre Sauvage’s tutorial
very weakly interacting), and when whilst the stoppers are grafted. The review ‘Design and Synthesis of
the molecule’s most stable geometry size and metal-binding properties Reference
Porphyrin-Containing Catenanes
is altered by an external stimulus. of porphyrins make them ideal J Faiz et al., Chem. Soc. Rev., and Rotaxanes’ in issue 2, 2009 of
Although seemingly simple when for stoppers for rotaxanes. This 2009, DOI: 10.1039/b710908n Chemical Society Reviews
Instant Insight_SAUVAGE.indd 40 15/12/2008 15:16:54

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s å
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Chemical Science
Interview
Lighting a billion lives
Rajendra K Pachauri speaks to Leanne Marle about shedding light on climate
change and giving light to humanity
What do you think have been the key achievements of other developing countries in the region but globally.
the Intergovernmental Panel on Climate Change (IPCC) Apart from the work on energy, climate change
during your time as chairman? and environmental issues, we are also involved
I think the IPCC as a whole has been an extremely in substantial scientific activities, for instance
significant success story. What I think we have done biotechnology research. We do a substantial amount
rather well with the Fourth Assessment Report [an of work at the grass roots level, too – the one thing
IPCC report on climate change] is to have closed a that I’m now focusing on, and which I think will
number of gaps in knowledge. We’ve produced some be my mission for the next 10 years, is what I call
very clear statements, largely because the scientific ‘lighting a billion lives’. What’s extremely tragic
basis is now much more robust. This includes a firm is the fact that 1.6 billion people in the world still
statement saying that warming of the climate system don’t have access to electricity or modern forms of
is unequivocal and that there’s a high probability energy – that’s a quarter of humanity. If you wait for
that during the last five decades or so, the warming all these places to be connected to the grid and to
that has taken place is a result of human actions. An get electricity, it will take a long, long time. We have
extremely significant step that we have been able to developed a set of solar lanterns and torches, which
take is with respect to disseminating the results of are really attractive to people in villages in several
Rajendra K Pachauri this particular report. parts of the world. If we can mobilise the resources
for making these available, it can create market
Rajendra K Pachauri is the What key areas will the IPCC focus on in the future? based solutions in these villages.
current chairman of the We’re actually in the midst of a detailed dialogue
Intergovernmental Panel within the IPCC in defining what our role and focus What are your thoughts on the new RSC journal Energy
on Climate Change and the should be in the future. The IPCC has decided & Environmental Science?
director general of the Energy to continue with the five or six year cycles of I think that any such medium by which knowledge
and Resources Institute in New comprehensive assessment reports and the fifth can be created and provided to people is an excellent
Delhi, India. assessment report will come out by 2014. This will initiative. I think the focus that you [the journal]
require some new efforts in terms of developing have, which embraces all aspects of chemistry,
scenarios of what’s going to happen in the future chemical engineering and so on, will be of great
and running climate models to come up with some value as it will be a major contribution to the
of the answers that will form the basis of the next creation of knowledge and the production of an
report. In addition, we will carry out work on area of literature where we still need an enormous
special reports, which would be in response to a amount of expansion and improvement.
need for focussed and very specific information on
subjects of relevance. We’re already working on the You have recently been awarded an honorary doctorate
production of a special report on renewable energy. from the University of East Anglia. What advice would
So I think essentially we are going to build on what you give to young scientists graduating today?
we have achieved so far and try to address demands Well, I would only say that this is a period of
as they come from our audience from all over the great excitement. We really have to start thinking
world and ensure that the IPCC plays the role that outside the box. When we have this privilege of
the world expects it to. getting higher education, we should ensure that
we do so because I really believe the world needs
You are also Director General for the Energy and to change on a massive scale. That has to be carried
Resources Institute. What research are they currently out by the people who have the benefit of higher
involved in? education and the exuberance of youth. So I would
This is an institute that I have been with for over a tell students that are in the university system
quarter of a century. When I started, all I had was right now to just look at the horizons beyond and
a part time secretary and one room. We are now a also look at the world in its entirety. As I said in
fairly large institution with over 750 people and a the acceptance speech for the Nobel Peace Prize,
presence in different parts of the world including we have a Hindu saying, which is Vasudhaiva
the UK, the US, Japan and more recently Africa, kutumbakam, which means ‘the universe is a
the Middle East and Malaysia. We have emerged family’. We have to keep that in focus whatever we
not merely as an institution that focuses on India or learn and whatever we do.
CT.interview pachauri.indd 15 15/12/2008 15:18:17

Chemical Science
Essential elements
Double debut And finally...
Materials science researchers
joined RSC Publishing last
This month sees the mice, cytotoxicity month at a celebration reception
debut of two highly of chemical warfare at the Fall MRS 2008 meeting.
interdisciplinary new degradation products, Authors and readers were
journals from RSC and identification and thanked for their continued
Publishing: Integrative characterisation of support, while RSC journal Soft
Biology: Quantitative metallodrug binding Matter announced its increase in
biosciences from nano to proteins. Visit frequency for 2009 and five years
macro and Metallomics: www.rsc.org/ of successful publication.
Integrated biometal science. metallomics Delegates were invited to
Integrative Biology is Authors from around pre-order the latest edition
a unique journal focused the globe have submitted of the bestselling textbook,
on quantitative multiscale work of the highest Nanochemistry by Geoff Ozin,
biology using enabling quality, knowing that and take part in a prize draw to
technologies and tools to they can rely on RSC staff win a solar powered charger in
exploit the convergence of samples and much more. for overseeing a rigorous celebration of the 2008 launch of
biology with physics, chemistry, Visit www.rsc.org/ibiology peer-review process, efficient Energy & Environmental Science.
engineering, imaging and Metallomics covers the manuscript handling and rapid
informatics. The first issue research fields related to metals publication.
contains articles on human in biological, environmental and The current issues of both
mammary progenitor cell clinical systems and is expected new journals are freely available
fate decisions, the analysis of to be the core publication for to all readers via the website.
aptamer binding sequence– the emerging metallomics Free institutional online access
activity relationships using community. First issue articles to all 2009/2010 content will
microarrays, and genome-wide include a look at the effect be available following a simple
transcriptome analysis of 150 cell of vanadium(IV) in diabetic registration process.
InChI collaboration with ChemSpider

The InChI Resolver will give The InChI Resolver will
researchers the tools to create be based on ChemSpider’s
standard InChI data for their own existing database of over 21
compounds, create and use search million chemical compounds
engine-friendly InChIKeys to and will provide the first stable
search for compounds, and deposit environment to promote the
An InChI Resolver, a unique their data for others to use in the use and sharing of compound Looking ahead, preparations
free service for scientists to share future. data. ‘With the introduction of are underway for the Third
chemical structures and data, is to ‘The wider adoption and the InChI Resolver, we hope to International ChemComm
be developed via a collaboration unambiguous use of the InChI expand the utility and value of Symposium, which is to be
between ChemZoo Inc., host of standard will be an important both InChI and the ChemSpider held in China next month. The
ChemSpider, and RSC Publishing. development for the future of service,’ adds Antony Williams of subject will be organic chemistry
Using the InChI – an IUPAC chemistry publishing, and further Chemspider. and keynote speakers include
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EDITORIAL www.rsc.org/njc | New Journal of Chemistry
Changes ahead for NJC in 2009

DOI: 10.1039/b820900f
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as NJC’s Editor-in-Chief for the past Australia is a new step for NJC. With impact factors rising, it is clear to see that
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LETTER www.rsc.org/njc | New Journal of Chemistry
Evidence of crystalline/glassy intermediates in bismuth phosphates

Marie Colmont,* Laurent Delevoye and Olivier Mentré
Received (in Montpellier, France) 3rd September 2008, Accepted 27th October 2008
First published as an Advance Article on the web 14th November 2008
DOI: 10.1039/b815388b
31
P and 17O NMR investigations have been achieved on bismuth local probes. Indeed, recent technical advances in solid state
oxide phosphates by a comparison between ordered and semi- NMR has led to the emergence of this technique by adapting it
ordered reference compounds; the wide chemical shift range for for use with low natural abundance nuclei having relatively
17
O is revealed to be a profitable source of information about small gyromagnetic ratios, such as 17O. In addition, it is worth
partially ordered materials. mentioning that impedance spectroscopy measurements on all
of these materials (ordered and disordered) show low ionic
Bi2O3–MO–P2O5, (M = Co, Cu, Cd, Zn, Mn. . .) ternary mobilities due to the strong P–O bonds involved for most of
systems have been well investigated, leading to the charac- the oxygen ions. Therefore, only the static aspect is considered
terization of new bismuth oxide phosphates having particular hereafter.
structural relationships.1–8 As intensively detailed,9 the Thus, the present work focuses on a comparison between a
rigid frameworks of these materials can be considered as an typical ordered and disordered compound, with the aim of
assembly by the edge sharing of O(Bi,M)4 polyhedra, leading establishing the pertinence, complementarities, and limits of
to infinite polycationic ribbons of variable width: one, two, both 31P and 17O nuclei as probes with regard to the structural
three, . . . tetrahedra wide, surrounded by isolated PO4 groups. aspects of ordered vs. semi-ordered materials. With that aim in
From XRD/ND crystal structure studies, we classified these mind, two compounds have been selected from among the
compounds as ‘‘disordered’’ or ‘‘ordered’’, depending on the series:
competition (or not) between several O4 configurations around (i) BiCd2PO6 was chosen as the archetype of ordered
the central P sites. Indeed, in ordered compounds such as compounds. Its structure is isostructural to BiZn2PO6,15,16
BiM2PO6,3,4,10,11 the Bi3+ cations strictly sit in the middle of and it is interesting because it crystallizes in the Bbmm space
ribbons, whereas the M2+ cations are located at their edges. group, while many members of the BiM2PO6 class (including
Similarly, in disordered compounds, e.g. Bi1.2M1.2PO5.5,7 Bi3+ the M = Zn term) adopt the less symmetrical Pnma space
cations still occupy the middle of the ribbons, whereas the group. The coordination around its unique phosphorus posi-
edges of the ribbons are filled by mixed site Bi3+/M2+. This tion is constituted by two independent O2 (2) and O3 (2)
statistical distribution leads to a variable orientation of the atoms, while O1 is located in the two tetrahedra-wide ribbons
PO4 groups, depending on the local nature of its first (Bi, M) at the center of a OBi2Cd2 tetrahedron (Fig. 1(a)).
cationic shell. The disorder is all the more important because it (ii) The simplest disordered compounds have the
also affects partially filled cationic channels (so-called tunnels BiB1.2MB1.2PO5.5 general formula (M = Mn, Co, Zn). Their
hereafter) surrounded by PO4 groups in between pairs of structure (space group Icma) is formed of triple ribbons with
ribbons. Of course, the notion of disorder is inexact because
of the existence at the microscopic scale of incommensurate
modulated phenomena (mainly along b*) in most of the
disordered compounds.12–14 This extra information does not
survive over long range scales, e.g., it is not observed in the
XRD of single crystals. Therefore, sometimes only ordered
fragments of the disordered PO4/tunnel interstitial areas can
be assumed from the average crystal structure, on the basis of
plausible interatomic distances.13 However, structural interac-
tions between the edges of the ribbons, PO4 groups and the
tunnel is far from being fully established, probably due to
various phenomena, including anti-phase boundary defects
within tunnels and the probable semi-ordered zones in these
materials. In view of a complementary approach to these
fascinating series and by an easy extension to different com- Fig. 1 The structures of (a) BiCd2PO6 and (b) Bi1.2Zn1.2PO5.5. BiCd2PO6
pounds, 31P and 17O NMR spectroscopy have been used as consist of [Cd4Bi2O2]-ordered double ribbons surrounded by six
isolated ordered phosphates. Bi1.2Zn1.2PO5.5 is disordered because of
(1) the presence of mixed Bi3+/Zn2+ sites at the edges of triple
UCCS, Unité de Catalyse et Chimie de Lille, UMR-CNRS 8181,
Ecole Nationale Supérieure de Chimie de Lille, Universite´ des [(Bi0.15Zn0.85)4Bi4O6] ribbons, (2) disordered tunnels, partially occupied
Sciences et Technologies de Lille, BP 90108, 59655 Villeneuve d’Ascq, by Zn2+, and (3) multiple PO4 configurations around the same
France. E-mail: marie.colmont@ensc-lille.fr phosphorus.
This journal is
mixed Bi/M edges (for M = Zn: 15% Bi3+/85% Zn2+). The presence of the quadrupolar interactions of the nuclei (spin
partially M-filled tunnels and surrounding disordered PO4 I = 5/2) that largely broaden signals. This requires suitable
groups are shown in Fig. 1(b). Only one phosphorus position techniques, such as double rotation (DOR),18 multiple-
exists, even if it has finally been split into two close satellites, quantum magic angle spinning (MQ-MAS)19 or satellite
P1 (B50%) and P2 (B50%), in the published model. To avoid transition magic angle spinning (ST-MAS),20 in order to
any paramagnetic perturbation, the M = Zn compound was remove the anisotropic broadenings that remain under magic
selected. It is noteworthy that the influence of Cd2+ for Zn2+ angle spinning conditions.
replacement in BiM2PO6 on the 31P NMR chemical shift has 17
O MAS NMR: Fig. 3 shows the high resolution MQ-MAS
already been fully quantified on the basis of the empirical z/a2 spectra of (a) BiCd2PO6 and (b) Bi1.2Zn1.2PO5.5. The horizontal
parameter,15 and no additional contribution is expected projections (top) correspond to MAS spectra still broadened by
between these two neighboring cations. The possibility of the second order quadrupolar interaction. The vertical projec-
quantifying the local cationic environment of the PO4 groups tions reveal 17O isotropic spectra of the two compounds, where
in a Bi(M,M 0 )PO6 statistical solid solution compounds has the quadrupolar broadening is removed, i.e., each maximum
also been enhanced. peak corresponds to a given oxygen environment. The
31
P MAS NMR: Fig. 2(a) and (b) show the 31P NMR spectra resonance at 90 ppm, marked with an asterisk, corresponds
of BiCd2PO6 against Bi1.2Zn1.2PO5.5, which clearly reveals the to a spinning sideband of site A on the isotropic dimension.
broadening of the signal for the latter due to the multitude of The two spectra show two groups of resonances, around
individual resonances in the disordered compound. It is com-
parable to the IR spectra of ordered vs. disordered compounds
presented elsewhere.13 In that sense, the broad envelope does
not show discrete contributions but rather a continuum. Here,
in addition to the local distortion of each individual PO4
group, the influence of the nature of the neighboring Zn/Bi
cationic shell has to be considered.15 Furthermore, the 31P
double quantum MAS-NMR spectrum shows no particular
privileged out-of-diagonal correlations (Fig. 2(c)) reminiscent
of a glass-like state from the 31P NMR resolution.
Since oxygen occupies both the polycationic regular
sublattice and the disordered interstitial regions, 17O NMR
analysis would be expected to give relevant information about
disorder. Here, samples were enriched via the 17O enrichment
method developed by Flambard et al.17 Due to the presence of
water vapor, the sample was checked by 1H NMR to ensure
that all protons disappeared at the end of the enrichment.
Another difficulty in obtaining 17O NMR spectra is the
Fig. 2 31P MAS-NMR (9.4 T) spectra of (a) BiCd2PO6 and (b)

Bi1.2Zn1.2PO5.5. The spectra were acquired at an MAS speed of Fig. 3 17O MQ-MAS NMR (18.8 T) spectra of (a) BiCd2PO6 and (b)
10 kHz, with a short pulse excitation of 1.5 ms (201) and a recycling Bi1.2Zn1.2PO5.5. The spectra were acquired at an MAS speed of
delay of 20 s. (c) 31P double quantum MAS-NMR spectrum of 20 kHz, with a recycling delay of 1 s, using the SPAM sequence.24
Bi1.2Zn1.2PO5.5. The spinning frequency was 10 kHz. The excitation The excitation and reconversion pulses were set to 3.75 ms and 1.20 ms,
and reconversion period was composed of back-to-back 901 pulses21 of respectively, corresponding to an RF field strength of 80 kHz,
4 ms, which gave a total excitation/reconversion time of 400 ms. The followed by a selective 901 pulse of 11 ms (RF field of 8 kHz). For
repetition time was 30 s, preceded by a presaturation period. A total of spectrum (a), each transient was accumulated with 72 scans, and 128 t1
16 scans were used and 64 t1 increments were collected. The data points were collected using the STATES method. For (b), a total
31
P chemical shift was referenced externally to an 85% H3PO4 solution of 4500 scans were needed and 30 t1 increments were collected. The
17
at 0 ppm. O chemical shift was referenced externally to tap water.

180–250 ppm and around 50–130 ppm (see the MAS projec-
tions). The region around 200 ppm (resonance A) is assigned to
O(Bi,M)4 tetrahedral sites in the polycationic ribbons. The
value of the chemical shifts are close to those determined for
OBi4 tetrahedra in related compounds, 195 ppm in Bi2O322 and
265 ppm in a-Bi4V2O11.23 Our assignment was indirectly con-
firmed by a 17O T2 relaxation measurement (using a saturation
recovery pulse sequence) performed on the BiCd2PO6 com-
pound. The A site exhibited a short T2 relaxation time of about
200 ms, maybe due to the presence of Bi quadrupolar nuclei in
its first-neighbour cationic shell (111Cd and 113Cd are non-
quadrupolar). A similar measurement was not possible for the
disordered compound due to the low efficiency of the isotopic
enrichment (probably because the 17O-enriched water had
already been used in previous experiments).
Ordered compound: The second region around 100–160 ppm
is typically in the chemical shift range of oxygens involved in
PO4 groups.25 In BiCd2PO6, it is composed of two resonances,
B (120 ppm, T2 = 5 ms) and C (100 ppm, T2 = 500 ms),
corresponding to O2 and O3. This assignment arises from their Fig. 4 The 31P–17O HMQC (18.8 T) spectrum of BiCd2PO6 was
proximity or otherwise to quadrupolar Bi nuclei in their obtained at a MAS speed of 25 kHz by following the pulse sequence
second cationic shell (Table 1). It was checked by a 31P–17O detailed by Massiot et al.26 An echo was applied to the observed 17O
heteronuclear multiple quantum correlation (HMQC)26 nuclei with respective 901 and 1801 pulses of 10 and 20 ms. Two 901
experiment that a correlation existed between the unique pulses of 4.5 ms were then applied on either sides of the 17O 1801 pulse.
31 The evolution delay was set to 3 ms for an evolution under J-coupling.
P site and the 17O–B sites (Fig. 4). However, no correlation
A total of 512 scans were accumulated with a recycling delay of 1 s.
signal was detected for the 17O–C sites due to the very short T2
relaxation time (500 ms). It is also noteworthy that both A and
C showed broad isotropic resonances compared to B. So far, with the 17O spectrum obtained for BiCd2PO6. One region
this is not understood in this ‘‘ordered’’ compound. Note the corresponds to oxygen atoms linked to ribbons (resonance A)
presence of a broad signal of low intensity in the 17O dimen- between 160 and 240 ppm. Referring to the structure presented
sion (Fig. 4), which is due to an impurity obtained after the in Fig. 1(b), two oxygen sites should be distinguishable in the
process of enrichment and was not detected by XRD. isotropic dimension, whether they are at the center (O1Bi4) or
Semi-ordered compound: Next, we analyzed a semi-ordered at the edge (O2Bi2Zn2) of the ribbon. A close look at the two-
compound, Bi1.2Zn1.2PO5.5. The 17O MQ-MAS NMR spec- dimensional contours clearly suggests the presence of more
trum is shown in Fig. 2(b). Two isolated regions are high- than two sites, probably due to the high sensitivity of the 17O
lighted in the 2D spectrum. The broadness of the peaks seen in NMR chemical shift to the cationic environment, even at a
the isotropic projection is a signature of the high disorder semi-local scale (second shell cationic neighbours). The
present in this system, as discussed in the first part of this presence of additional oxygen sites is easily explained by
work. The assignment of both regions was deduced by analogy the existence of a mixed Bi/Zn cationic site at the edge of
the ribbon. The assignment of each individual resonance is not
yet possible due to the current absence of a large 17O NMR
Table 1 The environment of the oxygen atoms (distances in Å) in chemical shift database for these systems. The development of
BiCd2PO6 and Bi1.2Zn1.2PO5.5. The first shell is given for the oxygen of such a database would require a series of model compounds
the ribbons and the first two shells are presented for the oxygen of the
PO4 groups.15,16 to be isotopically enriched for further 17O MAS NMR
analysis. The second option available is to profit from the
BiCd2PO6 Bi1.2Zn1.2PO5.5a recent development of first principles calculations of NMR
1st shell 2nd shell 1st shell parameters using periodic boundary conditions.27 The latter
approach, which is beyond the scope of this Letter, is definitely
O1–Bi1 2 2.27(2) O2–Bi1 2 2.243(1)
Cd2 2 2.18(2) Bi/Zn2 2 2.159(9) more realistic at present.
The chemical shift region centred on 50–150 ppm exhibits
O2–P 1 1.43(3) O1–Bi1 4 2.299(1) two main resonances in the isotropic projection. These can be
Cd2 2 2.22(2) 2 3.41(3) assigned to the oxygen atoms in the PO4 groups. First, it
Bi1 1 3.70(3)
should be noted that the 17O resonances are spread over a
O3–P 1 1.51(4) large chemical shift range, especially in the isotropic dimension
Cd2 1 2.11(4) 2 3.29(2) when the second order quadrupolar broadening is removed.
Bi1 2 3.41(2)
Bi1 1 3.65(4)
This large distribution of chemical shift values with respect to
a
the so-called ordered compound, BiCd2PO6, reveals the
The coordination of the disordered PO4 groups is not accurately
important disorder associated with the PO4 groups in these
known.
systems. Nevertheless, some discontinuities associated with
This journal is
discrete chemical shift values appear in the isotropic dimen- References
sion. This strongly suggests that some PO4 positions are
1 M. Huvé, M. Colmont and O. Mentré, Chem. Mater., 2004, 16,
privileged, as observed from the single crystal X-ray diffrac- 2628.
tion data. For example, two major competing PO4 positions 2 M. Ketatni, O. Mentré, F. Abraham, F. Kzaiber and B. Mernari,
have been located in Bi1.2M1.2PO5.5, while residual electronic J. Solid State Chem., 1998, 139, 274.
3 J. Huang, Q. Gu and A. W. Sleight, J. Solid State Chem., 1993,
density on Fourier difference maps is reminiscent of a number
105, 599.
of extra orientations. Again, the current 17O NMR chemical 4 F. Abraham, M. Ketatni, G. Mairesse and B. Mernari, Eur. J.
shift database is not sufficient to fully interpret the spectrum in Solid State Inorg. Chem., 1994, 31, 313.
the P–17O–M region. 5 M. Colmont, M. Huvé and O. Mentré, Inorg. Chem., 2006, 45(17),
6612.
This study highlights the informative data provided by 17O 6 M. Huvé, M. Colmont and O. Mentré, Inorg. Chem., 2006, 45(17),
NMR due to its broad range of chemical shifts compared to 6604.
the 31P nucleus. In disordered bismuth phosphates, 17O NMR 7 F. Abraham and M. Ketatni, Eur. J. Solid State Inorg. Chem.,
clearly provides evidence of preferential PO4 orientations, in 1995, 32, 429.
8 M. Ketatni, F. Abraham and O. Mentré, Solid State Sci., 1999, 1,
good agreement with the semi-ordering deduced from diffrac- 449.
tion data, which shows modulated microdomains with loss of 9 F. Abraham, O. Cousin, O. Mentré and M. Ketatni, J. Solid State
the order at long range scales. Of course, the methodology and Chem., 2002, 167, 168.
10 X. Xun, S. Uma, A. Yokochi and A. W. Sleight, J. Solid State
conclusions developed here are not restricted to our particular Chem., 2002, 167, 245.
chemical system, but can be generalized to other partially- 11 A. Mizrahi, J. P. Wignacourt and H. Steinfink, J. Solid State
ordered systems, solid solutions, composite structures and Chem., 1997, 133, 516.
so on. Finally, it is worth stating that, to the best of our 12 M. Ketatni, M. Huvé, F. Abraham and O. Mentré, J. Solid State
Chem., 2002, 172, 327.
knowledge, a successful 31P–17O through-bond correlation has 13 M. Colmont, M. Huvé, M. Ketatni, F. Abraham and O. Mentré,
been presented here for the first time. J. Solid State Chem., 2003, 176, 221.
14 M. Colmont, M. Huvé, F. Abraham and O. Mentré, J. Solid State
Chem., 2004, 177, 4149.
Experimental section 15 M. Colmont, L. Delevoye, E. M. Ketatni, L. Montagne and
O. Mentré, J. Solid State Chem., 2006, 179, 2111.
The different oxides reported in this Letter were prepared from 16 E. M. Ketatni, B. Mernari, F. Abraham and O. Mentré, J. Solid
stoichiometric mixtures of Bi2O3, MO (M = Cd, Zn) and State Chem., 2000, 153, 48.
17 A. Flambard, L. Montagne and L. Delevoye, Chem. Commun.,
(NH4)2HPO4. To avoid the problem of volatile species, they 2006, 28, 3426.
were removed by solid state reparative methods, implying 18 (a) A. Samoson, E. Lippmaa and A. Pines, Mol. Phys., 1998,
several heating–regrinding steps at temperatures from 200 to 65, 1013; (b) A. Llor and J. Virlet, Chem. Phys. Lett., 1998, 152,
700 1C. The purity of the samples was checked by powder 248.
19 L. Frydman and J. S. Harwood, J. Am. Chem. Soc., 1995, 117,
X-ray diffraction using a Siemens D-5000 diffractometer with 5367.
back-monochromatized Cu-Ka radiation. NMR experimental 20 Z. Gan, J. Am. Chem. Soc., 2000, 122, 3242.
information is given in the Figure captions. 17O enrichment 21 M. Feike, D. E. Demco, R. Graf, J. Gottwald, S. Hafner and
H. W. Spiess, J. Magn. Reson., Ser. A, 1996, 122, 214.
was achieved by heating samples at 650 1C for 8 h under 22 S. Yang, K. D. Park and E. Oldfield, J. Am. Chem. Soc., 1989, 111,
17
O-enriched water vapor.15 7278.
23 N. Kim and P. Grey, Science, 2002, 297, 1317.
24 J.-P. Amoureux, L. Delevoye, S. Steuernagel, Z. Gan,
Acknowledgements S. Ganapathy and L. Montagne, J. Magn. Reson., 2005, 172,
268.
The FEDER Région Nord Pas-de-Calais, Ministère de 25 M. Zeyer, L. Montagne, V. Kostoj, G. Palavit, D. Prochnow and
l’Education Nationale, de l’Enseignement Supérieur et de la C. Jaeger, J. Non-Cryst. Solids, 2002, 311, 223.
Recherche, CNRS, USTL and ENSC-Lille are acknowledged 26 D. Massiot, F. Fayon, B. Alonso, J. Trébosc and J.-P. Amoureux,
J. Magn. Reson., 2003, 164, 160.
for funding the NMR spectrometers. M. C. thanks the Région 27 C. J. Pickard and F. Mauri, Phys. Rev. B: Condens. Matter Mater.
Nord Pas-de-Calais for financial support. Phys., 2001, 63, 2451.

LETTER www.rsc.org/njc | New Journal of Chemistry
A supramolecular sensing system for AgI at nanomolar levels by the

formation of a luminescent AgI–TbIII–thiacalix[4]arene ternary complexw
Nobuhiko Iki,* Munehiro Ohta, Teppei Tanaka, Takayuki Horiuchi
and Hitoshi Hoshino
Received (in Durham, UK) 22nd September 2008, Accepted 10th November 2008
First published as an Advance Article on the web 1st December 2008
DOI: 10.1039/b816596c
The first example of the detection of AgI ions using supra- in an aqueous solution at pH 4 8.5 by the ligation of a
molecular chemistry is demonstrated, in which two thiacalix[4]- bridging sulfur and two adjacent phenol oxygen donors.
arene ligands are linked by analyte AgI ions and then coordinate Complex 1 exhibits strong luminescence due to the presence
to TbIII ions to form a luminescent ternary complex, AgI2TbIII2 of the TbIII ion, whose excitation energy is transferred from
TCAS2, enabling the detection of AgI at concentrations as low TCAS in a triplet excited state.6 The luminescence of 1 allows
as 3.210 9 M. the detection of the TbIII ion at nanomolar levels.7 Further-
more, TCAS, TbIII and AgI ions form a luminescent ternary
One of the most significant contributions of supramolecular complex, AgI2TbIII2TCAS2 (2), at a pH of around 6.8 In this
chemistry has been the development of a precise strategy to pH region, only a small fraction of the TbIII ions are com-
design fluorescent chemosensors with high selectivities and plexed by TCAS.6,8 This suggests that AgI can be detected by
sensitivities for heavy metal ions.1 This strategy involves the measuring the luminescence of complex 2, which is formed in
covalent joining of a specific binding unit of a metal ion and a the presence of TbIII ions and TCAS at a pH of 6 (see the
signal-transducing unit (Fig. 1).2 The former is a ligating graphical abstract).
group that is carefully selected after considering factors that Accordingly, when [TbIII]T = 1.0 10 6 and [TCAS]T =
will affect its selectivity, such as the affinity of donor atoms to 2.0 10 6 M at a pH of 6.1 (T = total), the dependence of the
analyte cations and the stereochemistry of the resulting com- luminescence intensity at 544 nm, assigned as the 5D4 - 7F5
plex. The latter is a fluorophore, whose photophysical proper- transition of TbIII, on the AgI concentration was investigated
ties are susceptible to changes such as excimer formation/ (Fig. 3). For a wide range of AgI concentrations, the intensity
dissociation, photoinduced electron transfer, charge transfer increased almost linearly as [AgI]T increased from nanomolar
and energy transfer caused by metal binding. The validity of to sub-micromolar levels. This demonstrates that AgI can be
this strategy, termed the covalent strategy, has been demon- detected by the formation of ternary complex 2. For higher
strated by many of the fluorescent sensors that have been [AgI]T levels (42.0 10 7 M), the dependence showed a slight
synthesized.2 For instance, a ratiometric sensor, where pyrene upward convex curve. This can be attributed to the fact that
is attached as a signaling unit to a ligand having N,O donors, [AgI]T attains a concentration level equivalent to that of TbIII
has been designed to enable the detection of AgI ions at and the availability of TbIII ions to form complex 2 is low.
micromolar levels in a 50 : 50 v/v EtOH–water mixture.3 When [AgI]T r 2.0 10 8 M, a linear calibration curve was
The strategy seems to have been derived on the premise that obtained by least-square fitting, as shown in eqn (1).
two different processes occurs in analyte sensing—recognition
Luminescence intensity = 76.5 108 ([AgI]T/M) + 437 (1)
and signaling. Although this strategy is useful, it does not
provide much scope for alternative methods of designing Surprisingly, the detection limit (DL) at S/N = 3 was
sensors or sensing systems. In this Letter, we present a system determined to be 3.2 10 9 M (0.35 ppb). This shows that
for sensing AgI ions by the formation of a luminescent
complex using supramolecular chemistry,4 where the analytes
and components are synergistically assembled to function as a
sensor.
Since the development of a facile one-step method to
synthesize thiacalix[4]arene, we have been interested in
its inherent complexing properties and applications.5 For
example, thiacalix[4]arene-p-tetrasulfonate (TCAS, Fig. 2)
reacts with a TbIII ion to form a 1 : 1 complex, TbIIITCAS (1),
Graduate School of Environmental Studies, Tohoku University,

6-6-07 Aramaki-Aoba, Aoba-ku, Sendai 980-8579, Japan.
E-mail: iki@orgsynth.che.tohoku.ac.jp; Fax: +81 22-795-7293;
Tel: +81 22-795-7222
w Electronic supplementary information (ESI) available: Experimental
details for sample preparation and ESI-MS of complex 3. Fig. 1 Covalent strategy for designing metal sensors.
This journal is
Fig. 2 The structure of TCAS, and complexes 1 and 2. Fig. 4 The effect of a five-fold increase in concentration of ‘‘foreign
ions’’ added to AgI on the luminescence signal. I and I0 indicate the
luminescence intensity for samples with and without foreign ions,
respectively. Samples: [foreign ion]T = 0 or 5.0 10 7 M, [AgI]T =
1.0 10 7 M, [TbIII]T = 1.0 10 6 M, [TCAS]T = 2.0 10 6 M
and [MES buffer]T = 4 10 3 M (pH = 5.9). lex = 323 and
lem = 544 nm.
form complex 2. Therefore, it is likely that CuII and FeIII ions

formed ternary complexes with TCAS and TbIII ions, thereby
reducing the availability of TbIII ions; this results in the for-
mation of an insufficient amount of 2. In addition, such an
M–TbIII–TCAS ternary complex would be non-luminescent
because paramagnetic CuII and FeIII ions readily quench the
excited states of the TCAS ligand. In contrast, CdII caused a
positive deviation (+116%) in the signal. Thus, it follows that
CdII should have formed a luminescent CdII–TbIII–TCAS
ternary complex that is luminescent, since CdII is a non-
Fig. 3 Calibration graphs for AgI ions. The inset shows the calibra- quenching ion due to its d10 electronic configuration. In fact,
tion curve for the lowest AgI concentrations. Samples: [AgI]T = the CdII–TbIII–TCAS ternary system ([CdII]T = [TbIII]T =
0–100 10 8 M, [TbIII]T = 1.0 10 6 M, [TCAS]T = 2.0 10 6 M 1.0 10 6 M, [TCAS] = 2.0 10 6 M; pH = 6.5)
and [MES buffer]T = 2 10 3 M (pH = 6.11). lex = 323 and yielded a luminescent complex, whose composition was
lem = 544 nm.
CdII2TbIII2TCAS2 (3), as suggested by electrospray ionization-
mass spectroscopy (ESI-MS) measurements, yielding a peak at
the system is more sensitive than covalently designed fluor- m/z = 1101.5983 that is assignable to [2Cd2+ + 2Tb3+ +
escent sensors, which afford the detection of AgI at the 10 6 M Na+ + 3H+ + 2TCAS8 + H2O]2 (Fig. 5; also see ESIw).
level.3,9 Notably, the DL of AgI with 2 is lower than that of In the present system, complex 3, which was formed con-
flame atomic absorption spectrometry (DL 3 ppb) and as comitantly, caused an increase in the luminescence. Among
low as that of inductively-coupled plasma atomic emission the halide ions, iodide caused a negative ( 43%) deviation from
spectroscopy (DL 0.2 ppb).10 the original intensity, I0, which can be attributed to its strong
The selectivity of this system with regard to AgI ions was ability to form the halo complexes [AgXn](n 1) (n = 1–4), as
investigated by adding five times the amount of transition indicated by their stability constants.11
metal cations (M = MnII, FeIII, CoII, NiII, CuII, ZnII, CdII In metal–ion sensors designed using a covalent strategy, the
and PbII) and halide anions (X = Cl , Br and I ) to a roles of each functional group are different (Fig. 1). On the
1.0 10 7 M AgI ion solution. The luminescence intensity other hand, in the present AgI sensing system, it is ambiguous
(at 544 nm), I, was measured and compared to the intensity which moiety of 2 is responsible for the functions of binding
measured in the absence of M or X , I0. As shown in Fig. 4, and signaling. As shown in the schematic drawing of 2 (Fig. 2),
the five-fold increase in MnII and ZnII concentration did not TCAS has four O and four S donors that form the tetrametal
affect the signal intensity of complex 2; however, PbII, CoII core, AgI2TbIII2. Furthermore, there is an antenna present to
and NiII caused a slight change in its intensity. Notably, CuII absorb photons, the energy from which is eventually trans-
and FeIII ions caused negative interference ( 67% and 57%, ferred to the TbIII center. Upon excitation, the TbIII center
respectively). In the TCAS–metal binary systems, CuII and emits light via an f–f transition. From a structural point of
FeIII ions formed complexes with M : TCAS ratios of 2 : 1 and view, TbIII ions accept two sets of O,S,O donations from the
1 : 1, respectively, at a pH of 6. If these complexes had been TCAS ligands. However, it is important to consider that in the
formed in the present system, 1.75 10 7 and 1.5 10 7 M of TbIII–TCAS binary system, TbIII does not form a complex
TCAS would have been available to AgI (1.0 10 7 M) to with TCAS at a pH of 6. Thus, analyte AgI is indispensable in

(2-morphorinoethanesulfonic acid (MES)) and doubly-
distilled water were added. Before the measurement of its
luminescence spectrum, each sample solution was allowed to
stand for 1 h at room temperature to ensure equilibration. The
luminescence spectra were measured using a Hitachi F-4500
fluorescent spectrometer.
Mass spectrometry
ESI-MS experiments were performed using a Fourier trans-
form ion cyclotron resonance mass spectrometer APEX III
(Bruker). Mass spectra were simulated using the program
iMass for Mac OS X version 1.1.12
Acknowledgements
This study was partly supported by a Grant-in-Aid for
Scientific Research (B) (16350039) from the Japan Society
for the Promotion of Science (JSPS).
Fig. 5 Part of the ESI mass spectrum of complex 3, showing
the isotopomer pattern for [2Cd2+ + 2Tb3+ + Na+ + 3H+ +
2TCAS8 + H2O]2 . (a) Observed pattern for a sample ([TCAS]T = References
[CdII]T = [TbIII]T = 2.5 10 5 M, [HCl]T = 5 10 5 M; pH 5.82
(adjusted with NH3)) and (b) simulated pattern. 1 J. M. Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995.
2 For reviews, see: A. P. de Silva, H. Q. Nimal Gunaratne,
T. Gunnlaugsson, A. J. M. Huxley, C. P. McCoy, J. T.
linking two TCAS ligands via S–AgI–S bridges to promote the Rademacher and T. E. Rice, Chem. Rev., 1997, 97, 1515;
coordination of TCAS to TbIII, to form 2. In fact, TCAS B. Valeur and I. Leray, Coord. Chem. Rev., 2000, 205, 3;
formed a 4 : 2 complex, AgI4TCAS2, in the binary system at L. Prodi, F. Bolletta, M. Montalti and N. Zaccheroni, Coord.
Chem. Rev., 2000, 205, 59.
pH 6.8 In conclusion, multidentate and photon-absorbing 3 R. H. Yang, W. H. Chan, A. W. M. Lee, P. F. Xia, H. K. Zhang
TCAS, luminescent TbIII and analyte AgI, with a linear and K. Li, J. Am. Chem. Soc., 2003, 125, 2884.
coordination geometry, were synergistically assembled to form 4 Examples of supramolecular sensing systems can be found in the
following reviews: E. V. Anslyn, J. Org. Chem., 2007, 72, 687;
a supramolecular structure that is capable of sensing AgI ions
T. Hayashita, A. Yamauchi, A. J. Tong, J. C. Lee, B. D. Smith and
at nanomolar concentrations (see graphical abstract). Since N. Teramae, J. Inclusion Phenom. Macrocyclic Chem., 2004, 50, 87.
the sensing function of this system originates from the supra- 5 N. Morohashi, F. Narumi, N. Iki, T. Hattori and S. Miyano,
molecular nature of complex 2, and not from TCAS and Chem. Rev., 2006, 106, 5291.
6 N. Iki, T. Horiuchi, H. Oka, K. Koyama, N. Morohashi,
TbIII individually, complex 2 truly demonstrates the ‘‘supra- C. Kabuto and S. Miyano, J. Chem. Soc., Perkin Trans. 2, 2001,
molecular strategy.’’ Here, it is very important to rationally 2219.
design molecules so that they form supramolecular assemblies 7 T. Horiuchi, N. Iki, H. Oka and S. Miyano, Bull. Chem. Soc. Jpn.,
that display functionalities absent from their individual 2002, 75, 2615.
8 N. Iki, M. Ohta, T. Horiuchi and H. Hoshino, Chem.–Asian J.,
components. 2008, 3, 849.
9 For other examples, see: H. Tong, L. Wang, X. Jing and F. Wang,
Macromolecules, 2002, 35, 7169; J. Raker and T. E. Glass, J. Org.
Experimental Chem., 2001, 66, 6505.
10 J. D. Ingle, Jr. and S. R. Crouch, Spectrochemical Analysis,
Procedure for the detection of AgI ions Prentice Hall, Englewood Cliffs, NJ, 1988.
To a sample solution containing silver(I) nitrate and a 11 R. M. Smith and A. E. Martell, Critical Stability Constants,
Plenum Press, New York, 1976, vol. 4.
particular foreign ion, if any, appropriate amounts of 12 U. Röthlisberger, iMass for Mac OS X v. 1.1, 2002 (http://home.
aqueous solutions of terbium(III) nitrate, TCAS, pH buffer datacomm.ch/marvin/iMass/).
This journal is
PAPER www.rsc.org/njc | New Journal of Chemistry
Ionic liquids with dual biological function: sweet and anti-microbial,

hydrophobic quaternary ammonium-based saltsw
Whitney L. Hough-Troutman,a Marcin Smiglak,a Scott Griffin,a
W. Matthew Reichert,b Ilona Mirska,c Jadwiga Jodynis-Liebert,d Teresa Adamska,d
Jan Nawrot,e Monika Stasiewicz,f Robin D. Rogers*ag and Juliusz Pernak*f
Received (in Montpellier, France) 30th July 2008, Accepted 29th August 2008
First published as an Advance Article on the web 22nd October 2008
DOI: 10.1039/b813213p
The dual nature of ionic liquids has been exploited to synthesize materials that contain two
independent biological functions by combining anti-bacterial quaternary ammonium compounds
with artificial sweetener anions. The synthesis and physical properties of eight new ionic liquids,
didecyldimethylammonium saccharinate ([DDA][Sac]), didecyldimethylammonium acesulfamate
([DDA][Ace]), benzalkonium saccharinate ([BA][Sac]), benzalkonium acesulfamate ([BA][Ace]),
hexadecylpyridinium saccharinate ([HEX][Sac]), hexadecylpyridinium acesulfamate ([HEX][Ace]),
3-hydroxy-1-octyloxymethylpyridinium saccharinate ([1-(OctOMe)-3-OH-Py][Sac]), and
3-hydroxy-1-octyloxymethylpyridinium acesulfamate ([1-(OctOMe)-3-OH-Py][Ace]), are reported,
as well as the single crystal structures for [HEX][Ace] and [1-(OctOMe)-3-OH-Py][Sac].
Determination of anti-microbial activities is described for six of the ILs. While some exhibited
decreased anti-microbial activity others showed a dramatic increase. For two of the ionic liquids,
[DDA][Sac] and [DDA][ACE], oral toxicity, skin irritation, and deterrent activity was also
established. Unfortunately, both ILs received a Category 4 (harmful) rating for oral toxicity and
skin irritation. However, deterrent activity experiments point to use as an insect deterrent, as both
ILs scored either ‘‘very good’’ or ‘‘good’’ against several types of insects.
Introduction themselves.17,18 In addition, those material applications which

have appeared, typically concentrated on a single desirable
Ionic liquids (ILs) are currently defined as salts that are property brought by either the cation or the anion. But ILs, by
composed solely of cations and anions which melt below definition, have at least two discrete types of ions, both of
100 1C. These salts have been studied for a variety of applica- which can provide a unique property or function. Thus, our
tions such as in electrochemistry,1–3 separation science,4–7 goal has been to explore how to exploit the dual nature of ILs
chemical synthesis,8–13 and catalysis,14–16 however, until by preparing materials that possess two functions, particularly
recently, very few, if any, ILs had been used as liquid materials two biological functions. Here, we present the combination of
anti-bacterial quaternary ammonium compounds (QACs)
a
The University of Alabama, Department of Chemistry and Center for with artificial sweeteners.
Green Manufacturing, Tuscaloosa, AL 35487, USA The anti-bacterial properties of QACs were first discovered
b
US Naval Academy, Department of Chemistry, Annapolis, during the late 19th century, amongst carbonium dye com-
MD 21402, USA
c
Poznań University of Medical Sciences, Department of
pounds, such as auramin, methyl violet, and malachite green.19
Pharmaceutical Bacteriology, S´wie˛cickiego, 4 60-781 Poznań, Poland Initially, QACs were found to be most effective against gram-
d
Poznań University of Medical Sciences, Department of Toxicology, positive organisms, until Jacobs and Heidelberger20–23 further
Dojazd 30, 60-631 Poznań, Poland exploited their anti-bacterial properties against other types of
e
Institute of Plant Protection, ul. We˛gorka 20, 60-318 Poznań,
Poland organisms. It was not until 1935 that the full potential of QACs
f
Poznań University of Technology, Faculty of Chemical Technology, was recognized by the chemical community, when the synthesis
pl. Sk!odowskiej-Curie 2, 60-965 Poznań, Poland. of benzalkonium chloride, a long-chain QAC, by Domagk24 and
E-mail: juliusz.pernak@put.poznan.pl
g further characterization of its anti-bacterial activities, proved that
The Queen’s University of Belfast, QUILL, School of Chemistry and
Chemical Engineering, Belfast, Northern Ireland BT9 5AG. QACs were effective against a wider variety of bacterial strains.
E-mail: r.rogers@qub.ac.uk Later, in the 20th century, researchers became more
w Electronic supplementary information (ESI) available: Charac- interested in the synthesis of water-soluble QACs for potential
terization data. Fig. S1: ORTEP (50% probability thermal ellipsoids)
of the asymmetric unit of [HEX][Ace]. Fig. S2: Close contacts around applications as surfactants,25,26 anti-electrostatic agents,27
the cations in [HEX][Ace]. Fig. S3: p-Stacking modes of the polymeric anti-corrosive agents,28 disinfectants,29 and phase-transfer
cation in [HEX][Ace]. Fig. S4: p-Stacking mode of the dimeric cation catalysts.30 These newly developed water-soluble QACs
in [HEX][Ace]. Fig. S5: ORTEP (50% probability thermal ellipsoids) showed anti-bacterial action against not only gram-positive
of the asymmetric unit of [1-(OctOMe)-3-OH-Py][Sac]. CCDC refer-
ence numbers 687477 and 687478. For ESI and crystallographic data and gram-negative bacteria, but also pathogen species of fungi
in CIF or other electronic format see DOI: 10.1039/b813213p and protozoa.31 These discoveries led to applications for

QACs in wood preservation32–34 and as preservatives in benzalkonium saccharinate ([BA][Sac]), benzalkonium acesulfa-
common household products,35 especially for general environ- mate ([BA][Ace]), hexadecylpyridinium saccharinate ([HEX][Sac]),
mental sanitation in hospitals and food production facilities. hexadecylpyridinium acesulfamate ([HEX][Ace]), 3-hydroxy-
Furthermore, QACs have been used as penetration enhancers 1-octyloxymethylpyridinium saccharinate ([1-(OctOMe)-3-OH-
for transnasal and transbuccal drug delivery, such as nasal Py][Sac]) and 3-hydroxy-1-octyloxymethylpyridinium acesulfa-
vaccinations.36 The ability of QACs to penetrate and open cell mate ([1-(OctOMe)-3-OH-Py][Ace]) (Fig. 1) were prepared in
membranes has been widely used in drug delivery such as high yield as hydrophobic salts from commercially available
liposomes, which consists of long alkyl chain QACs, and QACs benzalkonium chloride ([BA][Cl]), didecyldimethyl-
non-viral gene delivery.37 ammonium chloride ([DDA][Cl]), and hexadecylpyridinium
We have had specific interest in employing the IL concept to chloride ([HEX][Cl]), and from one pyridinium salt, 3-hydro-
pair the biological activity of a class of compounds such as xy-1-octyloxymethylpyridinium chloride [1-(OctOMe)-3-OH-
QACs, with a second biological activity inherent in the Py][Cl], which was prepared by a nucleophilic substitution
counterion.38 One such class of ions, which has also seen reaction of 3-hydroxypyridine by octyl chloromethyl ether
independent use in preparing ‘edible’ ILs, includes non- under anhydrous conditions. Each of the cations was paired
nutritive sweeteners such as saccharinate and acesulfame.39,40 with saccharinate or acesulfamate by a stoichiometric metathesis
Salts of these anions are currently used in food products and reaction in aqueous solution, using sodium saccharin ([Na]-
are approved as food additives by most national and global [Sac]) or potassium acesulfame ([K][Ace]). The hydrophobic
health agencies. Yet, only a handful of quaternary ammonium
saccharinates and acesulfamates have been reported in the
literature.41 Here we demonstrate the concept of preparing ILs
by pairing the biological activity inherent in the cation with a
separate biological function possessed by the anion with
the synthesis, physical properties, anti-microbial activities,
toxicity, and deterrent activity of new QAC-based ILs.
Results and discussion

Synthesis and characterization
Synthesis. Didecyldimethylammonium saccharinate ([DDA]-
[Sac]), didecyldimethylammonium acesulfamate ([DDA][Ace]),
Fig. 2 Packing diagram along the a crystallographic axis for [HEX][Ace]

(top) and overlay of the two cations in the asymmetric unit including the
Fig. 1 Structures of the synthesized ILs. anions with close contacts to each (bottom).
This journal is
nature of these salts allowed them to be easily extracted from
the aqueous phase into chloroform.
All of the newly prepared ILs were found to be low melting
solids at room temperature with the exception of [DDA]-
containing salts, the only cation without an aromatic ring,
which were found to be liquid at room temperature. The salts
studied are only sparingly soluble in cold and hot water, but
freely soluble and stable in many organic solvents (e.g., chloro-
form, methanol, ethanol, ethyl acetate, N,N-dimethyl-
formamide (DMF), and dimethyl sulfoxide (DMSO)).
Crystal structures. Single-crystal structures for two of the

compounds, [HEX][Ace] and [1-(OctOMe)-3-OH-Py][Sac],
also confirmed the syntheses. Although not the focus of this
paper, interesting packing behavior was observed which may
provide clues to the low melting nature of these compounds in
particular and QAC ILs in general.
The packing diagram for [HEX][Ace] (Fig. 2) reveals that
the cation tails interdigitate to create charge-rich and hydro-
phobic regions. Closer examination indicates that the two
unique cations are not equivalent with slight differences in
the orientation of the hexadecyl tail groups. This modest
difference leads to completely different packing environments.
One cation p-stacks in a polymeric fashion (Fig. 3) and has
only three close contacts with the anions. The second cation
forms a p-stacked dimer with anions capping each open face.
These cations have five close contacts with the anions.
Fig. 4 illustrates the packing in the structure of [1-(OctOMe)-
3-OH-Py][Sac]. Here the strong hydrogen bonding between the
cation and anion dominates and a single cation/anion pair is
found in the asymmetric unit. These hydrogen bonded ion pairs
stack in alternate directions.
Thermal behavior. The thermal properties of the ILs

(Table 1) were determined by differential scanning calorimetry
(DSC) and thermogravimetric analysis (TGA). All of the
synthesized salts exhibited melting points below 100 1C,
allowing their classification as ILs. Interesting phase transition
Fig. 4 Packing diagram along the a crystallographic axis for
[1-(OctOMe)-3-OH-Py][Sac] (top) and close up of the hydrogen
bonding and alternate stacking of the ion pairs (bottom).
behavior was observed for [DDA][Sac], [DDA][Ace] and

[HEX][Ace] which was not found for the other ILs. These
three ILs had a detectable glass transition-type transforma-
tion at 33, 53 and 11 1C, respectively. Following glass
transition, samples [DDA][Sac] and [Hex][Ace] exhibited
consecutive crystallization and melting transitions. On the
contrary, [DDA][Ace] was the only IL obtained that did not
exhibit any other thermal transition besides a glass transition.
As seen in Table 1, all the ILs were found to be thermally
stable to temperatures ranging between 160 and 210 1C. One-
step decomposition was found for [BA][Sac], [DDA][Sac],
[1-(OctOMe)-3-OH-Py][Sac] and [1-(OctOMe)-3-OH-Py][Ace].
Fig. 3 One cation in [HEX][Ace] p-stacks in a polymeric fashion The anions [Sac] and [Ace] normally display a two-step
(interplanar spacing 3.5 and 3.6 Å) (top), while the second cation decomposition, suggesting that the cations, [BA]+, [DDA]+
forms p-stacked dimers (interplanar spacing 3.4 Å) with acesulfamate and [1-(OctOMe)-3-OH-Py]+, play a role in the decomposition
anions capping both sides (bottom). of these ILs resulting in the single decomposition step observed.

Table 1 Thermal propertiesa
Tg Tc Ts s Tm Tonset5% Tonset
Ionic liquids
[BA][Sac] — 16b — 74 164 204
[DDA][Sac] 33 15c — 16 187 214
[HEX][Sac] — 30c — 66 207 253/412g
[1-(OctOMe)-3-OH-Py][Sac] — — — 95–98e 206 301
[BA][Ace] — 30c 36 90 184 187/249/394g
[DDA][Ace] 53 — — — 189 232/426g
[HEX][Ace] 11 5b — 57 212 267/494g
18c
[1-(OctOMe)-3-OH-Py][Ace] — — — 79–81e 203 267
Starting materials
Na[Sac] — 98c — 120 431 459/541g
K[Ace] — — — 68 190 192/260g
[BA][Cl] — 16bd — — 143 169
[DDA][Br]f — — — — 166 196
[HEX][Cl] — 45c — 73 184 213
[1-(OctOMe)-3-OH-Py][Cl] — — — 68–70e 178 247
a
Phase transition points (1C) were measured from transition onset temperatures determined by DSC from the second heating cycle at 5 1C min 1,
after initially heating and then cooling of the samples to 100 1C unless otherwise indicated: Tg = glass transition temperature; Tc =
crystallization temperature; Ts–s = solid–solid transition temperature on heating; Tm = melting point on heating. Decomposition temperatures
were determined by TGA, heating at 5 1C min 1 under air atmosphere and are reported as (Tonset 5%) onset to 5 wt% mass loss and (Tonset) onset to
total mass loss. b Transition measured on heating cycle. c Transition measured on cooling cycle. d Transition only during first heating e Visual
melting point range via hot-plate apparatus. f Multiple transitions due to presence of water in starting material. g Multiple decomposition steps.
Two-step decomposition was observed for samples [HEX]- mercially available [BA][Cl] and [DDA][Cl], although the ILs
[Sac], [DDA][Ace] and [HEX][Ace]. Increase in the thermal were not found to be limited to a specific class of bacteria or
stability (first decomposition step) in these salts, over the fungi. These same observations have been seen in previous
thermal stabilities of the starting materials may indicate an literature,42 where it was found that the anti-microbial
anion stabilizing effect on the parent cations; [HEX]+ and activities for imidazolium chlorides, tetrafluoroborates, and
[DDA]+. Similarly, the stabilizing effect of the anion can be hexafluorophosphates were independent of the counterion.
observed for the sample of [BA][Ace], which is the only sample It is thought that 1-alkoxymethylpyridinium chlorides are
that exhibits a three-step decomposition pathway. strongly active against microbes, yet in previous research,43 it
was concluded that the antimicrobial activities depended on the
Biological properties substituent at the 3-position of the pyridine ring. Unfortu-
nately, [1-(OctOMe)-3-OH-Py][Cl] and the ILs, [1-(OctOMe)-
Anti-microbial, anti-bacterial and anti-fungal activities. The 3-OH-Py][Sac] and [1-(OctOMe)-3-OH-Py][Ace] exhibited no
minimum inhibitory concentration (MIC) (Table 2) and mini- antimicrobial activity.
mum bactericidal or fungicidal concentration (MBC) (Table 3)
were determined for [BA][Sac], [DDA][Sac], [BA][Ace] and Acute oral toxicities. The acute oral toxicities of [DDA][Ace]
[DDA][Ace]. (The starting materials, [BA][Cl] and [DDA][Cl], and [DDA][Sac] were determined in three male and three
which inherently exhibit anti-microbial, anti-bacterial and female Wistar rats, where the rats received a dosage of
anti-fungal activities, included in Tables 2 and 3 for com- 300 mg/kg b.w. (mg of substance per kg of body weight) and
parison.) The activities of the ILs approach those of com- 2000 mg/kg b.w. of each IL. The ILs were suspended in water
Table 2 MIC valuesa
Ionic liquid Starting materials

Strain [BA][Sac] [DDA][Sac] [BA][Ace] [DDA][Ace] [BA][Cl] [DDA][Cl]
S. aureus 4 4 4 8 2 2
S. aureus (MRSA) 4 4 4 4 2 2
E. faecium 8 8 8 8 4 4
E. coli 16 16 31 16 8 8
M. luteus 8 4 8 8 4 2
S. epidermidis 4 4 4 4 2 2
K. pneumoniae 4 4 8 4 4 4
C. albicans 16 16 16 16 8 8
R. rubra 16 16 16 16 8 4
S. mutans 0.1 31 1 16 2 2
Mean value 8.0 10.7 10.0 10.0 4.4 3.8
a
In ppm.
This journal is
Table 3 MBC valuesa
Ionic liquids Starting materials

Strain [BA][Sac] [DDA][Sac] [BA][Ace] [DDA][Ace] [BA][Cl] [DDA][Cl]
S. aureus 31.2 62.5 31.2 16 62.5 31.2
S. aureus (MRSA) 31.2 31.2 31.2 31.2 31.2 31.2
E. faecium 16 16 31.2 31.2 31.2 31.2
E. coli 62.5 16 125 62.5 62.5 31.2
M. luteus 62.5 31.2 62.5 62.5 31.2 31.2
S. epidermidis 31.2 16 62.5 31.2 16 31.2
K. pneumoniae 62.5 16 31.2 31.2 31.2 16
C. albicans 31.2 16 31.2 31.2 16 16
R. rubra 62.5 31.2 62.5 62.5 31.2 31.2
S. mutans 0.5 62.5 16 125 16 16
Mean value 39.1 29.9 48.5 48.5 32.9 26.6
a
In ppm.
Table 4 Criteria for the estimation of the deterrent activity based on Skin irritation. Skin irritation of [DDA][Ace] and [DDA]-
the total coefficient [Sac] was determined on New Zealand albino rabbits. All of
Total coefficient Deterrent activity the exposed animals exhibited defined erythema after 1 h. The
erythema had increased to severe and severe eschar formation
200–151 Very good was also observed after 24 h. Although no edema occurred, the
150–101 Good
100–51 Medium skin irritation of these ILs is defined as category 4 (the highest)
50–0 Weak by standard OECD grading.45
prior to intragastric administration. After receiving the dosage Deterrent activity. The deterrent activity of [DDA][Ace] and
of 300 mg/kg b.w. for [DDA][Ace] or [DDA][Sac], one male [DDA][Sac] toward Tribolium confusum (larvae and beetles),
rat died during the first 24 h, while the other 5 rats remained Sitophilus granarius (beetles) and Trogoderma granarium
alive. But when the dosage was increased to 2000 mg/kg b.w., (larvae) was determined by using a known method, in which
all of the rats died between 24 and 96 h after administra- the amount of food consumed is monitored over a specific time
tion. Death was preceded by decrease in spontaneous motor interval. Three deterrent coefficients had to be calculated from
activity, excessive excretion from nostrils, and difficulty of the average amount of food consumed: (a) the absolute coeffi-
breathing. The above results indicate the acute toxicity range cient of deterrency, A = (CC TT)/(CC + TT) 100, (b) the
for both ILs is between 300–2000 mg/kg b.w. in male and relative coefficient of deterrency, R = (C T)/(C + T) 100,
female rats. Thus, these ILs would be classified as category 4 and (c) the total coefficient of deterrency, which is the sum of
(harmful) toxins according to standard OECD grading.44 the absolute and the relative coefficients, T = A + R.46 In these
Table 5 Feeding deterrent activity
Ionic liquid Relative coefficient Absolute coefficient Total coefficient Deterrent activity
Sitophilus granarius (beetles)
[DDA][Ace] 97.5 57.9 155.5 Very good
[DDA][Sac] 57.8 56.6 114.5 Good
Azadirachtina 100.0 74.3 174.3 Very good
LSD0.05b 57.8 28.8 60.1
Trogoderma granarium (larvae)

[DDA][Ace] 94.0 85.0 179.0 Very good
[DDA][Sac] 94.2 86.1 180.3 Very good
b
LSD0.05 0.3 7.6 7.8
Tribolium confusum (beetles)

[DDA][Ace] 96.2 19.1 115.3 Good
[DDA][Sac] 95.0 90.7 186.6 Very good
a
Azadirachtin 100.0 85.0 185.0 Very good
LSD0.05b 0.6 9.2 9.0
Tribolium confusum (larvae)

[DDA][Ace] 95.0 64.1 159.1 Very good
[DDA][Sac] 95.3 88.8 184.1 Very good
b
LSD0.05 2.1 29.4 29.1
a b
Natural deterrent. The least significant differences at the 5% level of significance.

equations, CC is the average weight of the food consumed in The Rhodotorula rubra was obtained from the Department
the control, TT is the average weight of the food consumed in of Pharmaceutical Bacteriology, Poznań University of
the no-choice test, and T and C are the average weights of the Medical Sciences, Poland.
food consumed in the choice test.
The total coefficient value T is compared to standard values General synthesis47
for deterrent activity in Table 4, where a value of 0 equals Solid (0.001 mol) Na[Sac] or K[Ace] was dissolved in distilled
neutral activity and a value of +150 to +200 corresponds to water and added to hot aqueous solutions containing
very high deterrent activity. The results of deterrent activity 0.001 mol of [BA][Cl], [DDA][Br] or [HEX][Cl]. The mixtures
for [DDA][Ace] and [DDA][Sac] are compared to a natural were stirred at 60 1C for 1 h and then cooled to room
deterrent, azadirachtin, in Table 5. The ILs received temperature. The hydrophobic product was extracted with
either ‘very good’ or ‘good’ deterrent activity for all tested chloroform and purified using distilled water washes, until
insects. In particular, [DDA][Sac] exhibited the same deterrent chloride or bromide ions were no longer detected in the
activity toward Tribolium confusum (larvae and beetles) as product phase using AgNO3. The chloroform was evaporated
azadirachtin and thus, could be classified as a potential and the IL was dried under vacuum.
synthetic insect deterrent. The starting material 3-hydroxy-1-octyloxymethyl-
pyridinium chloride was prepared according to previous
Conclusions literature.43 Solid (0.03 mol) K[Ace] or Na[Sac] was dissolved
in distilled water and then added to an aqueous solution
We have prepared ILs of two biologically active ions by containing 0.03 mol [1-(OctOMe)-3-OH-Py][Cl]. The reaction
combining anti-microbial QACs cations with sweetener anions. was completed by gentle heating and stirring in a water bath
Some of these ILs demonstrate properties such as limited water for 2 h. The heat was removed and stirring was continued at
solubility, high thermal stability, and good deterrent activity room temperature for 24 h. The mixture was filtered, and the
against insects; which suggest potential application as an precipitate was washed with cold distilled water (3 20 mL) to
insecticide. Although oral toxicity and skin irritation values give an oil or solid IL. The IL was dried under vacuum, and
were higher than hoped, there is still potential use, not only for recrystallized from ethyl acetate and then dried again under
these ILs, but also for new, related ILs which can be prepared vacuum. Karl–Fischer analysis indicated the water content of
by tuning the composition in such a manner to reduce toxicity. all dried ILs to be less than 500 ppm.
In general, research in the IL field has begun to shift from
random combinations of ions to a design scheme in which Thermal analysis
both the cation and anion are chosen based on the desired
Melting points and other thermal transitions of the ILs were
physical, chemical, and biological properties. All procedures
determined by DSC, with a TA Instruments model 2920
performed on these animals were in accordance with esta-
Modulated DSC (Newcastle, DE), cooled with a liquid nitro-
blished guidelines and were reviewed and approved by the
gen cryostat. The calorimeter was calibrated for temperature
University of Alabama’s Institutional Animal Care and Use
and cell constants using indium standard (mp 156.61 1C,
committee. As our fundamental understanding of IL behavior
DH = 28.71 J g 1). Data were collected at constant atmos-
increases, more control over the resultant properties of the
pheric pressure where the ILs were placed in aluminum pans
salts will be possible, and the number of potential applications,
with sample sizes from 5 to 15 mg. An empty sample pan was
such as those presented here, will continue to grow.
used as reference. All experiments were performed at a heating
rate and a cooling rate of 5 1C min 1. The DSC was adjusted
Experimental so zero heat flow was between 0 and 0.5 mW, and the
baseline drift was less than 0.1 mW over the temperature
Chemicals and microorganisms range 0–180 1C.
Benzalkonium chloride [BA][Cl] (molecular formula Thermal decomposition temperatures were measured in the
C6H5CH2N(CH3)2RCl where R = C12H25 (60%) and dynamic heating regime using a TGA, 2950 TA Instrument,
C14H29 (40%)), didecyldimethylammonium bromide under air atmosphere. The amount of IL used was between
[DDA][Br] (tech., 75 wt% gel in water), hexadecylpyridinium 2 and 10 mg in each case, and the samples were heated from
chloride [HEX][Cl] (monohydrate, minimum 99%) and 40 to 800 1C at a constant heating rate of 5 1C min 1.
sodium saccharinate Na[Sac] (hydrate, minimum 98%) were Decomposition temperatures (T5%dec) were determined from
purchased from Sigma Aldrich. Potassium acesulfamate onset to 5 wt% mass loss; this provides a more realistic
K[Ace] ( Z 99%) was purchased from Fluka. representation of thermal stability at elevated temperatures.
The following microorganisms were used: bacteria
X-Ray diffraction
Staphylococcus aureus ATCC 6538, Staphylococcus aureus
(MARSA) ATCC 43300, Enterococcus faecium ATCC Crystalline samples of [HEX][Ace] and [1-(OctOMe)-3-
49474, Escherichia coli ATCC 2592,2 Micrococcus luteus OH-Py][Sac] were mounted on a glass fiber on a goniometer
ATCC 9341, Staphylococcus epidermidis ATCC 12228, head of a Siemens SMART CCD diffractometer equipped
Klebsiella pneumoniae ATCC 4352, and fungi Candida albicans with a Mo-Ka source (l = 0.71073 Å) and a graphite
ATCC 10231, Rhodotorula rubra PhB and Streptococcus monochromator. Data collection was conducted at 100 1C
mutans PCM (Polish Collection of Microorganisms) 2502. which was achieved by streaming cold nitrogen over the
This journal is
crystal. Final unit cell parameters were determined by least- rabbit. Half a milliliter of the ILs (100%, pure) was distributed
squares refinement of the hemispherical data set obtained from on two 6 cm3 sites of the same animal. The application site was
20 s exposures. Data were corrected for Lorentz and polariza- then covered with a porous gauze dressing and secured in place
tion effects and absorption using SADABS.48 The initial with tape. After a 4 h exposure, the dressing was removed and
structure solution was carried out using the direct methods the application site was gently washed with water. Observa-
option in SHELXTL version 5.49 The positions of all non- tions were then conducted at 1, 24, 48, and 72 h, where the
hydrogen atoms were refined anisotropically. The hydrogen test sites were evaluated for erythema and edema using a
atoms were added and allowed to refine unconstrained in prescribed scale.45
order to obtain proper close contact interactions.
Feeding deterrent activity tests
Crystal data for [HEX][Ace]. C25H42N2O4S; Mr = 466.67; Three species of insects were selected for testing: Tribolium
triclinic, space group P1; T = 173 K; a = 7.921(3), b = confusum Duv. (larvae and beetles), Sitophilus granarius L.
13.374(5), c = 25.689(10) Å, a = 76.755(7), b = 82.225(7), g = (beetles), and Trogoderma granarium Ev. (larvae). Insects were
89.260(7)1; Z = 4; V = 2624.2(17) Å3; Dc = 1.181 g cm 3; 7459 grown on a wheat grain or whole-wheat meal diet in labora-
independent (Rint = 0.0249) and 5755 observed ([I 4 2s(I)]) tory colonies which was maintained at 26 1 1C and 60 5%
reflections; GooF = 1.070; R1, wR2 [I 4 2s(I)] = 0.0462, relative humidity. The laboratory assay was conducted
0.1208; R1, wR2 (all data) = 0.0641, 0.1411 according to the method developed and standardized for storage
insects feeding activity for both choice and no-choice test.46
Crystal data for [1-(OctOMe)-3-OH-Py][Sac]. C21H28N2O5S;
Wheat wafer discs (1 cm in diameter 1 mm thick) were
Mr = 420.51; triclinic, space group P1; T = 173 K; a =
saturated by dipping in either ethanol (96%) only (control) or
8.1626(15), b = 8.7141(16), c = 16.756(3) Å, a = 81.872(3),
in a 1% ethanol solution of [DDA][Ace] or [DDA][Sac]. After
b = 80.780(3), g = 62.850(3)1; Z = 2; V = 1043.7(3) Å3; Dc =
evaporation of the solvent by air-drying (30 min), the wafers
1.338 g cm 3; 2969 independent (Rint = 0.0170) and 2515
were weighed and offered as the only food source for the
observed ([I 4 2s(I)]) reflections; GooF = 1.033; R1, wR2
insects over a five day period. The feeding of the insects was
[I 4 2s(I)] = 0.0362, 0.0871; R1, wR2 (all data) = 0.0472, 0.0937
recorded under three conditions: (a) control test (two control
Antimicrobial characteristics discs (CC)), (b) choice test (a choice between one treated
disc (T) and one control disc (C)), and (c) no-choice test
Anti-microbial activity was determined by the tube dilution (two treated discs (TT)). Each of the three experiments was
method. Bacteria strains were cultured in Mueller–Hinton repeated five times with 3 beetles of Sitophilus granarius,
broth for 24 h and fungi were cultured on Sabouraud agar 20 beetles and 10 larvae of Tribolium confusum, and 10 larvae
for 48 h. Suspensions of the above microorganisms, at a of Trogoderma granarium. The number of individual insects
concentration of 106 cfu mL 1, were prepared from each depended on the intensity of their food consumption. The
culture. Two milliliters of serial twofold dilutions of IL were beetles utilized in the experiments were unsexed, 7–10 days
inoculated with the above-mentioned suspension to obtain a old, and the larvae were 5–30 days old. After five days of
final concentration of (1–5) 105 cfu mL 1. feeding, the discs were reweighed. The data from the experi-
Growth of the microorganism (or its lack) was determined ments have been statistically corrected by an analysis of
visually after incubation for 24 h at 35 1C (bacteria) or 48 h at variance.
22 1C (fungi). The lowest concentration at which there was no
visible growth (turbidity) was determined to be the minimal
inhibitory concentration (MIC). Then, from each tube con- Acknowledgements
tent, 10 mL (calibrated loop) was smeared on an agar medium This work was supported by Poznań University of Techno-
with inactivates (0.3% lecithin, 3% polysorbate 80, and 0.1% logy, BW 32-222/2008.
L-cysteine) and incubated for 48 h at 35 1C (bacteria) or for
5 days at 22 1C (fungi). The lowest concentration of the IL that
killed 99.9% or more of the microorganism was defined as the References
minimum biocidal concentration (MBC). 1 F. Endres, ChemPhysChem, 2002, 3, 145.
2 P. Wang, S. M. Zakeeruddin, I. Exnar and M. Graetzel, Chem.
Acute oral toxicity test Commun., 2002, 2972.
3 T. Sato, G. Masuda, M. Kotani and S. Iizuka, Chem. Abstr., 2004,
The toxicity was tested according to the method of acute toxic 140, 245004.
class.44 Three male (250 25 g) and three female (170 17 g) 4 A. E. Visser, R. P. Swatloski, W. M. Reichert, S. T. Griffin and
R. D. Rogers, Ind. Eng. Chem. Res., 2000, 39, 3596.
Wistar rats were used for each IL tested. The ILs were first 5 A. E. Visser, R. P. Swatloski, W. M. Reichert, J. H. Davis, Jr,
suspended in distilled water and then administered intra- R. D. Rogers, R. Mayton, S. Sheff and A. Wierzbicki, Chem.
gastrically at doses of 300 mg/kg b.w. and 2000 mg/kg b.w. Commun., 2001, 135.
After the dose was administered, the rats were observed for 6 S. Dai, Y. H. Ju and C. E. Barnes, J. Chem. Soc., Dalton Trans.,
1999, 1201.
14 days. 7 P. Wasserscheid, A. Boesmann, A. Jess, L. Datsevitch, C. Schmitz
and A. Lauter, Chem. Abstr., 2003, 138, 370660.
Skin irritation tests 8 C. Chiappe and D. Pieraccini, ARKIVOC, 2002, 11, 249.
9 L. Kiss, T. Kurtán, S. Antus and H. Brunner, ARKIVOC, 2003, 5, 69.
Each IL was tested on 3 male New Zealand albino rabbits, 10 T. Welton, Coord. Chem. Rev., 2004, 248, 2459.
where the fur was previously removed from the back of the 11 J. Mo, L. Xu and J. Xiao, J. Am. Chem. Soc., 2005, 127, 751.

12 J. Ding, V. Desikan, X. Han, T. L. Xiao, R. Ding, W. S. Jenks and 32 J. Oertel, Holztechnologie, 1965, 6, 243.
D. W. Armstrong, Org. Lett., 2005, 7, 335. 33 J. A. Butcher, A. F. Preston and J. Drysdale, For. Prod. J., 1977,
13 E. Janus, I. Goc-Maciejewska, M. Łożyński and J. Pernak, Tetra- 27, 19.
hedron Lett., 2006, 47, 4079. 34 J. A. Butcher and J. Drysdale, N. Z. J. For. Sci., 1978, 8, 403.
14 M. T. Carter, C. L. Hussey, S. K. D. Strubinger and R. A. 35 J. Cross, in Introduction, Cationic Surfactants, Analytical and
Osteryoung, Inorg. Chem., 1991, 30, 1149. Biological Evaluation Surfactant Science Series, eds. J. Cross and
15 K. N. Marsh, J. A. Boxall and R. Lichtenthaler, Fluid Phase E. J. Singer, Marcel Dekker, New York, 1994, vol. 53.
Equilib., 2004, 219, 93. 36 C. Klinguer, A. Beck, P. De-Lys, M. C. Bussat, A. Blaecke,
16 A. Hammerl, M. A. Hiskey, G. Holl, T. M. Klapotke, K. Polborn, F. Derouet, J. Y. Bonnefoy, T. N. Nguyen, N. Corvaia and
J. Stierstorfer and J. J. Weigand, Chem. Mater., 2005, 17, 3784. D. Velin, Vaccine, 2001, 19, 4236.
17 A. Pernak, K. Iwanik, P. Majewski, M. Grzymis"awski and 37 F. Liu and L. Huang, J. Controlled Release, 2002, 78, 259.
J. Pernak, Acta Histochem., 2005, 107, 149. 38 W. L. Hough, M. Smiglak, H. Rodrı́guez, R. P. Swatloski,
18 Ionic Liquids IIIB: Fundamentals, Progress, Challenges, and S. K. Spear, D. T. Daly, J. Pernak, J. E. Grisel, R. D. Carliss,
Opportunities—Transformations and Processes, eds. R. D. Rogers M. D. Soutullo, J. H. Davis, Jr and R. D. Rogers, New J. Chem.,
and K. R. Seddon, ACS Symposium Series 902, American 2007, 31, 1429.
Chemical Society, Washington DC, 2005. 39 E. B. Carter, S. L. Culver, P. A. Fox, R. D. Goode, I. Ntai,
19 R. S. Shelton, M. G. Van Campen, C. H. Tilford, H. C. Lang, M. D. Tickell, R. K. Traylor, N. W. Hoffman and J. H. Davis, Jr,
L. Nisonger, F. J. Bandelin and H. L. Rubenkoenig, J. Am. Chem. Chem. Commun., 2004, 630.
Soc., 1949, 69, 753. 40 J. Pernak, F. Stefaniak and J. Weglewski, Eur. J. Org. Chem., 2005,
20 W. A. Jacobs and M. Heidelberger, Proc. Natl. Acad. Sci. U. S. A., 650; M. Stasiewicz, A. Fojutowski, A. Kropacz and J. Pernak,
1915, 1, 226. Holzforschung, 2008, 62, 309.
21 W. A. Jacobs, J. Exp. Med., 1916, 23, 563. 41 A. Burgard, Eur. Pat., 1 270 580, 2003; A. Burgard, US Pat.,
22 W. A. Jacobs, M. Heidelberger and H. L. Amoss, J. Exp. Med., 2003023084 A1, 2003.
1916, 23, 569. 42 Z.-B. Zhou, H. Matsumoto and K. Tatsumi, Chem.–Eur. J., 2005,
23 W. A. Jacobs, M. Heidelberger and C. G. Bull, J. Exp. Med., 1916, 11, 752; J. Pernak, K. Sobaszkiewicz and I. Mirska, Green Chem.,
23, 577. 2003, 5, 52.
24 G. Domagk, Dtsch. Med. Wochenschr., 1935, 61, 829. 43 J. Pernak and M. Branicka, J. Surfactants Deterg., 2003, 6, 119.
25 Cationic Surfactants, ed. J. M. Richmond, Marcel Dekker, New 44 OECD Guideline for Testing of Chemicals No. 434: Acute Oral
York, 1990. Toxicity—Acute Toxic Class Method, 2001, 1.
26 Cationic Surfactants: Physical Chemistry, eds. D. N. Rubingh and 45 OECD Guideline for Testing of Chemicals No. 404: Acute Dermal
P. M. Holland, Marcel Dekker, New York, 1991. Irritation/Corrosion, 2002, 1.
27 S.-W. Kwak, E.-J. Lee, M.-S. Song, G.-I. Jung and J.-W. Ha, PCT 46 J. Nawrot, E. Bloszyk, J. Harmatha, L. Nowotny and B. Drożdż,
Int. Appl., 2 006 057 506, 2006. Acta Entomol. Bohemosl., 1986, 83, 327.
28 Y. I. Kuznetsov, L. V. Frolova and E. V. Tomina, Prot. Met., 47 Additional information regarding the ionic liquids synthesized is
2006, 42, 215. available in the ESIw.
29 A. N. Petrocci, Disinfection, Sterilization and Preservation, ed. 48 G. M. Sheldrick, Program for Semiempirical Absorption Correction
S. S. Block, Lea & Febiger, Philadelphia, 1983. of Area Detector Data, University of Göttingen, Germany,
30 M. Makosza, Pure Appl. Chem., 2000, 72, 1399. 1996.
31 F. C. Kull, P. C. Eisma and H. D. Sylwestrowicz, Environ. 49 G. M. Sheldrick, SHELXTL, version 5.05, Siemens Analytical
Microbiol., 1961, 9, 538. X-ray Instruments Inc., 1996.
This journal is
launching in 2009
Integrative Biology


ISSN 1757-9694
Pages 1–140
1757-9694(2009) 1:1;1
0959-9428(2008)18:1;1-J
060858
ISSN 1144-0546
PAPER
Metal ion-catalyzed oxidative degradation of Orange II by H2O2. High

catalytic activity of simple manganese salts
Erika Ember, Sabine Rothbart, Ralph Puchta and Rudi van Eldik*
Received (in Montpellier) 6th August 2008, Accepted 25th September 2008
DOI: 10.1039/b813725k
In an effort to develop new routes for the clean oxidation of non-biodegradable organic dyes,
a detailed study of some environmentally friendly Mn(II) salts that form very efficient in situ
catalysts for the activation of H2O2 in the oxidation of substrates such as Orange II under mild
reaction conditions, was performed. The studied systems have advantages from the viewpoint of
green chemistry in that simple metal salts can be used as very efficient catalyst precursors and
H2O2 is used as a green oxygen donor reagent. Oxidations were carried out in a glass reactor over
a wide pH range in aqueous solution at room temperature. Under optimized conditions it was
possible to degrade Orange II in a carbonate buffer solution in less then 100 s using 0.01 M H2O2
in the presence of only 2 105 M Mn(II) salt. To gain insight into the manganese catalyzed
oxidation mechanism, the formation of the active catalyst was followed spectrophotometrically
and appears to be the initiating step in the oxidative degradation of the dye. High valent
manganese oxo species are instable in the absence of a stabilizing coordinating ligand and lead to
a rapid formation of catalytically inactive MnO2. In this context, the role of the organic dye and
HCO3 as potential stabilizing ligands was studied in detail. In situ UV-Vis spectrophotometric
measurements were performed to study the effect of pH and carbonate concentration of the buffer
solution on the formation of the catalytically active species. Electrochemical measurements and
DFT (B3LYP/LANL2DZp) calculations were used to study the in situ formation of the catalytic
species. The catalytic cycle could be repeated several times and demonstrated an excellent stability
of the catalytic species during the oxidation process. A mechanism that accounts for the
experimental observations is proposed for the overall catalytic cycle.
Introduction One approach to solve these problems would be to develop

low-cost, highly efficient, and environmental friendly oxida-
Nowadays, one of the major environmental problems con- tion catalysts on the basis of transition metal complexes.6,7
cerns the strong increase in xenobiotic and organic substances Recently, photodegradation methods based on TiO2 as a
that are persistent in the natural ecosystem. Most of these photocatalyst,8 beside Fenton systems,9 emerged as one of
compounds have an aromatic structure, which makes them the most promising technologies and received increasing atten-
highly stable and thus difficult to degrade.1 A significant tion due to their practical and potential value in environmental
source of environmental pollution is industrial dye waste due protection. However, in some cases they are only successful
to their visibility and recalcitrance, since dyes are highly under specific pH and temperature conditions.
coloured and designed to resist chemical, biochemical and Several studies were performed during the last few years in
photochemical degradation.2 About half of the global produc- order to find good catalysts for the oxidative degradation of
tion of synthetic dyes (700 000 t per year) are classified as different organic dyes. From an environmental point of view,
aromatic azo compounds that have a –NQN– unit as chromo- first row transition metals are the most challenging. Highly
phore in their molecular structure. Over 15% of textile dyes effective Fe,10,14 Co,11 Cr12 and Mn13 based oxidation catalyst
are lost in waste water streams during the dyeing operation.3 were developed. In combination with different oxidizing
Azo dyes are known to be largely non-biodegradable under agents, the decomposition of stable organic substances was
aerobic conditions and to be reduced to more hazardous possible. A novel highly active and environmental benign
intermediates under anaerobic conditions.4 The decolorization catalytic system based on Fe-TAML (TAML = tetraamido
of wastewater has acquired increasingly importance in recent macrocyclic ligand) was recently reported by Chahbane et al.14
years, however, there is no simple solution to this problem In many cases tremendous synthetic efforts are required to
because the conventional physicochemical methods are costly obtain an effective catalytic system and in addition the pre-
and lead to the accumulation of sludges.5 sence of high concentrations of oxidizing agents is needed.
Among the possible oxidizing agents, H2O2 is one of the most
commonly used owing to its eco-friendly nature. The use of
Inorganic Chemistry, Department of Chemistry and Pharmacy,
University of Erlangen-Nürnberg, Egerlandstr. 1, 91058 Erlangen, H2O2 as a green oxidizing agent in these reactions is justified
Germany by a low organic content of the wastewater to be treated and a

low reaction temperature, thus requiring the presence of an measurements and DFT calculations were used to develop
adequate catalyst due to the high kinetic activation barrier of a better understanding of the coordination chemistry of
such reactions. Commonly used methods for activation of Orange II. The successful implementation of such catalytic
H2O2 include the formation of reactive peroxyacids from systems becomes a worthwhile objective when issues such as
carboxylic acids and peroxycarboximidic acid from aceto- environmental compatibility, high atom economy, availability,
nitrile (Payne oxidation),15 the generation of peroxyisourea and expenses are considered.24
from carbodiimide in the presence of either a weak acid or a
mild base,16 or the use of percarbonate, persulfate or perbo-
rate in strongly basic solution.17 In order to achieve fast
Experimental
oxidative transformations, the use of large amounts of co- Chemicals
catalyst additives is often required.18
Among these, the use of percarbonate, a versatile oxidizing Orange II, certified [Acid Orange 7, C.I. 15510, sodium 4-(2-
agent, is preferred for environmental reasons.19,20 Oxidation hydroxy-1-naphthylazo)benzenesulfonate], 99% was supplied
using environmentally benign oxidants has aroused much by Sigma–Aldrich and recrystallised from a Et2O/H2O mix-
interest,7,21 because chemical industry continues to require ture at 4 1C. 2,4,6-Tri-tert-butylphenol (TTBP) 96% was
cleaner oxidation, which is an advance over environmentally purchased from Sigma–Aldrich and recrystallised several
unfavoured oxidations and a step up from more costly organic times from EtOH/H2O (9 : 1) mixtures prior to use. Hydrogen
peroxides.22 peroxide 35 wt% as well as different manganese salt hydrates
In this report, we propose a fast and clean catalytic oxida- used in the experiments, were of analytical grade and provided
tive degradation of Orange II as model substrate by H2O2 in by Acros Organics (Germany). Carbonate buffer solutions
aqueous carbonate solution under mild reaction conditions, were prepared using Millipore Milli-Q purified water.
pH 8–10 and 25 1C, eqn (1). General procedure
The manganese salts were freshly dissolved in water before
use. To a freshly prepared sodium carbonate solution, an
adequate amount of NaOH was added to adjust the pH of
the solution. Under isothermal conditions, the desired amount
of a concentrated manganese solution was added together with
Orange II, previously dissolved in an aqueous carbonate
ð1Þ solution, and H2O2. In typical measurements, 0.01 M H2O2
was prepared from a 35 wt% solution of H2O2. In addition, to
Starting from commercially available Mn(NO3)2 in aqueous gain more information on the activation mode of the catalyst,
carbonate solution for catalytic applications, various aspects two further experimental procedures based on different activa-
of the in situ generation of very reactive high valent manganese tion and stabilization modes of the activated catalyst, were
intermediates in the presence of H2O2 were studied. Baes and followed. In one, the catalytic active species was generated
Mesmer have shown that manganese salts in aqueous solution in situ in the carbonate buffer solution by addition of the
are able to form very reactive aquated intermediates.23 More- desired amount of H2O2, followed by the addition of the
over, in an alkaline medium, the introduction of a hydroxy corresponding quantity of Orange II to the reaction mixture.
ligand trans to a water ligand is expected to produce more In the other, Orange II was added to the manganese solution
labile OH–Mn–H2O species, and their formation (eqn (2)) is and the formation of an Orange II MnII complex was
considered to be of major importance for their catalytic observed. The decomposition of the dye was initiated through
activity. the subsequent addition of H2O2. It is important to note that
the catalytic oxidation of the dye by H2O2 could only be
performed in an aqueous carbonate buffer solution. No other
buffer at the same pH, viz. TRIS, TAPS, HEPES or phos-
phate, showed the observed catalytic reaction.
Kinetic study of the manganese catalysed oxidative degradation

of Orange II by H2O2
In the present study, the formation of catalytically inactive
Mn(OH)2 species was observed at higher pH, leading to All kinetic data were obtained by recording time-resolved
deactivation of the produced Mn intermediates. The activation UV-Vis spectra using a Hellma 661.502-QX quartz Suprasil
of H2O2 in the presence of manganese salts as a function of pH immersion probe attached via optical cables to a 150 W Xe
and carbonate concentration was therefore monitored using lamp and a multi-wavelength J & M detector, which records
UV-Vis spectrophotometry. In situ formed, high valent man- complete absorption spectra at constant time intervals. In a
ganese intermediates are known to be highly unstable in the thermostated open glass reactor vessel equipped with a mag-
absence of a spectator ligand. As the study progressed, it was netic stirrer, a 2 105 M freshly prepared catalyst solution
of importance to investigate the role of the azo dye as a and 0.01 M H2O2 were added to 40 ml of 5 105 M dye
potential coordinating ligand to stabilize the produced inter- at a pH ranging from 8 to 10 at 25 1C. All kinetic measure-
mediate under different reaction conditions. Electrochemical ments were carried out under pseudo-first order conditions
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(i.e. 50 r [H2O2]/[Mn2+] r 1000). The pH of the aqueous DFT calculations
carbonate solution was carefully measured using a Mettler
Unrestricted B3LYP/LANL2DZp hybrid density functional
Delta 350 pH meter previously calibrated with standard buffer
calculations,25a–c i.e., with pseudo-potentials on the heavy
solutions at two different pH values (4 and 10). The kinetics
elements and the valence basis set25d–f augmented with
of the oxidation reaction was monitored at 480 nm. First
polarization functions,25g were carried out using the Gaussian
order rate constants, where possible, were calculated using
0326 suite of programs. The relative energies were corrected
Specfit/32 and Origin (version 7.5) software. To estimate the
for zero point vibrational energies (ZPE). The resulting struc-
effect of the catalyst and H2O2 concentrations on the catalytic
tures were characterized as minima by computation of vibra-
reaction at different carbonate concentrations, stopped-flow
tional frequencies, and the wave functions were tested for
kinetic measurements were carried out using an SX.18MV
stability.
stopped-flow instrument from Applied Photophysics.
Synthesis of insoluble MnCO3
Spectrophotometric titration
In a 150 ml round flask 3.36 g (0.4 M) NaHCO3 was dissolved
UV-Vis spectra were recorded on a Shimadzu UV-2101 in 100 ml doubly distilled water and the pH of the solution was
spectrophotometer at 25 1C. A 0.88 cm path length tandem set at 8.5 upon addition of small amounts of concentrated
cuvette with two separate compartments (0.44 cm path length NaOH solution. To the freshly prepared carbonate solution
each), was filled with 1 ml 5 105 M Orange II stock solution 1 g (0.04 M) Mn(NO3)2 was added. The mixture was stirred at
in one, and different concentrations of an aqueous Mn(NO3)2 room temperature for 15 min during which MnCO3 H2O
solution in the other compartment. The cuvette was placed in formed as a white precipitate. The product was filtered and
the thermostated cell holder of the spectrophotometer for washed several times with large amounts of water. Yield:
10 min. UV-Vis spectra were recorded before and after mixing 0.44 g MnCO3, 96.2%. IR (KBr pellets): n (cm1) 3421 (m),
the solutions. The resulting spectrum presents the sum of the 1416 (vs), 862 (s), 725 (m). Elemental analysis (%) for
two individual spectra before, and that of the reaction mixture, MnCH2O4: calc.: C 9.03, H 1.52; found: C 9.38, H 1.52.
after mixing. The observed spectral change is a result of
complex-formation between Mn(II) and Orange II. Synthesis of Orange II MnII complex
In a 50 ml Schlenk tube 0.014 g (2 103 M) Orange II was
Cyclovoltammetric measurements
dissolved in 20 ml doubly distilled water and an aqueous
Cyclovoltammetric (CV) measurements were performed in a solution of 0.01 g (2 103 M) Mn(NO3)2 was added
one-compartment three-electrode cell using a gold working dropwise under continuous stirring. The solution mixture
electrode (Metrohm) with a geometrical surface of 0.7 cm2 was kept for several hours at room temperature. The formed
connected to a silver wire pseudo-reference electrode and a precipitate was filtered and dried at room temperature. Yield:
platinum wire serving as counter electrode (Metrohm). 0.018 g Orange II MnII, 87.1%. IR (KBr pellets): n (cm1)
Measurements were recorded with an Autolab PGSTAT 3527 (vs), 1619 (s), 1511 (s), 1383 (vs), 1262 (m), 1171 (s),
30 unit at room temperature. The working electrode surface 1120 (s), 1034 (s), 1007 (s), 829 (s), 759 (s), 696 (m), 644 (m),
was cleaned using 0.05 mm alumina, sonicated and washed 595 (m). Elemental analysis (%) for MnC16H18O10N3SNa:
with water every time before use. The working volume of 10 ml calc.: C 36.79, H 3.47, N 8.04, S 6.14, O 30.63; found:
was deaerated by passing a stream of high purity N2 through C 29.44, H 3.39, N 8.05, S 4.77, O 30.31.
the solution for 15 min prior to the measurements and then
maintaining an inert atmosphere of N2 over the solution Synthesis of Orange II MnII Orange II complex
during the measurements. All CVs were recorded for the An aqueous solution of 0.005 g (1 103 M) Mn(NO3)2 was
reaction mixture with a sweep rate of 50 mV s1 at 25 1C. added under continuous stirring to a 0.014 g (2 103 M)
Potentials were measured in a 0.5 M NaCl/NaOH electrolyte Orange II water solution at room temperature. The pale
solution and are reported vs. an Ag/AgCl electrode. yellow precipitate was collected by filtration and dried in
air. Yield: 0.017 g Orange II MnII Orange II, 93.7%. IR
IR measurements (KBr pellets): n (cm1) 3390 (s), 1619 (s), 1570 (m), 1554 (m),
IR spectra were recorded as KBr pellets using a Mattson 1520 (vs), 1393 (m), 1260 (m), 1169 (vs), 1119 (vs), 1033 (vs),
Infinity FTIR instrument (60 AR) at 4 cm1 resolution in 1007 (s), 828 (s), 758 (s), 695 (m), 644 (m), 593 (m). Elemental
the 400–4000 cm1 range. analysis (%) for MnC32H32O15N5S2Na2: calc.: C 43.1, H 3.62,
N 7.23, S 7.19, O 26.91; found: C 42.99, H 3.75, N 7.23, S 7.00,
Elemental analysis O 25.67.
The measurements were carried out on an elemental analyzer
Euro EA 3000 instrument from Hekaltech Gmbh. The analy- Results and discussion
tical method is based on the complete instantaneous oxidation
General observations
of the sample by ‘‘flash combustion’’ at 1000 1C, which
converts all organic and inorganic substances into combustion A series of experiments were performed in order to investigate
products. The resulting combustion gases are swept into the the in situ generation of the highly reactive manganese catalyst
chromatographic column by the carrier gas (He) where they in the oxidative degradation of Orange II by H2O2 under mild
are separated and detected by a thermal conductivity detector. reaction conditions starting with a simple Mn(II) salt.

to the presence of aromatic groups, is very stable, and in the
presence of a powerful bleaching agent such as H2O2,
degradation of dye solutions occurs slowly under specific
reaction conditions. Surprisingly, the oxidation rate was tre-
mendously accelerated by addition of a simple manganese
salt. The reactivity of the in situ formed intermediate
was comparable with the catalytic activity of some earlier
postulated, well known manganese bleach catalysts13,32 and
manganese porphyrins.33 In our work, the formation and
stabilization of the active catalyst was studied in a carbonate
buffer solution.
Scheme 1 Orange II: R = SO3Na; pKA = 11.4, lmax = 480 nm. Complex-formation between Orange II and Mn2+
ortho-Hydroxy aromatic azo dyes, which are bidentate com-
Oxidation reactions are in general affected by the protonation plexing agents are of considerable practical and theoretical
state of the substrate, catalyst and oxidant, and the solvent interest because of their ability to form stable chelate com-
used. It is further important to note that the studied organic plexes with some metal ions.34 It is known that Orange II can
dye (Orange II) can exist in either one of two tautomeric act as a chelating agent since the hydroxy and sulfonate groups
forms, or in an equilibrium mixture, depending on the process allow a stabilized complex to be formed.35 Addition of Orange
parameters. This kind of rapid dynamic equilibrium is relevant II to a freshly prepared aqueous carbonate solution of a MnII
as one dye species may be more reactive than the other. Azo salt results in significant changes in the UV-Vis spectrum of
dyes containing a hydroxyl group in the ortho position to the Orange II as shown in Fig. 2.
azo group within naphthyl or higher fused ring systems, can UV-Vis spectra recorded before and after mixing (ca. 5 s
exist as azo and hydrazone tautomers,27 with the relative delay) of 5 105 M Orange II with 5 105 M Mn(NO3)2
amounts varying with reaction parameters such as solvent showed a significant increase in absorbance at 480, 310
and temperature.28 Furthermore, in aqueous solution these and 228 nm, respectively. The differences before and after
species are in a pH dependent equilibrium with a common mixing are not profound at low Mn2+ concentrations. On
anion, in which the negative charge is delocalised throughout increasing the Mn2+ concentration, a continuous increase in
the molecule (see Scheme 1).29 These are chemically distinct DAl=480 nm = A(dye+Mn(II)) Adye was observed, indicating
forms which have characteristically different visible spectra, the formation of an Orange II Mn2+ species according to
the azo form absorbs typically at 400–440 nm and the hydra- eqn (3). It should be noted that at higher Mn2+ concentration,
zone form at 475–510 nm (see Fig. 1).30 a precipitate started to form. The value of Keq was determined
The absorption spectrum of Orange II in an aqueous through a constant variation of the Mn2+ concentration. For
carbonate solution shows under the selected reaction condi- a correct determination of the complex-formation constant,
tions (Fig. 1) one main band at 480 nm, which correspond to independent measurements were performed at constant man-
the n - p* transition of the azo form. The other two bands at ganese concentration where the Orange II concentration was
300 and 270 nm are attributed to the p - p* transition of the continuously varied (see Fig. 3C). Independent measurements
benzene and naphthalene rings, respectively.31 Orange II, due were repeated between five and eight times. Selected data are
Fig. 2 (Blue curve) UV-Vis spectrum of a 5 105 M Orange II

carbonate (0.1 M HCO3) solution at pH 8.5 before mixing with a
Fig. 1 UV-Vis spectrum of 104 M Orange II in carbonate buffer 5 105 M Mn(NO3)2 solution at pH 8.5. (red curve) UV-Vis
solution at pH 8.5. spectrum recorded directly after mixing (ca. 5 s delay).
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Fig. 3 (A) Change in absorbance at 480 nm on addition of different concentrations of Mn2+ to 5 105 M Orange II in aqueous carbonate
solution (0.2 M HCO3) at pH 8.5 and 22 1C. (B) Job plot analysis for complex-formation between Orange II and Mn2+ in aqueous carbonate
solution (0.2 M HCO3) at pH 8.5. (C) Spectral changes at 480 nm on addition of different concentrations of Orange II to a freshly prepared
5 105 M Mn(NO3)2 carbonate solution (0.2 M HCO3) at pH 8.5 and 22 1C. (D) Job plot analysis for the complex-formation in aqueous
carbonate solution (0.2 M HCO3).
shown in Fig. 3A, where the solid line represents a fit of eqn (4) concentration the formation of a complex with a stoichiometry
to the data. of 1 : 1 can be assumed. On increasing the Orange II concen-
Keq tration further, complexes with a higher stoichiometry are
Orange II þ Mn2þ Ð ðOrange II MnII Þ ð3Þ possibly formed (see Fig. 4A and B).
Similar structures have been reported earlier by Nadtochenko
Ax A0 = (AN A0)Keq[Orange II]/(1 + Keq[Orange II]) and Kiwi when a Fe3+ salt was added to an Orange II solution
DA = DANKeq[Orange II]/(1 + Keq[Orange II]) (4) in acidic medium.40 Bauer also reported a TiIV complex,
where TiIV is coordinated by two oxygen atoms from the
The values of A0 and AN represent the absorbances of sulfonato group and the oxygen of the carbonyl group of the
Orange II and of the complex Orange II MnII, respectively,
and Ax is the absorbance at any MnII concentration. The value
of Keq was calculated from eqn (4) to be (2.9 0.9) 104 M1,
indicating a relatively weak coordination of the dye to the metal
center. Experimentally, through addition of a 4 105 M
Mn(NO3)2 solution to a 5 105 M Orange II aqueous
carbonate solution (0.2 M HCO3), a decrease in the pH of
the solution from 8.5 to 8.3 was observed, which suggests
phenolic proton release due to Mn(II) coordination to Orange
II with the formation of a six-membered ring structure instead
of coordination to the terminal sulfonato group. At higher
concentrations (above ca. 103 M) Orange II forms dimers and
higher aggregates in aqueous solutions,30,36 and has a marked
effect on the observed spectra, particularly UV-Vis and NMR.37
A Benesi-Hildebrand treatment of the optical data to determine Fig. 4 (A) Proposed structure for a 1 : 1 Orange II Mn2+ complex
Keq could not be applied since the concentration of Orange II formed in a carbonate buffer solution at a low concentration of Mn2+.
and MnII were close to each other.38 Using Job’s method,39 the (B) Proposed structure for a 1 : 2 Orange II Mn Orange II
stoichiometry of the formed complex could be determined. complex formed in a carbonate buffer solution at a high concentration
According to the data shown in Fig. 3B and D, at lower MnII of Orange II.

hydrazone tautomer.41 In the enzyme manganese peroxidase, one-electron reductions with CV half-wave potentials at
the double role of Orange II as a stabilizer, forming a complex Ered1 = 0.19 V and Ered2 = +0.11 V (vs. Ag/AgCl) with a
with MnIII, and as a substrate that permits the regeneration of difference between the cathodic and anodic wave of 0.02 and
MnII, was recently postulated by López et al.35 Although, the 0.204 V, respectively. Furthermore, the reduction potential of
coordination of organic dyes, viz. Alizarin, Alizarin S42 and Mn3+ decreased from +0.35 V to +0.28 V when Orange II
Orange II,3 to several transition metal centres has been known was added to the solution, indicating the stabilization of
for years, comparatively little has appeared on their use as Mn3+ ions. In the presence of a chelating substrate, the
potential stabilizing ligands in oxidative degradation of generated Mn3+ complex becomes more stable and the redox
organic dyes. potentials attain lower values.43 When the concentration of
The formed Orange II MnII complex was isolated and the Orange II was increased up to 2 105 M, the presence of
validity of its composition was confirmed by elemental ana- further reduction peaks along with changes in the oxidation
lysis. In control experiments the reactivity of the isolated 1 : 1 peak intensity were observed, indicating the formation of
Orange II MnII and 2 : 1 complexes were studied. The other manganese–Orange II species as specified above.
isolated complexes exhibit the same catalytic activity and
stability under the experimental conditions employed for the DFT calculations
in situ generation of the complex. Due to the weak coordina- To assess the coordination mode of Orange II to the Mn(II)
tion mode of the ligand, no differences between the catalytic center, DFT (B3LYP/LANL2DZp) calculations were per-
activity of the 1 : 1 and 2 : 1 complex were found. formed for a series of plausible complexes. Orange II in
Beside UV-Vis measurements and DFT calculations, aqueous solution under the selected experimental conditions
electrochemical measurements were used to study the in situ dissociates into an anionic sulfonate group and a cationic
formation of highly reactive MnII catalytic species in sodium ion. In the presence of an unsolvated SO3 group
the presence of Orange II under the selected experimental involving charge transfer from the electron-rich sulfonate
conditions. group onto the rest of the molecule, may in general not give
satisfactory DFT results.28 Solvent Yellow 14, a model com-
CV studies on the complex-formation between Orange II
pound for Orange II containing no sulfonate group was
and Mn2+
selected for the DFT study of the interaction between the
CV measurements of a 4 105 M Mn2+ solution in the Mn(II) and the chosen azo dye. A picture of the calculated
presence of different Orange II concentrations were performed conformers of the model compound 1 is shown in Fig. 6.
in order to determine the interaction between the fully aquated The optimized geometry of 1a was calculated to be
Mn2+ ions and Orange II present in the reaction mixture. ca. 5.8 kcal mol1 lower in energy than that of 1b. Further-
Fig. 5 shows the results of MnII Orange II complex forma- more, the calculated structure of 1a was compared with X-ray
tion in NaCl electrolyte solution, performed using a standard structural data of Solvent Yellow 14.44 A good agreement
three electrode electrochemical setup as described above. between calculated and crystallographically determined struc-
To avoid the oxidation of MnII to MnIV, which precipitates ture was found.
as MnO2, the potential scan was discontinued at +1.0 V, after According to the UV-Vis and electrochemical data pre-
which the reverse scan from +1.0 to 0.8 V was started. The sented above, Orange II can coordinate to a fully aquated
CVs of Mnaq2+ in the absence of any coordinating substrate Mn2+ center. Different plausible interaction modes of Solvent
exhibit one quasi-reversible oxidation peak at E = +0.59 V Yellow 14 MnII (2) and Solvent Yellow 14 MnII Solvent
vs. Ag/AgCl and one quasi-reversible reduction peak at E = Yellow 14 (3) were studied in detail. Optimized structures of 2
+0.35 V, corresponding to the one electron Mn3+/Mn2+ adopting different coordination modes are presented in Fig. 7.
redox couple. In addition, CV measurements on a freshly The studied organic dye can coordinate to aquated Mn2+
prepared 4 105 M Orange II electrolyte solution at ion by forming two new bonds, one between Mn2+ and the
pH 8.5 and 22 1C were performed. Orange II, as it can be seen deprotonated phenolic OH-group of 1a and the second
in Fig. 5, undergoes two electrochemically quasi-reversible, between Mn2+ and one of the azo nitrogen atoms, leading
Fig. 5 CVs of a 4 105 M Mn2+ electrolyte (0.1 M NaCl) solution in the presence of different Orange II concentrations at pH 8.5 (adjusted by
addition of NaOH) and 22 1C.
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Fig. 6 Optimized (B3LYP/LANL2DZp) structures of 1a and 1b with a planar geometry and dihedral angles of (a) 180.01 and (b) 178.71 about the
azo group, C–N–N–C.
Fig. 7 Optimized structures of complex 2a, b and c (B3LYP/LANL2DZp).
to the formation of either a planar six-membered (2a) or five- (2.213–2.294 Å),46a 2-[N,N-bis(2-pyridylmethyl)amoniumethyl]-6-
membered (2b) chelate complex. Furthermore, a second inter- [N-(3,5-di-tert-butyl-2-oxidobenzyl)-N-(2-pyridylamino)amino-
action mode for 2 involving a hydrogen bond between one methyl]-4-methylphenol (H2Ldtb) (2.118–2.237 Å)46b and
coordinated water molecule and the azo nitrogen atom (2c) 1,4,7-triazacyclononane (tacn) (2.118–2.146 Å).46c
was taken into consideration. The calculated energies indi- As expected, upon coordination of two dye molecules in 3,
cate that 2a is energetically favoured over 2b by about the N–N bond distance becomes longer (1.29 Å) than observed
3 kcal mol1. The N–N bond length of 1.30 Å for 2a is nearly in the crystal structure of 1a due to the partial neutralization
identical to that found in the free model molecule 1a (1.28 Å), of the delocalized negative charge of the nitrogen atom.
indicating a weak interaction between the nitrogen atoms and The elongation of the Mn–O bond trans to the azo group
the positively charged manganese center. (Mn–O = 2.38 Å vs. 2.06–2.27 Å for 2, and Mn–O = 2.27/
In addition to these structures, DFT calculations were 2.26 Å vs. 1.81/2.11 Å for 3) exerts a significant trans influence
performed for a further possible interaction of a second dye
molecule with the Mn(II) center leading to the formation of
chelated Mn(II) inner-sphere complexes. Similar transition
metal complexes of ortho-hydroxy azo dyes were prepared
and characterised by Drew and Landquist.45 The introduction
of a second dye molecule is expected to have certain advan-
tages. In addition to the usual stabilization by the chelate-
effect, the introduction of a second molecule of 1a could result
in a protecting effect on the coordination framework. The
optimized structure of 3 is presented in Fig. 8.
The calculated structure of 3 shows a C2-symmetry and the
axial positions are nearly equivalent. The calculated Mn–N
bond lengths in the equatorial plane for the energetically
favoured 2a (2.15 Å) and 3 (2.30 Å) are comparable with the
X-ray structural data for Mn(II) complexes with nitrogen
containing ligands such as 1,2-bis(imidazol-1-yl)ethane (bim) Fig. 8 Optimized structure of 3 (B3LYP/LANL2DZp).

opposite to the Mn–N bond. The increased lability of the axial
ligand allows the subsequent interaction of the substituted
transition metal atom with an oxidant, leading to the
rapid formation of active oxidizing species. Moreover, DFT
calculations performed by Blomberg et al.47 suggest that in the
presence of weak-field ligands for Mn(II) and Mn(III), five-
coordination is also accessible whereas Mn(IV) has a much
stronger preference for six-coordination.47
Complex-formation between bicarbonate and Mn(II)
The reactions between bicarbonate ions (HCO3) and differ-
ent manganese species have been studied for several years,
Fig. 10 Plot of observed first order rate constant (kobs) for the
since aquated Mn2+ cations themselves are actually not able formation of Mn2+ HCO3 vs. the bicarbonate concentration in
to catalyze H2O2 disproportionation. Depending on the the presence of 4 104 M Mn2+ at pH 8.5 and 25 1C.
HCO3 concentration in the reaction mixture, MnII HCO3
complexes of different stoichiometry can be formed. Recently,
it was suggested that only the neutral MnII(HCO3)2 complex in situ formed manganese intermediate occurs. A significant
can facilitate H2O2 disproportionation.48 In this study the time dependent loss in catalytic efficiency of the formed
complex-formation reaction between Mn2+ and HCO3 was MnII HCO3 intermediate was observed. An irreversible
monitored using UV-Vis spectrophotometric beside CV mea- deactivation of the catalyst occurs within less than 20 min.
surements as a function of carbonate concentration at pH 8.5. On the other hand, no precipitate formation as well as no
UV-Vis spectra recorded before and after addition of HCO3 deactivation of the catalytically active manganese intermediate
to an aqueous Mn2+ solution showed the formation of a new could be observed in the presence of a coordinating organic
broad band at 300 nm as illustrated in Fig. 9A. The time substrate, i.e. Orange II, over a long period of time (1–4 days)
course of the absorption band formation is shown in Fig. 9B. in a high carbonate (0.5 M) containing buffer solution under
It can be seen from Fig. 9B that the rate of formation of the these conditions. Moreover, the stabilization of the in situ
manganese carbonate intermediate is enhanced at higher formed active catalyst in the presence of an organic substrate
carbonate concentration. The observed first order rate con- is of considerable practical interest, because its successful
stants following the induction period in Fig. 9B, are directly implementation could offer a more efficient alternative for
proportional to the [HCO3] in the range 0.01–0.1 M clean oxidation reactions.
(see Fig. 10) with a second order rate constant of (3.6 0.2) CV measurements of freshly prepared aqueous Mn(NO3)2
102 M1 s1 at 25 1C. Moreover, the observed induction solutions were performed in the presence of different carbo-
period is probably related to the displacement of water from nate concentrations in a 0.1 M NaCl electrolyte solution at
the first coordination sphere of the fully aquated Mn2+ ion by pH 8.5 (adjusted by careful addition of NaOH) and 22 1C. In
HCO3 and subsequent rearrangement of the coordinated the presence of a coordinating substrate, the displacement of a
ligand, viz. formation of bidentate carbonate complexes. It coordinated water molecule from the manganese coordination
should be noted that under these experimental conditions sphere takes place. By coordination of a negatively charged
(high carbonate concentration and pH 8.5) insoluble MnCO3 ligand such as HCO3 to a positively charged metal, the peak
is formed as a very fine white precipitate at longer reaction potentials are shifted to more negative potentials compared to
times. Its composition was confirmed by elemental analysis the fully aquated Mn2+ (see Fig. 11A and 12).41 On increasing
and IR spectroscopy. the carbonate concentration in solution a decrease in the peak
The reactivity of the produced intermediate was tested in current intensity occurs concomitantly with peak broadening
the oxidative degradation of Orange II by H2O2 at pH 8.5 and because of complexation by carbonate. Typical multiple scan
25 1C. During the first 200 s, no change in the reactivity of the CVs of a 4 105 M Mn2+ solution in the presence of 0.2 M
Fig. 9 (A) UV-Vis spectra of an aqueous 4 104 M Mn2+ solution before (black curve) and after (red curve) addition of 0.4 M HCO3 at pH
8.5 and 25 1C. (B) Time course of the band formation at 300 nm of an aqueous 2 104 M Mn2+ solution containing different amounts of HCO3.
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Fig. 11 (A) Cyclovoltammograms for 4 105 M Mn2+ solution in an aqueous solution of 0.1 M NaCl and different concentrations of HCO3.
(B) Typical multiple scan CVs of a 4 105 M Mn2+ solution in the presence of 0.2 M NaHCO3 and 0.1 M NaCl at pH 8.5 and 22 1C.
Fig. 13 Second-order carbonate concentration dependence of kobs.

Experimental conditions: 2 105 M Mn(NO3)2, 5 105 M Orange II,
0.01 M H2O2, pH 8.5, 25 1C.
Fig. 12 Plot of peak potential E as function of [HCO3]; E vs.
Ag/AgCl electrode, [Mn2+] = 4 105 M, [HCO3] = 0.1–05 M
in 0.1 M NaCl electrolyte solution at pH 8.5 and 22 1C. In the present case, the catalytic reaction leads to a square
dependence of kobs on the HCO3 concentration (Fig. 13) with
NaHCO3 and 0.1 M NaCl at pH 8.5 and 25 1C is presented in a third rate constant (8.3 0.3) 102 M2 s1, suggesting
Fig. 11B. In the presence of a chelating substrate, the gener- that 2 equivalents of HCO3 are involved in the oxidation
ated Mn3+ complex becomes more stable and the redox mechanism. It is suggested, among other possibilities, that one
potentials attain lower values. Moreover, at higher carbonate equivalent of HCO3 is required for the formation of the more
concentrations in the reaction mixture the presence of a second reactive [MnII(H2O)5(HCO3)]+ intermediate, and the second
oxidation peak at E = +0.41 V, attributed to the formation equivalent of HCO3 is required for the formation of the more
of further complexes such as proposed in eqn (5), was reactive peroxocarbonate species, known to be a versatile
observed. oxidizing agent. It should also be noticed that no oxidation
of Orange II by H2O2 was observed in the absence of a
K1
½MnII ðH2 OÞ6 2þ þ HCO3 Ð ½MnII ðH2 OÞ5 ðHCO3 Þþ carbonate buffer. In the view of these findings we decided to
study the influence of carbonate on the manganese catalyzed
K2
½MnII ðH2 OÞ5 ðHCO3 Þþþ HCO3 Ð ½MnII ðH2 OÞ4 ðHCO3 Þ2 oxidation of Orange II by H2O2 and HCO4, respectively.
ð5Þ The reaction of carbonate with H2O2 at pH 8.5 and 25 1C
By plotting the peak potential E as a function of the Peroxycarbonate ions, known to be several orders of magni-
hydrogen carbonate concentration (see Fig. 12), the presence tude more reactive toward nucleophilic substrates than H2O2
of different complex species at different carbonate concentra- itself,49 are formed in a relatively fast pre-equilibrium
tions is revealed. (K = 0.32 0.02 M1)40 between hydrogen carbonate ions
and H2O2 shown in eqn (6).
Carbonate concentration dependence of the catalytic reaction
course HCO3 + H2O2 " HCO4 + H2O (6)
The effect of the carbonate concentration on the oxidative Moreover, the reaction of H2O2 and HCO3
to form the more
degradation of the dye was studied at a constant pH of 8.5. electrophilic HOOCO2 (HCO4) occurs rapidly (t1/2 E 300 s)
The total carbonate concentration was varied between at near neutral pH and 25 1C.50 This step is also regarded to be
0.05 and 0.5 M. a key aspect of several oxidation reactions.51,52 The higher

Fig. 14 (A) Spectral changes observed at 480 nm for the 2 105 M Mn(NO3)2 catalyzed oxidative degradation of 2.5 105 M Orange II in the
presence of (black curve) 0.01 M H2O2 and (red curve) 0.01 M HCO4, respectively, at pH 8.5 and 0.5 M total carbonate concentration.
(B). Comparison of the absorbance changes at 480 nm vs. time for the 2 105 M Mn2+ catalyzed oxidative degradation of 5 105 M Orange II
by 0.01 M H2O2 at pH 8.5 and different carbonate concentrations.
reactivity of peroxycarbonate compared to that of H2O2 is observations the formed complex with an absorption band at
attributed to carbonate being a better leaving group than 400 nm could be attributed to a MnIV–Z2-peroxycarbonate
hydroxide.40 intermediate.53 Based on spectroscopic observations and data
By performing the oxidation reactions in the presence of reported in the literature,54 the formed intermediate can be
peroxycarbonate instead of H2O2 in a 0.5 M carbonate con- regarded as most likely to be a high valent manganese com-
taining buffer solution at pH 8.5, no difference in the reactivity plex. Similar Rh,55 Pt56 and Fe57 peroxycarbonate complexes
was observed (Fig. 14A). have been isolated before and were characterized spectro-
The Mn(II) catalyzed oxidative degradation of Orange II by scopically. The time course of the absorption band at 400 nm
using HCO4 as an oxidizing agent could be significantly at different pH is illustrated in Fig. 15B.
enhanced through increasing the total carbonate concentra- In the absence of any stabilizing ligand, the formed complex
tion in the reaction mixture. This can be explained in terms of rapidly decomposes with the formation of catalytically
the equilibrium formulated in eqn (6). Based on our experi- inactive MnIVO2 that precipitates from solution (see Fig. 15B).
mental observations and aspects reported in the literature41 for The decomposition of the active intermediate is accelerated at
the Mn(II) catalyzed oxidation reaction by H2O2 in a carbo- higher pH (see Fig. 15B). To ascertain that the formulated
nate containing solution, the reaction sequence presented in reaction steps in Scheme 2 are valid under our reaction
Scheme 2 can be suggested to occur. conditions, a systematic spectroscopic investigation at differ-
ent pH values was performed. Representative data for the
Complex-formation between Mn2+ and H2O2 in an aqueous reaction course at 400 nm at pH 8.5 and 9.5 are presented in
carbonate solution Fig. 15B. Contrary to our expectations, an increase of one unit
in pH resulted in an increase of the induction period and a
Addition of H2O2 to hexaaqua Mn2+ in a carbonate solution
decrease in the manganese peroxycarbonate complex forma-
leads to significant spectral changes in the UV-Vis spectra
tion rate under the mentioned reaction conditions. This could
during the reaction (see Fig. 15A). The initial rapid increase
be partly due to subsequent formation of Mn(OH)2 precipi-
of the intensity of the broad band at 300 nm, as it is illustra-
tates at higher pH and to deprotonation of HCO3 that
ted in Fig. 15A, is attributed to the fast formation of
becomes significant at pH above 8 to 9.51 This results in a
[MnII(H2O)5(HCO3)]+. An isosbestic point at 330 nm suggests
decrease in the HCO3 concentration in the equilibrium
the formation of a new manganese intermediate by addition of
presented in eqn (6), reducing the concentration of peroxy-
an oxidizing agent, i.e. H2O2. According to our spectroscopic
carbonate present in solution.
Reactivity profile as function of pH

The reactivity of the catalytic system is generally influenced by
the protonation state of the substrate, the catalyst and oxidiz-
ing agent. In our work the kinetics was studied in 0.4 M
HCO3 containing buffer solution in the pH range between
8.0 and 9.5 at 25 1C. The pH of the carbonate buffer solution
was adjusted carefully using small amounts of concentrated
NaOH solution to avoid dilution. A typical manganese cata-
Scheme 2 In situ formation of catalytically active Mn intermediates lyzed oxidative degradation of Orange II by H2O2 in a
in the presence of hydrogen peroxide in a carbonate containing carbonate buffer solution is presented in Fig. 16A. The
aqueous solution at pH 8.5 and 25 1C. catalytic degradation is usually complete within 1–10 min
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Fig. 15 (A) UV-Vis spectra recorded for the reaction of 2 104 M Mn(NO3)2 with 0.01 M H2O2 in a 0.5 M HCO3 containing solution at
pH 8.4 and 25 1C. (B) Comparison of typical absorbance at 400 nm vs. time plots at pH 8.5 (black curve) and 9.5 (red curve).
Fig. 16 (A) UV-Vis spectra of a 2 105 M Mn(NO3)2 catalyzed oxidative degradation of 5 105 M Orange II by 0.01 M H2O2 in a 0.4 M total
carbonate containing solution at pH 8.5 and 25 1C. The inset in Fig. 16A shows the first spectrum of Orange II before the addition of the catalyst
and H2O2, and the final spectrum recorded after 250 s. (B) Comparison of absorbance at 480 nm vs. time plots for the 2 105 M Mn(NO3)2
catalyzed oxidative degradation of 5 105 M Orange II by 0.01 M H2O2 in a 0.4 M total carbonate containing solution at different pH values
and 25 1C.
depending on the pH of the solution, the catalyst concentra- (see Fig. 17). Increasing the pH to 49 leads to a decrease in
tion, and the H2O2 and carbonate concentrations. The decom- the oxidation rate for the bicarbonate-activated peroxide,
position of the dye was followed by monitoring the spectral which is presumably the result of the deprotonation of
changes at 480 nm. The depletion of the band at 480 nm is in HOOCO2 to form CO42, a less electrophilic oxidant.58
general correlated with cleavage (heterolytic or homolytic) of At even higher pH, the decomposition of the peroxide is
the azo group leading to colorless oxidation products due to accelerated and may reduce the oxidation reaction rate.
the induced discontinuity in the conjugation of the p-system in Contrary to our expectations, the observed rate constants
the dye molecule. The inset in Fig. 16A shows the first for the decolorization reaction of Orange II are similar to
spectrum of Orange II before the addition of the catalyst the destruction rate constants of naphthalene and benzene
and H2O2, and the final spectrum recorded after 250 s. rings, long-lived intermediates, under the studied conditions
A decrease in the intensity of the two other bands at (see Fig. 17). Thus, for a complete oxidation of these stable
270 and 300 nm was observed, showing that further bleaching molecules higher concentrations of oxidant and catalyst are
also occurs under these reaction conditions. The isolation and required.
characterization of reaction products is extremely difficult and A similar screening using MnCl2, Mn(Ac)2 and Mn(SO4)2
requires large synthetic efforts, particularly as different reac- showed identical catalytic activity in the oxidative degradation
tion intermediates tend to react further under experimental of Orange II by H2O2. In all cases, the manganese catalyzed
conditions. A comparison of the reaction course at different oxidative degradation of Orange II is favored by moderate
pH values is shown in Fig. 16B. alkaline pH values and vanishes completely at very high or
The Mn(II) catalyzed decolorization and oxidative decom- very low (strong acidic) values. According to the experimental
position of Orange II was found to be sensitive to the pH of observations mentioned above, the manganese catalyzed
the solution. According to our experimental data, an increase oxidative degradation of Orange II by H2O2 in a carbonate
in pH resulted in a slight decrease in the reaction rate under containing solution is considerably inhibited at higher
the above-mentioned reaction conditions and the highest pH values due to the lower formation of the high valent
reactivity is observed at a pH between 8.2 and 8.6 manganese Z2-peroxycarbonate complex (see Fig. 15B).

Table 1 The constants k and K for the Mn(NO3)2 catalyzed oxidation
of Orange II by H2O2 at pH 8.5 and 25 1C (see Scheme 3)
[HCO3]/M k/s1 103K/M1

0.1 0.0033 34.6
0.3 0.032 17.6
0.4 0.051 17.8
0.5 0.138 15.2
Scheme 3 Proposed reactions steps for the formation of the cata-

lytically active manganese intermediate in the presence of H2O2 in a
carbonate containing solution.
Fig. 17 Plot of observed rate constant (kobs) calculated for the
decoloring reaction followed at 480 and 300 nm, respectively. Experi-
degradation of Orange II by H2O2 in a low carbonate con-
mental conditions: 2 105 M Mn(NO3)2, 5 105 M Orange II,
centration containing solution (0.1–0.3 M HCO3) are
0.01 M H2O2, 0.4 M total carbonate and 25 1C.
strongly curved (higher K values, see Table 1) and reach a
limiting value at higher catalyst concentration. In contrast,
Effect of the manganese concentration on the oxidative reaction
similar data at higher carbonate concentrations (0.4–0.5 M
course
HCO3) result in a less curved dependence of kobs on the
To evaluate the effect of the catalyst concentration on the catalyst concentration, i.e. lower K values (see Table 1). The
manganese catalyzed oxidative degradation of Orange II by observed rate profile can be explained by the general reaction
H2O2 under catalytically relevant experimental conditions, mechanism proposed in Scheme 2 and simplified in Scheme 3.
kinetic studies were performed for solutions in which the The observed rate law for the proposed reaction steps in
carbonate containing water solution with various amounts Scheme 3 is given by eqn (7). The calculated k and K values
of Mn(NO3)2 was added in the presence of 0.01 M H2O2 to a from the non-linear concentration dependences in Fig. 18 are
5 105 M Orange II solution at 25 1C. The obvious summarized in Table 1.
accelerating ability of the HCO3 ions prompted us to study
the catalytic reaction course in more detail at four different kK½MnðIIÞ
kobs ¼ ð7Þ
carbonate concentrations. The in situ produced catalyst con- 1 þ K½MnðIIÞ
centration dependence was studied at 480 nm using in situ
UV-Vis spectroscopic measurements and the kinetic traces
Effect of the H2O2 concentration on the manganese-catalyzed
could be adequately fitted to a single exponential function.
oxidative degradation of Orange II
Plots of the observed rate constant as a function of [Mn2+] at
different carbonate concentrations are presented in Fig. 18. The effect of H2O2 on the oxidation reaction course was
As it is evidenced in Fig. 18, the [Mn2+] dependences of the studied by varying its initial concentration over a wide range,
observed rate constants for the manganese catalyzed oxidative between 5 and 30 mM (Fig. 19). At lower H2O2 concentrations
(1 and 5 mM) a fast oxidation reaction occurs in the first few
seconds followed by a rapid consumption of H2O2 resulting
finally in a partial and inefficient decolorization of the dye.
This prompted us to study the H2O2 concentration effect on
the catalytic oxidation of the dye at higher concentrations of
H2O2. The kobs values were calculated from a single exponen-
tial fit to the absorbance at 480 nm vs. time plots and showed a
linear dependence on the initial H2O2 concentration over the
studied concentration range.
Stability of the in situ formed catalyst

In control experiments the stability of the in situ generated
catalyst was studied by repeated addition of dye and H2O2 to a
solution of 2 105 M Mn(NO3)2 at pH 8.5 (0.4 M HCO3)
and 25 1C (see Fig. 20A and B).
As it can be seen in Fig. 20A, the catalytic cycle could be
repeated several times without any significant loss of activity
Fig. 18 Mn(NO3)2 concentration dependence of kobs. Reaction con- during the oxidation reaction, indicating an excellent stability
ditions: 5 105 M Orange II, 0.01 M H2O2, pH 8.5 and 25 1C. of the in situ formed catalyst. After the fifth cycle the reaction
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By performing the reaction under inert reaction conditions
no significant differences in the decomposition reaction rate was
observed, indicating that HO or HOO radical formation
is not prevalent for this oxidation reaction. This is further
supported by the observation that addition of radical traps
such as TTBP had no effect on the reaction course (see Fig. 21).
Taking into account all obtained spectroscopic and kinetic
data, the following reaction schemes can be proposed for the
Mn2+ catalyzed oxidative degradation of Orange II by H2O2
in carbonate solution under catalytically relevant experimental
conditions.
A key feature of the proposed reaction mechanism outlined
Fig. 19 H2O2 concentration dependence of kobs. Reaction conditions: in Scheme 4 is that the overall oxidation of Orange II occurs in
5 105 M Orange II, 2 105 M Mn(NO3)2, pH 8.5 and 25 1C. a two electron oxidation step leading to the formation of a
relatively stable high-valent MnQO intermediate and transfer
solution containing the active catalyst was allowed to stay at of the oxo group to the substrate. Most of the earlier reported
ambient temperature for 48 h. Subsequently, the catalytic papers22,59 on the oxidation reaction catalyzed by several
activity of the in situ formed manganese complex was evalu- isolated and structurally well defined manganese complexes
ated again by performing the oxidation reaction in the have emphasized the formation of a high-valent MnQO
presence of freshly added Orange II and H2O2. The experi- intermediate by the reaction of manganese with the appro-
mental results illustrated in Fig. 20B provide clear evidence for priate oxidant. According to our observations, HCO3 ions
the high efficiency of the in situ formed catalyst under the are involved in two catalytically relevant reactions. HCO3
above mentioned experimental reaction conditions. ions react with aquated MnII present in solution to form a
catalytically active Mn–HCO3 complex. HCO3 is also in-
volved in a fast equilibrium with H2O2 to form HOOCO2,
Mechanistic aspects of the manganese-catalyzed oxidative
a versatile heterolytic oxidant. In the following step, through
degradation of Orange II by H2O2 in carbonate solution
nucleophilic attack of the oxidizing agent on the MnII center, a
Throughout this study, the oxidation reactions were carried MnII–Z2-peroxycarbonate complex is formed. The remaining
out in a thermostated open glass reactor vessel at ambient coordination sites in the first shell will be occupied by water
temperature in aqueous hydrogen carbonate containing solu- and hydroxyl at a pH between 8 and 10. The principal mode of
tions. The readily available manganese salts, the mild reaction the formation of relatively stable high-valent MnQO inter-
conditions and the operation simplicity and practicability mediates is believed to involve the heterolytic cleavage of the
allow for an easy and green oxidative degradation of the peroxide bond, as shown in Scheme 4. An important role in
studied organic dye. In control experiments the catalytic the stabilization of the formed MnQO species is played by the
activity of the in situ generated manganese complex was electron donating bicarbonate ions. This may also account for
investigated under an inert atmosphere. By performing the the unique requirement of HCO3 in the oxidative decom-
catalytic reaction in a closed glass reactor under inert reaction position of Orange II catalyzed by simple manganese salts.
conditions no change in the decomposition reaction rate was The further coordination of the substrate followed by an
noticed. A comparison of the reaction course carried out oxygen transfer step along with the second electron, leads to
under different experimental conditions is illustrated in the formation of several oxidation products and finally to the
Fig. 21. regeneration of the catalyst. It must be noted that in the
Fig. 20 (A) Spectral changes observed at 480 nm for the repeated addition of 5 105 M Orange II to a 2 105 M Mn(NO3)2 solution in the
presence of 0.01 M H2O2 at pH 8.5 and 0.4 M total carbonate concentration. (B) Spectral changes observed at 480 nm for a new addition of
5 105 M Orange II and 0.01 M H2O2 to a 48 h old reaction mixture containing the catalyst solution under the same experimental conditions as
mentioned in A.

Scheme 5 Proposed reaction mechanism involving first substrate
Fig. 21 Comparison of typical absorbance at 480 nm vs. time plots of coordination to MnII in a pre-equilibrium step during the catalyzed
a 2 105 M Mn(NO3)2 catalyzed oxidative degradation of 5 105 M oxidative degradation of Orange II by H2O2 in a carbonate containing
Orange II by 0.01 M H2O2 in a 0.4 M HCO3 containing solution at aqueous solution at pH between 8–9 and 25 1C.
pH 8.5 and ambient temperature performed in the presence of atmos-
pheric oxygen (black curve), inert atmosphere (red curve) and TTBP
(blue curve), respectively. stoichiometry, followed by nucleophilic attack of the oxidant
on the MnII center leading to the formation of Orange
II–MnII–peroxycarbonate species. The subsequent scission of
the peroxo bond leads to the formation of high-valent oxo
intermediates, as formulated in Scheme 4. In this case, the
formed MnIVQO intermediate is stabilized by Orange II, an
electron rich organic molecule with chelating capacity. The
importance of Orange II as an equatorial ligand is also to
favor the heterolytic scission of the peroxo bond leading to the
MnIVQO intermediate and bicarbonate.
Conclusions
A fast and environmentally benign method for the oxidative
degradation of Orange II could be achieved using H2O2 in
conjunction with catalytic amounts of relatively non-toxic
manganese salts as catalyst precursors in a carbonate contain-
ing aqueous solution under mild reaction conditions. Screen-
ing and spectroscopic methods allowed us to study the
Scheme 4 Proposed reaction mechanism for the Mn(II) catalyzed
oxidative degradation of Orange II by H2O2 in a carbonate containing
catalytic reaction course and to identify some key features of
aqueous solution at pH between 8–9 and 25 1C. the reaction that reflect upon its mechanism. Our study
revealed that the oxidative degradation of the model substrate
Orange II is catalytic only in carbonate containing aqueous
solution. No other buffer containing aqueous solution could
absence of a catalyst, the oxidative degradation of Orange II induce the oxidative degradation of Orange II by H2O2 and
by addition of an electrophilic bleaching agent, HOOCO2, this led to the implication of peroxycarbonate as a key
occurs very slowly under certain reaction conditions. The molecular entity. The reported experimental data suggests that
oxidation mechanism involves nucleophilic attack of the dye the in situ formed high-valent manganese intermediate posses-
at the electrophilic oxygen of HOOCO2. In aqueous solution, sing one hydrogen carbonate ligand is able to activate
proton transfer can lead to the displacement of HCO3 and H2O2, but decomposes rapidly with the formation of neutral
the slow formation of oxidized substrate. MnCO3, which precipitates from solution as an insoluble
If substrate binding to MnII occurs before the addition of white solid. One of the main factors affecting the process
HOOCO2 to the catalyst solution, following reactions can be efficiency was the stabilization of the catalytically active Mn
assumed to take place during the reaction cycle under the complex. Furthermore, by addition of Orange II, the forma-
chosen experimental conditions. tion of MnII Orange II complexes with different stoichio-
In line with the concerns mentioned above, the first step in metry was observed. The simultaneous s,p-coordination of
Scheme 5 involves the prior coordination of Orange II to MnII the organic dye is well-precedented, and recent DFT studies
and formation of MnII–Orange II complexes of different support this type of complex formation.28 The catalytic
This journal is
activity of the formed intermediates was tested under catalytic 22 N. Nakayama, S. Tsuchiya and S. Ogawa, J. Mol. Catal. A: Chem.,
reaction conditions. 2007, 277, 61.
23 C. F. Baes, J. R. Mesmer and R. E. Mesmer, Am. J. Sci., 1981, 281,
The kinetic investigations performed at different pH could 935.
provide relevant information about the nature of the oxidizing 24 S.-Y. Liu and D. G. Nocera, Tetrahedron Lett., 2006, 47, 1923.
agent involved in the reaction. It was found that the pH is a 25 (a) A. D. Becke, J. Phys. Chem., 1993, 97, 5648; (b) C. Lee, W. Yang
critical issue for the rate of the oxidation process due to its and R. G. Parr, Phys. Rev. B, 1988, 37, 785; (c) P. J. Stephens,
F. J. Devlin, C. F. Chabalowski and M. J. Frisch, J. Phys. Chem.,
influence on the deprotonation of the bicarbonate ions, the 1994, 98, 11623; (d) P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985,
formation of peroxycarbonate in solution, and the deprotona- 82, 270; (e) P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 284;
tion of aquated Mn2+. The ongoing studies are presently (f) P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 299;
(g) Gaussian Basis Sets for Molecular Calculations, ed. S. Huzinaga,
complemented by investigations on different organic sub- Elsevier, Amsterdam, 1984.
strates with various functional groups in order to determine 26 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
the influence of substrate modification on the catalytic M. A. Robb, J. R. Cheeseman, J. A. Montgomery Jr, T. Vreven,
reaction cycle. DFT studies beside further kinetic and spectro- K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi,
V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
scopic investigations should contribute to a better understanding G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
of the catalytic system. R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian,
J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
Acknowledgements O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski,
P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador,
The authors kindly acknowledge fruitful discussions with J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels,
Dr Anette Nordskog and Dr Wolfgang von Rybinski, Henkel M. C. Strain, O. Farkas, D. K. Malick, A. D. Rabuck,
KGaA, Düsseldorf, Germany. K. Raghavachari, J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul,
S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko,
P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith,
References M. A. Al-Laham, C. Y. Peng, A. Nanayakkara, M. Challacombe,
P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez and
1 I. Mielgo, C. López, M. T. Mareira, G. Feijoo and J. M. Lema, J. A. Pople, Gaussian, Inc., Wallingford, CT, 2004.
Biotechnol. Prog., 2003, 19, 325. 27 H. Zollinger, Color Chemistry, Wiley-VCH, Weinheim Germany,
2 J. Hastie, D. Bejan, M. Teutli–León and N. J. Bunce, Ind. Eng. 3rd edn, 2003, ch. 2, pp. 18–50.
Chem. Res., 2006, 45, 4898. 28 L. C. Abbott, S. N. Batchelor, J. Oakes, B. C. Gilbert,
3 H. Park and W. Choi, J. Photochem. Photobiol., A, 2003, 159, 241. A. C. Whitwood, J. R. Lindsay Smith and J. N. Moor, J. Phys.
4 G. L. Baughman and E. J. Weber, Environ. Sci. Technol., 1994, 28, Chem., 2005, 109, 2894.
267. 29 G. R. Hodges, J. R. Lindsay Smith and J. Oakes, J. Chem. Soc.,
5 T. Robinson, G. McMullan, R. Marchant and P. Nigam, Bio- Perkin Trans. 2, 1998, 617.
resource Technol., 2001, 77, 247. 30 J. Oakes and P. Gratton, J. Chem. Soc., Perkin Trans. 2, 1998,
6 T. J. Collins, Acc. Chem. Res., 1994, 27, 279. 1857.
7 R. Hage, J. E. Iburg, J. Kerschner, J. H. Koek, E. L. M. Lempers, 31 W. Feng, D. Nansheng and H. Helin, Chemosphere, 2000, 41, 1233.
R. J. Martens, U. S. Racherla, S. W. Russel, T. Swarthoff, M. R. 32 J. R. Lindsay Smith, B. C. Gilbert, A. M. Payeras, J. Murray,
P. van Vliet, J. B. Warnaar, L. van der Wolf and B. Krijnen, T. R. Lowdon, J. Oakes, R. P. Prats and P. H. Walton, J. Mol.
Nature, 1994, 369, 637. Catal. A: Chem., 2006, 251, 114.
8 A. Battacharyya, S. Kawi and M. B. Ray, Catal. Today, 2004, 98, 33 J. Tokuda, R. Oura, T. Iwasaki, Y. Takeuchi, A. Kashiwada and
431. M. Nango, Coloration Technol., 2000, 116, 42.
9 J. H. Ramirez, F. J. Maldonado-Hódar, A. F. Pèrez-Cadenas, 34 T. Yoshida and S. Sawada, Bull. Chem. Soc. Jpn., 1975, 48, 345.
C. Moreno-Castilla, C. A. Costa and L. M. Madeira, Appl. Catal., 35 C. López, J. C. Garcı́a-Monteagudo, M. T. Madeira, G. Feijoo
B, 2007, 75, 312. and J. M. Lema, Enzyme Microb. Technol., 2007, 42, 70.
10 J. H. Ramirez, C. A. Costa, L. M. Madeira, G. Mata, 36 (a) R. L. Reeves, M. S. Maggio and S. A. Harkaway, J. Phys.
M. A. Vicente, M. L. Rojas-Cervantes, A. J. López-Peinado and Chem., 1979, 83, 2359; (b) T. Asakura and M. Ishida, J. Colloid
R. M. Martin-Aranda, Appl. Catal., B, 2007, 71, 44. Interface Sci., 1989, 130, 184.
11 (a) Y. Zhiyong, M. Bensimon, D. Laub, L. Kiwi–Minsker, 37 K. Murakami, Dyes Pigm., 2002, 53, 31.
W. Jardim, E. Mielczarski, J. Mielczarski and J. Kiwi, J. Mol. 38 H. A. Benesi and J. H. Hildebrand, J. Am. Chem. Soc., 1949, 71,
Catal. A: Chem., 2007, 272, 11; (b) X. Chen, X. Qiao, D. Wang, 2703.
J. Lin and J. Chen, Chemosphere, 2007, 67, 802. 39 P. Job, Compt. Rend., 1925, 180, 928.
12 T. W. Kim, S. G. Hur, S.-J. Hwang, H. Park, W. Choi and 40 V. Nadtochenko and J. Kiwi, J. Chem. Soc., Faraday Trans., 1997,
J.-H. Choy, Adv. Funct. Mater., 2007, 17, 307. 93, 2373.
13 T. Wieprecht, J. Xia, U. Heinz, J. Dannacher and G. Schlingloff, 41 C. Bauer, P. Jacques and A. Kalt, Chem. Phys. Lett., 1999, 307,
J. Mol. Catal. A: Chem., 2003, 203, 113. 397.
14 N. Chahbane, D.-L. Popescu, D. A. Mitchell, A. Chanda, 42 A. Ya. Sychev, U. Pfannmueller and V. G. Isak, Zh. Fiz. Khim.,
D. Lenoir, A. D. Ryabov, K.-W. Schramm and T. J. Collins, Green 1983, 8, 1974.
Chem., 2007, 9, 49. 43 (a) D. Lesht and J. E. Bauman, Inorg. Chem., 1978, 17, 3332;
15 G. B. Payne, P. H. Deming and P. H. Williams, J. Org. Chem., (b) J. Dasgupta, A. M. Tyryshkin, Y. N. Kozlov, V. V. Klimov and
1961, 26, 659. G. C. Dismukes, J. Phys. Chem. B, 2006, 110, 5099.
16 G. Majetich and R. Hicks, Synlett, 1996, 649. 44 A. C. Olivieri, R. B. Wilson, I. C. Paul and D. Y. Curtin, J. Am.
17 A. McKillop and W. R. Sanderson, Tetrahedron, 1995, 51, 6145. Chem. Soc., 1989, 111, 5525.
18 J. E. Barker and T. Ren, Tetrahedron Lett., 2004, 45, 4681. 45 H. D. K. Drew and J. K. Landquist, J. Chem. Soc., 1939, 292.
19 J Oakes, Eur. Pat. Appl., 145091, 1985. 46 (a) X. Zhu, B. Li, X. He and Y. Zhang, J. Chem. Crystallogr., 2005,
20 X.-M. Feng, Z. Wang, N.-S. Bian and Z.-L. Wang, Inorg. Chim. 35, 443; (b) A. J. Bortoluzzi, A. Neves, R. A. A. Couto and
Acta, 2007, 360, 4103. R. A. Perelta, Acta Crystallogr., Sect. C: Cryst. Struct. Commun.,
21 (a) C. Kim, K. Chen, J. Kim and L. Que Jr, J. Am. Chem. Soc., 2006, C62, m27; (c) T. H. Bennur, D. Srinivas, S. Sivasanker and
1997, 119, 5964; (b) D. D. Vos and T. Bein, Chem. Commun., 1996, V. G. Puranik, J. Mol. Catal. A: Chem., 2004, 219, 209.
917; (c) P. Battioni, J. P. Renaud, J. F. Bartoli, M. Rein-Artiles, 47 M. R. Blomberg, P. E. M. Siegbahn, S. Styring, G. T. Babeock,
M. Fort and D. Mansuy, J. Am. Chem. Soc., 1988, 110, 8462. B. Akermark and P. Korall, J. Am. Chem. Soc., 1997, 119, 8285.

48 K. G. Tikhonov, O. M. Zastrizhanaya, Yu N. Kozlov and 56 P. J. Hayward, D. M. Blake, G. Wilkinson and C. J. Nyman,
V. V. Klimov, Biochemistry, 2006, 71, 1270. J. Am. Chem. Soc., 1970, 92, 5873.
49 D. Swern, Organic Peroxides, Wiley, New York, 1970, pp. 313. 57 K. Hashimoto, S. Nagatomo, S. Fujinami, H. Furutachi, S. Ogo,
50 D. E. Richardson, H. Yao, K. M. Frank and D. A. Bennett, J. Am. M. Suzuki, A. Uerhara, Y. Maeda, Y. Watanabe and T. Kitagawa,
Chem. Soc., 2000, 122, 1729. Angew. Chem., Int. Ed., 2002, 41, 1202.
51 B. S. Lane, M. Vogt, V. J. DeRose and K. Burgess, J. Am. Chem. 58 B. Balagam and D. E. Richardson, Inorg. Chem., 2008, 47, 1173.
Soc., 2002, 124, 11946. 59 (a) A. M. Khenkin, D. Kumar, S. Shaik and R. Neumann, J. Am.
52 D. E. Richardson, C. A. S. Regino, H. Yao and J. V. Johnson, Free Chem. Soc., 2006, 128, 15451; (b) P. E. M. Siegbahn and
Radical Biol. Med., 2003, 35, 1538. R. H. Crabtree, J. Am. Chem. Soc., 1999, 121, 117;
53 MnIV in the presence of further MnII ions leads to the formation of (c) M. Kondo, T. Mitsui, S. Ito, Y. Kondo, S. Ishigure,
MnIII, a strong but highly unstable oxidant, according to the T. Dewa, K. Yamashita, J. Nakamura, R. Oura and M. Nango,
reaction: MnIV + MnII " 2MnIII. J. Colloid Interface Sci., 2007, 310, 686; (d) G. B. Shuĺpin,
54 K. Hashimoto, S. Nagatomo, S. Fujinami, H. Furutachi, S. Ogo, M. G. Matthes, V. B. Romakh, M. I. F. Barbosa, J. L.
M. Suzuki, A. Uehara, Y. Maeda, Y. Watanabe and T. Kitagawa, T. Aoyagi and D. Mandelli, Tetrahedron, 2008, 64, 2143;
Angew. Chem., 2002, 114, 1251. (e) A. E. Anastasi, P. H. Walton, J. R. Lindsay Smith, W. M.
55 M. Aresta, I. Tommasi, E. Quaranta, C. Fragale, J. Mascetti, C. Sameera and J. E. McGrady, Inorg. Chim. Acta, 2008, 361,
M. Tranquille, F. Galan and M. Fouassier, Inorg. Chem., 1996, 35, 4254. 1079.
This journal is
launching in 2009
NJC
060877
Metallomics
Metallomics
Number 1 | 2008

Metallomics

the Americas.
ISSN 1756-5901
Pages 1–100
1754-5692(2008)1:1;1-6
1756-5901(2009) 1:1;l-m

Pages 1–212
Supporting the
ISSN 1144-0546
PAPER
The solubility and recrystallization of 1,3,5-triamino-2,4,6-trinitrobenzene

in a 3-ethyl-1-methylimidazolium acetate–DMSO co-solvent system
T. Yong-Jin Han,* Philip F. Pagoria, Alexander E. Gash, Amitesh Maiti,
Christine A. Orme, Alexander R. Mitchell and Laurence E. Fried
Received (in Gainesville, FL, USA) 17th June 2008, Accepted 6th August 2008
First published as an Advance Article on the web 18th September 2008
DOI: 10.1039/b810109d
Ionic liquids have previously been shown to dissolve strong inter- and intramolecular hydrogen-
bonded solids, including natural fibers. Much of this solubility is attributed to the anions in ionic
liquids, which can disrupt hydrogen bonding. We have studied the solubility and recrystallization
of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB), a very strong inter- and intramolecular hydrogen-
bonded solid, in various ionic liquid solvent systems. We discovered that acetate-based ionic
liquids were the best solvents for dissolving TATB, while other anions, such as Cl , HSO4 and
NO3 showed moderate improvements in the solubility compared to conventional organic
solvents. Ionic liquid–DMSO co-solvent systems were also investigated for dissolving and
recrystallizing TATB.
1. Introduction been a topic of intense discussion,8,9 since the original crystal

structure determined by Cady and Larson showned4 TATB to
Ionic liquids (ILs) have recently been shown to be ideal have a centrosymmetric structure with the space group P 1,
solvents for dissolving hydrogen-bonded solids, including Z = 2, which is incompatible with NLO activity. Some have
cellulose1 and natural fibers.2,3 The use of imidazolium-based attributed the NLO activity of TATB to a small amount of a
cations with halides as counter-anions has significantly im- second, presently unidentified, TATB polymorph mixed in
proved the solubilities of these natural products. Successful with the bulk centrosymmetric TATB crystals.10,11 Therefore,
dissolution of these highly hydrogen-bonded solids is largely identifying a suitable solvent system that can increase the
attributed to the ability of ILs’ anions to act as hydrogen bond
acceptors and disrupt the hydrogen bonds in these materials.1
With a graphite-like crystalline structure,4 1,3,5-triamino-
2,4,6-trinitrobenzene (TATB) is one of the most strongly
hydrogen-bonded solids known. Owing to its inter- and intra-
molecular hydrogen bonds, both in-plane and out-of-plane
(see Fig. 1), the solubility of TATB in conventional organic
solvents is minuscule. With a capacity to dissolve 70 ppm
(0.007% w/v) at room temperature,5 DMSO is the best con-
ventional organic solvent known to dissolve TATB. Super-
acids, such as concentrated sulfuric acid, have been shown to
dissolve up to ca. 240 000 ppm (24% w/v) at room tempera-
ture,5 but due to their highly corrosive nature are often
avoided. There is a need to find a desirable solvent for TATB
as it has become necessary to control the particle size, as well
as the morphology, of TATB crystals.
TATB is of particular interest in the energetic materials
(EM) community due to its extreme insensitivity to impact,
shock and heat, while providing a good detonation velocity.6
This combination of insensitivity with good performance
characteristics makes TATB an ideal insensitive high explosive
(IHE) in numerous applications. TATB has also attracted
researchers from the field of optics, due to its unexpectedly
strong secondary harmonic generation (SHG) efficiency.7 The
source of the nonlinear optical (NLO) property of TATB has
Chemistry, Materials, Earth and Life Sciences Directorate, Lawrence

Livermore National Laboratory, Livermore, CA 94551, USA. Fig. 1 The crystal structure of TATB, a centrosymmetric structure
E-mail: han5@llnl.gov with space group P1, Z = 2. (a) A–B plane view, (b) C plane view.

solubility of TATB may also allow a new opportunity to cooled back down to room temperature without stirring.
crystallize and isolate the potential second polymorph with Occasionally, an Omega (series 2010) programmable controller
exceptional SHG efficiency. was used to control the cooling rate.
Herein, we report the solubility of highly hydrogen-bonded For a typical anti-solvent crystallization, 20 mL of an 80 : 20
TATB in both commercially available and custom synthesized DMSO–EMImOAc solution was placed in a four-necked
imidazolium-based ILs. In particular, 3-ethyl-1-methylimida- 100 mL round-bottomed flask equipped with an overhead
zolium acetate (EMImOAc) was extensively investigated in stirrer, drying tube, thermocouple and septum inlet. To this
its pure form, as well as in combination with DMSO as a was added TATB (0.5 g), and the mixture was stirred and
co-solvent. heated slightly (50 1C) until all of the TATB had dissolved and
a red-orange solution had formed. The temperature of the
2. Experimental sample was maintained at the desired temperature using a
J-KEM temperature controller. The mixture was stirred slowly
2.1 Materials as a solution of acetic acid (4 g) in dry DMSO (40 mL) was
3-Ethyl-1-methylimidazolium chloride (EMImCl), 3-butyl-1- added via a syringe and long needle connected to a syringe
methylimidazolium chloride (BMImCl), 3-ethyl-1-methyl- pump, set to deliver at 2 mL h 1. The resulting TATB was
imidazolium acetate (EMImOAc), 3-ethyl-1-methylimidazolium collected by suction filtration, and washed with water (25 mL)
nitrate (EMImNO3), 3-butyl-1-methylimidazolium hydrogen and MeOH (10 mL) to yield 0.46 g of a yellow microcrystalline
sulfate (BMImHSO4) and DMSO were purchased from solid. Raman spectroscopy was used to determine the purity of
Sigma-Aldrich, and used without purification unless otherwise the recrystallized TATB.
noted. Vacuum distillation was performed on EMImOAc to
remove any impurities prior to experiments.
3-Allyl-1-methylimidazolium chloride (AllylMImCl) was 3. Results
synthesized according to a published report.12 3-(Methoxy- 3.1 Solubility of TATB in ILs
methyl)-1-methylimidazolium chloride (MeOMImCl) was
synthesized using a modification of the procedure reported There are certain advantages that ILs have over conventional
for the synthesis of AllylMImCl. solvents that make them an attractive alternative for the
dissolution of TATB. ILs, because of their inherent low vapor
Synthesis of 3-(methoxymethyl)-1-methylimidazolium chloride pressure and high-temperature stability, have reduced environ-
(MeOMImCl). Into a 500 mL round-bottomed flask equipped mental and safety concerns compared to conventional
with a stirrer bar, argon inlet and addition funnel, was organic solvents. Also, in theory, the IL is recoverable after
dissolved 1-methylimidazole (25 g, 0.31 mol) in trichloro- precipitation or distillation of impurities from it.
ethylene (100 mL). With stirring, chloromethyl methyl ether The solubility of TATB was first investigated in BMImCl,
(35 g, 0.43 mol) was added dropwise over a 0.5 h period. The since BMImCl has previously been shown to dissolve
mixture was warmed and a turbid, two-layer mixture formed. cellulose,1 Bombyx mori silk fibers2 and wool keratin fibers3
The mixture was refluxed for 2 h, cooled and poured into a in relatively high concentrations (10, 13.2 and 4 wt%, respec-
separating funnel. The organic layer was separated, filtered and tively at 100 1C). A solution of 0.5 wt% of TATB in BMImCl
the solvent removed under vacuum at 45 1C to yield a was stirred rapidly at 100 1C for 20 h. However, at the end of
tan-beige viscous liquid (52 g). the 20th hour, there were still TATB particles present in the
flask. The color of the solution was only slightly yellow
2.2 Solubility measurements
(the color of the original TATB powder), signifying that only
Small scale solubility tests (o10 mg) of TATB in ILs a small amount of TATB had dissolved. Similar results were
were monitored with a Nikon optical microscope equipped observed for other ILs with Cl anions, including EMImCl
with a temperature controlled heating stage, under cross- and custom synthesized AllylMImCl (see Table 1). As noted
polarized light. previously, short chain-substituted imidazolium-based ILs
Large scale solubility measurements were performed using a with Cl anions have been effective in dissolving natural
three-necked round-bottomed flask in a silicone oil bath polymers. The hydrogen bond-accepting Cl anion is thought
at a constant temperature of 100 1C. Due to its high density to be the crucial component in disrupting hydrogen bonding in
(1.93 g cm 3) and bright yellow color, visual inspection of the biopolymer.1 However, for TATB the hydrogen bond
TATB particles in solutions was easily achieved with the aid of disruption caused by the Cl ions was not strong enough to
a hand-held flashlight. significantly dissolve TATB particles.
In an attempt to improve the solubility of TATB, a new
2.3 Crystallization
imidazolium-based cation, 3-methoxymethyl-1-methylimida-
A non-agitated cooling crystallization method was employed zolium chloride (MeOMImCl), was synthesized. Unlike the
to grow TATB crystals from a DMSO–EMImOAc co-solvent BMIm and EMIm cations, which may have limited, if any,
system. Typically, in a 250 mL round-bottomed flask equipped hydrogen bond-accepting capability, the ether side chain of
with a drying tube and a thermocouple, TATB (4 g) was MeOMImCl is a hydrogen bond acceptor13 and may assist in
added, along with 100 g of DMSO–EMImOAc (80 : 20 w/w). disrupting the strong hydrogen bonding of TATB. However,
The solution was slowly heated to 90 1C with constant stirring. when 0.5 wt% of TATB was added to MeOMImCl and heated
Once all of the TATB had dissolved, the solution was slowly with stirring at 100 1C for 20 h, no significant quantity of
This journal is
Table 1 The solubility of TATB in various IL systems at 100 1C
IL R X TATB solubility (wt%)

BMImCl CH3CH2CH2CH2 Cl o0.5
EMImCl CH3CH2 Cl o0.5
AllylMImCl CH2QCH Cl o0.5
MeOMImCl CH3OCH2 Cl o0.5
BMImHSO4 CH3CH2CH2CH2 HSO4 o0.5
EMImNO3 CH3CH2 NO3 o0.5
EMImOAc CH3CH2 CH3COO 10
TATB dissolved, similar to BMImCl and EMImCl, which was

visually evident. This result suggests that even with an active
cation, the overall hydrogen bond-accepting capacity of
MeOMImCl is not significant enough to disturb the hydrogen
bonding network of TATB crystals.
The effects of anions other than Cl in dissolving TATB
were also examined. For this study, BMImHSO4, EMImNO3,
and EMImOAc were selected and tested. These ILs were
chosen for their anions’ hydrogen bond-accepting capability.
As anticipated, BMImHSO4 and EMImNO3 had very similar
results compared to BMImCl, each showing less than 0.5 wt%
solubility of TATB at 100 1C. However, EMImOAc showed a
surprisingly good solubility of TATB. At 100 1C in a large
scale test, EMImOAc was able to dissolve up to 10 1.0 wt%
of TATB, confirmed by visual inspection. There was, however,
a noticeable difference in the color of the acetate solution when
compared to the solutions from the other anions (Fig. 2A
inset). When TATB was added to EMImOAc and heated, the
entire mixture turned a dark blood-red color, whereas in the
other ILs, no color change was observed (at times, some
turned slightly yellow, the original color of the TATB crys-
tals). The source of this color change was investigated by
UV-vis spectrophotometry. As seen in Fig. 2A, TATB added
to EMImOAc (diluted 100 times with DMSO) clearly shows a
pronounced peak at lmax = 409 nm, whereas TATB dissolved
in DMSO only shows a TATB absorbance at lmax = 357 nm.
The origin of the peak at lmax = 409 nm can be assigned to a
s-complex. We also carried out a Raman spectroscopy measure-
ment of the s-complex (Fig. 2B). The peaks observed at
807 and 1149 cm 1 correspond well to a previously reported
signature of a s-complex.14 The formation of a s-complex
with TATB was described during the synthesis of TATB by the
vicarious nucleophilic substitution of hydrogen.15 Selig also Fig. 2 (A) UV-vis spectra of TATB dissolved in DMSO and the
assigned the absorption band at 409 nm to a s-complex DMSO–EMImOAc system. The inset shows a photograph of TATB
dissolved in DMSO (left) and in EMImOAc (right). (B) Raman
between strong bases and TATB.5
spectra of (a) TATB, (b) EMImOAc in DMSO, (c) TATB dissolved
in EMImOAc–DMSO solution; the peaks at 807 and 1149 cm 1 are
3.2 Crystallization of TATB signatures of a s-complex.
The primary need for a solvent system that will readily dissolve
TATB is to improve overall processability. More specifically,
high solubility is necessary to produce high quality crystals this temperature until all of the particles had dissolved (Fig. 3a
from a supersaturated solution of TATB. Therefore, crystal- and b). The homogeneous solution was cooled slowly by
lization experiments were performed using EMImOAc via a natural convection. From the saturated solution, crystals
non-agitated cooling method. An optical microscope fitted started to emerge when the temperature reached 70 1C. Over
with a heating stage was used to study the recrystallization of time, single, well-faceted crystals of TATB appeared and grew
TATB in EMImOAc. A few drops of TATB particles in larger (Fig. 3c and d). These crystals were far better than the
EMImOAc (4 wt% solution) were placed on a cover slip on starting TATB crystals, which were almost all aggregates with
a heating stage. The mixture was heated to 100 1C and kept at few, if any, well defined facets.

Fig. 5 SEM micrographs of TATB (a) recrystallized from EMImOAc,
(b) starting material and (c) H2O-precipitated material.
Fig. 3 Optical images of TATB dissolving and recrystallizing in
EMImOAc: (a) at room temperature, (b) at 100 1C, (c) at 70 1C and micrographs of the recrystallized TATB crystals showed good
(d) cross-polarized light view of image (c). crystal morphology (Fig. 5a) compared to the starting crystals
(Fig. 5b). The crystal sizes of the recrystallized TATB ranged
Similar recrystallization experiments were performed on a from 10–50 mm. On the other hand, the water crash-precipi-
larger scale (100 mL volume). However, due to the viscosity of tated crystals showed an irregular crystal morphology, with
EMImOAc at room temperature, it was difficult to filter and crystal sizes that ranged from sub-500 nm–5 mm (Fig. 5c). The
isolate the recrystallized TATB. In order to lower the viscosity Raman spectrum of the recrystallized TATB crystals con-
of EMImOAc, DMSO was added as a co-solvent. When firmed that the structure of the recrystallized TATB matched
DMSO was added, the solubility of TATB decreased linearly well with that of the starting material (Fig. 6).
with respect to the DMSO concentration (Fig. 4). Besides the non-agitated cooling method of TATB crystal-
However, even with the DMSO concentration as high as lization, we also investigated an anti-solvent crystallization
80 wt%, the solubility of TATB was still significantly high, method. As seen from the non-agitated crystallization method
approximately 4 wt%. Recrystallization experiments were above, a s-complex, which forms when TATB is dissolved in
performed using an 80 : 20 DMSO–EMImOAc solution EMImOAc, requires a proton source to fully convert it back to
(80 wt% DMSO, 20 wt% EMImOAc). Upon heating this TATB at room temperature. Thus, we employed acetic acid as
solution with TATB to 90 1C, a color change was once again an anti-solvent to provide the necessary proton for the reac-
observed, signifying the formation of a s-complex. Once the tion. Acetic acid, a weak acid, was chosen to limit the rate of
added amount of TATB had fully dissolved, the solution was reaction to avoid the crash precipitation of TATB. Preliminary
allowed to cool to room temperature by natural convection, experiments showed that the concentration and rate of addi-
allowing crystals to form. The recrystallized TATB was re- tion of acetic acid is critical in controlling the overall size of
covered by simple vacuum filtration. It was visually apparent the recrystallized TATB. The overall morphology of the
that the filtrate contained a significant amount of the s-complex. TATB crystals formed by this method showed a significant
Therefore, the addition of excess water or another proton improvement compared to the starting materials. By carefully
donor (i.e. acetic acid) was necessary in order to fully recover controlling the rate of addition, significantly large TATB
the remaining TATB dissolved (ca. 1 wt%) in the filtrate. SEM crystals (o500 mm) could be formed via this method.
Fig. 4 The solubility curve of TATB in the DMSO–EMImAOc Fig. 6 Raman spectra of (a) starting TATB and (b) recrystallized
system. TATB.
This journal is
4. Discussion the nitro groups, thus stabilizing the s-complex. Most studies
on the formation of s-complexes investigated 1-substituted-
In order to determine the ineffectiveness of ILs in solubilizing 2,4-dinitro- or 1-substituted-2,4,6-trinitrobenzenes, and very
TATB compared to cellulose, the cohesive energy density few s-complexes of fully-substituted aromatic rings are
(CED) of the two systems was compared. CED is often known. In the TATB molecule, because of its high-symmetry,
expressed in its square-root form, known as the solubility there are three equivalent positions at which the acetate anion
parameter, d. For cellulose, a variety of measurements, in- may react to produce the s-complex. The s-complex would be
cluding mechanical and surface free energy measurements, stabilized by the presence of the three nitro groups at the 2-, 4-
1
suggest a value of d B 25 MPa2.16 For TATB, the heat and 6-positions relative to the tetrahedral carbon containing
of sublimation (i.e. cohesive energy per molecule) is the acetate group. In addition, the stability of the s-complex
B40.2 kcal mol 1.17 This, coupled with a molar volume of relative to TATB would be enhanced by relieving steric
1
221.2 Å3 in the crystal phase,4 yields a value of d B 35.5 MPa2. crowding on the TATB ring of the adjacent amino and nitro
2
In other words, the CED (= d ) of TATB is approximately groups upon forming the tetrahedral carbon center at the site
2 times that of cellulose, explaining why the former is more of base addition.
difficult to dissolve than the latter. The above-obtained solu- TATB added to EMImCl does not form a s-complex. In
bility parameter can be used as an approximate tool to screen order to understand the difference between the action of the
solvents for TATB. As an example, we note that the conven- acetate and chloride anions on TATB, we carried out DFT-
tional water-soluble IL, BMIm+BF4 , has a solubility para- based investigations using a state-of-the-art quantum chemical
1
meter near to d = 26.5 MPa2.18 Given that TATB has a much conductor-like screening model (COSMO)25 and its extension
higher value of d, we expect the solubility of TATB to be poor to real solvents (COSMO-RS).26 This model computes the
in such prototypical solvents in the absence of chemical chemical potential of a solute in its own environment and in
modification. In order to understand the reason for the higher solvent environments. From the difference between these
CED in TATB, we employed first-principles density functional chemical potentials, one can estimate the solubility of the
theory (DFT) using the program DMol3 19–22 to compute the solute in the solvent. Details of the procedure are described
interlayer van der Waals binding and the intralayer (inter- elsewhere.27 Table 2 (column 2) displays the computed solu-
molecular) hydrogen bond contribution to the total cohesive bility of TATB in EMImCl and EMImOAc, respectively. The
energy. We found that these two energies were comparable, computed solubility in EMImCl is in line with the observed
with the van der Waals contribution being almost 90% that of low solubility (i.e. o0.5 wt%) in this solvent. In contrast, the
the hydrogen bond contribution. The hydrogen bonds them- computed solubility in EMImOAc is 250 times smaller than
selves have an average strength of B3.5 kcal mol 1, slightly the experimentally observed value of 10 wt% at 100 1C. This
stronger than the hydrogen bonds in cellulose.23 result, in conjunction with color changes observed in the
The remarkable solubility of TATB in EMImOAc com- acetate IL solution, indicates that while TATB dissolves in
pared to other ILs was initially very puzzling. Since the cation its pure form in EMImCl, it undergoes some chemical reaction
of the ILs doesn’t seem to affect the solubility of TATB, we during its dissolution in EMImOAc. We have also computed
concluded that the acetate moiety plays a key role in solubiliz- the possibility of a deprotonation mechanism for the observed
ing TATB. TATB dissolved in EMImOAc produces a deep red solubility in EMImOAc. To do this, we have investigated one
color, observed at lmax = 409 nm. The origin of this peak can of the simplest reactions, i.e. an NH2 group of TATB loses a
be assigned to a s-complex. There are many reviews on the proton to a neighboring anion of the IL (thereby forming an
mechanism of the formation of s-complexes in intermolecular acetic acid molecule in the acetate IL or a HCl molecule in the
nucleophilic displacement reactions involving electrophilic, chloride IL), while the unpaired cation of the IL binds to the
nitro-activated aromatic substrates.24 The mechanism gener- ortho position of the deprotonated TATB anion. Column 3 of
ally involves the addition of a nucleophile to a position on the Table 2 lists the computed heat of reaction for such a chemical
electrophilic aromatic ring that results in the stabilization of process using the program Dmol3.20–22 The reaction is highly
the negative charge by an ortho- and/or para-substituted nitro endothermic and clearly prohibitive in the chloride IL, but
group. The structure of the s-complex is shown in Fig. 7 and exothermic and likely to occur in the acetate IL. The above
consists of a cyclohexadienyl anion, in which the carbon center results can be qualitatively explained based on the stronger
that undergoes substitution is converted to an sp3-hybridized basicity of an OAc group compared to Cl . The computed
center. The resulting negative charge may be delocalized into UV-vis spectrum (using the semi-empirical program
Table 2 COSMO-RS results for TATB dissolution in EMImOAc

and EMImCl
TATB solubility
1b
Solvent at 100 1C (wt%)a DEdeprotonation/kcal mol
EMImOAc 0.04 1.6
EMImCl 0.10 +22.0
a
1 wt% = 1 g 100 mL 1 = 10 g L 1. b Energy of the reaction: TATB +
EMIm+Anion - EMIm+[TATBdeprotonated] + H-Anion; DE is
positive (negative) for an endothermic (exothermic) reaction.
Fig. 7 Schematic of s-complex formation from TATB.

acid, were also found to be effective. A limiting factor in the
ability of these inorganic salts to act as an efficient anti-solvent
was their solubility in DMSO. Some had limited solubility,
rendering them less effective in precipitating TATB in good
yields. The addition of gaseous CO2 to the solvent mixture also
precipitated TATB in excellent yields. It is not clear whether
the CO2 acted to neutralize the mixture, making it less basic,
or actually acted as a counter-solvent to precipitate the TATB.
The use of gaseous CO2 is attractive because of its cost and
availability, but it was hard to control the particle size of the
recrystallized TATB when adding CO2 in gaseous form.
The anti-solvent of choice was acetic acid because it was
reasoned that it could be removed from the IL to yield
Fig. 8 An optical micrograph of recrystallized TATB prepared by the
slow cooling method.
recovered EMImOAc without contamination from other salts.
Preliminary results show that crystal size and shape are
strongly dependent on the rate of addition and the concentra-
ZINDO)28 of the deprotonated TATB displayed a sharp peak tion of the anti-solvent. Detailed information regarding the
at B410 cm 1, which is also in excellent agreement with our crystallization of TATB via the anti-solvent method will be
experimental observations. Therefore, we cannot at this point published elsewhere.
discount the possibility of alternative chemical pathways of
s-complex formation and the deprotonation mechanism.
We have also attempted to dissolve cellulose in EMImOAc. 5. Conclusion
Although a recent report29 showed a high solubility of cellu-
ILs previously shown to dissolve highly hydrogen-bonded
lose (Avicel PH-101) in EMImOAc (15 wt%) at 110 1C, the
solids were ineffective with TATB. This may be due to the
solubility of our cellulose (Eastman Kodak) in EMImOAc at
cohesive energy of TATB, which is almost 2 times that of
100 1C was less than 0.5 wt%. This discrepancy can be
cellulose. The remarkable solubility of TATB in EMImOAc
attributed to different cellulose sources and therefore the level
was attributed to the formation of a s-complex or to the
of recalcitrance of the cellulose tested. Our cellulose experi-
deprotonation of TATB. Owing to the basicity and nucleo-
ment result supports the idea that the mechanism of solubility
philicity of the OAc anion, the s-complex could easily form
for TATB in EMImOAc is indeed by chemical modification
in EMImOAc, but not in the presence other anions such as
(rather than by hydrogen bond disruption). It is important to
Cl . Therefore, the solubility of TATB in EMImOAc is
note that ILs can potentially modify the solute, as with TATB,
proportional to the concentration of EMImOAc. The dis-
to increase its solubility. Therefore, one must be very cautious
solved s-complex can revert back to TATB, either via cooling
in determining the solubility of various solutes in ILs to make
or by the addition of an anti-solvent. The recrystallized TATB
sure that chemical modification of the solute is not the cause of
shows a much improved crystal morphology compared to the
the observed increase in solubility.
starting material. We are currently performing experiments to
Crystallization of TATB via the non-agitated cooling
further control the crystallization of TATB by the anti-solvent
method in EMImOAc resulted in an improved morphology
crystallization method.
of the TATB crystals obtained compared to the starting
materials. Cooling by natural convection yielded crystals in
the size range of 10–50 mm (Fig. 5a). However, when the Acknowledgements
cooling rate was controlled, larger crystals were obtained. As
seen in Fig. 8, when the crystallization solution was cooling at This work performed under the auspices of the US Depart-
a rate of 1 1C min 1, 200–500 mm sized crystals were obtained. ment of Energy by Lawrence Livermore National Laboratory
One drawback of the cooling crystallization method is that at under Contract DE-AC52-07NA27344. The project 06-SI-005
room temperature, the amount of recovered TATB is less than was funded by the Laboratory Directed Research and Develop-
the original amount of TATB added, due to dissolved TATB ment Program.
in the 80 : 20 solution; the addition of a protic solvent is
necessary to recover the remaining TATB. Thus, an anti-
solvent crystallization scheme was employed as an alternative. References
As mentioned above, during our initial attempts to recrystal- 1 R. P. Swatloski, S. K. Spear, J. D. Holbrey and R. D. Rogers,
lize of TATB from DMSO–EMImOAc solution, the recovery J. Am. Chem. Soc., 2002, 124, 4974.
of the TATB was rather poor because it is soluble in the 2 D. M. Phillips, L. F. Drummy, D. G. Conrady, D. M. Fox,
R. R. Naik, M. O. Stone, P. C. Trulove, H. C. De Long and
mixture at a 1 wt% level at room temperature. The most R. A. Mantz, J. Am. Chem. Soc., 2004, 126, 14350.
effective anti-solvents of all those tested were hydroxylic 3 H. B. Xie, S. H. Li and S. B. Zhang, Green Chem., 2005, 7, 606.
compounds such as organic alcohols and acids. These solvents 4 H. H. Cady and A. C. Larson, Acta Crystallogr., 1965, 18, 485.
provided a proton source that released the acetate from the 5 W. Selig, Lawrence Livermore National Laboratory Report
UCID-17412, 1977.
s-complex and precipitated the TATB. In addition, some 6 C. M. Tarver, J. W. Kury and R. D. Breithaupt, J. Appl. Phys.,
inorganic acids, such as sodium hydrogen phosphate and boric 1997, 82, 3771.
This journal is
7 S. F. Son, B. W. Asay, B. F. Henson, R. K. Sander, A. N. Ali, total cohesive energy was computed by taking the difference of
P. M. Zielinski, D. S. Phillips, R. B. Schwarz and C. B. Skidmore, the total energy of a TATB unit cell (normalized per TATB
J. Phys. Chem. B, 1999, 103, 5434. molecule) from that of an isolated TATB molecule. Next, a
8 J. L. Bredas, F. Meyers, B. M. Pierce and J. Zyss, J. Am. Chem. vacuum slab normal to the basal plane was created in order to
Soc., 1992, 114, 4928. isolate the hydrogen-bonded layers of TATB from each other. The
9 G. Filippini and A. Gavezzotti, Chem. Phys. Lett., 1994, 231, 86. total energy of such a cell yielded a contribution to the total CED
10 I. G. Voigt-Martin, G. Li, A. Yakimanski, G. Schulz and coming from just the intralayer hydrogen bond interactions.
J. J. Wolff, J. Am. Chem. Soc., 1996, 118, 12830. 20 B. Delley, J. Chem. Phys., 1990, 92, 508.
11 I. G. Voigt-Martin, G. Li, A. A. Yakimanski, J. J. Wolff and 21 B. Delley, J. Chem. Phys., 2000, 113, 7756.
H. Gross, J. Phys. Chem. A, 1997, 101, 7265. 22 B. Delley, Phys. Rev. B: Condens. Matter Mater. Phys., 2002, 66,
12 H. Zhang, J. Wu, J. Zhang and J. S. He, Macromolecules, 2005, 38, 155125.
8272. 23 B. E. Dale and G. T. Tsao, J. Appl. Polym. Sci., 1982, 27, 1233.
13 M. Palusiak and S. J. Grabowski, J. Mol. Struct., 2002, 642, 97. 24 G. A. Artamkina, M. P. Egorov and I. P. Beletskaya, Chem. Rev.,
14 P. S. Santos and N. S. Goncalves, J. Raman Spectrosc., 1989, 20, 1982, 82, 427.
551. 25 A. Klamt and G. Schuurmann, J. Chem. Soc., Perkin Trans. 2,
15 A. R. Mitchell, M. D. Coburn, R. D. Schmidt, P. F. Pagoria and 1993, 799.
G. S. Lee, Thermochim. Acta, 2002, 384, 205. 26 A. Klamt, COSMO-RS: From Quantum Chemistry to Fluid Phase
16 R. J. Roberts and R. C. Rowe, Int. J. Pharm., 1993, 99, 157. Thermodynamics and Drug Design, Elsevier, Amsterdam, 2005.
17 J. M. Rosen and C. Dickinson, J. Chem. Eng. Data, 1969, 14, 120. 27 A. Maiti, P. F. Pagoria, A. E. Gash, T. Y. J. Han, C. A. Orme,
18 H. Jin, B. O’Hare, J. Dong, S. Arzhantsev, G. A. Baker, R. H. Gee and L. E. Fried, Phys. Chem. Chem. Phys., 2008, 10,
J. F. Wishart, A. J. Benesi and M. Maroncelli, J. Phys. Chem. B, 5050.
2008, 112, 81. 28 M. Zerner, Reviews in Computational Chemistry, VCH, New York,
19 We performed all-electron calculations employing the double vol. 2, 1991.
numeric polarized (DNP) basis set on a fine integration grid and 29 H. Zhao, G. A. Baker, Z. Y. Song, O. Olubajo, T. Crittle and
the gradient-corrected PBE exchange correlation function. The D. Peters, Green Chem., 2008, 10, 696.

Supramolecular synthesis of some molecular adducts of 4,4 0 -bipyridine

N,N 0 -dioxidew
Kapildev K. Arora, Mayura S. Talwelkar and V. R. Pedireddi*
Received (in Durham, UK) 8th May 2008, Accepted 8th September 2008
First published as an Advance Article on the web 29th October 2008
DOI: 10.1039/b807853j
Molecular adducts (1a–1e) of 4,4 0 -bipyridine N,N 0 -dioxide, 1, respectively with cyanuric acid,
trithiocyanuric acid, 1,3,5-trihydroxybenzene (phloroglucinol), 1,3-dihydroxybenzene (resorcinol)
and 1,2,4,5-benzenetetracarboxylic acid have been reported. The major interactions observed in
the structures 1a–1e are N–H O, N–H S, O–H O and C–H O, in the form of homomeric
and heteromeric patterns of the constituents, either as a single or cyclic hydrogen-bonded motifs.
While in the adduct 1a, both homomeric and heteromeric units of both the constituents were
observed, no heteromeric interactions were observed in 1b and 1c. In addition, in 1b, homomeric
aggregation of molecules of 1 occurred in association with water molecules. However, while
heteromeric interactions prevail between the constituents in 1d and 1e, only one of the
co-crystallizing species gave homomeric interactions (4,4 0 -bipyridine N,N 0 -dioxide in 1d; 1,2,4,5-
benzenetetracarboxylic acid in 1e). Further, in either type of the patterns, the cyclic motifs are
formed as a pair-wise hydrogen bonds comprising of strong and weak hydrogen bonds
(N–H O/C–H O or O–H O/C–H O). In three-dimensions, the ensembles of molecules
yield planar sheets, ladders and pseudorotaxane type assemblies.
Introduction considered in the synthesis of coordination assemblies, but

corresponding organic supramolecular assemblies are limited.5
Design and synthesis of molecular complexes/adducts employ- Since the N-oxide, 1 is a potential hydrogen bond acceptor to
ing noncovalent interactions such as hydrogen bonds, which is establish interaction with complementary functionalities such as
broadly defined as supramolecular synthesis, aims at creation –OH, –COOH, –NH, –CONH2 etc., it is rather surprising that
of exotic functional solids and in this connection, exploration 1 was not utilized, so effectively, in the supramolecular synthesis
of novel ligands is a continuous process.1 Thus, a variety of of organic assemblies, as only a few reports are known in the
ligands of different molecular dimensions and functional literature.6 Apart from it, the native structure of 1 itself is not
properties were utilized for the preparation of numerous known in the literature. Thus, we are interested to elucidate the
supramolecular assemblies of exotic architectures as reported structure of 1 and also study its application in the molecular
in the recent literature.2 Among those, 4,4 0 -bipyridine (bpy) is recognition and supramolecular synthesis with different organic
well studied, especially as a spacer molecule, both in organic functional moieties such as –OH, –COOH, which are well
and organic–inorganic hybrid complexes. It was mainly due to known to yield discrete molecular recognition patterns.1c,3b,d
the ability of bpy to form either O–H N only or O–H N/ In this direction, our attempts to obtain single crystals of
C–H O pair-wise hydrogen bonds and also dative bonds suitable quality for structure elucidation of 1 are not successful
with metal ions in conjunction with carboxyl/carboxylate and yet, but co-crystallization experiments of 1 with cyanuric acid,
many other functional moieties.3 trithiocyanuric acid, 1,3,5-trihydroxybenzene (phloroglucinol),
In further exploration and thrust to identify other spacer 1,3-dihydroxybenzene (resorcinol) and 1,2,4,5-benzenetetra-
molecules, compounds that mimic bpy topologically, for ex- carboxylic acid, possessing different functional moieties, as
ample, 1,2-bis(4-pyridyl)ethene and ethane, 1,3-bis(4-pyridyl)- shown in Chart 1, gave molecular complexes in the form of
propane etc., evolved as novel ligands for the preparation of single crystals. The structural features of these unusual
the tailor-made supramolecular assemblies of desired archi- molecular adducts, unravel by single-crystal X-ray diffraction
tectures and properties.4 Also, in recent times, 4,4 0 -bipyridine methods, are described in this article.
N,N 0 -dioxide (N-oxide derivative of bpy), 1, has been well

Solid State & Supramolecular Structural Chemistry Unit, Division of
Organic Chemistry, National Chemical Laboratory, Dr. Homi Bhabha Solid state structure of molecular complex, 1a, of 4,4 0 -bipyridine
Road, Pune, 411008, India. E-mail: vr.pedireddi@ncl.res.in; N,N 0 -dioxide, 1 and cyanuric acid (CA)
Fax: +91 20 25892629; Tel: +91 20 25902097
w Electronic supplementary information (ESI) available: ORTEP Co-crystallization of 1 and cyanuric acid, CA, from a methanol
diagrams of 1a–1e. Search overview details for Cambridge Structural solution gave good quality single crystals, 1a, in a 1:2 ratio of the
Database (CSD). CCDC reference numbers 672332–672336. For ESI
and crystallographic data in CIF or other electronic format see DOI: reactants and it was characterized by X-ray diffraction methods.
10.1039/b807853j The pertinent crystallographic information is given in Table 1.
This journal is
Chart 1
Analysis of molecular packing reveals that in the complex H O distances being in the range, 1.70–2.02 Å (N O,
1a, each molecule of 1 establish interaction with two dimers of 2.60–2.85 Å), molecules of 1 gave such patterns through a
CA, as shown in Fig. 1, by forming two different pair-wise cyclic pattern of C–H O hydrogen bonds and the corres-
hydrogen bonding patterns of N–H O (H O, 1.70 and ponding H O distances are 2.36 and 2.40 Å, (C O, 3.31
1.71 Å; N O, 2.69 and 2.68 Å) and C–H O (H O, 2.38 and 3.33 Å). Further, the molecular tapes of 1 and CA are
and 2.44 Å; C O, 3.34 and 3.33). Such a recognition pattern arranged alternatively in two-dimensional sheets. In fact, the
gave a three-dimensional structure, as stacked layers, which is homomeric patterns observed for 1 and CA are the most
shown in Fig. 1(b). commonly observed arrangement in many of their molecular
However, the arrangement of molecules in a typical sheet is complexes.7 It is interesting to note that pure crystal structure
quite intriguing. Although 1 and CA established heteromeric of CA also is due to the aggregation of such molecular tapes,8
pattern, each one in turn form one-dimensional crinkled tapes, as observed in 1a, held together by single N–H O hydrogen
through homomeric pattern by holding the adjacent molecules, bonds, as shown in Fig. 2(b). However, such an inference
as shown in Fig. 2. While CA molecules form homomeric could not be established about the arrangement of molecules
patterns through cyclic N–H O hydrogen bonds, with of 1 as its pure crystal structure is not known. However, since
Table 1 Crystallographic details of crystal structures of molecular adducts, 1a–1e
1a 1b 1c 1d 1e
Formula C10H8N2O2: C10H8N2O2: 1.5(C10H8N2O2): 2(C10H8N2O2): C10H8N2O2:
2(C3H3N3O3) 2(C3H3N3S3):2(H2O) C6H6O3 2(C6H6O2):4(H2O) C10H6O8
Mr 446.35 578.74 408.38 668.65 442.33
Crystal morphology Blocks Blocks Blocks Rectangular blocks Blocks
Crystal color Colorless Colorless Pale-yellow Colorless Colorless
Crystal system Triclinic Monoclinic Triclinic Triclinic Monoclinic
Space group P1 C2/c P1 P1 P21/c
a/Å 8.218(3) 22.129(8) 10.111(2) 7.129(1) 12.926(5)
b/Å 9.299(4) 13.217(5) 10.277(2) 10.253(2) 7.948(3)
c/Å 12.168(5) 8.531(3) 10.405(2) 23.220(4) 19.059(7)
a/1 91.93(1) 90 70.61(1) 82.15(1) 90
b/1 91.44(1) 105.82(1) 84.88(1) 85.26(1) 106.54(1)
g/1 108.10(1) 90 61.60(1) 70.40(1) 90
V/Å3 882.7(6) 2400.6(15) 902.7(3) 1582.7(5) 1877.0(1)
Z 2 4 2 2 4
Dc/g cm3 1.679 1.601 1.502 1.403 1.565
T/K 298(2) 298(2) 298(2) 298(2) 273(2)
l(Mo-Ka) 0.71073 0.71073 0.71073 0.71073 0.71073
m/mm1 0.138 0.612 0.112 0.109 0.128
2y range/1 46.60 46.68 56.54 46.54 56.56
Limiting indices 9 r h r 9 24 r h r 24 13 r h r 13 7 r h r 7 15 r h r 17
10 r k r 8 14 r k r 14 13 r k r 13 11 r k r 10 10 r k r 6
13 r l r 11 9 r l r 7 13 r l r 13 25 r l r 25 25 r l r 24
F(000) 460 1192 426 704 912
No. reflns measured 3845 5055 10278 6950 10778
No. unique reflns [R(int)] 2526 [0.0281] 1739 [0.0229] 4062 [0.0418] 4524 [0.0333] 4347 [0.0238]
No. reflns used 1983 1539 3342 1999 3401
No. parameters 345 193 344 465 345
Reflection 7.32 9.01 11.80 9.73 12.6
GOF on F2 1.043 1.139 1.038 0.821 1.018
R1 [I 4 2s(I)] 0.0612 0.0353 0.0558 0.0438 0.0480
wR2 0.1520 0.0896 0.1571 0.0971 0.1196
Drmax, min/e Å3 0.38, 0.44 0.44, 0.39 0.26, 0.34 0.24, 0.23 0.249, 0.288

Fig. 1 (a) Molecular recognition between 1 and CA in the crystal structure of 1a. (b) Three-dimensional arrangement of molecules in the crystal
structure of 1a, in the form of stacked layers.
Fig. 2 (a) Molecular tapes of 1 and CA through homomeric patterns which are held together by heteromeric in the structure of 1a. (b)
Arrangement of molecules in the crystal structure of CA.
the majority of N-oxide structures possess the homomeric Further, in contrast to the structure of 1a, a heteromeric pattern
patterns of 1, as shown in Fig. 2(a), following the analogy between the molecules of 1 and TCA is not observed. Instead,
observed for CA, the pure structure of 1 could be visualized as the interaction between 1 and TCA is established through water
a combination of such tapes and this may provide means to molecules. Thus, TCA forms N–H O hydrogen bonds
establish the structure of 1 by other methods, such as powder (H O, 1.66 Å, N O, 2.61 Å) with water molecules, while 1
X-ray diffraction techniques, as it fails to yield single crystals forms O–H O hydrogen bonds (H O, 1.86 and 1.91 Å with
so far, without additional molecules (either solvent of crystal- corresponding O O, 2.73 and 2.70 Å), as shown in Fig. 3(b).
lization or co-crystallizing agent). Such an ensemble ultimately self-assembles, leading to the
Thus, 1a could be visualized as a representative example for formation of two-dimensional sheets with tapes of TCA mole-
the combination of unity and diversity with the observation of cules separated by the aggregates of 1 and water. Within each
homomeric and heteromeric patterns of both the co-crystal- molecular tapes of TCA, the adjacent molecules are held
lizing species simultaneously. Also, the dual role of N-oxide 1, together by N–H S hydrogen bonds with H S distances of
as a spacer and structure directing, could be established, unlike 2.52 and 2.54 Å (N S distances of 3.39 and 3.41 Å).
4,4 0 -bipyridine, which often play a role of spacer, except in the To evaluate, further, the nature of the variable hydrogen-
recently reported assemblies, wherein it acts as a guest.9 In bonding patterns of 1 in the presence of other molecular
order to corroborate such features through a large number of entities with potential hydrogen bond donor functionalities,
molecular complexes of 1, co-crystallization of it with trithio- co-crystallization of 1 with 1,3,5-trihydroxybenzene (THB)
cyanuric acid, TCA, which is an analogue of CA, has been which may be regarded as analogue of CA in its enol form,
carried out, expecting formation of an iso-structural complex as shown below, has been carried out.
with that of 1a, by which relative competition for homomeric
and heteromeric patterns could also be programmed.
Solid state structure of adduct, 1b, of 4,4 0 -bipyridine

N,N 0 -dioxide, 1 and trithiocyanuric acid (TCA)
N-oxide, 1 gave co-crystals with TCA as a hydrate and it has
been labeled as 1b. Further, the asymmetric unit consists of
1:2 ratio of the reactants, and the important crystallographic
Supramolecular assembly in molecular complex, 1c, of
information is given in Table 1. The molecular arrangement in
4,4 0 -bipyridine N,N 0 -dioxide, 1, and 1,3,5-trihydroxybenzene
two- and three-dimensions in the crystal structure of 1b is
(phloroglucinol), THB
shown in Fig. 3.
In 1b, three-dimensional structure is alike in 1a, but through Co-crystallization of 1 and THB from a methanol solution
stacked crinkled sheets (Fig. 3), rather than planar sheets. gave a molecular complex, 1c in a 3:2 ratio of the reactants 1
This journal is
Fig. 3 (a) Stacking of layers comprising of molecules of 1 and TCA in the crystal structure of 1b. (b) Two-dimensional arrangement of molecules
showing the molecular tapes of TCA separated by the molecules of 1 and water, which are held together by O–H O hydrogen bonds.
and THB. Analysis of three-dimensional packing reveals known to exist for decades, often, being synthesized by con-
several quite exciting features, especially a pseudorotaxane ventional means. Looking at the tapes formed by THB, it
type network in the form of a host–guest type assembly, as appears that such tapes could be even possibly synthesized by
shown in Fig. 4. dihydroxybenzene as well, which may possibly also can yield a
Although each THB interacts with three molecules of 1, pseudorotaxane type structure as observed in 1c. Hence, co-
forming a heteromeric pattern by O–H O hydrogen bonds crystallization of 1 with 1, 3-dihydroxybenzene (DHB) has
with H O distances of 1.71, 1.73 and 1.75 Å (O O, 2.63, been carried out.
2.60, 2.67 Å), as shown in Fig. 5(a), the homomeric patterns
formed by both 1 and THB play a crucial role in the formation
Molecular complex, 1d, of 4,4 0 -bipyridine N,N 0 -dioxide, 1 and
of ultimate exotic structure in 1c. The homomeric pattern of
1,3-dihydroxybenzene, DHB
THB is shown in Fig. 5(b) and the corresponding patterns of 1
are shown in Fig. 6. N-Oxide, 1 and DHB form co-crystals, 1d, in a 1:1 ratio along
The molecules of THB were found to be yielding a molecular with two molecules of water and crystallize in triclinic space
tape, through homomeric pattern, constituted by C–H O group, P 1. The three-dimensional arrangement of these mole-
hydrogen bonds (see Fig. 5(b)), which is, in fact, unknown cules is indeed quite interesting with a stair-case type structure.
either in its pure structure or in its molecular complexes.10 A typical arrangement is shown in Fig. 7.
Further, two molecules of 1 in the asymmetric unit of 1c also A detailed analysis of the arrangement reveals that both the
form molecular tapes independently. Interestingly, while one of symmetry independent molecules of 1, form homomeric pat-
these remains like infinite tapes, the tapes belonging to the terns independently, as observed in 1a and 1c, yielding mole-
second molecule are held together by cyclic C–H O hydrogen cular tapes through C–H O hydrogen bonds (H O, 2.40
bonding patterns constituting layers with void space (Fig. 6). In and 2.51; 2.47 and 2.51 Å with corresponding C O, 3.31 and
those cavities the tapes of THB molecules fit like a thread, 3.38 Å; 3.40 and 3.40 Å). Infinite tapes corresponding to a
yielding a pseudorotaxane type structure (Fig. 4(b)). Earlier, particular symmetry are only shown in Fig. 8(a), for the
in our investigations on 1,10-phenanthroline complexes, we purpose of clarity, while the tapes of the other symmetry
demonstrated the feasibility of such structures entirely engraved independent molecules is shown in the inset of Fig. 8(a). The
by noncovalent interactions.11 tapes correspond to both the symmetry independent mole-
Thus, molecular complex, 1c further demonstrates the cules, are held together by two water molecules through
elegancy of noncovalent synthesis to mimic the ensembles O–H O (H O, 1.67 Å; O O, 2.77 Å) and C–H O
Fig. 4 (a) Pseudorotaxane type network in the crystal structure of 1c, with void space being filled by a molecular tape of 1. Schematic
representation is shown as inset. (b) A typical pseudorotaxane network with molecules of 1 as rings and molecules of THB as rods.

Fig. 5 (a) Molecular recognition between 1 and THB, yielding heteromeric patterns. (b) Homomeric pattern of THB.
–COOH functionality, and in particular, the recent reports

of preparation of such architectures by co-crystallizing bpy
with 1,2,4,5-benzenetetracarboxylic acid (BTCA),12 further
studies have been directed to create supramolecular assembly
of 1 and BTCA.
Supramolecular assembly in molecular complex, 1e, of

4,4 0 -bipyridine N,N 0 -dioxide, 1, and
1,2,4,5-benzenetetracarboxylic acid, BTCA
Co-crystallization of 1 and BTCA gave a 1:1 molecular com-
plex, 1e. In this structure (Fig. 9), in two-dimensional arrange-
ment, each molecule of 1 interacts with BTCA forming
heteromeric pattern through the formation of O–H O/
C–H O hydrogen bonding patterns, H O, 1.60/2.30;
Fig. 6 Homomeric patterns of N-oxide, 1 in the crystal structure of 1c. 1.49/2.59 Å (O O, 2.53/3.23; 2.48/3.53 Å). But, molecules
of 1 did not undergo homomeric aggregation, in the structure
of 1e. In contrast, molecules of BTCA show homomeric
(H O, 2.54 Å; C O, 3.31 Å) hydrogen bonds, constituting recognition pattern through well known R22(8) hydrogen
cavities. The water molecules, in turn, are held together by bonding pattern, with H O distances of 1.67 and 1.70 Å
O–H O hydrogen bond with a H O distance of 1.94 Å (O O, 2.63 and 2.65 Å), via the remaining –COOH groups,
(O O, 2.83 Å). In the cavities, two DHB molecules, which that did not interact with the molecules of 1.
are held together by C–H O (H O, 2.90 and 2.91 Å; C O, Thus, the arrangement ultimately could be visualized as
3.51 and 3.52 Å) hydrogen bonds are situated. These DHB sheets with layers of molecules of BTCA stuffed by the
molecules are further glued to the tapes of 1 by O–H O and molecules of 1 with appreciable void space. However, in
C–H O hydrogen bonds. Such adjacent ensembles are three-dimensional arrangement, the adjacent layers are
further held together, as shown in Fig. 8(a), by water mole- arranged in such a manner that molecules from the adjacent
cules connecting the two molecular tapes corresponding to layers effectively fill the void space; thus, 1e could not yield a
the same symmetry molecules by O–H O and C–H O channel structure. It is noteworthy to mention that among all
hydrogen bonds. A schematic representation of the arrange- the structures studied in this series (1a–1e), molecules of 1 did
ment is shown in Fig. 8(b). not undergo homomeric recognition only in the structure of 1e,
Thus, in complex 1d, only the molecules of 1 aggregated to perhaps, due to the strong interaction between –COOH and
yield homomeric patterns, while DHB remains as monomers N - O moieties, thus exhibiting the ability of 1 also to
forming interactions with 1 yielding heteromeric patterns. perform the role of spacer, like its analogue bpy, and suggests
Taking into account the facile formation of ladders and the importance of the complementarity between the functional
stair-case type structures by 4,4 0 -bipyridine (bpy) with groups undergoing the molecular recognition process.
Fig. 7 Three-dimensional packing of molecules in the crystal structure of 1d.
This journal is
Fig. 8 Arrangement of molecules within a two-dimensional layer in the crystal structure of 1d.
Fig. 9 (a) Two-dimensional arrangement of molecules in the crystal structure of 1e. (b) Stacking of sheets in three-dimensions.
Conclusions purification. The solvents employed for the crystallization

purpose were of spectroscopy grade of highest available
In this study, we have shown the ability of 4,4 0 -bipyridine purity. Co-crystals have been prepared by dissolving 4,4 0 -
N,N 0 -dioxide to yield different types of supramolecular assem- bipyridine N,N 0 -dioxide, 1, and cyanuric acid, trithiocyanuric
blies from simple stacked sheet structures to pseudorotaxane acid, 1,3,5-trihydroxybenzene, 1,3-dihydroxybenzene and
and stair-case type structures depending upon its interaction 1,2,4,5-benzenetetracarboxylic acid in 1:1 or 1:2 ratio either
with the co-crystallizing agents. Unlike its analogue, bpy, the in CH3OH or H2O as solvent and slowly evaporating the
N-oxide shows preference for the homomeric patterns, although obtained solution. Single crystals were obtained over a period
its spacer role is visualized in the structure 1e. Further, ob- of 48 h in all the cases. In typical preparation, 0.0941 g
servation of the homomeric patterns formed by 1 in the crystal (0.5 mmol) of 1 and 0.127 g (0.5 mmol) of 1,2,4,5-benzenetetra-
structures, 1a–1d, and also in some of the examples found in the carboxylic acid were dissolved in 15 mL of CH3OH by gently
literature, it may be possible to extrapolate it to predict the warming on a water bath. The resultant solution was kept for
three-dimensional structure of 1 as a stacked sheets with each evaporation at ambient conditions by protecting the conical
sheet as an aggregation of molecular tapes formed by the flask from external mechanical disturbances and within 48 h,
mutual recognition of the adjacent molecules through C–H O colorless and good quality crystals of 1e, were obtained that
hydrogen bonds. Thus, we strongly believe that this can be a are suitable for studies by single-crystal X-ray diffraction
good starting model to determine the three-dimensional struc- methods.
ture of 1 by other techniques such as powder X-ray diffraction
methods or by computational procedures and we have already Crystal structure determination of 1a–1e
initiated process in this direction.
Good quality single crystals of 1a–1e have been chosen by
viewing under microscope and glued to a glass fiber using an
Experimental adhesive to mount on a goniometer of Bruker single crystal
X-ray diffractometer equipped with APEX CCD detector. The
Preparation of molecular adducts of the molecular complexes,
data collection was smooth in all the cases without any
1a–1e
complications and all the crystals were found to be stable
All the chemicals used in this study were obtained from throughout data collection period. The intensity data were
commercial suppliers and used as such without any further processed using Bruker suite programmes, SAINT,13 followed

by absorption correction by SADABS.14 The structures were Des., 2005, 5, 1683; (h) S. A. Barnett and N. R. Champness, Coord.
solved by using XS and refined by least-square methods using Chem. Rev., 2003, 246, 145; (i) V. R. Pedireddi, M. R. Shimpi and
J. V. Yakhmi, Macromol. Symp., 2006, 241, 83.
XL.15 All the non-hydrogen atoms were refined by anisotropic 4 (a) O. M. Yaghi, Nat. Mater., 2007, 6, 92; (b) R. Atencio, A. Briceno,
methods and the hydrogen atoms were either refined or placed P. Silva, J. A. Guez and J. C. Hanson, New J. Chem., 2007, 31, 33;
in the calculated positions. All the structural refinements (c) T. R. Shattock, P. Vishweshwar, Z. Wang and M. J. Zaworotko,
converged to good R-factors as listed in Table 1. Cryst. Growth Des., 2005, 5, 2046; (d) G. S. Papaefstathiou and
L. R. MacGillivray, Org. Lett., 2001, 3, 3835; (e) A. Jayaraman,
V. Balasubramaniam and S. Valiyaveettil, Cryst. Growth Des., 2006,
Acknowledgements 6, 636; (f) A. J. Blake, N. R. Champness, S. S. M. Chung, W. S. Li and
M. Schröder, Chem. Commun., 1997, 1675; (g) L. Carlucci, G. Ciani,
We thank Department of Science and Technology (DST) for V. Gudenberg and D. M. Proserpio, Inorg. Chem., 1997, 36, 3812.
5 A search performed on Cambridge Structural Database (CSD)
the financial support and also greatly acknowledge Professor using version 1.10, retrieved 140 entries possessing 4,4 0 -bipyridine
Judith A. K. Howard (Durham, UK) for her generous support N,N 0 -dioxide, in which 118 are found to be organometallic while 22
to Mayura by awarding scholarship. Also one of us (K. A.) are only the organic molecular complexes (see ESIw).
thanks Council of Scientific and Industrial Research (CSIR), 6 (a) R. Thaimattam, D. S. Reddy, F. Xue, T. C. W. Mak, A. Nangia
and G. R. Desiraju, J. Chem. Soc., Perkin Trans. 2, 1998, 1783;
for the Research Fellowship. (b) L. S. Reddy, N. J. Babu and A. Nangia, Chem. Commun., 2006,
1369; (c) M. T. Messina, P. Metrangolo, W. Panzeri, T. Pilati and
References G. Resnati, Tetrahedron, 2001, 57, 8543.
7 (a) A. Ranganathan, V. R. Pedireddi, G. Sanjayan, K. N. Ganesh
1 (a) J. C. MacDonald and G. M. Whitesides, Chem. Rev., 1994, 94, and C. N. R. Rao, J. Mol. Struct., 2000, 522, 87; (b) M. T. Messina,
2383; (b) G. R. Desiraju, Angew. Chem., Int. Ed., 2007, 46, 8342; P. Metrangolo, W. Panzeri, T. Pilati and G. Resnati, Tetrahedron,
(c) K. K. Arora and V. R. Pedireddi, J. Org. Chem., 2003, 68, 9177; 2001, 57, 8543; (c) J. A. Bis, P. Vishweshwar, D. Weyna and
(d) V. R. Pedireddi and J. PrakashaReddy, Tetrahedron Lett., M. J. Zaworotko, Mol. Pharm., 2007, 4, 401; (d) T. C. Lewis,
2003, 44, 6679; (e) S. Ahn, J. Prakashareddy, B. M. Kariuki, D. A. Tocher and S. L. Price, Cryst. Growth Des., 2005, 5, 983;
S. Chatterjee, A. Ranganathan, V. R. Pedireddi, C. N. R. Rao (e) V. R. Pedireddi and D. Belhekar, Tetrahedron, 2002, 58, 2937.
and K. D. M. Harris, Chem. Eur. J., 2005, 11, 2433; (f) A. V. Trask, 8 (a) G. C. Verschoor and E. Keulen, Acta Crystallogr., Sect. B, 1971,
W. D. S. Motherwell and W. Jones, Cryst. Growth Des., 2005, 5, 27, 134; (b) H. Dietrich, C. Scheringer, H. Meyer, K.-W. Schulte and
1013; (g) C. B. Aakeroy, N. Schultheiss, J. Desper and C. Moore, A. Schweig, Acta Crystallogr., Sect. B, 1979, 35, 1191.
New J. Chem., 2006, 30, 1452; (h) D. S. Lawrence, T. Jiang and 9 V. R. Pedireddi and J. PrakashaReddy, Tetrahedron Lett., 2003,
M. Levett, Chem. Rev., 1995, 95, 2229; (i) M. W. Hosseini, Chem. 44, 6679.
Commun., 2005, 5825; (j) J. W. Steed, Supramolecular Chemistry, 10 (a) K. Maartmann-Moe, Acta Crystallogr., 1965, 19, 155;
John Wiley and sons Ltd, Chichester, 2000. (b) R. Liu, K.-F. Mok and S. Valiyaveettil, New J. Chem., 2001,
2 (a) J. L. Atwood, J. Barbour and A. Jerga, Angew. Chem., Int. Ed., 25, 890; (c) K. Biradha and M. J. Zaworotko, J. Am. Chem. Soc.,
2004, 43, 2948; (b) J. D. Wuest, Chem. Commun., 2005, 5830, and 1998, 120, 6431.
references therein; (c) S. C. Zimmerman, F. Zeng, D. C. 11 K. K. Arora and V. R. Pedireddi, Cryst. Growth Des., 2005, 5,
C. Reichert and S. V. Kolotuchin, Science, 1996, 271, 1095; 1309.
(d) L. Applegarth, A. E. Goetra and J. W. Steed, Chem. Commun., 12 (a) N. Shan, A. D. Bond and W. Jones, Cryst. Eng., 2002, 5, 9;
2005, 18, 2405. (b) J. J. Kane, R.-F. Liao, J. W. Lauher and F. W. Fowler, J. Am.
3 (a) V. R. Pedireddi, S. Chatterjee, A. Ranganathan and C. N. Chem. Soc., 1995, 117, 12003.
R. Rao, J. Am. Chem. Soc., 1997, 119, 10867; (b) S. Varughese and 13 SAINT, Version 6.02; Bruker AXS, Inc., Analytical X-ray
V. R. Pedireddi, Chem. Eur. J., 2006, 12, 1597; (c) S. Varughese Systems, 5465 East Cheryl Parkway, Madison, WI 53711-5373,
and V. R. Pedireddi, Chem. Commun., 2005, 1824; (d) C. V. 2000.
K. Sharma and M. J. Zaworotko, Chem. Commun., 1996, 2655; 14 SADABS [Area-Detector Absorption Correction]; Siemens Indus-
(e) V. R. Pedireddi and N. S. Lekshmi, Tetrahedron Lett., 2004, 45, trial Automation, Inc.: Madison, WI, 1996.
1903; (f) T. Friscic and L. R. MacGillivray, Chem. Commun., 2005, 15 G. M. Sheldrick, SHELXTL, University of Göttingen, Göttingen,
5748; (g) B. R. Bhogala, S. Basavoju and A. Nangia, Cryst. Growth Germany, 1997.
This journal is
Synthesis and characterisation of bulky guanidines and

phosphaguanidines: precursors for low oxidation state metallacyclesw
Guoxia Jin,b Cameron Jones,*a Peter C. Junk,a Kai-Alexander Lippert,b
Richard P. Roseab and Andreas Stascha
Received (in Durham, UK) 29th May 2008, Accepted 20th August 2008
DOI: 10.1039/b809120j
Reactions of alkali metal amides or phosphides with the bulky carbodiimide, ArNQCQNAr
(Ar = C6H3Pri2-2,6), followed by aqueous work-ups, have yielded several guanidines,
ArNC(NR2)N(H)Ar (R = cyclohexyl (GisoH) or Pri (PrisoH); NR2 = cis-NC5H8Me2-2,6
(PipisoH)), a bifunctional guanidine, {ArNCN(H)Ar}2{m-N(C2H4)2N} (Pip(GisoH)2), and two
phosphaguanidines, ArNC(PR2)N(H)Ar (R = cyclohexyl (CyP-GisoH) or Ph (PhP-GisoH)).
A very bulky guanidine, ArNC{N(Ar)SiMe3}N(H)Ar (ArSi-Giso), and an aryl coupled
bifunctional guanidine, {ArN(H)C(NPri2)NC6H2Pri2-2,6-}2 (PrisoH)2, have been prepared by
other routes. All compounds have been crystallographically characterised and shown to exist in
a number of isomeric forms in the solid state. These appear to be largely retained in solution.
The deprotonation of GisoH with BunLi in either hexane or THF led to crystallographically
characterised dimeric and monomeric complexes respectively, viz. [Li{Li(k2-N,N 0 -Giso)2}] and
[Li(THF)(Z1-N,Z3-Ar-Giso)]. Deprotonation of PrisoH and Pip(GisoH)2 with K[N(SiMe3)2] gave
the unsolvated polymer, [{K(Z1-N,Z6-Ar-Priso)}N], and the solvated complex,
[{K(THF)2}{Pip(Giso)2}{K(THF)3}], respectively.
Introduction e.g. [(ArNCR)2CH] (R = Me or But).6 Although complexes

of b-diketiminates are widely used in catalytic processes, they are
The coordination chemistry of anionic amidinate perhaps more notable for their capacity to kinetically stabilise
([RNC(R)NR], R = H, alkyl, aryl etc.) and guanidinate complexes containing low oxidation state metal centres. A salient
([RNC(NR2)NR]) ligands has been extensively studied, giving illustration of this is the synthesis and structural characterisation
rise to numerous complexes incorporating metals from across the of the homologous series of monomeric, N,N0 -chelated group 13
periodic table.1 In these, the ligands have displayed an impressive metal(I) complexes, [:M{(ArNCMe)2CH}] (M = Al, Ga, In or
array of coordination modes which depend upon the nature and Tl),7 which have shown remarkable further chemistry.
bulk of the substituents (R), and the metal involved. This In contrast to b-diketiminates, bulky amidinates (e.g. Piso)
structural diversity is one of the main factors that have led had rarely been employed in the preparation of low oxidation
to such complexes finding many applications in catalysis,2–4 state metal complexes. In 2005, we began to address this
materials science5 and synthesis,1 to name but a few. paucity with the preparation of the group 13 metal(I) com-
Recent developments in this area have concentrated on the use plexes [:M(Piso)] (M = In or Tl).8 However, unlike their
of very bulky amidinates to stabilise low nuclearity s- and b-diketiminate counterparts, [:M{(ArNCMe)2CH}], the Piso
p-block metal complexes which show significant potential as, ligand in these complexes is localised and chelates the metal
for example, lactide polymerisation catalysts.2 Of most note here centre in an Z1-N,Z3-arene-fashion. In addition, the analogous
is the Piso ligand, [ArNC(But)NAr], which incorporates GaI and AlI complexes could not be stabilised. These results
sterically demanding 2,6-diisopropylphenyl (Ar) substituents at suggested that related, but bulkier ligands would need to be
its N-centres and a tert-butyl group on the backbone carbon. accessed to enforce N,N 0 -chelation and allow stabilisation of
The spatial profile and ligating abilities of this ligand have lighter group 13 metal(I) centres. To this end, the very large
been likened to those of b-diketiminates, the most commonly guanidinate ligand, [ArNC(NCy2)NAr] (Giso; Cy = cyclo-
utilised examples of which also possess N–Ar substituents, hexyl), was developed and used in the syntheses of the
remarkably stable monomeric four-membered heterocycles,
a
School of Chemistry, PO Box 23, Monash University, 3800 VIC, Australia [:M(k2-N,N 0 -Giso)] (M = Ga or In; N.B. the Al(I) heterocycle
b
School of Chemistry, Main Building, Cardiff University, Cardiff, has not yet been accessed),9 the coordination chemistry of
UK CF10 3AT which was later explored.10 In addition to the increased steric
w Electronic supplementary information (ESI) available: ORTEP dia-
grams for 2 and 3. Crystallographic data (excluding structure factors) bulk of Giso over Piso, the greater stabilising ability of the
for the structures of 1–12. CCDC reference numbers 704662 (1), guanidinate can be attributed to the fact that it is a more
704663 (2), 704664 (3), 704665 (42CHCl3), 704666 (5), 704667 (6), N-electron rich donor than the amidinate, a result of it
704668 (7), 699384 (8hexane), 704669 (9), 704670 (10), 704671 (11),
704672 (122THF). For ESI and crystallographic data in CIF or other possessing a zwitterionic resonance form containing two nega-
electronic format see DOI: 10.1039/b809120j tively charged N-donor centres, viz. [Cy2N+QC(NAr)2].

Over the last three years we have extended our application
of Giso, and a range of other Ar-substituted guanidinate and
phosphaguanidinate ([ArNC(PR2)NAr])11 ligands, to the
stabilisation of heterocyclic complexes containing low oxida-
tion state metal centres from all blocks of the periodic table
(e.g. Mg(I),12 Ge(I),13 As(I),14 various d-block metal(I)15 and
f-block metal(II)16 species) with considerable success. More-
over, we have used these ligands in the synthesis of a variety of
gallyl–metal complexes, including examples exhibiting un-
precedented Ga–Zn17 and Ga–Sn18 bonds. In all these studies,
the ligands have been prepared by the deprotonation of
neutral guanidines or phosphaguanidines with alkali metal
reagents. Although some preliminary details of the synthesis of
the neutral ligand precursors have been previously been des-
cribed by us,9–16 it seemed that a full report of the preparation
and characterisation of these compounds would aid other
researchers seeking to harness their unique properties for their
own purposes. The value of this is highlighted by the fact that
prior to our involvement in this field, only one guanidine
bearing 2,6-diisopropylphenyl substituents at its N-centres,
viz. ArNC{N(H)Ar}2, had appeared in the literature.19 Here,
we report on the synthesis, structures and properties of eight
N–Ar substituted guanidines and phosphaguanidines, and
some of their alkali metal derivatives.

(i) Synthesis of bulky guanidines and phosphaguanidines
A number of synthetic routes are known for the preparation
of guanidines.1 One of the most versatile of these involves
the addition of metallated amides to carbodiimides
(RNQCQNR), followed by aqueous work-up. Here, this Scheme 1 Reagents and conditions: (i) ArNQCQNAr, THF, 20 1C
or reflux; (ii) H2O.
route has been employed to synthesise the guanidines GisoH
(1), PrisoH (2), PipisoH (3), as well as the bifunctional
guanidine, Pip(GisoH)2 (4), in high to quantitative yields group of these ligands is pyramidal, unlike the planar amino
(Scheme 1). In all preparations, THF was used as the solvent substituent of guanidinates. Therefore, the zwitterionic reso-
and the initial addition reactions were carried out at either nance form of these ligands, [R 0 2P+QC(NR)2], does not play
ambient temperature and/or under reflux conditions. a significant role in their chemistry. As a result, phospha-
It appears that this route does have steric and electronic guanidinates are coordinatively versatile, and in many of their
limitations, as the attempted addition of some amides to complexes the phosphino group acts a P-lone pair donor.1d,21
the carbodiimide (ArNQCQNAr) were not successful. For Despite this emerging importance, there had been no reports
example, lithiated cis-2,6-dimethylpiperidine adds to the of N–Ar substituted phosphaguanidinates or phospha-
carbodiimide to give compound 3, whereas lithiated 2,2,6,6- guanidines in the literature. We have reversed this situation
tetramethylpiperidine does not react with ArNQCQNAr in with the synthesis of CyP-GisoH, 5, and PhP-GisoH, 6, via the
THF at reflux. Moreover, M[N(SiMe3)2] (M = Li, Na or K) addition of the relevant lithium phosphide to ArNQCQNAr
do not react with ArNQCQNAr under similar conditions, (Scheme 1). Aqueous work-ups of these compounds were
though these reagents are known to add to smaller carbodii- performed under an inert atmosphere to prevent oxidation
mides at room temperature.20 of the phosphorus atom. However, we have found that the
Although considerably less sterically demanding than some products can be handled in moist air as solids or in solution
of the amide precursors mentioned above, lithium carbazolyl without significant oxidation occurring, as judged by 31P
did not react with ArNQCQNAr in THF at reflux, and only NMR spectroscopy. It is noteworthy that the addition of
carbazole and the carbodiimide were recovered after work-up. phosphines to smaller carbodiimides to form phospha-
This lack of reactivity probably derives from the lower nucleo- guanidines, in the presence of catalytic amounts of s-block
philicity of the aromatic carbozyl anion, relative to the bulkier amide or alkyl bases, has recently been reported.22,23
amides used in the preparation of 1–3. Although the addition of metal amides to ArNQCQNAr is
Interest in the coordination chemistry of phosphaguanidi- a versatile route to bulky guanidine compounds, its limitations
nates, [RNC(PR 0 2)NR], has recently begun to escalate.1d,21 centre on the bulk of the reacting amide complex (as men-
One of the main reasons behind this is that the phosphino tioned above). Because of this, a different approach was used
This journal is
Scheme 2 Reagents and conditions: (i) BunLi, THF; (ii) Me3SiCl,
THF reflux.
Scheme 3 Reagents and conditions: (i) K[N(SiMe3)2], THF; (ii) MnI2,

THF.
to synthesise the exceedingly bulky guanidine, ArSi–GisoH 7 Fig. 1 Molecular structure of 1 (25% thermal ellipsoids are shown;
(Scheme 2). This involved lithiation of the known guanidine, hydrogen atoms, except H(1), omitted for sake of clarity).
ArNC{N(H)Ar}2, the product of which was subsequently
quenched with Me3SiCl in THF at reflux to give 7 in amino (–NR2) fragment which in no case is co-planar with
good yield. the CN3 core of the molecule. Therefore, any interaction of the
One further bifunctional guanidine has been prepared in this amino N-lone pair within the p-system of the largely localised
study via a route not involving carbodiimide addition. Though guanidine CN3 backbone must be limited. It is noteworthy
this synthesis was originally not intended, it is moderately that the –NR2 fragments of 4 are significantly more distorted
yielding, reproducible and thus is included here. In an attempt from planar than those of the monofunctional guanidines.
to form a Mn(II) complex of Priso, K[Priso] was reacted with Similarly, the two phosphaguanidines display distorted pyra-
commercially available MnI2 in THF. This, instead led to the midal phosphorus centres, the lone pairs of which are direc-
isolation of the aryl-coupled guanidine, (PrisoH)2 8, in a 30% tional and therefore cannot be involved with the p-system of
yield (Scheme 3) without aqueous work-up. When the reaction their localised CN2P cores. The bond lengths and angles
was repeated with a pure sample of [MnI2(THF)3], compound within these core fragments (see Table 1) are consistent with
8 was not obtained. Presumably, the commercially sourced these descriptions.
MnI2 initially employed, was contaminated with significant Several different isomeric forms of the compounds have
amounts of higher oxidation state manganese species. It is been identified in this study. To allow comparisons with
believed that the reaction of the impure MnI2 with K[Priso] led related amidines, the backbone unit (R2N or R2P) has been
to the oxidative coupling of two Priso anions through aryl defined as the lower priority in determining the stereo-configu-
para-positions on each. This seems reasonable in light of the ration of the compounds (see refs. 1d and 1e for a description
fact that we have recently shown that Priso can coordinate of the four isomeric and tautomeric forms of amidines, viz.
the Rh(COD) fragment (COD = 1,5-cyclooctadiene) solely Z-anti, Z-syn, E-anti and E-syn). The guanidines, 1–3 (see
through one aryl substituent in a Z5-cyclohexadienyl fashion.15 Fig. 1 for the structure of 1), and the phosphaguanidine, 5
A Mn(4II)-Priso complex in which the ligand exhibits this (Fig. 3), exist in the Z-anti-form which is common for guani-
cyclohexadienyl binding mode can easily be envisaged as an dines but not for uncoordinated phosphaguanidines which
intermediate in the oxidative coupling that gave 8. The possi- normally occur in the solid state in their E-syn-form.1d,21
bility that 8 was alternatively formed via the oxidative cou- Indeed, this is the isomer adopted by the phosphaguanidine,
pling of two Priso anions by a diiodine contaminant in the 6, in the solid state (Fig. 4). In contrast, the extremely bulky
impure sample of MnI2 was examined and discounted. guanidine, 7 (Fig. 5), crystallises in the rarely observed Z-syn-
form, probably because of steric buttressing of its aryl groups
by the larger N(Ar)SiMe3 substituent. It is of note that the
(ii) Structural and spectroscopic properties of prepared
Z-syn-isomer of amidines with very bulky backbone C-substitu-
compounds
ents have been previously reported, e.g. (tript)C{N(H)R}(NR)
The crystal structures of all compounds 1–8 have been deter- (tript = 9-triptycenyl, R = Cy or Pri).24 Both the bifunctional
mined (see Fig. 1–6 for the molecular structures of 1, 4–8; amidines, 4 and 8 (Fig. 2 and 6, respectively), exist in the
those of 2 and 3 can be found in ESIw). The compounds solid state as Z-anti-,Z-anti-isomers, as has been previously
display solid state structures comparable to those of previously documented for bifunctional amidines.1
characterised guanidines and phosphaguanidines.1,21 Each of Often, amidines and guanidines will be present in solution in
the guanidines, 1–3, possesses a close to planar backbone more than one of their four possible isomeric forms. This can

Fig. 2 Molecular structure of 4 (25% thermal ellipsoids are shown; hydrogen atoms, except H(1), omitted for sake of clarity). Symmetry
operation: 0 x + 1, y + 1, z.
Fig. 4 Molecular structure of 6 (25% thermal ellipsoids are shown;

hydrogen atoms, except H(1), omitted for sake of clarity).
Although the isomeric forms adopted by the guanidines,

Fig. 3 Molecular structure of 5 (25% thermal ellipsoids are shown; 1–4, in solution cannot be certain without two-dimensional
hydrogen atoms, except H(2), omitted for sake of clarity). NMR experiments, some insight into the solution conforma-
tions of the phosphaguanidines, 5 and 6, can be gained from
lead to complicated NMR spectra for such compounds. their 1H NMR spectra. That for 5 shows only one isomer, the
However, the guanidines and phosphaguanidines, 1–6, display NH resonance of which exists as a doublet (3JPH = 14.1 Hz;
relatively simple 1H and 13C{1H} NMR spectra, which are 31
P{1H} NMR: d 2.9 ppm). The spectrum of 6 reveals the
suggestive of only one, or predominantly one, isomer occur- compound to exist as two isomers in solution in an approxi-
ring in solution. These spectra imply that each compound has mately 90 : 10 ratio. The NH resonance of the major isomer
two chemically inequivalent Ar substituents, and that both (31P{1H} NMR: d 18.5 ppm) is a singlet, while that for
alkyl or aryl groups on the backbone –ER2 (E = N or P) the minor isomer (31P{1H} NMR: d 13.3 ppm) is a doublet
groups are equivalent. If the compounds retain their solid state (3JPH = 18.2 Hz). In an excellent paper on phosphaguanidinate
isomeric forms in solution, which seems likely, the latter solution behaviour, Coles et al. have shown that isomer
observation requires their –ER2 groups to partially rotate on interconversion can readily occur by one or more of a number
the NMR timescale, thus leading to the compounds possessing of possible pathways.21e Importantly, they also showed that
averaged mirror planes incorporating their ECN2 fragments. the closely related phosphaguanidine, Cy2PC{N(H)Pri}(NPri),
This journal is
is present in solution in both its E-syn- (major) and Z-anti-
(minor) forms (14 : 1 ratio at 298 K). The NH resonance of the
E-syn-form shows no coupling to the P-centre, while that of
the minor Z-anti-isomer does (3JPH = 14.5 Hz). Accordingly,
we conclude that compound 5 exists solely as its Z-anti-form
in solution (as in the solid state), whereas the major solution
state isomeric form of 6 is E-syn (as in the solid state), and the
minor form is Z-anti.
Many of the signals in the 1H NMR spectrum of ArSi-
GisoH, 7, are very broad and suggest one or more dynamic
processes are occurring in solution. Despite efforts, the spec-
trum could not be resolved, and thus we could not shed light
on the nature of the dynamic behaviour. One possibility,
however, is that it involves a restricted rotation of the Ar
and/or SiMe3 groups about the N–C or N–Si bonds of 7. In
this respect, it should be noted that similar solution dynamic
behaviour has been observed for the closely related com-
pound, ArNC{N(H)Ar}2, an exhaustive variable-temperature
NMR study of which showed this behaviour to be derived
from restricted rotation of its three Ar groups.19 Another
possibility for 7 is that there is a fluxional interconversion
between two or more isomers of the compound, which is
occurring at close to the NMR timescale. This seems less
hydrogen atoms, except H(3), omitted for sake of clarity). Selected
bond lengths (Å) and angles (1): Si(1)–N(1) 1.7762(16), N(1)–C(1) likely, however, when the imposing sterics of the compound
1.410(2), C(1)–N(2) 1.285(2), C(1)–N(3) 1.383(2); N(2)–C(1)–N(3) are taken into account.
130.87(17), N(2)–C(1)–N(1) 116.38(16), N(3)–C(1)–N(1) 112.73(16), Little information could be gained from the solution NMR
C(1)–N(1)–C(5) 119.99(15), C(1)–N(1)–Si(1) 119.94(12), spectra of the bifunctional guanidine, 8. These are very
C(5)–N(1)–Si(1) 119.81(12). complicated and point towards more than one isomer existing
Fig. 6 Molecular structure of 8 (25% thermal ellipsoids are shown; hydrogen atoms, except H(1) and H(6), omitted for sake of clarity). Selected
bond lengths (Å) and angles (1): N(1)–C(1) 1.391(3), C(1)–N(3) 1.290(4), C(1)–N(2) 1.378(4), N(4)–C(44) 1.290(3), N(5)–C(44) 1.383(4),
N(6)–C(44) 1.387(4); N(3)–C(1)–N(2) 121.1(2), N(3)–C(1)–N(1) 122.2(3), N(2)–C(1)–N(1) 116.7(3), C(1)–N(2)–C(17) 120.2(2), C(1)–N(2)–C(14)
119.8(2), C(17)–N(2)–C(14) 115.5(2), C(44)–N(5)–C(45) 119.5(2), C(44)–N(5)–C(48) 119.9(2), C(45)–N(5)–C(48) 116.0(2), N(4)–C(44)–N(5)
120.8(3), N(4)–C(44)–N(6) 122.0(3), N(5)–C(44)–N(6) 117.3(2).
Table 1 Selected bond lengths (Å) and angles (1) for 1–6 (E = N or P)
1 2 3 4 5 6
ArNQC 1.290(2) 1.2911(16) 1.285(2) 1.287(2) 1.2909(19) 1.311(2)
ArN–C 1.384(3) 1.3910(16) 1.394(2) 1.373(2) 1.375(2) 1.346(2)
C–ER2 1.388(2) 1.3807(16) 1.385(2) 1.398(2) 1.8708(17) 1.8798(18)
ArN–CQN 121.26(17) 122.02(11) 124.10(17) 124.67(15) 123.26(14) 121.51(16)

R2E–CQN 121.66(18) 120.57(11) 119.91(16) 119.84(15) 121.76(11) 119.98(13)
R2E–C–N
P 117.08(17) 117.42(10) 115.99(16) 115.48(14) 114.96(11) 118.51(13)
angles about E 353.3 357.0 353.5 341.9 302.3 304.4

in solution. For example, several overlapping N–H resonances scopic data for 9–11 are more symmetrical than their solid
were seen in its 1H NMR spectrum, where only one would be state structures (vide infra) would suggest and imply that
expected if it retained its solid state Z-anti-, Z-anti-isomeric fluxional processes are occurring in solution that are rapid
form in solution. As a result, the spectra proved difficult to on the NMR timescale. This is not uncommon for alkali-metal
assign. amidinates and guanidinates,1 and therefore no efforts were
made to investigate these dynamic behaviours by variable
(iii) Metallation of bulky guanidines and phosphaguanidines temperature NMR studies. Once crystallised from the reaction
The guanidines and phosphaguanidines prepared here (with mixture, compound 12 has negligible solubility in normal
the exception of ArSi-Giso 7), can be easily deprotonated deuterated solvents (including D8-THF) and therefore no
by standard metallation procedures. The reactions of these meaningful NMR spectroscopic data could be obtained for
ligands with one equivalent of BunLi or K[N(SiMe3)2] proceed this compound.
rapidly and near quantitatively in common solvents such as The molecular structure of 9 is depicted in Fig. 7 and shows
hexane, toluene, THF or diethyl ether at ambient temperature it to be dimeric with two different lithium coordination
or below. The solvent and metal involved in the reaction can environments. Li(1) is coordinated by two chelating Giso
have a striking bearing on the nuclearity of the formed ligands that have largely localised N(1)–C(1)–N(2) fragments.
complex, and the conformation adopted by the guanidinate The Li(1)–N bond lengths of 2.072(2) Å (to N(2) and N(2) 0 )
or phosphaguanidinate ligand. This is important as it can and 2.240(5) Å (to N(1) and N(1) 0 ), although different, lie
influence the product obtained from, for example, further salt within the normal range for amidinate and guanidinate N–Li
metathesis reactions of these alkali metal complexes with other interactions.25 The two more distant N-atoms (N(1) and
metal halides. In this study, we have structurally and spectro- N(1) 0 ) also coordinate the bent two-coordinate Li(2) centre
scopically characterised four lithium or potassium salts of the with short interactions (1.954(4) Å). The coordination sphere
ligands prepared above. of the both Li atoms is completed by agostic interactions to
The lithiation of GisoH, 1, with BunLi in hexane led to the ligand hydrogen atoms; Li(1) has two such interactions (both ca.
solvent free dimeric complex, 9, whilst in THF the monomeric 2.23 Å), whereas Li(2) has four (from ca. 2.03 Å to ca. 2.27 Å).
solvated complex, 10, was formed (Scheme 4). In contrast, When these close contacts are taken into account, both
metallation of PrisoH, 2, with K[N(SiMe3)2] in toluene Li-centres can be thought of as having heavily distorted
afforded the polymeric, solvent free complex, 11, whereas octahedral geometries. A survey of the Cambridge Crys-
metallation of Pip(GisoH)2 with the same reagent in THF tallographic Database revealed two similar dimeric lithium ami-
gave the solvated complex, 12 (Scheme 4). The NMR spectro- dinates, [Li{k2-N,N 0 -(SiMe3)NC(R)N(SiMe3)}2{Li(OEt2)}]
(R = C6H5CF3-4 or C6H5F-2),26 though the non-chelated
Li centre of both is further coordinated by an ether molecule.

hydrogen atoms omitted for sake of clarity). Selected bond lengths (Å)
and angles (1): N(1)–C(1) 1.394(3), N(2)–C(1) 1.323(3), N(3)–C(1)
1.409(3), N(1)–Li(2) 1.954(4), N(1)–Li(1) 2.240(5), N(2)–Li(1)
Scheme 4 Reagents and conditions: (i) BunLi, hexane (Cy = cyclo- 2.072(2); N(2)–C(1)–N(1) 114.3(3), N(2)–Li(1)–N(1) 63.78(12),
hexyl); (ii) BunLi, THF; (iii) K[N(SiMe3)2], toluene; (iv) K[N(SiMe3)2], N(2) 0 –Li(1)–N(1) 119.6(2), N(1) 0 –Li(2)–N(1) 121.7(4). Symmetry
THF. operation: 0 x, y, z + 1/2.
This journal is
The molecular structure of monomeric 10 is shown in Fig. 8. Li-centre with the Ar-substituent of N(1). The coordi-
The localised guanidinate ligand is acting as an amide that nation sphere on the Li(1) is completed by one THF molecule.
coordinates the Li atom in an Z1-fashion through N(2). A similar coordination mode (but minus the coordi-
In addition, there is an approximately Z3-interaction of the nated THF) has been reported for the thallium(I) complex,
[Tl(Z1-N,Z3-Ar-Giso)].8
Like the structure of 10, the guanidinate moieties of the
potassium complexes, 11 and 12 (Fig. 9 and 10, respectively),
adopt the Z-anti-configuration but with more localised
coordinated NCN fragments. In addition, the arene-K inter-
actions in both are close to Z6-, as opposed to the Z3-Ar-Li
coordination seen in 10. In 11, this leads to a one-dimensional
polymeric structure in which one Ar-group of each ligand
bridges two K-centres. Compound 12 is monomeric, and in
addition to arene and N-attachments, one K-centre is coordi-
nated by two THF molecules, while the other is ligated by
three. All the distances to the K-centres in both complexes are
in the normal range.25
Conclusion
In conclusion, the synthesis and characterisation of a variety
of guanidine, bifunctional guanidine and phosphaguanidine
compounds, all bearing 2,6-diisopropylphenyl N-substituents,
have been described. In the solid state, the Z-anti-isomeric
Fig. 8 Molecular structure of 10 (25% thermal ellipsoids are shown; form is observed for all guanidines, except in one extremely
hydrogen atoms omitted for sake of clarity). Selected bond lengths (Å) bulky example, ArSi-GisoH 7. The sterics of this necessitate
and angles (1): N(1)–C(1) 1.3149(16), C(1)–N(2) 1.3587(16), C(1)–N(3)
it occurring as the rarely observed Z-syn-isomer. Of the
1.4092(16), Li(1)–N(2) 1.943(3), Li(1)–C(2) 2.290(3), Li(1)–C(3)
phosphaguanidinates, the bulkier example, CyP-GisoH 5,
2.458(3), Li(1)–C(7) 2.591(3), O(1)–Li(1) 1.889(3); N(1)–C(1)–N(2)
121.56(11), N(1)–C(1)–N(3) 117.46(11), N(2)–C(1)–N(3) 120.98(11), crystallises in the Z-anti-form, while PhP-GisoH, 6, adopts
C(1)–N(3)–C(32) 117.05(10), C(1)–N(3)–C(26) 120.82(10), the E-syn-conformation. In solution, most of the described
C(32)–N(3)–C(26) 115.51(10), C(1)–N(2)–Li(1) 117.59(11). compounds appear to retain their stereochemistry, though in
some cases isomer mixtures were observed. Several of the
prepared compounds have been deprotonated with alkali
metal reagents and the resulting salts crystallographically
characterised. In the case of the deprotonation of GisoH 1
with BunLi, the nuclearity and guanidinate coordination mode
displayed by the formed complexes are dependent upon the
reaction solvent employed. We are currently systematically
exploring the use of bulky guanidinates and phosphaguanidi-
nates, prepared from the neutral compounds 1–8, for the
stabilisation of low oxidation metallacycles incorporating
metals from all blocks of the periodic table.
Experimental
General considerations
All manipulations were performed under an inert atmosphere
(dinitrogen or argon) using Schlenk or glove box techniques.
Aqueous organic work-ups were carried out in air, except those
for the phosphaguanidines, 5 and 6. Melting points were
determined in sealed capillaries under a dinitrogen atmosphere,
except those for the guanidines, 1–4, which were determined in
hydrogen atoms omitted for sake of clarity). Selected bond lengths (Å)
open capillaries. Reaction solvents were dried over potassium
and angles (1): K(1)–N(1) 2.755(3), K(1)–Ar centroid 3.077(1), K(1)0 –Ar
centroid 2.945(1), C(1)–N(2) 1.329(5), C(1)–N(3) 1.402(5), N(1)–C(1) or Na/K alloy prior to use, except dichloromethane and chloro-
1.340(5); N(2)–C(1)–N(1) 121.7(3), N(2)–C(1)–N(3) 115.1(3), form which were used as received. Mass spectra were recorded
N(1)–C(1)–N(3) 123.2(3), C(1)–N(3)–C(26) 122.0(3), C(1)–N(3)–C(29) at the EPSRC National Mass Spectrometric Service, Swansea
121.5(3), C(26)–N(3)–C(29) 114.7(3), C(1)–N(1)–K(1) 128.2(2). Sym- University. Microanalyses were obtained from either Medac
metry operation: 0 x 1/2, y + 1/2, z. Ltd or Campbell Microanalytical, Ottago. IR spectra were

Fig. 10 Molecular structure of 12 (25% thermal ellipsoids are shown; hydrogen atoms and isopropyl groups omitted for sake of clarity). Selected
bond lengths (Å) and angles (1): K(1)–O(1) 2.681(3), K(1)–O(2) 2.698(3), K(1)–O(5) 2.780(3), K(1)–N(1) 2.823(2), K(2)–O(3) 2.646(3), K(2)–O(4)
2.710(3), K(2)–N(5) 2.735(3), K(1)–Ar centroid 3.007(1), K(2)–Ar centroid 2.915(1), N(1)–C(1) 1.328(4), N(2)–C(1) 1.321(4), N(3)–C(1) 1.437(4),
N(4)–C(30) 1.426(4), N(5)–C(30) 1.336(4), N(6)–C(30) 1.322(4); N(2)–C(1)–N(1) 124.6(3), N(2)–C(1)–N(3) 114.8(3), N(1)–C(1)–N(3) 120.6(2),
C(1)–N(1)–K(1) 123.88(18), C(30)–N(5)–K(2) 129.42(18), N(6)–C(30)–N(5) 123.6(3), N(6)–C(30)–N(4) 115.2(2), N(5)–C(30)–N(4) 121.2(2).
recorded using a Nicolet 510 FT-IR spectrometer as Nujol CH(CH3)2), 4.95 (s, 1 H, NH), 6.89–7.17 (m, 6 H, ArH); 1H
mulls between NaCl plates. 1H and 13C{1H} NMR spectra were NMR (250 MHz, 298 K, C6D6): d 0.96 (d, J = 6.8 Hz, 6 H,
recorded on either Bruker DXP400, Bruker DPX300, Jeol CH(CH3)2), 1.12–1.32 (m, 6 H, CH2), 1.44 (d, J = 6.8 Hz, 6 H,
Eclipse 300 or Bruker WM250 spectrometers and were refer- CH(CH3)2), 1.50–1.68 (m, 2 H, CH2), 1.54 (d, J = 6.8 Hz, 12
enced to the resonances of the solvent used. 31P{1H} NMR H, CH(CH3)2), 1.75–1.92 (m, 8 H, CH2), 2.21–2.44 (m, 4 H,
spectra were recorded on a Jeol Eclipse 300 spectrometer and CH2), 3.23 (tt, J = 11.7, 3.3 Hz, 2 H, CHN), 3.60 (sept, J =
were referenced to external 85% H3PO4. Cy2NH, Pri2NH, 6.8 Hz, 4 H, CH(CH3)2), 5.32 (s, 1 H, NH), 7.06–7.44 (m, 6 H,
cis-2,6-dimethylpiperidine and piperazine were obtained com- ArH); 13C{1H} NMR (75.5 MHz, 298 K, CDCl3): d 21.6
mercially, dried over molecular sieves, and distilled under (CH(CH3)2), 22.5 (CH(CH3)2), 24.9 (CH2), 26.0 (CH(CH3)2),
dinitrogen prior to use. K[N(SiMe3)2] was prepared by treating 26.1 (CH(CH3)2), 27.1 (CH(CH3)2), 28.6 (CH(CH3)2), 29.0
(SiMe3)2NH with KH in toluene at 20 1C. ArNQCQNAr27 (CH2), 32.6 (CH2), 58.0 (HCN), 121.6, 122.8, 123.5, 126.9,
and ArNC{N(H)Ar}219 were synthesised according to literature 135.9, 140.0, 145.5, 145.6, (ArC), 148.0 (CN3), 13C{1H} NMR
procedures. All other reagents were obtained from commercial (75.5 MHz, 298 K, C6D6): d 21.7 (CH(CH3)2), 22.3
sources and used as received. (CH(CH3)2), 25.2 (CH2), 26.2 (CH(CH3)2), 27.3 (CH(CH3)2),
28.7 (CH(CH3)2), 29.3 (CH(CH3)2), 32.9 (CH2), 39.8 (CH2),
Preparation of GisoH 1 58.2 (HCN), 122.6, 123.3, 123.7, 127.1, 136.1, 139.9, 145.5,
BunLi (5.33 cm3 of a 1.6 M solution in hexanes, 8.52 mmol) 145.6 (ArC), 148.5 (CN3); IR (Nujol): n/cm1 = 3384 (m),
was added to a solution of Cy2NH (1.58 g, 1.73 cm3, 1614 (s), 1583 (s), 1259 (m), 1163 (m), 1110 (m), 1072 (m),
8.69 mmol) in THF (40 cm3) at 20 1C over 5 min and the 986 (m), 954 (w), 894 (m), 799 (m), 761 (m), 700 (w);
resultant solution stirred for 1 h. ArNQCQNAr (3.00 g, MS/APCI: m/z (%) = 544.7 (MH+, 100).
8.27 mmol) was then added, the suspension stirred for
Preparation of PrisoH 2
15 min, followed by heating at reflux for 1.5 h (or alternatively
stirred at room temperature for 4 h). All volatiles were A procedure analogous to that used to prepare 1 was em-
removed under reduced pressure and diethyl ether (40 cm3) ployed, but using Pri2NH (colourless crystals: crude yield
and H2O (10 cm3) added to the residue. The mixture was 99%; ca. 90% after recrystallisation); mp 144–145 1C; 1H
stirred for 30 min to give two clear solution phases. The NMR (250 MHz, 298 K, CDCl3): d 0.89 (d, J = 6.8 Hz, 6 H,
organic phase was separated and the aqueous layer was CH(CH3)2), 1.12 (overlapping d, J = 6.8 Hz, 18 H,
extracted with CH2Cl2 (3 30 cm3). The combined organic CH(CH3)2), 1.20 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.37 (d,
phases were dried (MgSO4), filtered, and volatiles evaporated J = 6.8 Hz, 6 H, CH(CH3)2), 3.17 (sept, J = 6.8 Hz, 2 H,
from the filtrate under vacuum. The oily residue solidified CH(CH3)2), 3.25 (sept, J = 6.8 Hz, 2 H, CH(CH3)2), 3.49
upon standing to give 1 as colourless crystals (yield 4.40 g, (sept, J = 6.8 Hz, 2 H, CH(CH3)2), 4.80 (s, 1 H, NH),
98%). The product can be recrystallised from hot hexane 6.80–7.18 (m, 6 H, ArH); 1H NMR (400 MHz, 298 K,
(yield 80%); mp 140–141 1C. 1H NMR (300 MHz, 298 K, C6D6): d 0.98 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.36 (over-
CDCl3): d 0.91 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.08–0.90 lapping d, J = 6.8 Hz, 18 H, CH(CH3)2), 1.51 (d, J = 6.8 Hz,
(m, 8 H, CH2), 1.21 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.36 (d, J = 6 H, CH(CH3)2), 1.54 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 3.68
6.8 Hz, 6 H, CH(CH3)2), 1.38 (d, J = 6.8 Hz, 6 H, (sept, J = 6.8 Hz, 6 H, CH(CH3)2), 5.25 (s, 1 H, NH),
CH(CH3)2), 1.47–1.70 (m, 8 H, CH2), 2.05 (m, 4 H, 7.09–7.39 (m, 6 H, ArH), 13C{1H} NMR (75.5 MHz, 298 K,
CH2CHN), 2.97 (tt, J = 11.7, 3.3 Hz, 2 H, CHN), 3.22 (sept, CDCl3): d 21.6 (CH(CH3)2), 21.9 (NCH(CH3)2), 22.7
J = 6.8 Hz, 2 H, CH(CH3)2), 3.32 (sept, J = 6.8 Hz, 2 H, (CH(CH3)2), 24.7 (CH(CH3)2), 25.7 (CH(CH3)2), 28.2
This journal is
(CH(CH3)2), 28.8 (CH(CH3)2), 47.7 (HCN), 121.7, 122.7, mp 196–198 1C; 1H NMR (400 MHz, 298 K, CDCl3): d 0.89
123.6, 126.9, 135.4, 139.8, 145.3, 145.8 (ArC), 148.3 (CN3); (br d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.00 (d, J = 6.8 Hz, 12 H,
13
C{1H} NMR (100.6 MHz, 298 K, C6D6): d 22.2 (CH(CH3)2), CH(CH3)2), 1.15 (br d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.23 (d,
22.5 (NCH(CH3)2), 23.1 (CH(CH3)2), 25.5 (CH(CH3)2), 26.0 J = 6.8 Hz, 12 H, CH(CH3)2), 2.89 (br s, 8 H NCH2), 3.04 (mc
(CH(CH3)2), 28.8 (CH(CH3)2), 29.7 (CH(CH3)2), 48.3 (HCN), of overlapping sept., J = 6.8 Hz, 8 H, CH(CH3)2), 4.93 (s, 2 H,
123.2, 123.8, 124.3, 127.7, 136.1, 140.3, 145.9, 146.2 (ArC), NH), 6.90–7.16 (m, 12 H, ArH); 13C{1H} NMR (100.6 MHz,
149.1 (CN3); IR (Nujol): n/cm1 = 3364 (m), 1608 (s), 1580 298 K, CDCl3): d 22.8 (CH(CH3)2), 23.3 (CH(CH3)2), 24.5
(s), 1303 (m), 1245 (m), 1184 (m), 1154 (m), 1109 (m), 1046 (CH(CH3)2), 25.7 (CH(CH3)2), 28.8 (CH(CH3)2), 28.9
(m), 1002 (m), 932 (m), 828 (m), 798 (m), 767 (m), 714 (m); (CH(CH3)2), 47.3 (NCH2), 123.1, 123.4, 124.3, 127.3, 134.1,
MS/APCI: m/z (%) = 464.4 (MH+, 100). 140.1, 144.4, 145.2 (ArC), 150.8 (N3C); IR (Nujol): n/cm1 =
3391 (m), 1623 (s), 1585 (m), 1261 (m), 1196 (m), 1145 (m),
Preparation of PipisoH 3 1109 (m), 1041 (m), 988 (m), 935 (m), 840 (m), 799 (m), 759
(m); MS/APCI: m/z (%) = 811.4 (MH+, 100).
A procedure analogous to that used to prepare 1 was em-
ployed, but using cis-2,6-dimethylpiperidine (colourless crys-
Preparation of CyP-GisoH 5
tals: crude yield 98%; ca. 88% after recrystallisation); mp
128–130 1C. 1H NMR (400 MHz, 298 K, CDCl3): d 0.89 (d, BunLi (4.00 cm3 of a 1.6 M solution in hexanes, 6.40 mmol) was
J E 6.1 Hz, 6 H, NCH(CH3)), 1.11 (d, J = 6.8 Hz, 6 H, added to a solution of Cy2PH (1.27 g, 6.40 mmol) in THF
CH(CH3)2), 1.16 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.18–1.76 (20 cm3) at 0 1C over 5 min. The resultant solution was stirred
(m, 6 H, CH2), 1.26 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 3.12 for 1 h at room temperature. A solution of ArNQCQNAr
(sept, J = 6.8 Hz, 2 H, CH(CH3)2), 3.16 (sept, J = 6.8 Hz, 2 (2.54 g, 6.28 mmol) in THF (15 cm3) was then added to the
H, CH(CH3)2), 3.70 (mc, 2 H, NCH(CH3)), 4.85 (s, 1 H, NH), mixture which was subsequently heated at reflux for 1.5 h.
6.88–7.18 (m, 6 H, ArH); 1H NMR (400 MHz, 298 K, C6D6): d After cooling, degassed water (1 cm3) was added, the mixture
1.01 (d, J E 6.0 Hz, 6 H, NCH(CH3)), 1.28–1.73 (m, 6 H, vigorously stirred for 1 h, and all volatiles removed under
CH2), 1.42 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 1.49 (d, J = 6.8 reduced pressure. The residue was extracted with warm hexane
Hz, 6 H, CH(CH3)2), 1.54 (d, J = 6.8 Hz, 6 H, CH(CH3)2), (2 50 cm3). The extract was dried over MgSO4, then filtered
1.56 (d, J = 6.8 Hz, 6 H, CH(CH3)2), 3.55 (sept, J = 6.8 Hz, 4 and concentrated to ca. 15 cm3. Slow cooling of the filtrate to
H, CH(CH3)2), 4.11 (mc, 2 H, NCH(CH3)), 5.34 (s, 1 H, NH), 30 1C overnight yielded colourless crystals of 5 (yield: 2.85 g,
7.11–7.39 (m, 6 H, ArH); 13C{1H} NMR (75.5 MHz, 298 K, 81%); mp 150–152 1C. 1H NMR (400 MHz, 298 K, CDCl3): d
CDCl3): d 14.4 (CH2), 20.8 (NCH(CH3)), 21.5 (CH(CH3)2), 0.81 (d, J = 6.7 Hz, 6 H, CH(CH3)2), 1.09 (d, J = 6.7 Hz, 6 H,
22.9 (CH(CH3)2), 24.1 (CH(CH3)2), 25.6 (CH(CH3)2), 28.2 CH(CH3)2), 1.10–1.25 (m, 8 H, CH2), 1.23 (d, J = 6.7 Hz, 6 H,
(CH(CH3)2), 28.9 (CH(CH3)2), 30.0 (CH2), 48.3 (HCN), 121.8, CH(CH3)2), 1.25 (d, J = 6.7 Hz, 6 H, CH(CH3)2), 1.58–2.04
122.6, 123.5, 126.7, 135.1, 139.4, 145.3, 145.6 (ArC), 149.8 (m, 14 H, CHP and CH2), 3.00 (sept., J = 6.7 Hz, 2 H,
(CN3); 13C{1H} NMR (100.6 MHz, 298 K, C6D6): d 15.0 CH(CH3)2), 3.18 (sept., J = 6.7 Hz, 2 H, CH(CH3)2), 5.44 (d,
(CH2), 21.4 (NCH(CH3)), 22.2 (CH(CH3)2), 23.4 (CH(CH3)2), JPH = 14.1 Hz, 1 H, NH), 6.92–7.18 (m, 6 H, ArH); 13C{1H}
25.0 (CH(CH3)2), 25.9 (CH(CH3)2), 28.9 (CH(CH3)2), 29.8 NMR (100.6 MHz, 298 K, CDCl3): d 22.3 (CH2), 22.4 (CH2),
(CH(CH3)2), 30.7 (CH2), 49.0 (HCN), 123.3, 123.7, 124.3, 25.2 (CH(CH3)2), 26.1 (CH(CH3)2), 27.0 (CH(CH3)2), 27.8
127.6, 135.9, 140.0, 145.8, 146.1 (ArC), 150.7 (CN3); IR (CH(CH3)2), 27.9 (CH(CH3)2), 28.0 (CH(CH3)2), 28.1 (CH2),
(Nujol): n/cm1 = 3378 (m), 1616 (s), 1579 (s), 1303 (m), 28.8 (CH2), 29.1 (CH2), 29.1 (CH2), 32.2 (d, J = 20 Hz, CH2),
1258 (m), 1183 (m), 1145 (m), 1169 (m), 1079 (m), 1023 (m), 33.7 (d, J = 13.2 Hz, CH2), 123.3, 123.4, 123.5, 128.4, 133.9,
934 (m), 803 (m), 765 (m), 755 (m); MS/APCI: m/z (%) = 139.0, 145.2, 147.2 (ArC), 160.1 (d, J = 13.1 Hz, backbone
476.4 (MH+, 100). PCN2); 31P{1H} NMR (121 MHz, 298 K, C6D6): d –2.9 (s); IR
(Nujol): n/cm1 = 3354 (NH), 1620 (m), 1592 (m), 1568 (s),
Preparation of Pip(GisoH)2 4 1324 (m), 1259 (s), 1173 (m), 1109 (m), 1043 (m), 934 (m),
884 (m), 852 (m), 799 (s), 756 (s); MS/EI: m/z (%) = 560.4
BunLi (5.00 cm3 of a 1.6 M solution in hexanes, 8.00 mmol) was
(M+, 4), 517.4 (M+ C3H7, 100). Accurate mass (EI), m/z:
added to a solution of piperazine (0.339 g, 3.94 mmol) in THF
calc. for M+: 560.4254, found: 560.4251.
(40 cm3) at 20 1C over 5 min and the resultant solution stirred
for 1 h. ArNQCQNAr (2.93 g, 8.08 mmol) was then added
Preparation of PhP-GisoH 6
and the mixture stirred for 30 min, before being heated at
reflux for 2 h. After cooling to ambient temperature, water BunLi (2.80 cm3 of a 1.6 M solution in hexanes, 4.52 mmol)
(ca. 3 cm3) was added and volatiles removed under reduced was added to a solution of Ph2PH (0.85 g, 4.56 mmol) in THF
pressure. More water (ca. 30 cm3) and CH2Cl2 (60 cm3) were (10 cm3) at 70 1C over 5 min then warmed to room
then added to the residue and the mixture vigorously stirred temperature and stirred for 2 h. To the resultant red solution
until two clear solution phases were formed. The organic was added ArNQCQNAr (1.61 g, 4.43 mmol) in THF
phase was separated and the aqueous layer was extracted with (10 cm3) at 70 1C. The mixture was subsequently heated
CH2Cl2 (3 30 cm3). The combined organic phases were dried under reflux for 1.5 h. It was then cooled to room temperature
(MgSO4), filtered and volatiles removed from the filtrate under and ca. 0.3 cm3 degassed H2O was added with stirring.
reduced pressure. The residue was recrystallised from CHCl3 Volatiles were removed in vacuo and the residue extracted
at –30 1C to give 4 as colourless crystals (yield: 1.88 g, 75%); into diethyl ether (80 cm3) and filtered. The filtrate was

concentrated and stored at –30 1C to give colourless blocks of CH(CH3)2), 47.60 (CHN), 121.32, 121.41, 121.89, 122.68,
6 (yield: 1.66 g, 68%); mp 160–162 1C. 1H NMR (400 MHz, 123.55, 123.61, 139.69, 139.78, 140.12, 145.59, 145.78 (ArC),
298 K, CDCl3): d 0.83 (4 overlapping d, J = 6.8 Hz, 24 H, 148.24, 148.33 (CN3), NB: more than one isomer present. Only
CH3), 2.78 (sept, J = 6.8 Hz, 2 H, CH), 3.15 (sept, J = 6.8 Hz, major resonances reported with tentative assignments; IR
2 H, CH), 5.60 (s, 1 H, NH), 6.85–7.51 (m, 16 H, Ar–H); (Nujol): n/cm1 = 3364 (m), 1611 (s), 1589 (s), 1376 (s),
13
C{1H} NMR (100.6 MHz, 298 K, CDCl3): d 21.9, 22.1, 24.4, 1342 (m), 1261 (m), 1184 (m), 1111 (m), 999 (m), 870 (m),
25.4 (CH(CH3)2), 28.5, 28.8 (CH(CH3)2), 122.2, 122.8, 123.0, 802 (m), 761 (m), 715 (m); MS/EI: m/z (%) = 924.7 (M+, 14),
123.1, 127.6, 128.0, 128.4, 129.1, 129.7, 137.4, 138.7, 145.9, 881.7 (M+ –C3H7, 52). Accurate mass (EI), m/z: calc. for M+:
146.1, 146.4 (ArC), 155.6 (J = 16.1 Hz, PCN2); 31P{1H} NMR 924.7691, found: 924.7688; CHN: C62H96N6 requires: C
(121 MHz, 298 K, CDCl3,): d 18.5; MS/APCI, m/z (%): 549 80.46%, H 10.45%, N 9.08%; found: C 79.77%, H 10.99%,
(M+, 100); IR (Nujol): n/cm1 = 1607 (s), 1579 (s), 1434 (m), N 9.31%.
1258 (s), 1185 (m), 1099 (m), 742 (m), 693 (m); C37H45N2P
requires: C 80.99%, H 8.27%, N 5.10%, found: C 80.84%, H Preparation of [Li{Li(Giso)2}] 9
8.38%, N 5.25%.
BunLi (0.70 cm3 of a 1.6 M solution in hexanes, 1.12 mmol)
was added over 5 min to a solution of GisoH 1 (0.58 g, 1.07
Preparation of ArSi-GisoH 7
mmol) in hexane (20 cm3) at 20 1C. The resultant solution was
BunLi (1.64 cm3 of a 1.6 M solution in hexanes, 2.62 mmol) stirred for 30 min then concentrated under reduced pressure to
was added to a solution of ArNC{N(H)Ar}2 (1.35 g, 2.50 mmol) ca. 8 cm3. It was then stored at 4 1C overnight to afford
in THF (15 cm3) at room temperature over 5 min. The solution colourless crystals of 9 (yield: 0.42 g, 71%); mp 190–192 1C
was then stirred for 1 h. Me3SiCl (0.36 g, 2.85 mmol) (melts with slow decomposition); 1H NMR (300 MHz, 298 K,
was added at room temperature and the mixture subsequently C6D6): d 0.85–1.17 (m, 16 H, CH2), 1.18 (d, J = 6.8 Hz, 24 H,
heated at reflux for 2.5 h. All volatiles were removed under CH(CH3)2), 1.49 (d, J = 6.8 Hz, 24 H, CH(CH3)2), 1.78–1.48
reduced pressure and the residue was extracted into warm (m, 16 H, CH2), 2.03 (m, 8 H, CH2CHN), 3.35 (br t, J E
hexane (60 cm3). The solution was concentrated under reduced 11 Hz, 4 H, CHN), 3.57 (br sept, J = 6.8 Hz, 8 H, CH(CH3)2),
pressure to ca. 12 cm3 and cooled to 4 1C to obtain colourless 7.26–6.94 (m, 12 H, ArH); 13C{1H} NMR (75.5 MHz, 298 K,
crystals of 7 (yield 0.96 g, 63%); mp 257–258 1C. 1H NMR C6D6): d 23.7, 25.0, 26.9, 27.9, 28.7, (CH2), CH(CH3),
(400 MHz, 298 K, CDCl3): d 0.3 (v br s, 9 H, Si(CH3)3), CH(CH3)), 35.1 (CH2), 58.6 (HCN), 120.8 (ArC), 124.0
0.92–0.64 (m, 12 H, CH(CH3)2), 1.14 (d, J = 6.8 Hz, 12 H, (ArC), 141.3 (ArC), 150.2 (br, ArC), 160.6 (v br, CN3);
7
CH(CH3)2), 1.17 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 2.81 (sept, Li NMR (155.5 MHz, 298 K, C6D6): d 2.6 (s); IR (Nujol):
J = 6.8 Hz, 2 H, CH(CH3)2), 3.54–3.14 (m, 4 H, CH(CH3)2), n/cm1 = 1612 (s), 1583 (s), 1236 (s), 1156 (m), 1110 (m), 1027
5.59 (s, 1 H, NH), 7.28–6.54 (m, 9 H, ArH); 13C{1H} NMR (m), 933 (m), 895 (m), 792 (m), 748 (m); MS/EI: m/z (%) =
(75.5 MHz, 298 K, CDCl3): only resonances of one aryl 543.7 (GisoH+, 5), 500 (GisoH+ C3H6, 62).
substituent are resolved. Others, as well as those for the SiMe3
group, are too broad to be detected. d 23.2, 26.0, 28.2, Preparation of [Li(THF)(Giso)] 10
(CH(CH3)2 and CH(CH3)2), 122.4, 126.6, 134.2, 145.5
BunLi (2.00 cm3 of a 1.6 M solution in hexanes, 3.20 mmol)
(ArC), 146.8 (CN3); IR (Nujol): n/cm1= 3378 (m), 1618
was added over 5 min to a solution of GisoH 1 (1.71 g, 3.14
(s), 1578 (s), 1378 (m), 1246 (m), 1223 (m), 1107 (m), 1007 (m),
mmol) in THF (20 cm3) at 0 1C. The solution was then stirred
970 (m), 843 (m), 822 (m), 752 (m); MS/EI: m/z (%) = 611
for 1 h and volatiles removed under reduced pressure. Hexane
(M+, 14), 596 (M+ CH3, 5), 568 (M+ C3H7, 15), 539
(15 cm3) was added to the residue and the resultant solution
(M+ SiMe3, 15), 496 (M+ SiMe3 C3H6, 18).
concentrated to ca. 6 cm3. This was filtered and cooled to
30 1C to yield large colourless crystals of 10. Concentration
Preparation of (PrisoH)2 8
of the supernatant solution at room temperature yielded
A solution of K[N(SiMe3)2] (0.65 g, 3.24 mmol) in THF another crop of 10 (yield 1.52 g; 78%); mp 208–210 1C. 1H
(10 cm3) was added to PrisoH 2 (1.50 g, 3.24 mmol) in THF NMR (400 MHz, 298 K, C6D6): d 0.97 (mc, 4 H, THF-CH2),
(10 cm3) at 20 1C and the mixture stirred for 1 h. A solution of 1.27 (br mc, 12 H, CH(CH3)2), 1.30–1.45 (m, 6 H, CH2), 1.63
impure MnI2 (Aldrich Chemical Company, 1.00 g, 3.24 mmol) (d, 3JHH = 6.8 Hz, 12 H, CH(CH3)2), 1.71 (mc, 2 H, CH2),
in THF (20 cm3) was then added at 78 1C and the reaction 1.93 (mc, 4 H, CH2), 2.06 (mc, 4 H, CH2), 2.52 (mc, 4 H, CH2),
mixture slowly warmed to room temperature overnight. All 2.63 (mc, 4 H, THF-OCH2), 3.38 (mc, 2 H, NCH), 3.85 (sept, J
volatiles were removed in vacuo and the residue was extracted = 6.8 Hz, 4 H, CH(CH3)2), 6.98 (t, J = 7.5 Hz, 2 H, p-ArH),
with hexane (40 cm3). Filtration, concentration and slow 7.26 (d, J = 7.5 Hz, 4 H, m-ArH); 13C{1H} NMR (100.6 MHz,
cooling overnight to 30 1C yielded colourless crystals of 8 298 K, C6D6): d 22.8 (CH(CH3)2), 23.4 (CH2), 25.3 (CH2), 26.3
(yield 0.44 g, 30%); mp 223–225 1C. 1H NMR (400 MHz, 298 K, (CH2, THF), 27.1 (CH(CH3)2), 32.3 (CH2), 56.5 (NCH), 66.7
C6D6): d 0.81–1.01 (m of overlapping br d, 18 H, CH(CH3)2), (OCH2), 118.8, 122.2, 140.1, 149.7 (ArC), 156.6 (backbone,
1.05–1.47 (m of overlapping broad d, 54 H, CH(CH3)2), CN3); 7Li NMR (116.8 MHz, 298 K, C6D6): d 1.64 (s);
3.11–3.49 (m of overlapping br sept, 12 H, CH(CH3)2), IR (Nujol): n/cm1 = 3378 (m), 1618 (s), 1578 (m), 1378
4.74–4.91 (m, 2 H, NH), 6.88–7.29 (m, 10 H, ArH); 13C{1H} (m), 1246 (s), 1228 (m), 1198 (m), 1107 (m), 1008 (m), 970 (m),
NMR (100.6 MHz, 298 K, C6D6): d 21.83, 21.87, 22.70, 22.75, 843 (m), 822 (m), 752 (m); MS/EI: m/z (%) = 543.7
24.73, 25.69, 28.12, 28.28, 28.81, 28.94, 31.63 (CH(CH3)2 and (GisoH+, 100).
This journal is
Preparation of [{K(Priso)}N] 11 Preparation of [{K(THF)2}{Pip(Giso)2}{K(THF)3}] 12
3
Toluene (30 cm ) was added to a mixture of PrisoH 2 (1.02 g, A solution of K[N(SiMe3)2] (0.336 g, 1.68 mmol) in THF
2.20 mmol) and K[N(SiMe3)2] (0.45 g, 2.26 mmol) and the (15 cm3) was added to a solution of Pip(GisoH)2 4 (0.65 g,
resultant suspension stirred vigorously for 4 h at room tem- 0.801 mmol) in THF (25 cm3) at 20 1C. The resultant mixture
perature. All volatiles were removed under reduced pressure was stirred for 1 h, concentrated to ca. 15 cm3 and then cooled
and the residue washed with hexane (15 cm3). Recrystallisation to 30 1C to afford colourless crystals of 12 (yield 0.46 g,
from a toluene solution at 30 1C yielded colourless crystals of 52%); mp 4300 1C; IR (Nujol): n/cm1 = 1620 (s), 1584 (m),
11 (yield 0.95 g, 86%); mp 4300 1C. 1H NMR (400 MHz, 298 1238 (m), 1195 (m), 1050 (m), 987 (m), 840 (m), 799 (m), 758
K, C6D6): d 1.08 (d, J = 6.8 Hz, 12 H, CH(CH3)2), 1.43 (d, (m), 736 (m); MS/APCI: m/z (%) = 811.4 (Pip(GisoH)2H+,
J = 6.8 Hz, 12 H, CH(CH3)2), 1.51 (d, J = 6.8 Hz, 12 H, 100). N.B. The very low solubility of 12 in common deuterated
CH(CH3)2), 3.41 (sept, J = 6.8 Hz, 2 H, CH(CH3)2), 3.68 (two solvents precluded the acquisition of meaningful NMR data.
overlapping sept, J = 6.8 Hz, 4 H, CH(CH3)2), 6.76–7.18 (m,
X-Ray crystallography
6 H, ArH); 13C{1H} NMR (100.6 MHz, 298 K, C6D6): d 22.7
(NCH(CH3)2), 24.0 (CH(CH3)2), 24.2 (CH(CH3)2), 27.4 Crystals of 1–12 suitable for X-ray structural determination
(CH(CH3)2), 47.0 (HCN), 117.3, 122.5, 141.1, 145.5 (ArC), were mounted in silicone oil. Crystallographic measurements
153.2 (CN3); IR (Nujol): n/cm1 = 1613 (s), 1584 (m), 1261 were made using a Nonius Kappa CCD diffractometer. The
(m), 1152 (m), 1098 (m), 933 (m), 779 (m); MS/EI: m/z (%) = structures were solved by direct methods and refined on F2 by
501.3 (M+, 3), 420.3 (M+ K C3H6, 100). Accurate mass full-matrix least squares (SHELX97)28 using all unique data.
(EI), m/z: calc. for M+: 501.3480, found: 501.3484. Hydrogen atoms have been included in calculated positions
Table 2 Crystal data for compounds 1–12
Compound 1 2 3 42CHCl3 5 6
Empirical formula C37H57N3 C31H49N3 C32H49N3 C56H80Cl6N6 C37H57N2P C37H45N2P
Mr 543.86 463.73 475.74 1049.96 560.82 548.72
T/K 123(2) 150(2) 150(2) 150(2) 150(2) 150(2)
Crystal system Monoclinic Orthorhombic Monoclinic Monoclinic Monoclinic Triclinic
Space group P21/n Pbca P21/c P21/c P21/n P1
a/Å 12.265(3) 18.397(4) 19.236(4) 13.042(3) 10.960(2) 10.847(2)
b/Å 17.424(4) 15.542(3) 16.327(3) 12.030(2) 26.459(5) 10.942(2)
c/Å 15.775(3) 20.168(4) 19.536(4) 18.989(4) 12.934(3) 14.156(3)
a/1 90 90 90 90 90 96.42(3)
b/1 90.43(3) 90 106.01(3) 91.97(3) 112.61(3) 101.60(3)
g/1 90 90 90 90 90 102.50(3)
V/Å3 3371.2(12) 5767(2) 5898(2) 2977.7(10) 3462.6(12) 1585.4(6)
Z 4 8 8 2 4 2
Dc/Mg m3 1.072 1.068 1.072 1.171 1.076 1.149
m(Mo-Ka)/mm1 0.062 0.062 0.062 0.328 0.105 0.114
F(000) 1200 2048 2096 1120 1232 592
No. reflections collected 38 325 19 664 21 080 10 581 14 712 10 001
No. independent reflns 7339 5343 11498 5520 7517 5420
Rint 0.1167 0.0382 0.0500 0.0272 0.0299 0.0306
Final R1 (I 4 2s(I)) 0.0629 0.0435 0.0603 0.0465 0.0479 0.0464
Final wR2 (all data) 0.1584 0.1069 0.1527 0.1147 0.1227 0.1159
Compound 7 8hexane 9 10 11 122THF

Empirical formula C40H61N3Si C68H110N6 C74H112Li2N6 C41H64LiN3O C31H48KN3 C82H132K2N6O7
Mr 612.01 1011.62 1099.58 621.89 501.82 1392.14
T/K 123(2) 150(2) 123(2) 150(2) 123(2) 150(2)
Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Orthorhombic Monoclinic
Space group P21/c P21/c C2/c P21/c P212121 P21/n
a/Å 35.510(7) 15.467(3) 20.707(4) 18.807(4) 11.462(2) 24.500(5)
b/Å 9.9877(2) 22.956(5) 12.031(2) 11.783(2) 11.997(2) 16.473(3)
c/Å 21.966(4) 19.774(4) 26.802(5) 18.773(4) 21.319(4) 20.494(4)
a/1 90 90 90 90 90 90
b/1 104.59(3) 111.87(3) 104.33(3) 113.20(3) 90 93.48(3)
g/1 90 90 90 90 90 90
V/Å3 7456(3) 6516(2) 6469(2) 3823.8(13) 2931.6(10) 8256(3)
Z 8 4 4 4 4 4
Dc/Mg m3 1.090 1.031 1.129 1.080 1.137 1.120
m(Mo-Ka)/mm1 0.093 0.059 0.064 0.063 0.204 0.168
F(000) 2688 2240 2416 1368 1096 3040
No. reflections collected 58 137 16 169 18 157 24 208 22 486 27 961
No. independent reflns 16 069 11 404 5651 8282 5060 14 497
Rint (0.0810) (0.0423) (0.1428) (0.0304) (0.1036) (0.0408)
Final R1 (I 4 2s(I)) 0.0546 0.0755 0.0669 0.0501 0.0737 0.0713
Final wR2 (all data) 0.1380 0.1828 0.1301 0.1236 0.1371 0.1858

(riding model) for all structures, with the exception of the 7 (a) C. Cui, H. W. Roesky, H.-G. Schmidt, M. Noltemeyer, H. Hao
methyl hydrogens of C(21) and C(24) in the structure of 11 and F. Cimpoesu, Angew. Chem., Int. Ed., 2000, 39, 4274;
(b) N. J. Hardman, B. E. Eichler and P. P. Power, Chem. Commun.,
which were not included in the refinement. Two crystallo- 2000, 1991; (c) M. S. Hill and P. B. Hitchcock, Chem. Commun.,
graphically independent molecules were refined in the asym- 2004, 1818; (d) M. S. Hill, P. B. Hitchcock and
metric units of the crystal structures of 3 and 7. No significant R. Pongtavornpinyo, Dalton Trans., 2005, 273.
geometric differences were found between the two molecules in 8 C. Jones, P. C. Junk, J. A. Platts, D. Rathmann and A. Stasch,
Dalton Trans., 2005, 2497.
each structure and therefore only the metrical parameters for 9 C. Jones, P. C. Junk, J. A. Platts and A. Stasch, J. Am. Chem. Soc.,
one molecule from each structure are reported here. The Flack 2006, 128, 2206.
parameter for the crystal structure of compound 11 is 0.01(6). 10 S. P. Green, C. Jones and A. Stasch, Inorg. Chem., 2007, 46, 11.
11 G. Jin, C. Jones, P. C. Junk, A. Stasch and W. D. Woodul, New J.
Crystal data, details of data collections and refinement are
Chem., 2008, 32, 835.
given in Table 2. 12 S. P. Green, C. Jones and A. Stasch, Science, 2007, 318, 1754.
13 S. P. Green, C. Jones, P. C. Junk, K.-A. Lippert and A. Stasch,
Chem. Commun., 2006, 3978.
Acknowledgements 14 S. P. Green, C. Jones, G. Jin and A. Stasch, Inorg. Chem., 2007, 46, 8.
15 C. Jones, D. P. Mills and A. Stasch, Dalton Trans., 2008,
We gratefully acknowledge financial support from the Aus- 4799.
tralian Research Council (fellowships for C. J. and A. S.), the 16 D. Heitmann, C. Jones, P. C. Junk, K.-A. Lippert and A. Stasch,
Leverhulme Trust (fellowship for A. S.), the Erasmus scheme Dalton Trans., 2007, 187.
17 C. Jones, R. P. Rose and A. Stasch, Dalton Trans., 2007, 2997.
of the European Union (travel grant for K. L.), the Royal 18 S. P. Green, C. Jones, K.-A. Lippert, D. P. Mills and A. Stasch,
Society (fellowship for G. J.), and the US Air Force Asian Inorg. Chem., 2006, 45, 7242.
Office of Aerospace Research and Development. Thanks also 19 R. E. Boeré, R. T. Boeré, T. Masuda and G. Wolmershäuser, Can.
go to the EPSRC Mass Spectrometry Service, Swansea. J. Chem., 2000, 78, 1613.
20 Z. Lu, G. P. A. Yap and D. S. Richeson, Inorg. Chem., 1999, 38,
5788.
References 21 See for example (a) M. P. Coles and P. B. Hitchcock, Chem.
Commun., 2002, 2794; (b) J. Grundy, M. P. Coles and P. B.
1 For general references on the structure and reactivity of amidinate Hitchcock, Dalton Trans., 2003, 2573; (c) N. E. Mansfield,
and guanidinate complexes, see: (a) J. Barker and M. Kilner, M. P. Coles and P. B. Hitchcock, Dalton Trans., 2005, 2833;
Coord. Chem. Rev., 1994, 133, 219; (b) F. T. Edelmann, Coord. (d) N. E. Mansfield, M. P. Coles and P. B. Hitchcock, Dalton
Chem. Rev., 1994, 137, 403; (c) P. J. Bailey and S. Price, Coord. Trans., 2006, 2052; (e) N. E. Mansfield, J. Grundy, M. P. Coles,
Chem. Rev., 2001, 214, 91; (d) M. P. Coles, Dalton Trans., 2006, A. G. Avent and P. B. Hitchcock, J. Am. Chem. Soc., 2006, 128,
985; (e) P. C. Junk and M. L. Cole, Chem. Commun., 2007, 1579, 13879.
and references therein. 22 W.-X. Zhang, M. Nishiura and Z. Hou, Chem. Commun., 2006,
2 N. Nimitsiriwar, V. C. Gibson, E. L. Marshall, A. J. P. White, 3812.
S. H. Dale and M. R. J. Elsegood, Dalton Trans., 2007, 4464. 23 M. R. Crimmin, A. G. M. Barrett, M. S. Hill, P. B. Hitchcock and
3 S. R. Foley, Y. Zhou, G. P. A. Yap and D. S. Richeson, Inorg. P. A. Procopiou, Organometallics, 2008, 27, 497.
Chem., 2000, 39, 924. 24 R. J. Baker and C. Jones, J. Organomet. Chem., 2006, 691, 65.
4 S. Dagorne, I. A. Guzei, M. P. Coles and R. F. Jordan, J. Am. 25 As determined from a survey of the Cambridge Crystallographic
Chem. Soc., 2000, 122, 274. Database, May, 2008.
5 J. Barker, N. C. Blacker, P. R. Phillips, N. W. Alcock, 26 C. Knapp, E. Lork, P. G. Watson and R. Mews, Inorg. Chem.,
W. Errington and M. G. H. Wallbridge, J. Chem. Soc., Dalton 2002, 41, 2014.
Trans., 1996, 431. 27 K. Ogawa and M. Akazawa, Jpn. Pat. Appl., JP 91-208987910517,
6 L. Bourget-Merle, M. F. Lappert and J. R. Severn, Chem. Rev., 1993.
2002, 102, 3031. 28 G. M. Sheldrick, SHELX-97, University of Göttingen, 1997.
This journal is
The hydrogen bond acidity and other descriptors for oximes

Michael H. Abraham,*a Javier Gil-Lostes,a J. Enrique Cometto-Muňiz,b
William S. Cain,b Colin F. Poole,c Sanka N. Atapattu,c Raymond J. Abrahamd
and Paul Leonardd
Received (in Durham, UK) 9th July 2008, Accepted 20th August 2008
DOI: 10.1039/b811688a
The solvation descriptors for cyclohexanone oxime and acetone oxime have been obtained from
measurements on water–solvent partitions, and gas–liquid chromatographic retention data. These
yield values of 0.33 and 0.37 for the Abraham hydrogen bond acidity, A, in reasonable agreement
with a value of 0.37 for cyclohexanone oxime obtained by our recent NMR method. The other
descriptors E, S, B, L and V have also been obtained for cyclohexanone oxime and acetone
oxime, and have been estimated for a number of other oximes as well. The value for A, the
overall or effective hydrogen bond acidity of the oximes is reasonably close to the 1 : 1 hydrogen
bond acidity, a2H = 0.39 to 0.46, that can be deduced from previous literature measurements on
oximes, and to the 1 : 1 hydrogen bond acidity, a2H = 0.43 for another NOH compound,
N,N-dibenzylhydroxylamine, that again can be deduced from literature measurements.
Introduction surrounded by solvent molecules, or is present in the gas phase

as an isolated molecule. A related acidity is the 1 : 1 hydrogen
The oximes were important derivatives of aldehydes and bond acidity, a2H, in which a solute complexes with a hydrogen
ketones, often used for identification in the 19th and early bond base in an inert solvent such as tetrachloromethane.1,4
20th century. Their use as derivatives has declined, but a The defining equations for a2H are eqn (1),4 where K is the 1 : 1
number of oximes are important. Nifuroxime is a drug, and complexation constant for an acid against a reference base B,
diacetylmonooxime is a cholinesterase reactivator. In order to eqn (2) in which log K is put on a general scale of hydrogen
predict physicochemical and biochemical properties of the bond acidity KAH, and finally eqn (3) in which KAH is
oximes, a knowledge of their Abraham descriptors1,2 transformed into the a2H scale. In eqn (2), LB and DB are
(or solvation parameters) is needed. One of the key descriptors the fitting coefficients.
is the overall, or effective, hydrogen bond acidity, A, in which
we were particularly interested, especially as we have recently A–H + :B - A–H B; K (1)
developed a new method for the experimental determination
of this parameter.3 In this work, we showed that the difference log K (for an acid against a reference base B) = LB log
(Dd) in the 1H NMR chemical shift of a protic hydrogen in KAH + DB (2)
DMSO vs. CDCl3 solvent is directly related to the hydrogen
bond acidity. This correlation was valid over 54 compounds a2H = (1.1 + KAH)/4.636 (3)
and 72 protic hydrogens varying from cyclohexane to the OH
proton of phenol. An important advantage of the NMR The term (1.1 + KAH) serves to define the origin of the scale
method is that it allows the determination of A values for where a2H = 0 for zero acidity, and the factor 4.636 is used
individual protic hydrogens in multifunctional solutes. only to provide a suitable range of the scale. A number of
As we have pointed out,1 the overall or effective hydrogen equations on the lines of eqn (2) were constructed for various
bond acidity, A, is the important type of acidity when con- reference bases.
sidering processes in which a solute is in dilute solution and The only acid–base measurements that seem to have been
made on oximes are those of Ossart et al.,5 who measured 1 : 1
a
Department of Chemistry, University College London, 20 Gordon
complexation constants for a number of oximes against the
Street, London, UK WC1H OAJ. E-mail: m.h.abraham@ucl.ac.uk. base tetrahydrofuran in tetrachloromethane. The 1 : 1 com-
E-mail: j.lostes@ucl.ac.uk plexation constants, K, in units of mol1 dm3, are in Table 1,
b
Chemosensory Perception Laboratory, Department of Surgery together with the corresponding values of a2H that we have
(Otolaryngology), University of California, San Diego, La Jolla,
CA 92093-0957, USA. E-mail: ecometto@ucsd.edu deduced from the LB and DB values for the base tetrahydro-
c
Department of Chemistry, Wayne State University, Detroit, furan4 in Table 2, through eqn (2) and (3). Feuer et al.6 have
MI 48202, USA. E-mail: cfp@chem.wayne.edu. measured 1 : 1-complexation constants for the NOH com-
E-mail: sanka@chem.wayne.edu pound N,N-dibenzylhydroxylamine against a number of
d
Chemistry Department, The University of Liverpool, P.O. Box 147,
Liverpool, UK L69 3BX. E-mail: abrahamr@liverpool.ac.uk. hydrogen bond bases in tetrachloromethane, as shown in
E-mail: pleonard@liverpool.ac.uk Table 2, where we give the deduced values of a2H.

Table 1 Values of the 1 : 1 complexation constant, K, for some partition coefficient or some measure of gas chromatographic
oximes against tetrahydrofuran in tetrachloromethane, and the corres- retention. The coefficients in eqn (5) and 6 are evaluated
ponding values of a2H
through multiple linear regression analysis (MLRA).
Oxime K (ref. 5) a2H The use of eqn (5) and (6) in the determination of descrip-
tors has been described in detail,2 and numerous examples are
Acetaldehyde oxime 3.75 0.44
Acetone oxime 3.51 0.43 available.13–16 In brief, equations on the lines of eqn (5) and (6)
Butanone oxime 4.08 0.45 are set up for a number of physicochemical processes, using
Cyclohexanone oxime 2.45 0.39 solutes whose descriptors are known. The SP values for the
Acetophenone oxime 4.24 0.45
Benzophenone oxime 4.49 0.46 investigated compound are then obtained by experiment for
Benzaldehyde oxime (b) 4.65 0.46 the same processes under exactly the same conditions as used
in the calibration experiments. There are six descriptors that
are required for any compound. However, V can be calculated
Results from atomic and bond contributions,1,12 and E can then be
The complexation constants of Ossart et al.5 can be trans- obtained by one of a variety of methods. If the refractive index
formed into KAH and then into a2H values through eqn (2) and of the liquid compound at 20 1C is available, E can be
(3). The deduced values of a2H range from 0.39 to 0.46 as obtained directly. Otherwise E can be calculated by addition
shown in Table 1. Similarly, the complexation constants of of fragments, either by hand or by a commercial program,17 or
Feuer et al.6 yield the a2H values given in Table 2. No equation can be obtained from a calculated refractive index.18
on the lines of eqn (2) has been constructed for benzene as a Cyclohexanone oxime and acetone oxime are solids, but a
reference base, and so we are left with three independent number of lower oximes are liquids whose refractive index has
values of a2H for N,N-dibenzylhydroxylamine. There is not been measured,19 and for which we have calculated E, see
very good agreement, but we can say that the 1 : 1 hydrogen Table 3. Also included are values of E calculated from the
bond acidity of N,N-dibenzylhydroxylamine is around 0.43 ACD refractive index,18 and values of E calculated through
units. Once a2H is known, the general equation, eqn (4),7 can the PharmaAlgorithm (PHA) program.17 The ACD values are
be used to estimate the 1 : 1 complexation constant of the all too low, but the PHA values show good agreement with the
oximes or of the hydroxylamine with any base for which the experimental values. We take the PHA value of 0.58 for
1 : 1 hydrogen bond basicity b2H has been determined.8–11 cyclohexanone oxime and a value of 0.39 for acetone oxime
(slightly larger than that for butanone oxime).
log K = (7.354a2Hb2H) 1.094 (4) This then leaves four descriptors, S, A, B and L to be
Of more practical utility is the overall hydrogen bond acidity, obtained by experiment. In principle, if four values of SP are
A, which is one of the descriptors in our linear free energy obtained in four calibrated systems, we have four unknowns
relationships, LFERs, eqn (5) and (6).1,2 (S, A, B and L) that can be deduced from four equations. In
practice, it is much better to have a larger number of equations
SP = c + eE + sS + aA + bB + vV (5) and then to find the best solution of the equations by trial-and-
error, the best solution being the values of the descriptors that
SP = c + eE + sS + aA + bB + lL (6)
provide the best fit of calculated and experimental SP values.
In eqn (5) and (6), the independent variables are solute We used the procedure in Microsoft ‘Solver’ to obtain the best
descriptors as follows. E is the solute excess molar refractivity fit descriptors. We can extend the number of equations
in units of (cm3 mol1)/10, S is the solute dipolarity/polariz- through eqn (7), where Ps is a water-to-solvent partition
ability, A and B are the overall or summation hydrogen bond coefficient, Ks is the corresponding gas-to-solvent partition
acidity and basicity, V is the McGowan characteristic volume coefficient, and Kw is the corresponding gas-to-water partition
12
in units of (cm3 mol1)/100 and L is the logarithm of the gas coefficient. In the case of a solvent such as octanol, that takes
to hexadecane partition coefficient at 25 1C. Eqn (5) is used for
transfer of solutes from one condensed phase to another, and Table 3 Some experimental and calculated values of E for oximes
eqn (6) is used for processes that involve the transfer of solutes
from the gas phase to a solvent phase. The dependent variable, ACD PHA
Oxime Z(20) V E(exptl.)a (calc.) (calc.)
SP, is a set of solute properties in a given system. For example,
SP in eqn (5) could be the water-to-octanol partition coeffi- Formaldehyde oxime 0.3650 0.37
Acetaldehyde oxime 1.4264 0.5059 0.390 0.300 0.40
cient, as log Poct, and SP in eqn (6) could be a gas-to-solvent Propanal oxime 1.4303 0.6468 0.366 0.293 0.40
Butanal oxime 1.4367 0.7877 0.357 0.288 0.40
Table 2 Values of LB and DB in eqn (2), the 1 : 1 complexation Isobutanal oxime 0.7877 (0.37) 0.41
constant, K, in tetrachloromethane and derived values of a2H for Acetone oxime 0.6468 (0.39) 0.296 0.38
N,N-dibenzylhydroxylamine Butanone oxime 1.4431 0.7877 0.383 0.292 0.38
Pentan-2-one oxime 1.4455 0.9286 0.369 0.290 0.37
Base LB DB K (ref. 6) a2H Pentan-3-one oxime 1.4465 0.9286 0.375 0.290 0.37
Hexan-2-one oxime 1.4470 1.0695 0.354 0.288 0.37
Triethylamine 1.0486 0.0517 14 0.462 Heptan-4-one oxime 1.4475 1.2104 0.335 0.288 0.37
Diethyl ether 0.7129 0.3206 2.3 0.444 Cyclopentanone oxime 0.8200 (0.58) 0.59
Dimethyl sulfoxide 1.2399 0.2656 11 0.372 Cyclohexanone oxime 0.9609 (0.58) 0.728 0.58
Benzene N/A N/A 0.5 a
Tetrahydrofuran 0.8248 0.1970 Values in parenthesis are estimated.
This journal is
up a considerable amount of water when in equilibrium with and so eqn (7) can be applied to wet octanol as well as to
water, both log Ps and log Ks refer to the water-saturated solvents that take up only very small quantities of water.
octanol. Then eqn (7) can be applied provided that log Kw as
log Ps = log Ks log Kw (7)
obtained for pure water is the same for water saturated with
octanol. There is a considerable amount of experimental If we allow the value of log Kw to float, we have increased the
evidence that log Kw is indeed the same, within any realistic number of ‘descriptors’ to be determined from four to five.
experimental error, for water and octanol saturated water,20 However, the log Ps values for the four solvents listed in
Table 4 Coefficients in the equations used to calculate descriptors for cyclohexanone oxime, and the corresponding observed and calculated
values (Ps is the water-to-solvent partition coefficient, Ks is the corresponding gas-to-solvent partition coefficient, Kw is the corresponding gas-to-
water partition coefficient, k is the gas to stationary phase partition coefficient, tr 0 is the retention time relative to the standard)
SP
System SP c e s a b v/l Obs Calc
a
Water–octanol log Ps 0.088 0.562 1.054 0.034 3.460 3.814 0.988 1.031
Water–chloroform log Ps 0.327 0.157 0.391 3.191 3.437 4.191a 0.821 0.944
Water–hexane log Ps 0.361 0.579 1.723 3.599 4.764 4.344a 0.599 0.773
Water–toluene log Ps 0.143 0.527 0.720 3.010 4.824 4.545a 0.260 0.232
Gas–waterb log Kw 0.994 0.577 2.549 3.813 4.841 0.869a 5.115 5.011
Gas–octanol log Ks 0.198 0.002 0.709 3.519 1.429 0.858 6.103 6.181
Gas–chloroform log Ks 0.116 0.467 1.203 0.138 1.432 0.994 5.936 6.141
Gas–hexane log Ks 0.292 0.169 0.000 0.000 0.000 0.979 4.516 4.423
Gas–toluene log Ks 0.121 0.222 0.938 0.467 0.099 1.012 5.375 5.423
Gas–waterc log Kw 1.271 0.822 2.743 3.904 4.814 0.213 5.115 4.979
CW-20M log tr 0 3.270 0.144 1.420 1.950 0.000 0.467 0.824 0.752
OV-275 log tr 0 2.822 0.355 1.650 1.797 0.325 0.341 1.106 1.133
Hp-Innowax log tr 0 2.675 0.033 1.290 1.703 0.051 0.386 0.765 0.704
DEGS log tr 0 3.296 0.327 1.568 1.882 0.297 0.424 0.964 0.939
HP-5 80 log k 1.927 0.051 0.360 0.303 0.000 0.636 1.258 1.215
100 log k 1.970 0.022 0.329 0.243 0.000 0.573 0.916 0.869
120 log k 2.008 0.000 0.305 0.200 0.000 0.518 0.613 0.570
160 log k 2.552 0.050 0.229 0.145 0.000 0.389 0.557 0.589
SPB-Octyl 80 log k 2.645 0.165 0.062 0.000 0.000 0.703 0.600 0.543
100 log k 2.719 0.181 0.057 0.000 0.000 0.644 0.267 0.219
120 log k 2.738 0.189 0.076 0.000 0.000 0.578 0.016 0.063
160 log k 1.980 0.174 0.059 0.000 0.000 0.431 0.084 0.036
180 log k 1.996 0.182 0.060 0.000 0.000 0.391 0.104 0.147
200 log k 1.965 0.186 0.048 0.000 0.000 0.350 0.250 0.302
240 log k 1.979 0.192 0.052 0.000 0.000 0.287 0.530 0.581
Rtx-440 80 log k 2.452 0.038 0.505 0.389 0.000 0.667 1.001 0.990
100 log k 2.537 0.000 0.461 0.316 0.000 0.613 0.647 0.630
120 log k 2.584 0.021 0.427 0.271 0.000 0.559 0.337 0.317
160 log k 2.419 0.046 0.336 0.211 0.000 0.427 0.168 0.176
180 log k 2.398 0.048 0.312 0.192 0.000 0.382 0.368 0.376
200 log k 2.403 0.067 0.288 0.181 0.000 0.346 0.549 0.550
220 log k 2.479 0.077 0.270 0.174 0.000 0.323 0.730 0.739
240 log k 2.393 0.098 0.226 0.156 0.000 0.284 0.842 0.854
DB-1701 160 log k 2.119 0.007 0.553 0.575 0.000 0.409 0.238 0.331
180 log k 2.078 0.001 0.511 0.488 0.000 0.362 0.024 0.106
200 log k 2.083 0.020 0.471 0.419 0.000 0.328 0.164 0.092
220 log k 2.070 0.039 0.428 0.356 0.000 0.295 0.333 0.270
Rxi-50 160 log k 2.104 0.124 0.592 0.283 0.000 0.390 0.264 0.279
180 log k 2.110 0.145 0.536 0.258 0.000 0.352 0.059 0.062
200 log k 2.118 0.160 0.486 0.250 0.000 0.319 0.114 0.127
220 log k 2.111 0.169 0.446 0.216 0.000 0.288 0.297 0.296
240 log k 2.093 0.181 0.402 0.192 0.000 0.259 0.446 0.444
80 log k 2.192 0.090 0.807 0.398 0.000 0.623 1.448 1.409
120 log k 2.236 0.117 0.713 0.302 0.000 0.505 0.778 0.755
140 log k 2.242 0.143 0.648 0.269 0.000 0.455 0.504 0.479
HP-Innowax 160 log k 2.568 0.215 1.157 1.544 0.000 0.356 0.634 0.645
180 log k 2.383 0.202 0.998 1.363 0.000 0.299 0.367 0.374
200 log k 2.350 0.204 0.926 1.198 0.000 0.265 0.133 0.142
220 log k 2.334 0.209 0.854 1.071 0.000 0.237 0.077 0.067
DB-225 160 log k 2.784 0.055 0.980 0.853 0.000 0.340 0.210 0.120
180 log k 2.833 0.074 0.909 0.776 0.000 0.311 0.354 0.372
200 log k 2.826 0.091 0.842 0.691 0.000 0.278 0.600 0.586
220 log k 2.775 0.096 0.754 0.612 0.000 0.251 0.731 0.754
a b
These coefficients are for v, the remainder are for l. Eqn (5). c Eqn (6).

Table 5 Solvation descriptors for cyclohexanone and acetone oxime between the NH and OH protons in hydroxylamines in
DMSO solution which was noted by Feuer et al.6 in their
Oxime E S A B V L log Kw
measurements of the self-association of these compounds in
Cyclohexanone oxime 0.58 0.90 0.33 0.61 0.9609 4.320 5.11 this solvent. However the OH chemical shift in oximes in
Acetone oxime 0.39 0.66 0.37 0.56 0.6488 2.557 4.46 DMSO solution is independent of concentration and this was
used by Kurtz and D’Silva23 in their estimation of the pKa of
Table 4 then yield four extra log Ks values, and in addition we twenty oximes in DMSO solvent. The 1H NMR data of ca.
have two equations, one from eqn (5) and one from eqn (6) for forty oximes in CDCl3 solution, including acetone and cyclo-
log Kw, making an extra six equations. In Table 4 are given the hexanone oxime are given in the Aldrich Spectral catalogue.24
systems that we have used for cyclohexanone oxime, the coeffi- The OH proton chemical shift is always very deshielded,
cients in eqn (5) and (6), and the observed and calculated SP for example acetone oxime 9.97 ppm, cyclohexanone oxime
values. The extra equations lead to a total of 53 equations for 9.78 ppm. Very similar shifts are obtained in DMSO solution:
which the SP values can be fitted with a standard deviation, SD, 10.12,23 10.14 (this work) for acetone oxime, and 10.02,23
of only 0.063 log units with the descriptors shown in Table 5. 10.05 (this work) for cyclohexanone oxime. The values
For acetone oxime, we have the GLC data obtained at UCL. for chloroform are for relatively concentrated solutions
We also have an equation derived from the retention indices, I, (8/10%, weight to volume,24 i.e. for cyclohexanone oxime
obtained by Zenkevich21 on Porapak Q for a large number of 0.9 mol dm3). The chemical shift of the OH proton in oximes
volatile compounds. Application of eqn (6) yielded eqn (8). in CDCl3 solvent is known to be concentration dependent6 due
to intermolecular hydrogen bonding; thus a dilution experi-
I = 154.68 69.354E + 38.611B + 175.622L (8)
ment was performed in CDCl3 solution on cyclohexanone
oxime to obtain the N dilution chemical shift required for
N = 214, R2 = 0.9873, SD = 28.7, F = 2702.6 this study. The oxime concentration was decreased until
In eqn (8), N is the number of compounds, R is the correlation the OH chemical shift showed very little change with concen-
coefficient, SD is the standard deviation and F is the F-statis- tration (Table 7). The concentrations were measured by
tic. There is also a set of GLC data on a Perkin–Elmer column using the integral of the a-CH2 protons of the oxime with
that includes acetone oxime.22 The relevant equation is respect to the residual CHCl3 peak. The results are given in
eqn (9), making a total of 16 equations for acetone oxime. Table 7. The plot of d(OH) vs. concentration is linear until a
Details of the calculations for acetone oxime are in Table 6; dilution of ca. 0.06 mol dm3 is reached when the plot is
the standard deviation between observed and calculated values essentially independent of concentration. Thus the value of
is only 0.040 log units. 4.45 ppm may be regarded as the N dilution chemical shift in
this experiment. However the OH peak of the oxime at the
I = 83.84 19.68E + 63.46S + 118.44A + 11.85B lowest concentration measured was a broad peak of intensity
+ 196.853L (9) 2H, with respect to the a-CH2 protons of the oxime
(see above). This value was interpreted as due to the oxime
N = 48, R2 = 0.9880, SD = 13.9, F = 713.13 OH (intensity 1) plus an equal amount of water protons
present despite careful drying of the CDCl3 solvent over
The 1H NMR spectra of oximes in CDCl3 and DMSO molecular sieves. There is rapid exchange on the NMR time
solvents have been recorded previously. There is exchange scale between the oxime OH proton and the water protons
to give the broad peak observed. The chemical shift of this
peak is therefore the weighted average of the chemical shifts of
Table 6 Observed and calculated values for acetone oxime (see
Table 4 for definitions) the oxime OH and the water protons. Thus eqn (10) applies
where dobs, d and d2 are the observed chemical shift and
SP the chemical shifts of the oxime OH and the water protons
System SP Obs. Calc. at these concentrations and n1 and n2 the mole fractions of the
two species.
Water–octanol log Ps 0.120 0.154
Water–chloroform log Ps 0.351 0.264 dobs = n1d1 + n2d2 (10)
Water–hexane log Ps 1.725 1.740
Water–toluene log Ps 0.960 1.002
Gas–watera log Kw 4.464 4.472 The N dilution chemical shift of water in CDCl3 solvent is
Gas–octanol log Ks 4.584 4.580 1.56 ppm25 and inserting this in eqn (10) with dobs = 4.45 ppm
Gas–chloroform log Ks 4.113 4.137
Gas–hexane log Ks 2.739 2.744
and n1 = n2 = 1/2 gives the N dilution value for the OH
Gas–toluene log Ks 3.504 3.484 shift in cyclohexanone oxime as 7.34 ppm. This value,
Gas–waterb log Kw 4.464 4.452 when inserted into the A vs. Dd, eqn (3), gives an A value
CW-20M log tr 0 0.287 0.354 of 0.37.
OV-275 log tr 0 0.058 0.129
HP-Innowax log tr 0 0.227 0.217
DEGS log tr 0 0.152 0.181
Porapak Q21 I/100 5.980 6.009 Table 7 d(OH) vs. concentration of cyclohexanone oxime in CDCl3
See text22 I/100 6.700 6.748
Conc. (mol dm3 102) 2.00 6.97 9.26 11.76 20.0
a b
Eqn (5). Eqn (6). d(OH) 4.45 4.68 5.77 6.27 8.82
This journal is
Discussion Table 8 Approximate solvation descriptors for some oximes
Oximes E S A B V L log Kw
The descriptors for cyclohexanone oxime have been derived
from fits to 53 equations and can be regarded as soundly based. Cyclopentanone oxime 0.580 0.94 0.33 0.61 0.8200 3.700 5.23
Those for acetone oxime are based on 16 equations, and so Acetaldehyde oxime 0.390 0.50 0.35 0.54 0.5059 1.931 3.98
Propanal oxime 0.366 0.52 0.35 0.54 0.6468 2.498 3.92
should also be quite reliable. The value of the hydrogen bond Butanal oxime 0.357 0.58 0.35 0.54 0.7877 3.149 3.96
acidity descriptor, A, is 0.33 or 0.37 for cyclohexanone oxime Isobutanal oxime 0.370 0.59 0.35 0.57 0.7877 2.992 4.13
and 0.37 for acetone oxime, as compared to the 1 : 1 hydrogen Butanone oxime 0.383 0.71 0.35 0.56 0.7877 3.173 4.40
bond acidity 0.39 and 0.43, respectively, see Table 1, and 0.43
for the NOH compound, N,N-dibenzylhydroxylamine, see
Table 2. For alcohols, A and a2H do not differ too much : but this is only possible if rather unusual HPLC systems are
0.37 and 0.32 for propan-1-ol, 0.33 and 0.33 for isopropanol, used. Du et al.28 and Valko et al.29 have shown that most of the
and 0.31 and 0.32 for tert-butanol. Hence, for N,N-dibenzyl- common isocratic elution and gradient elution systems have
hydroxylamine we expect A to be near 0.43 units. The hydro- similar coefficients, with rather small a-coefficients. Hence if
gen-bond acidity of the two types of NOH compound, the HPLC systems are used, it is preferable to include some
oximes and the hydroxylamines, are thus quite close. water-to-solvent partition systems as well as GLC systems.
The value of 0.37 for the hydrogen bond acidity of cyclo- Probably the best set of experimental data to use in order to
hexanone oxime by the NMR method is a little higher than the obtain all the descriptors is a combination of retention data on
value of 0.33 from the GLC and partition measurements. GLC stationary phases and partition coefficients in a number
However, the NMR method is rendered more difficult than of water-to-solvent partition systems, as we have used here.
usual because of the large concentration dependence of the
chemical shift in CDCl3, and the necessity of obtaining the N Experimental
dilution chemical shift of the oxime from the observed shift
due to the oxime and water. For other acyclic oximes, we Partition coefficients
suggest that an A-value of 0.35 could be taken. Cyclohexanone oxime and acetone oxime were used as
In the calculation of the descriptors for the oximes, we used received. Solvents were pre-equilibrated with water, and the
the method of fitting by trial-and-error. If, for a given oxime, water saturated with the solvent and the solvent saturated with
we have four unknown descriptors S, A, B and L, then four water were used in the experiments. Dilute solutions of the
equations of the type of eqns (5) and (6) would suffice to yield oximes in water were gently shaken with the organic solvent
values for the four descriptors. It is obviously better to have and left to equilibrate at 25 1C for 30 min. Portions of the
more equations, but then the solution can only be obtained by organic layer and the aqueous layer were carefully withdrawn
trial-and-error. We used the ‘Solver’ add-on programme in using hypodermic syringes and directly injected into a Perkin-
Microsoft Excel to obtain the best-fit descriptors. Inspection Elmer F-33 gas chromatograph with a stationary phase of
of Table 4 shows that the various equations that can be used in Carbowax 20M at 101 1C. The volumes withdrawn (Vo and
the calculation of descriptors have very different coefficients. Vw) were arranged so that the area under the GC peaks was
The larger the coefficient the more accurately can the corre- almost the same for the aqueous and organic layers. The ratio
sponding descriptor be obtained. Several of the GLC phases of the areas (Ao/Aw) could then be taken as the ratio of the
have reasonably large values of the s- and a-coefficients, quantities of oxime in the withdrawn volumes (Qo/Qw). Then
because they are dipolar and are hydrogen bond bases and the partition coefficient, P, is given by P = (Qo/Vo)/
so they are useful in the determination of the S and A (Qw/Vw) = (Ao/Vo)/(Aw/Vw). The partition coefficients in each
descriptors: note that the solvent hydrogen bond basicity is water-to-solvent system are given in Table 9; this includes a
complementary to the solute hydrogen bond acidity. However, value for the water-to-octanol partition coefficient from the
the values of the a-coefficients for the GLC phases are never MedChem data base.26 From the replicate measurements we
more than 2.0, whereas a number of other processes, including
partitions from water to non-polar solvents, have a-coeffi-
cients numerically almost twice as large. It is therefore an Table 9 Partition coefficients for cyclohexanone oxime and acetone
oxime between water and various solvents
advantage to include water-to-solvent partitions in the set of
equations when calculating S and A. Of course, since there are Solvent log P log P taken
no commercially available GLC stationary phases with any Cyclohexanone oxime
significant hydrogen bond acidity (the b-coefficients are zero), Octanol 0.988 0.988
it is then absolutely essential to include other processes such as Toluene 0.260 0.260
water to solvent partitions in order to obtain the B descriptor. Chloroform 0.805, 0.818, 0.839 0.821
For a few other oximes, water-to-octanol partition coeffi- Hexane 0.570, 0.596, 0.630 0.599
cients26 and retention data by Zenkevich21 are available, and Acetone oxime
we give in Table 8 approximate values for descriptors, with A
Octanol 0.1226
fixed at 0.35 for the acyclic oximes, and at 0.33 for Toluene 0.980, 0.982 0.981
cyclopentanone oxime. Chloroform 0.297 0.297
Reversed phase HPLC systems have been used instead of Hexane 1.784, 1.669, 1.751 1.725
1.738, 1.682
water-to-solvent systems in the calculation of descriptors,27

estimate that the standard deviation is about 0.03–0.04 log References
units. In the GC experiments, a flame ionisation detector was
1 M. H. Abraham, Chem. Soc. Rev., 1993, 22, 73–83.
used; we encountered no particular problems in the analysis of 2 M. H. Abraham, A. Ibrahim and A. M. Zissimos, J. Chromatogr.,
the aqueous solutions. A, 2004, 1037, 29–47.
3 M. H. Abraham, R. J. Abraham, J. Byrne and L. Griffiths, J. Org.
GLC retention data Chem., 2006, 71, 3389–3394.
4 M. H. Abraham, P. L. Grellier, D. V. Prior, P. P. Duce,
At UCL, four GLC stationary phases were each calibrated J. J. Morris and P. J. Taylor, J. Chem. Soc., Perkin Trans. 2,
using 45–65 solutes of known descriptors: CW-20M at 101 1C, 1989, 699–711.
DEGS at 87 1C, HP-Innowax at 100 1C and OV-275 at 89 1C. 5 T. Ossart, H. Sauvaitre and P. Pineau, J. Chim. Phys., 1967, 64,
953–956.
The obtained coefficients are in Table 4, together with coeffi- 6 H. Feuer, D. Pelle, D. M. Braunstein and C. N. R. Rao, Spectro-
cients for all the other equations used. Cyclohexanone oxime chim. Acta, Part A, 1969, 25, 1393–1398.
or acetone oxime were then injected onto a given phase 7 M. H. Abraham, P. L. Grellier, D. V. Prior, R. W. Taft, J. J. Morris,
P. J. Taylor, C. Laurence, M. Berthelot, R. Doherty, M. J. Kamlet,
together with standard compounds as references, and reten-
J.-L. M. Abboud, K. Sraidi and G. Guiheneuf, J. Am. Chem. Soc.,
tion data obtained under the same conditions as the calibra- 1988, 110, 8534–8536.
tion. The coefficients in Table 4 refer to log tr 0 , where tr 0 is the 8 J. Graton, M. Berthelot and C. Laurence, J. Chem. Soc., Perkin
retention time relative to the standard. The internal standards Trans. 2, 2001, 2130–2135.
9 B. Illien, M. Berthelot, D. G. Morris and C. Laurence, J. Phys.
were heptanol for CW-20M, DEGS, and HP-Innowax and Org. Chem., 2000, 13, 293–299.
hexanol for OV-275. A number of secondary standards were 10 M. Berthelot, F. Besseau and C. Laurence, Eur. J. Org. Chem.,
also used. At Wayne State, retention factors at 20 1C intervals 1998, 925–931.
11 M. H. Abraham, P. L. Grellier, D. V. Prior, J. J. Morris and
over the temperature range 60–140 or 180–240 1C were
P. J. Taylor, J. Chem. Soc., Perkin Trans. 2, 1990, 521–529.
obtained with an Agilent Technologies HP-6890 gas chromato- 12 M. H. Abraham and J. C. McGowan, Chromatographia, 1987, 23,
graph (Palo Alto, CA, USA) fitted with a split/splitless injector 243–246.
and flame ionization detector. Nitrogen was used as carrier gas 13 M. H. Abraham and A. J. M. Al-Hussaini, J. Environ. Monit.,
2001, 3, 377–381.
at a constant linear velocity of 40 cm s1 and methane 14 M. H. Abraham and A. J. M. Al-Hussaini, J. Environ. Monit.,
was used to determine the column hold-up time. Measure- 2002, 4, 743–746.
ments were made for seven different stationary phases on 15 M. H. Abraham, J. Environ. Monit., 2003, 5, 747–752.
30 m 0.25 mm I.D. open-tubular columns with a film thick- 16 M. H. Abraham and A. J. M. Al-Hussaini, J. Environ. Monit.,
2005, 7, 295–301.
ness of 0.25 mm for 60–140 1C and 1.00 mm for 180–240 1C. 17 The Absolv data base, PharmaAlgorithms Inc., 591 Indian Road,
The system constants at each temperature were determined by Toronto, ON, M6P 2C4, Canada.
calibration using 60–100 varied compounds exactly as before30 18 Advanced Chemistry Development, Inc., 90 Adelaide Street West,
Toronto, Canada.
and are summarized with the retention factors for cyclo-
19 A. I. Vogel, W. T. Cresswell, G. H. Jeffery and J. Leicester,
hexanone oxime in Table 4; k in log k is the gas to stationary J. Chem. Soc., 1952, 514–549.
phase partition coefficient. 20 M. H. Abraham and W. E. Acree, Jr, J. Phys. Org. Chem., 2008,
21, 823–832.
NMR experiments 21 I. G. Zenkevich, Zh. Anal. Khim. (USSR), 1998, 53, 932–945;
I. G. Zenkevich, J. Anal. Chem. USSR, 1998, 53, 816–828 (English
These were conducted exactly as described before.3 All the translation).
compounds and solvents were obtained commercially. The 22 Compilation of Gas Chromatographic Data ASTM Data Series No
DS 25A, eds. O. E. Schupp III and J. S. Lewis, ASTM, 1916 Race
CDCl3 and DMSO solvents were commercial samples (Sigma-
Street, Philadelphia, PA 19013, 1967.
Aldrich). The CDCl3 was bought in 1 ml ampoules and used 23 A. P. Kurtz and T. D. J. D’Silva, J. Pharm. Sci., 1987, 76, 599–610.
directly in the experiments. Solutions of B10 mg mL1 24 C. J. Puchert and J. Behnke, Aldrich Library of 13C and 1H FT
concentration were run with TMS as internal standard in NMR Spectra, Aldrich Chemical Co., Milwaukee, WI, 1993.
25 H. E. Gottleb, V. Kotlyar and A. Nudelman, J. Org. Chem., 1997,
DMSO solvent. The 1H spectra were obtained on a Bruker 62, 7512–7515.
Avance 400 MHz NMR spectrometer operating at 400.13 MHz. 26 A. J. Leo, The MedChem data base 2007, BioByte Corp. and
Typical running conditions were 128 transients, spectral width Pomona College, Daylight Chemical Information Systems, 27401
Los Altos, #360 Mission Viejo, CA 92691, USA.
3300 Hz and 32 K data points, giving an acquisition time of
27 A. Zissimos, M. H. Abraham, C. M. Du, K. Valko, C. Bevan,
5 s. The FIDs were zero-filled to 64 K. The spectra were first D. Reynolds, J. Wood and K. Y. Tam, J. Chem. Soc., Perkin
order, and the assignments were straightforward. Trans. 2, 2002, 2001–2010.
28 C. M. Du, K. Valko, C. Bevan, D. Reynolds and M. H. Abraham,
J. Chromatogr. Sci., 2000, 38, 503–511.
Acknowledgements 29 K. Valko, S. Espinosa, C. M. Du, E. Bosch, M. Roses, C. Bevan
and M. H. Abraham, J. Chromatogr., A, 2001, 933, 73–81.
This work was supported in part by Philip Morris USA, Inc., 30 C. F. Poole and S. K. Poole, J. Chromatogr., A, 2008, 1184,
and Philip Morris International. 254–280.
This journal is
Electrochemical methodology for determination of imidazolium ionic

liquids (solids at room temperature) properties: influence of the
temperaturew
M. P. Stracke,a M. V. Migliorini,a E. Lissner,a H. S. Schrekker,a D. Back,b
E. S. Lang,b J. Dupont*a and R. S. Gonçalves*a
Received (in Gainesville, FL, USA) 17th July 2008, Accepted 29th August 2008
DOI: 10.1039/b812258j
A set of six imidazolium ionic liquids (1a–b, 2a–c, 3), that were solids at room temperature, were
characterized by electrical impedance spectroscopy to obtain information about their polarization
resistance (Rp), conductivity (s) and charge transfer activation energy (Ea). These experiments
were performed at different temperatures in a glass micro-cell, equipped with three platinum
electrodes. The observed conductivities were due to charge transfer processes of molecular oxygen
at the electrode surface and mass transfer processes within the IL matrix. Higher temperatures
resulted for all ionic liquids in increased conductivities. X-Ray diffraction of the ionic liquids 2a–c
suggested that a higher degree of supramolecular two-dimensional organization, higher density, is
related to an easier oxygen-electrode approximation, lower Ea. Two distinct temperatures ranges
were observed. The larger conductivity increases in the higher temperature range were explained
by melting (ILs 1–2) and fluxional behavior/reorientation phenomena of the ionic liquids and are
due to enhanced oxygen diffusion (IL 3). In general, the understanding of imidazolium ionic
liquid electrochemical properties could facilitate the development of new applications.
1. Introduction RTILs are numerous and found in the fields of, for instance,
extraction and separation processes,4,12,13 synthetic chemistry,4,6
The discovery of air- and water-stable imidazolium room- catalysis (organometallic,5,6,14,15 transition-metal nanoparticle,14–19
temperature ionic liquids (RTILs) by the suitable choice of the bio20), and materials science.4,21
anion initiated intensive research efforts towards their appli- Another important imidazolium RTIL research area is in
cation.1 Further attractive physical and chemical properties of the field of electrochemistry, which is due to their chemical and
the imidazolium RTILs include,2–6 a negligible vapor pressure; electrochemical stability, wide electrochemical windows, and
low inflammability; thermal stability; liquidity over a wide high electrical conductivities and ionic mobilities.3–6,22–24
temperature range; easy recycling; and being a good solvent Electrochemical applications of imidazolium RTILs as
for a wide variety of organic and inorganic chemical com- electrolytes are found in, e.g., fuel cells,25 electrodeposition,26
pounds. Besides, imidazolium RTILs are ‘‘designable’’ as capacitors,27–29 solar cells,30,31 batteries32 and water electro-
structural modifications in both the cation (especially the lysis for hydrogen generation.33 However, the use of imida-
1 and 3 positions of the imidazolium ring) and anion permit zolium RTILs could suffer from sealing problems due to
the tuning of properties such as, e.g., miscibility with water leakage issues. Possible alternatives are, e.g., imidazolium RTIL
and organic solvents,7 melting point and viscosity.3 This polymer homologues such as gel34 or solid35 polyelectrolytes,
adaptability is also responsible for the easy preparation of and imidazolium RTILs confined in silica-derived networks
task-specific imidazolium ionic liquids, ionic liquids that con- (ionogels)36 and polymers.27 Without doubt, the direct appli-
tain a specific functionality covalently incorporated in either cation of imidazolium ionic liquids (ILs), that are solids at
the cation or anion.8–11 As a result, applications of imidazolium room temperature, instead of imidazolium RTILs, would be
another attractive option. As a consequence, we were inter-
a
Laboratory of Electrochemistry, Laboratory of Molecular Catalysis ested in the electrochemical properties of imidazolium ILs
and Laboratory of Technological Processes and Catalysis, Institute (solids at room temperature). In general, understanding the
of Chemistry, Universidade Federal do Rio Grande do Sul, Av. Bento
Gonçalves 9500, P.O. Box 15003, CEP: 91501-970 Porto Alegre-RS, physicochemical properties of ILs is of great importance
Brazil. E-mail: dupont@iq.ufrgs.br; E-mail: reinaldo@iq.ufrgs.br; to provide information about their application scope.37,38
Fax: +55-51-3308-7304; Fax: +55-51-3308-7304; Herein, we report the results obtained with the imidazolium
Tel: +55-51-3308-6321; Tel: +55-51-3308-7236
b
Departamento de Quı´mica, Laboratório de Materiais Inorgânicos, ILs 1–3, presented in Fig. 1, which can be divided in two
Universidade Federal de Santa Maria, CEP: 97105-900 Santa classes: (1) hydrophilic ILs 1a–b and 3, and (2) hydrophobic
Maria-RS, Brazil ILs 2a–c. Electrical impedance spectroscopy (EIS), a non-
w Electronic supplementary information (ESI) available: Experimental destructive technique, was used to determine their temperature
section. CCDC 607218 (2a: room temperature), 607812 (2b: room
temperature) and 671958 (2c: 100 K). For ESI and crystallographic dependent polarization resistance (Rp), conductivity (s) and
data in CIF or other electronic format see DOI: 10.1039/b812258j charge transfer activation energy (Ea).

50 kHz to 5 Hz and the amplitude of the applied sine wave
voltage was 10 mV. The experimental data were corrected
by the software, taking into consideration the influence of
connecting cables and other parasite capacitances, to obtain
the polarization resistance (Rp) of the samples. The RP values
were obtained from the intercepts of the electrode impedance
arc on the real impedance axis and were used to calculate the
corresponding conductivities (s).
2.3 Differential scanning calorimetry

Fig. 1 Imidazolium ionic liquids (solid at room temperature) applied
in this work. The melting points of the ILs 1a–b and 2a–c were determined
using a TA Instruments DSC 2010 differential scanning
calorimeter, equipped with a manual cooling unit. The DSC
2. Experimental
instrument was calibrated using an indium primary standard.
2.1 Imidazolium ionic liquids An average sample weight of 7–12 mg was sealed in an
aluminium pan in a nitrogen-filled glove box. The DSC
The de-aerated imidazolium ILs 1a–b,39,40 2a–c41–44 and 345
measurements were carried out under a nitrogen atmosphere.
were prepared according to known procedures, and the NMR
The melting points (Tm, determined at the maximum of the
spectral data were in agreement with the literature data.
endothermic peaks) were determined on heating in the second
Recrystallizations were performed to obtain high purity ILs
heating run.
as white solids at room temperature.
2.4 X-Ray diffraction studies
2.2 Electrical impedance spectroscopy
Crystallographic data were collected at room temperature
The device used to perform the electrical impedance measure-
and/or 100 1C on a Bruker Kappa Apex II CCD diffracto-
ments of the room-temperature ionic solids consisted of a
meter using Mo-Ka radiation (l = 0,71073 Å). The experi-
home-made glass micro-cell (Fig. 2) with a free area of
mental set-up did not allow full rotations. Hence, the data sets
0.65 cm2, equipped with three platinum wire electrodes. This
are of lower coverage. Crystal structures were refined with full-
micro-cell was inserted in a three-way round-bottom flask
matrix least squares on F2 using all data (SHELXTL crystal
allowing the control of the gas atmosphere and humidity.
structure solution software). Non-hydrogen atoms were
The working electrode was located at the center of the micro-
refined anisotropically. Hydrogen atoms were fixed on geo-
cell, the counter electrode was placed at the full length of the
metrically ideal positions during the refinement. The free
inner wall, and the reference electrode was located in between
refinement of hydrogen atom parameters gave low data/
the working and counter electrodes. A computer-controlled
parameter ratios and led to high correlations. Relevant crystallo-
potentiostat Autolab PGSTAT 30 was connected to the ionic
graphic data, and collection and refinement details, are
solid in the glass-cell by the corresponding electrodes, and the
compiled in Table S5 of ESI.w The structures presented in
temperature were kept under control. The electrical impedance
Fig. 6 were obtained from the original X-ray data using the
spectra were measured over the frequency sweep range from
DIAMOND software (version 2.1c, Crystal Impact GbR,
http://www.crystalimpact.com/diamond/).
3. Results and discussion

3.1 Impedance spectrum analysis
A home-made glass micro-cell (Fig. 2), equipped with three
platinum wire electrodes, was used for the electrical impedance
spectroscopy measurements of the imidazolium ILs 1–3
(Fig. 1). Furthermore, the partial oxygen pressure of the gas
atmosphere was kept constant. The Nyquist plots of IL
[PhC3MIm][NTf2] 2b at different temperatures are presented
in Fig. 3(a). As for most of the ILs 1–3, electrical impedance
spectroscopy measurements with 2b afforded partial semi-
circles. An equivalent circuit is proposed taking into account
that there exists a semicircle corresponding to one time constant
that represents an electrochemical circuit with two resistances
and one parallel combination of phase constant (CPE, Fig. S1,
ESIw). In contrast, complete semicircles were observed with IL
[C2O2MIm][Cl] 3 at higher temperatures (Fig. 3(b)). Perfor-
Fig. 2 Illustration of the home-made glass micro-cell: (a) top view; mance of these electrical impedance spectroscopy measure-
(b) section. ments under vacuum resulted in confuse and irreproducible
This journal is
Fig. 4 Conductivities of (a) IL [PhC3MIm][NTf2] 2b and (b) IL
[C2O2MIm][Cl] 3 at different temperatures.
Fig. 3 (a) Nyquist diagram of [PhC3MIm][NTf2] 2b at 19 1C (’),
26 1C (K), 42 1C (m) and 60 1C (window); (b) Nyquist diagram of
[C2O2MIm][Cl] 3 at 5 1C (’), 17 1C (K), 31 1C (m), 34 1C (E) and
42 1C (.). conductivity (s) of oxygen within the ILs, where l (0.1 cm)
and A (3.14 10 2 cm2) represent the length and active
surface area of the working platinum electrode, respectively.
Nyquist plots. This strongly suggested that a charge transfer These conductivities were due to charge transfer processes and
process of molecular oxygen at the platinum electrode surface transport phenomena of molecular oxygen and were not
was responsible for the observed phenomena, which is repre- related to the ionic conductivities of the bulk ILs. This strategy
sented by the equilibrium reaction of Scheme 1. was applied to determine the activation energies of the oxygen
This was further supported by the Nyquist plots obtained
when the experiments were performed under a pure argon
atmosphere and a pure oxygen atmosphere (Fig. S2, ESIw).
The charge transfer process was not observed under an argon
atmosphere. However, this process did take place in the
presence of a pure molecular oxygen atmosphere.
The polarization resistance (RP) values were determined by
fitting the obtained impedance semicircles. The Rp values
represent the polarization resistances related to the charge
transfer process of oxygen on the platinum electrode surface,
since the platinum electrode is inactive under the applied
conditions. For all ILs 1–3, RP decreased with increasing
temperatures. Eqn (1) was used to convert RP into the
Scheme 1 Charge transfer processes of molecular oxygen at the

platinum electrode surface. Fig. 5 Arrhenius conductivity plot of IL [PhC3MIm][NTf2] 2b.

Table 1 Activation energy, conductivity intersection and melting and their structures at room temperatures are presented in
point of the ILs 1–3 Fig. 6. The electrostatic interactions of IL 2a generate a
Entry IL Eaa/kJ mol 1
Eaa/eV Tisb/1C Tmc/1C tri-dimensional structural organization (Fig. 6(a)). In contrast,
the existing interactions in the ILs 2b and 2c are of
1 [C4MIm][Mes] 1a 78.1 0.81 63 77 two-dimensional nature, generating structures in the form of
2 [C10MIm][Mes] 1b 79.0 0.82 31 57
3 [Ph2C2MIm][NTf2] 2a 73.7 0.76 40 62 layers as can be verified in Fig. 6(b) and (c). This structural
4 [PhC3MIm][NTf2] 2b 51.6 0.53 42 50 organization at room temperature is reflected by the
5 [PhC2MIm][NTf2] 2c 56.6 0.58 28 41 density of these ILs at room temperature, which decreases
6 [C2O2MIm][Cl] 3 110 1.14 42 197 (204)d
in the order: [PhC3MIm][NTf2] 2b (d = 1.553 g cm 3) 4
a
Activation energy calculated from the Arrhenius formula. b Tem- [PhC2MIm][NTf2] 2c (d = 1.539 g cm 3) 4 [Ph2C2MIm]-
perature at the intersection of the low- and high-temperature range of [NTf2] 2a (d = 1.47 g cm 3). This suggests that a higher degree
the temperature dependent conductivity. c Melting point determined
by differential scanning calorimetry on heating. d Ref. 42.
of two-dimensional organization as in IL 2b results in a more
dense packing. However, the observed activation energies
decrease in exactly the opposite order: [Ph2C2MIm][NTf2]
redox processes on the platinum electrode surface as 2a 4 [PhC2MIm][NTf2] 2c 4 [PhC3MIm][NTf2] 2b. As a
described below. consequence, it is possible to infer that the diffusion of
molecular oxygen is faster in two-dimensional organized ILs.
s = l/RPA (1) Importantly, it is not possible to verify the formation of
structures in the form of channels or tunnels.
Fig. 4(a) and (b) show the conductivities of the ILs
[PhC3MIm][NTf2] 2b and [C2O2MIm][Cl] 3 at different 3.3 Differential scanning calorimetry
temperatures. The same conductivity–temperature correlation
was observed for all ILs 1–3. Higher temperatures resulted in The melting points of the ionic liquids 1–3 were determined by
higher conductivities. As such, the transport of the species differential scanning calorimetry (DSC) to check if there exists
involved in the charge transfer reaction is temperature depen- a correlation with their temperature dependent conductivities
dent. Furthermore, the conductivity was characterized by two (Table 1). Most of these ionic liquids have melting points that
distinct temperature dependences: (1) small conductivity in- are close to their intersection temperatures as determined from
creases in the lower temperature range; and (2) large conducti- the conductivity plots (e.g. Fig. 4). This indicates that the
vity increases in the higher temperature range. In case of the ILs change from the slowly to the faster changing conductivity is
2b and 3, these dependences showed their intersection at 42 and most likely due to the changeover from the solid to the liquid
35 1C, respectively, which indicates that the transport processes state. In strong contrast, IL [C2O2MIm][Cl] 3 showed an
are differently affected below and above this temperature. intersection temperature (42 1C, Fig. 4(b)) far below
It was found that the experimental conductivity data of the its melting point (197 1C). As a consequence, IL 3 was not
lower temperature range fitted the conventional Arrhenius melted at the beginning of the second temperature range. This
eqn (2), where Ea is the activation energy for the charge behavior allows us to infer that the faster increasing conduc-
transfer process. Fig. 5 shows the Arrhenius conductivity plot tivity in the second temperature range of IL 3 should be
of IL 2b and the activation energies calculated from the associated with the oxygen diffusion inside the crystal arrays.
Arrhenius formula are presented in Table 1. The hydrophilic A possible explanation could be an increase in fluxional
ILs showed the higher charge transfer activation energies, behavior/reorientation phenomena in the solid state, which
which decreased in the order: [C2O2MIm][Cl] 3 4 enhances the molecular oxygen diffusion.50,51 This was further
[C10MIm][Mes] 1b 4 [C4MIm][Mes] 1a 4 [Ph2C2MIm][NTf2] supported by the low degree of organization of IL 2c observed
2a 4 [PhC2MIm][NTf2] 2c 4 [PhC3MIm][NTf2] 2b. Now, it is at 25 1C by X-ray diffraction, and high quality data were only
important to remember that these activation energies were obtained at 100 K due to a more defined organization.
measured in the presence of atmospheric oxygen. The values of
51.6 kJ mol 1 (0.53 eV) to 110 kJ mol 1 (1.14 eV) are very 4. Conclusions
close to those observed for charge transfer processes of oxygen
In conclusion, electrical impedance spectroscopy is a suitable
at polycrystalline oxide surfaces,46 LSCF-SDC composite47
analytical tool for the determination of important imida-
and multi-metallic electrodes.48 Apparently, the determined IL
zolium IL properties, including polarization resistance (Rp),
charge transfer processes are due to electrochemical reactions
conductivity (s) and activation energy (Ea) for a charge
of molecular oxygen at the electrode surface.49
transfer reaction involving molecular oxygen. Increased tem-
ln s = ln s0 (Ea/RT) (2) peratures result in higher conductivities, showing two distinct
temperature ranges. The detected conductivities were due to
charge transfer processes of molecular oxygen at the platinum
3.2 X-Ray diffraction studies
electrode surface and mass transfer processes of oxygen inside
The charge transfer processes involving molecular oxygen the IL matrix. Comparison of the oxygen charge transfer
should be the same for all ILs 1–3. As a consequence, it is process activation energies with the X-ray diffraction data of
reasonable to infer that the IL crystalline structure influences 2a–c suggests that the oxygen mobility in the ionic liquids
the transport of molecular oxygen inside the crystal. The (solids at room temperature) is affected by their nature
crystal data concerning the ILs 2a–c are listed in Table S5 (ESIw) of structural supramolecular organization: tri-dimensional
This journal is
Fig. 6 X-Ray diffraction crystal structures of (a) [Ph2C2MIm][NTf2] 2a (room temperature); (b) [PhC3MIm][NTf2] 2b (room temperature) and
(c) [PhC2MIm][NTf2] 2c (100 K).
vs. two-dimensional. Furthermore, the changeover from the liquid (solid at room temperature) applications and the sub-
solid to the liquid state and fluxional behavior/reorientation stitution of ionic liquids where beneficial.
phenomena in the solid state are most likely the responsible
factors for the faster increasing conductivity in the second
Acknowledgements
temperature range. As such, electrical impedance spectroscopy
could accelerate the discovery of new electrochemical ionic The authors thank the CNPq for financial support.

References 27 A. Lewandowski and A. Świderska, Appl. Phys. A, 2006, 82,
579–584.
1 P. A. Z. Suarez, J. E. L. Dullius, S. Einloft, R. F. de Souza and 28 Q. Zhu, Y. Song, X. Zhu and X. Wang, J. Electroanal. Chem.,
J. Dupont, Polyhedron, 1996, 15, 1217–1219. 2007, 601, 229–236.
2 F. Endres, D. MacFarlane and A. Abbott, Electrodeposition from 29 A. B. McEwen, H. L. Ngo, K. LeCompte and J. L. Goldman,
Ionic Liquids, Wiley-VCH, Weinheim, Germany, 1st edn, 2008. J. Electrochem. Soc., 1999, 146, 1687–1695.
3 P. Wasserscheid and T. Welton, Ionic Liquids in Synthesis, Wiley- 30 E. Stathatos, P. Lianos, V. Jovanovski and B. Orel, J. Photochem.
VCH, Weinheim, Germany, 1st edn, 2002, ch. 3–4, pp. 127–171. Photobiol., A, 2005, 169, 57–61.
4 J. Dupont, C. S. Consorti and J. Spencer, J. Braz. Chem. Soc., 31 N. Papageorgiou, Y. Athanassov, M. Armand, P. Bonhôte,
2000, 11, 337–344. H. Pettersson, A. Azam and M. Grätzel, J. Electrochem. Soc.,
5 J. Dupont, R. F. de Souza and P. A. Z. Suarez, Chem. Rev., 2002, 1996, 143, 3099–3108.
102, 3667–3692. 32 E. Markevich, V. Baranchugov and D. Aurbach, Electrochem.
6 T. Welton, Chem. Rev., 1999, 99, 2071–2084. Commun., 2006, 8, 1331–1334.
7 H. S. Schrekker, M. P. Stracke, C. M. L. Schrekker and J. Dupont, 33 R. F. de Souza, J. C. Padilha, R. S. Gonçalves, M. O. de Souza and
Ind. Eng. Chem. Res., 2007, 46, 7389–7392. J. Rault-Berthelot, J. Power Sources, 2007, 164, 792–798.
8 S. G. Lee, Chem. Commun., 2006, 10, 1049–1063. 34 F. Yang, L. Jiao, Y. Shen, X. Xu, Y. Zhang and L. Niu,
9 J. H. Davis, Chem. Lett., 2004, 33, 1072–1077. J. Electroanal. Chem., 2007, 608, 78–83.
10 Z. F. Fei, T. J. Geldbach, D. B. Zhao and P. J. Dyson, Chem.–Eur. 35 N. Matsumi, K. Sugai, M. Miyake and H. Ohno, Macromolecules,
J., 2006, 12, 2122–2130. 2006, 39, 6924–6927.
11 H. S. Schrekker, M. A. Gelesky, M. P. Stracke, C. M. L. 36 M.-A. Néouze, J. L. Bideau, P. Gaveau, S. Bellayer and A. Vioux,
Schrekker, G. Machado, S. R. Teixeira, J. C. Rubim and Chem. Mater., 2006, 18, 3931–3936.
J. Dupont, J. Colloid Interface Sci., 2007, 316, 189–195. 37 F. Endres and S. Z. E. Abedin, Phys. Chem. Chem. Phys., 2006, 8,
12 J. G. Huddleston, H. D. Willauer, R. P. Swatloski, A. E. Visser 2101–2116.
and R. D. Rogers, Chem. Commun., 1998, 1765–1766. 38 J. Dupont and P. A. Z. Suarez, Phys. Chem. Chem. Phys., 2006, 8,
13 M. H. Abraham, A. M. Zissimos, J. G. Huddleston, H. D. Willauer, 2441–2452.
R. D. Rogers and W. E. Acree, Jr, Ind. Eng. Chem. Res., 2003, 42, 39 C. C. Cassol, G. Ebeling, B. Ferrera and J. Dupont, Adv. Synth.
413–418. Catal., 2006, 348, 243–248.
14 T. Welton, Coord. Chem. Rev., 2004, 248, 2459–2477. 40 H. S. Schrekker, D. O. Silva, M. A. Gelesky, M. P. Stracke,
15 V. I. Pârvulescu and C. Hardacre, Chem. Rev., 2007, 107, C. M. L. Schrekker, R. S. Gonçalves and J. Dupont, J. Braz.
2615–2665. Chem. Soc., 2008, 9, 426–433.
16 D. Astruc, F. Lu and J. R. Aranzaes, Angew. Chem., Int. Ed., 2005, 41 M. P. Stracke, G. Ebeling, R. Cataluña and J. Dupont, Energy
44, 7852–7872; D. Astruc, F. Lu and J. R. Aranzaes, Angew. Fuels, 2007, 21, 1695–1698.
Chem., 2005, 117, 8062–8083. 42 S. V. Dzyuba and R. A. Bartsch, ChemPhysChem, 2002, 3,
17 P. Migowski and J. Dupont, Chem.–Eur. J., 2007, 13, 32–39. 161–166.
18 A. Roucoux, J. Schulz and H. Patin, Chem. Rev., 2002, 102, 3757–3778. 43 J. K. Lee and M. J. Kim, J. Org. Chem., 2002, 67, 6845–6847.
19 L. S. Ott and R. G. Finke, Coord. Chem. Rev., 2007, 251, 1075–1100. 44 M. E. Moret, A. B. Chaplin, A. K. Lawrence, R. Scopelliti and
20 Z. Yang and W. Pan, Enzyme Microb. Technol., 2005, 37, 19–28. P. J. Dyson, Organometallics, 2005, 24, 4039–4048.
21 M. A. Klingshirn, S. K. Spear, J. D. Holbrey and R. D. Rogers, 45 Z. Fei, D. Zhao, T. J. Geldbach, R. Scopelitti and P. J. Dyson,
J. Mater. Chem., 2005, 15, 5174–5180. Chem.–Eur. J., 2004, 10, 4886–4893.
22 P. A. Z. Suarez, V. M. Selbach, J. E. L. Dullius, S. Einloft, 46 H. Liu, C. Mojica-Calderon, S. B. Lyon and M. M. Stack, Solid
C. M. S. Piatnicki, D. S. Azambuja, R. F. de Souza and State Ionics, 1999, 126, 363–372.
J. Dupont, Electrochim. Acta, 1997, 42, 2533–2535. 47 C. Fu, K. Sun, N. Zhang, X. Chen and D. Zhou, Electrochim.
23 R. K. Donato, M. V. Migliorini, M. A. Benvegnú, J. Dupont, Acta, 2007, 52, 4589–4594.
R. S. Gonçalves and H. S. Schrekker, J. Solid State Electrochem., 48 P. S. Zhang, W. Zhang, F. Gerlach, K. Alborn and U. Guth, Sens.
2007, 11, 1481–1487. Actuators B: Chem., 2005, 108, 797–802.
24 M. V. Migliorini, R. K. Donato, M. A. Benvegnú, J. Dupont, 49 A. Hetznecker, H. Kohler and U. Guth, Sens. Actuators B: Chem.,
R. S. Gonçalves and H. S. Schrekker, Catal. Commun., 2008, 9, 2007, 120, 378–385.
971–975. 50 K. Pogorzelec-Glaser, J. Garbarczyk, C. Z. Pawlacczyk and
25 R. F. de Souza, J. C. Padilha, R. S. Gonçalves and J. Dupont, E. Markiewicz, Mater. Sci. Pol., 2006, 24, 245–252.
Electrochem. Commun., 2003, 5, 728–731. 51 G. R. Goward, K. Saalwächter, I. Fischbach and H. W. Spiess,
26 S. Z. E. Abedin and F. Endres, Chem. Phys. Chem., 2006, 7, 58–61. Solid State Nucl. Magn. Reson., 2003, 24, 150–162.
This journal is
A new family of biocompatible and stable magnetic nanoparticles:

silica cross-linked pluronic F127 micelles loaded with iron oxides
Zhaoyang Liu,* Jun Ding and Junmin Xue*
Received (in Montpellier, France) 18th June 2008, Accepted 4th September 2008
DOI: 10.1039/b810302j
A new family of magnetic nanoparticles, silica cross-linked pluronic F127 micelles loaded with
iron oxides having the properties of high biocompatibility, physical and chemical stability, high
magnetism, and low-cost production, have been synthesized.
1. Introduction steps (multi-pot).18 Therefore, a simple and one-pot method is

in demand.
Iron oxide (IO) nanoparticles are emerging as promising In this work, we have developed a simple and one-pot
candidates for various biomedical applications, such as mag- method to fabricate a new family of biocompatible and stable
netic resonance imaging (MRI),1 targeted drug delivery,2 magnetic nanoparticles that are coated with a hybrid layer of
hyperthermia treatment,3 the labelling and sorting of cells,4 silica cross-linked pluronic F127 (SCL-P@IO). Pluronic F127
and the separation of biochemical products,5 due to their (PF127) is an ABA-type triblock copolymer consisting of
superparamagnetic properties. Most of these applications hydrophobic poly(propylene oxide) (PPO) and hydrophilic
require the nanoparticles to be biocompatible, water soluble, PEO. The PEO blocks present a high biocompatiblity by
and physically and chemically stable in a physiological environ- effectively preventing aggregation, the adsorption of proteins,
ment.6 To date, the most promising synthetic strategy for the adhesion to tissues, and recognition by the reticulo-
iron oxide nanoparticles is based on the high temperature endothelial system in vivo.20 Silica has been extensively studied
decomposition of iron salts in the presence of organic solvents, as an inorganic coating for a long period of time due to its rich
which can produce monodisperse and highly crystalline IO surface chemistry, which means it is able to conjugate biofunc-
nanoparticles.7 However, their uses in biomedicine are quite tional moieties easily. Compared to polymer coatings, silica
limited because the particles synthesized through this route coatings are more chemically stable and resistant to diffusion
can only be dispersed in hydrophobic solvents. Before bio- for encapsulated components. PF127 copolymer and silica
medical applications are possible, they have to be transferred have also been selected as suitable surface coating candidates
into an aqueous medium. Moreover, the reactivity of iron oxide because they are highly safe in vivo and have been approved by
particles have been shown to greatly increase as their dimen- the Food and Drug Administration.20,21
sions are reduced to the nano scale. Therefore, it is necessary A double-layer coating of PEO and silica on the surface of
to engineer the surface of IO nanoparticles to improve IO nanoparticles is proposed, as shown in Fig. 1a. Like
their biocompatibility, solubility and stability in physiological conventional mesoporous silica synthesis using PF127 surfac-
environments for various biomedical applications.8 tants,22 the silica was controlled so as to be deposited on the
Several natural and synthetic polymers have been employed interior PEO blocks of the PF127 micelle, leaving the exterior
to coat the surface of IO nanoparticles to transfer their surface PEO blocks stretched out in aqueous media. Therefore, a
wettability. These polymers include dextran,9 lipids,10 dendri- double-layer structure of PEO and silica on the surfaces of
mers,11 polyethylene glycol (PEG)12 or polyethylene oxide the IO nanoparticles was formed (Fig. 1a). The advantages of
(PEO),13 and polyvinylpyrrolidone (PVP).14 All the polymers the resulting magnetic nanoparticles are follows: (1) high
used are known to be biocompatible and able to promote the biocompatibility and stability due to the presence of PEO
dispersion of IO nanoparticles in an aqueous medium. How- blocks on the surface of the nanoparticles, (2) high chemical
ever, these polymer coatings are not robust and can be and physical stability due to the robust and dense silica cross-
detached from particle surfaces easily under in vivo condi- linked micelles, and (3) simple and low-cost synthesis, since
tions.10,12 To improve the stability of the polymer coatings silica cross-linking is much easier in comparison with tradi-
in vivo, a cross-linking technique has been developed.15 For tional polymer cross-linking, and since both PF127 and the
example, the stability of dextran coatings on IO nanoparticles silica precursor are commercially available. Therefore, the
can be improved when the dextran polymer chains are chemi- present magnetic nanoparticles possess great potential in a
cally cross-linked. Although cross-linking is considered a variety of biomedical applications.
promising method for strengthening the polymer coatings of
IO nanoparticles,16–19 this method requires multiple synthetic
2. Experimental
Department of Materials Science and Engineering, National 2.1 Materials
University of Singapore, Singapore, 117576, Republic of Singapore.
E-mail: mselz@nus.edu.sg. E-mail: msexuejm@nus.edu.sg; Dioctyl ether, oleic acid, iron(III) chloride, tetraethoxysilane
Fax: +65 67763604; Tel: +65 65164655 (TEOS), diethoxydimethylsilane (Me2Si(OEt)2, DEDMS) and

2.3 Synthesis of SCL-P@IO nanoparticles
A hexane solution (0.2 mL) of IO nanoparticles was added to
an aqueous solution (8 mL) of PF127 (1.3 g). After 3 h of
stirring at room temperature, the mixture was dried under
nitrogen gas. The obtained powder could be readily redis-
persed in de-ionized water (8 mL) with shaking. Then, a 0.3 M
HCl solution (0.4 g) and TEOS (0.2 g) were added to the
mixture with stirring. After stirring at room temperature for
48 h, DEDMS (0.1 g) was added. Stirring was continued for
another 3 h.
2.4 Cell culture

The cell viability of the nanoparticles was carried out by
testing the viability of 3T3 fibroblasts after incubation with
DMEM, supplemented with 10% FBS, 1 mM L-glutamine and
100 IU mL 1 penicillin via an 3-(4,5-dimethylthiazol-2-yl)-2,5-
diphenyl tetrazolium bromide (MTT) assay. Mouse macro-
phage cells (RAW 264.7) were used to assess the cellular
uptake of the nanoparticles. The RAW 264.7 cells were
cultured in RPMI-1640 medium, supplemented with 10%
FBS, 2 mM L-glutamine, 100 IU mL 1 penicillin and
100 mg mL 1 streptomycin. The cell concentrations were
determined by hemacytometry, and the Fe concentrations
Fig. 1 a: Synthetic scheme for silica cross-linked pluronic F127 were determined by Thermal Jarrell Ash Duo Iris inductively-
micelles loaded with IO nanoparticles (SCL-P@IO). Left: an as- coupled plasma optical emission spectrometer (ICP-OES).
synthesized hydrophobic IO nanoparticle. Right: an IO nanoparticle
with its surface covered by a double-layer of PEO and silica. b: A TEM 2.5 Characterization
of as-synthesized hydrophobic IO nanoparticles. The inset photo
shows that the IO nanoparticles can only be dispersed in hexane. c: TEM measurements were taken using a JEOL JEM 3010
A TEM of SCL-P@IO nanoparticles. The right bottom inset is a instrument. The hydrodynamic diameters of the nanoparticles
higher magnification TEM of typical SCL-P@IO nanoparticles. The were measured by a Malvern Zeta Sizer Nano S-90 dynamic
inset photo shows that the SCL-P@IO nanoparticles can be readily light scattering (DLS) instrument. TGA analyses were per-
dispersed in water. d: Size distribution histogram of the nanoparticles formed by a TA Instruments Q500 thermogravimetric analyzer.
in c. e: XRD patterns of IO and SCL-P@IO nanoparticles. f: 29Si IR studies were run on an ATI Mattson Infinity Series
NMR spectra corresponding to samples (a) with and (b) without the FT-IR spectrophotometer. Magnetic properties were mea-
addition of DEDMS, respectively.
sured on a superconducting quantum interference device
(SQUID, Quantum Design, USA) and a Lakeshore 7300 series
vibrating sample magnetometer (VSM). The fluorescence
pluronic F127 (PF127) were purchased from Aldrich emission spectra of pyrene were measured by a fluorescence
Chemical Co. Fibroblasts 3T3 were purchased from ATCC. photometer (FP-777 Jasco) at 254 nm excitation. 29Si NMR
RPMI-1640 medium, Dulbecco’s modified Eagle’s medium spectra were recorded with an Advance 500 Bruker spectro-
(DMEM), fetal bovine serum (FBS), L-glutamine, penicillin meter at 99.36 MHz. The pulse length was 6 ms (theta = p/6)
and streptomycin were purchased from Sigma. All other with 6 s repetitions.
solvents and chemicals were purchased from Aldrich and used
as received.
29
2.2 Synthesis of IO nanoparticles (Fe3O4) 3.1 TEM, XRD and Si NMR
FeCl36H2O (3.3 mmol) and sodium oleate (10 mmol) were In a typical synthesis, 10.5 nm monodisperse and hydrophobic
dissolved in a mixture of ethanol (25 mL), de-ionized water Fe3O4 nanoparticles were synthesized separately (Fig. 1b).23
(20 mL) and hexane (45 mL). After refluxing for 4 h at 62 1C, The as-synthesized Fe3O4 nanoparticles were coated with a
the iron oleate complex was washed with de-ionized water layer of oleic acid, which made them only soluble in hydro-
three times. The iron oleate complex (3.3 mmol) and oleic acid phobic solvents (Fig. 1b inset photo). With the addition of
(1.67 mmol) were dissolved in dioctyl ether (20 mL) at 70 1C. PF127 surfactants, these polymeric surfactants self-assembled
After heating for 1.5 h at 290 1C, ethanol (30 mL) was added into a micellar structure, encapsulating the IO nanoparticles in
to the mixture, and the nanoparticles were collected by their cores. The hydrophobic PPO block in the middle of the
centrifugation at 6000 rpm. The nanoparticles were washed PF127 associated with the alkyl tail of the oleic acid through a
with hexane and ethanol three times. Finally, the nanoparticles hydrophobic interaction, while the two hydrophilic PEO
were dispersed in hexane (40 mL) and oleic acid (100 ml). blocks stretched out in aqueous media (Fig. 1a). Then, TEOS
This journal is
was added as a silica precursor to polymerize and cross-link be observed by TEM due to the low contrast of the PEO
the PF127 micellar shells. polymers.25 This result also confirms the double-layer struc-
Fig. 1c shows a TEM image of the SCL-P@IO nanoparti- ture of PEO and silica on the surface of SCL-P@IO nano-
cles. The formation of well-defined core/shell morphologies is particles instead of just a single layer of silica; that is, the silica
readily confirmed, since the Fe3O4 within the micelle cores is is deposited on the interior PEO chains, while the exterior
more electron-dense than the silica/PF127 hybrid shell. PEO chains are stretched out into the aqueous solution, as
A higher magnification TEM of typical SCL-P@IO nano- suggested in Fig. 1a. The surface coating of the SCL-P@IO
particles is shown in the right bottom of Fig. 1c. These nanoparticles was further studied by IR analysis. As shown
nanoparticles have a number-average diameter of around in Fig. 2b, silica formation is confirmed, since a band at
21 nm, as shown in the histogram in Fig. 1d, with an ultrathin 1080 cm 1, assigned to Si–O–Si, is observed for these
(about 5 nm) silica shell deposited outside the Fe3O4 nano- SCL-P@IO nanoparticles.26 After calcination at 700 1C, the
particles. A size distribution analysis, as shown in the characteristic band of C–H at 1726 cm 1 disappears com-
histogram in Fig. 2a, reveals that the spherical NPs are pletely, while the band assigned to thermally stable silica is still
monodisperse and have an average size of 7.9 1.5 nm. The observed.
inset photo shows that the resulting nanoparticles can be
readily dispersed in water. The XRD patterns of the IO and 3.3 Magnetism characterization
SCL-P@IO nanoparticles (Fig. 1e) can be assigned to the
The magnetic properties of the IO and SCL-P@IO nanopar-
(220), (311), (400), (422), (511) and (440) reflections of the
ticles were examined at room temperature by using a VSM. As
spinel structure of magnetite (JCPDS no. 19-0629). The broad
shown in Fig. 3a, the saturated magnetization of the IO and
band at 20–301 is due to the presence of amorphous
SCL-P@IO nanoparticles were 63.1 and 28.3 emu g 1, res-
silica, while the labelled peaks are associated with Fe3O4
pectively. The reduction in saturated magnetization for the
nanocrystals.
SCL-P@IO nanoparticles accounts for the diamagnetic
The condensation of silicate during the preparation was
properties of the silica and the PF127 shell surrounding
studied by NMR techniques. Fig. 1f (a) and (b) correspond to
the IO cores. The inset photo in Fig. 3a shows the magnetic
the sample with and without the addition of DEDMS, respec-
manipulation ability of the SCL-P@IO nanoparticles.
tively. In the 29Si NMR spectra, three peaks at ca. 94, 104
When an external magnet is placed beside the glass vial, the
and 114 ppm are assigned to Q2, Q3 and Q4 species with
aqueous dispersion of SCL-P@IO nanoparticles could be
progressively increasing cross-linking (condensation).24 After
directed towards the magnet. This efficient magnetism will
automatic calculation of the integrated area, the Q4 : Q3 ratio
allow these nanoparticles to be useful in many biomedical
decreased from 0.91 (b) to 0.83 (a), indicating a slightly lower
applications, such as targeted delivery and separation. The
condensation of silicate with the addition of DEDMS.
magnetization change of the SCL-P@IO nanoparticles with
storage time was monitored by VSM measurements. As shown
3.2 DLS and FT-IR in Fig. 3b, the saturated magnetization of the SCL-P@IO
The obtained SCL-P@IO nanoparticles were characterized by nanoparticles was almost constant (at around 28 emu g 1)
DLS. The DLS measurements of the IO and SCL-P@IO during 90 d storage, suggesting that the PF127/silica hybrid
nanoparticles are shown in Fig. 2a. The hydrodynamic coating is dense enough to be non-permeable, preventing the
diameter of the SCL-P@IO nanoparticles is 43.3 nm, which encapsulated IO cores from degrading and leading to lower
is larger than that measured by TEM in Fig. 1c. This is magnetism.
because the light scattering measurement includes the PEO
chains stretching out into the aqueous solution, which cannot 3.4 Cell viability and uptake
The biocompatibility of the SCL-P@IO nanoparticles was
examined by the cell viability of 3T3 fibroblast lines through
Fig. 2 a: Hydrodynamic sizes of IO and SCL-P@IO nanoparticles in

aqueous solution determined by DLS measurements. b: IR spectra of
PF127 triblock copolymer (top), SCL-P@IO nanoparticles (middle)
and SCL-P@IO nanoparticles after calcination at 700 1C (bottom). Fig. 3 a: Magnetization curves (M–H) of IO and SCL-P@IO nano-
The IR spectra of the SCL-P@IO nanoparticles are characteristic of particles. The inset photo shows that the SCL-P@IO nanoparticles
both the silica network (Si–O–Si stretch at 1080 cm 1) and the can be driven by an external magnet. b: The magnetization change of
copolymer (C–H stretch at 1730 cm 1). This C–H band disappears the SCL-P@IO nanoparticles with storage time, as observed by VSM
after calcination. measurements.

Fig. 5 (a) Hydrodynamic size changes of SCL-P@IO nanoparticles
with incubation time in PBS buffer solution plus 10% FBS. (b)
The fluorescence intensity ratio, Im1/Im3, of pyrene encapsulated in
Fig. 4 a: Cell viability of 3T3 fibroblast lines after 72 h incubation
SCL-P@IO nanoparticles as a function of PF127 concentration. The
with SCL-P@IO nanoparticles at different Fe concentrations. b: A
Im1/Im3 ratio for SCL-P@IO nanoparticles shows no obvious altera-
macrophage uptake assay of oleic acid-stabilized nanoparticles (Oleic
tion, meaning the silica cross-linked micellar structure is stable under
acid-IO) and SCL-P@IO nanoparticles with incubation time.
dilution.
an MTT assay. As shown in Fig. 4a, the SCL-P@IO nano- administration. Pyrene is an effective fluorescent probe to test
particles were biologically inert up to an iron concentration of micelle stability. The ratio between the first (375 nm) and third
1000 mg mL 1. This result indicates that the SCL-P@IO (386 nm) emission intensities (Im1/Im3) of the pyrene spectrum
nanoparticles are highly non-toxic and biocompatible. When depends on the environmental polarity of the solvent.27 Here,
injected into the bloodstream, nanoparticles are often con- the fluorescence spectra of pyrene molecules encapsulated in
sidered as an intruder by the innate immunity system, and can silica-cross-linked PF127 micelles were measured as a function
be readily recognized and become engulfed by the macrophage of PF127 surfactant concentration (different dilution levels) to
cells. The nanoparticles will then be removed from the blood study the micelle stability. As shown in Fig. 5b, the low and
circulation system, and lose their efficiency in diagnostics and almost constant Im1/Im3 ratio (about 1.2 : 1) meant that the
therapeutics. silica deposition effectively cross-linked the PF127 micellar
Fig. 4b shows the uptake of the oleic acid-stabilized (Oleic chains and stabilized the micelles from dissociation under
acid-IO) and PEO-stabilized (SCL-P@IO) nanoparticles dilution.
by macrophage cells with an initial Fe concentration of
0.23 mg mL 1. The Oleic acid-IOs were quickly internalized
4. Conclusions
into the cells within 24 h, with an uptake of 163 pg Fe cell 1.
The amount taken in by the cells decreased with time because In conclusion, we have fabricated a new family of magnetic
of the rapid growth and division of the macrophage cells. nanoparticles based on silica cross-linked PF127 block co-
After grafting with PEO, the SCL-P@IO nanoparticles’ polymer micelles loaded onto IO nanoparticles. The advan-
uptake by macrophage cells was much lower, at only tages of high biocompatibility, physical and chemical stability,
3 pg Fe cell 1, compared with Oleic acid-IO nanoparticles. high magnetism, and the low-cost of production of these new
The very low uptake of SCL-P@IO nanoparticles could be magnetic nanoparticles make them promising for a wide range
due to surface PEO grafting of the SCL-P@IO nanoparticles of biomedical applications, such as bioimaging, bioseparation
lowering the adsorption of the proteins and decreasing the and drug delivery.
possibility of macrophage recognition.
Acknowledgements
3.5 Stability test
This work was supported by the Singapore MOE’s ARF Tier 1
The stability of the SCL-P@IO nanoparticles under physio- funding WBS R-284-000-050-133.
logical conditions was also studied by DLS measurements.
The size change of the SCL-P@IO nanoparticles with incuba-
tion time in phosphate-buffered saline (PBS) plus 10% FBS References
were monitored. As shown in Fig. 5a, the sizes of SCL-P@IO 1 L. J. D. Thorek, A. K. Chen, J. Czupryna and A. Tsourkas, Ann.
nanoparticles were almost constant over 90 d incubation, Biomed. Eng., 2006, 34, 23.
2 C. C. Berry and A. S. G. Curtis, J. Phys. D: Appl. Phys., 2003, 36,
indicating that these nanoparticles did not aggregate and were R198.
fairly dispersed in the physiological medium. This is mainly 3 A. Ito, M. Shinkai, H. Honda and T. Kobayashi, J. Biosci. Bioeng.,
attributed to the anti-aggregation and anti-biofouling proper- 2005, 100, 1.
ties of the PEO blocks of PF127 on the surfaces of SCL-P@IO 4 Y. R. Chemla, H. L. Crossman and Y. Poon, Proc. Natl. Acad. Sci.
U. S. A., 2000, 97, 14268.
nanoparticles. The stability of micelles under dilution is also 5 S. Mornet, S. Vasseur, F. Grasset, P. Veverka, G. Goglio and
a big issue because they are highly diluted in vivo after A. Demourgues, Prog. Solid State Chem., 2006, 34, 237.
This journal is
6 L. Yu, Y. Yin, B. T. Mayers and Y. Xia, Nano Lett., 2002, 2, 183. 17 L. Josephson, C. H. Tung, A. Moore and R. Weissleder, Bio-
7 Y. Sahoo, A. Goodarzi, M. T. Swihart, T. Y. Ohulchamskyy, conjugate Chem., 1999, 10, 186.
E. P. Furlani and P. N. Prasad, J. Phys. Chem. B, 2005, 109, 3879. 18 H. Choi, S. R. Choi, R. Zhou, H. F. Kung and I. W. Chen, Acad.
8 H. Lee, E. Lee, D. K. Kim, Y. Y. Heong and S. Jon, J. Am. Chem. Radiol., 2004, 11, 996.
Soc., 2006, 128, 7383. 19 A. Tsourkas, V. R. Shinde-Patil, K. A. Kelly, P. Patel, A. Wolley,
9 L. M. Lacava, Z. G. M. Lacava, M. F. Da Silva, O. Silva, J. R. Allport and R. Weissleder, Bioconjugate Chem., 2005, 16,
S. S. Chaves, R. B. Azevedo, F. Pelegrini, C. Gansau, N. Buske 576.
and P. C. Morais, Biophys. J., 2001, 80, 2483. 20 S. M. Shishido, A. B. Seabra, W. Loh and M. G. de Oliveira,
10 H. Y. Fan, E. W. Leve, C. Scullin, J. Gabaldon, D. Tallant, S. Bungo, Biomaterials, 2003, 24, 3543.
T. Boyle, M. C. Wilson and C. J. Brinker, Nano Lett., 2005, 5, 645. 21 Z. Y. Liu, G. S. Yi, H. T. Zhang, J. Ding, Y. W. Zhang and
11 E. Strable, J. W. M. Bulte, B. Moskowitz, K. Vivekanandan, J. M. Xue, Chem. Commun., 2008, 6, 694.
M. Allen and T. Donglas, Chem. Mater., 2001, 13, 2201. 22 P. D. Yang, D. Y. Zhao, D. I. Margolese, B. F. Chmelka and
12 N. Kohler, C. Sun, A. Fichtenholtz, J. Gunn, C. Feng and G. D. Stucky, Nature, 1998, 396, 152.
M. Q. Zhang, Small, 2006, 2, 785. 23 S. H. Sun and H. Zeng, J. Am. Chem. Soc., 2002, 24, 8204.
13 F. Quaglia, L. Ostacolo, G. De Rosa, R. La, I. Maria, 24 F. Pal, K. Viktoria, L. Karoly, M. Istvan and B. N. Janos,
M. Ammendola, G. Nese, G. Maglio, R. Palumbo and Microporous Mesoporous Mater., 2008, 112, 377.
C. Vauthier, Int. J. Pharm., 2006, 324, 56. 25 Y. M. Lam, N. Grigorieff and G. Goldbeck-Wood, Phys. Chem.
14 A. K. Gupta and M. Gupta, Biomaterials, 2005, 26, 3995. Chem. Phys., 1999, 1, 3331.
15 P. Wunderbaldinger, L. Josephson and R. Weissleder, Acad. 26 Z. Y. Liu, X. Quan, H. B. Fu, X. Y. Li and K. Yang, Appl. Catal.,
Radiol., 2002, 9, S304. B, 2004, 52, 33.
16 A. Moore, E. Marecos, A. Bogdanov and R. Weissleder, Radio- 27 E. S. Lee, K. T. Oh, D. Kim, Y. S. Youn and Y. H. Bae,
logy, 2000, 214, 568. J. Controlled Release, 2007, 123, 19–26.

Novel thiophene-conjugated indoline dyes for zinc oxide solar cells

Takuya Dentani,a Yasuhiro Kubota,a Kazumasa Funabiki,a Jiye Jin,b
Tsukasa Yoshida,c Hideki Minoura,c Hidetoshi Miurad and Masaki Matsui*a
Received (in Montpellier, France) 28th May 2008, Accepted 21st August 2008
DOI: 10.1039/b808959k
The application of a series of thiophene-conjugated indoline dyes for zinc oxide solar cells,
prepared by the one-step cathode deposition template method, was examined. The introduction
of thiophene ring(s) into D131-type indoline dye improved the cell performance due to their
appropriate energy levels and bathochromic shift in the UV-vis absorption band on zinc oxide.
It is important for the oxidation potential (Eox) of dyes to have a more positive value than
ca. 0.25 V vs. Fc/Fc+ in acetonitrile in order to show a high (470%) incident photon-to-
current efficiency.
Introduction NBS (2) to give 3, followed by a reaction with thiophene

1 2 3
boronic acids esters 4–7 to provide 8–11, which were formy-
Organic dyes, such as coumarins, styryls, polyenes, dimethyl- lated to give 12–15. These compounds were allowed to react
fluorenyl-containing derivatives4 and indoline derivatives,5 with cyanoacetic, mono- and double-rhodanic acids 16–19 to
have been reported to act as good sensitizers for titanium provide 20–28. D131, D102 and D149 were prepared in a
oxide. Bathochromic organic dyes, such as squaryliums,6 similar way.
phthalocyanines7 and heptamethinecyanines,8 have also been
reported to sensitize semiconductors. In particular, D149 UV-vis absorption and fluorescence spectra
has been reported to show the highest solar-light-to-electricity
The UV-vis absorption and fluorescence spectra of 20–28,
conversion efficiency (Z) of 9.0% among organic dyes.5a
D131, D102 and D149 are shown in Fig. 1, Fig. 2 and
One promising approach to improve the performance of
Fig. 3. The results are also listed in Table 1. All the indoline
sensitizers is the expansion of the p-conjugation system to
dyes showed first and second absorption bands at around 500
absorb more photons. The introduction of ethylene and
and 400 nm, respectively. The first absorption maximum
thiophene units into chromophores is a good methodology
(lmaxfirst) of monothiophene derivatives 20, 23, 24, 25 and 26
to expand p-conjugation.9 On the other hand, a convenient
were more bathochromic than thiophene-free derivatives
preparation process for zinc oxide thin films has been
D131, D102 and D149. Interestingly, no further bathochromic
reported.10 The key point of this method is the formation
shift was observed for di- and trithiophene derivatives 21, 22,
of porous zinc oxide films at low temperature (o70 1C).
27 and 28 compared to monothiophene derivatives 20, 23, 24,
Indoline dyes D131, D102 and D149, in which cyanoacrylic,
25 and 26, respectively. The molar absorption coefficients at
monorhodanic and double rhodanic acids are used as
the first absorption band (efirst) of 20–28 were less than those of
anchor moieties, respectively, are known to show good
thiophene-free derivatives D131, D102 and D149. The half-
performances.5f We report herein the application of novel
widths of 20–28 (99–146 nm) were larger than those of D131,
thiophene-conjugated indoline dyes having a series of anchor
D102 and D149 (65–79 nm). No marked difference in efirst
moieties to zinc oxide dye-sensitized solar cells.
among mono-, di- and trithiophene derivatives was observed,
being in the range 37 700 to 47 900. The second absorption
Results and discussion maximum (lmaxsecond) of thiophene derivatives 20–28 showed
Synthesis of indoline dyes a bathochromic shift, and at the same time, their molar
absorption coefficients (esecond) were larger with increasing
Thiophene-conjugated indoline dyes 20–28 were synthesized, numbers of thiophene units. No remarkable differences in
as shown in Scheme 1. Compound 1 was allowed to react with the UV-vis absorption spectra between 20 and 23, and between
25 and 26, were observed. The fluorescence maximum (Fmax)
a showed a bathochromic shift by the introduction of a
Department of Materials Science and Technology, Faculty of
Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan. thiophene unit.
E-mail: matsui@apchem.gifu-u.ac.jp; Fax: +81 58 293 2794;
Tel: +81 58 293 2601
b
Department of Chemistry, Faculty of Science, Shinshu University, Electrochemical properties
3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
c
Environmental and Renewable Energy System Division, Graduate The oxidation potentials (Eox) of D131, D102, D149 and 20–25
School of Engineering, Gifu University, Yanagido, Gifu 501-1193, were measured by using an Ag/Ag+ electrode in acetonitrile to
Japan
d
Chemicrea Co. Ltd., 2-1-6 Sengen, Tsukuba, Ibaragi 305-0047, compare the energy levels of Eox and Eox E0–0 of the dyes,
Japan the I/I3 potential, and the conduction band of zinc oxide.
This journal is
Scheme 1 The synthesis of indoline dyes 20–28.
Fig. 1 UV-vis absorption and fluorescence spectra of indoline dyes Fig. 2 UV-vis absorption and fluorescence spectra of indoline dyes
D131, 20, 21, 22 and 23 at a concentration of 1.0 105 mol dm3 in D102 and 24 at a concentration of 1.0 105 mol dm3 in chloroform.
chloroform. Solid and dotted lines represent UV-vis absorption and Solid and dotted lines represent UV-vis absorption and fluorescence
fluorescence spectra, respectively. spectra, respectively.
Fc/Fc+ was used as a standard. The Eox of ferrocene was energy level.9 The E0–0 of 20 was observed at 589 nm,
observed at +0.13 V vs. Ag/Ag+ in acetonitrile. Fig. 4 shows corresponding to 2.11 eV. Therefore, the Eox E0–0 value of
that the Eox of 20 was observed at +0.38 V vs. Ag/Ag+ in 20 was calculated to be 1.86 V vs. Fc/Fc+ in acetonitrile. The
acetonitrile, corresponding to +0.25 V vs. Fc/Fc+ in aceto- energy levels of free indoline dyes measured in solution
nitrile. The I/I3 potential level was observed at +0.09 V vs. differed from those of adsorbed ones. Unfortunately, ferro-
Ag/Ag+ in acetonitrile, corresponding to 0.04 V vs. Fc/Fc+ cene and indoline dyes on a zinc oxide-coated ITO electrode
in acetonitrile. did not give distinct redox responses due to a slow charge
The potential level of Eox E0–0, where E0–0 represents the transfer process. Hence, the Eox of ferrocene and indoline dyes
intersection of the normalized absorption and fluorescence could not be determined. The Eox and Eox E0–0 of all the
spectra in solution, is considered to correspond to the LUMO indoline dyes are listed in Table 1.

Fig. 3 UV-vis absorption and fluorescence spectra of indoline dyes Fig. 4 The electrochemical measurement of 20 in acetonitrile (2 ml)
D149, 25, 26, 27 and 28 at a concentration of 1.0 105 mol dm3 in containing tetrabutylammonium perchlorate (0.1 mol dm3). Ag/Ag+
chloroform. Solid and dotted lines represent UV-vis absorption and in acetonitrile was used as a reference electrode. Platinum wire
fluorescence spectra, respectively. was used as the working and counterelectrode. The scan rate was
100 mV s1.
UV-vis absorption and IR spectra of 20
The UV-vis absorption spectra of 20 are shown in Fig. 5. The
lmaxfirst of 20 in chloroform and on zinc oxide were observed at
519 and 449 nm, respectively. Thus, large hypsochromic shift
of lmaxfirst was observed on zinc oxide. The lmaxfirst of 20 in the
presence of an equimolar amount of triethylamine (TEA) in
chloroform was observed at 470 nm, there being slightly more
bathochromic than that on zinc oxide.
FTIR spectra of 20 are shown in Fig. 6. The IR spectrum of
20 in a potassium bromide disk showed an absorption band at
around 1680 cm1, which was assigned to a carbonyl stretch-
ing absorption. When indoline dye 20, adsorbed onto a zinc
oxide film, was scraped off and its IR spectrum was measured Fig. 5 The UV-vis absorption spectra of 20 in chloroform and on
in a potassium bromide disk, the absorption band at around zinc oxide.
1680 cm1 disappeared and new absorption was observed at
around 1600 cm1. This spectrum is similar to that of the absorption of the carboxylate anion. It was also observed
triethylammonium salt of 20, in which the absorption band at that indoline dye 20 showed negative solvatochromism
around 1600 cm1 is assigned to the asymmetric stretch in solution (lmaxfirst = 516 (toluene), 519 (chloroform),
Table 1 Optical and electrochemical properties of indoline dyes
Compound lmax/nm (e)a Fmax/nma RFIb Eox vs. Fc/Fc+ in MeCN/V Eox E0–0 vs. Fc/Fc+ in MeCN/V
D131 463 (55 400) 591 83 +0.41 2.00
325 (15 600)
20 519 (43 300) 659 77 +0.25 1.86
373 (27 300)
21 517 (37 700) 712 27 +0.23 1.81
393 (38 300)
22 519 (41 700) 701 4 +0.22 1.83
409 (47 100)
23 523 (47 300) 653 203 +0.25 1.85
373 (29 100)
D102 514 (54 700) 621 68 +0.37 1.83
368 (25 200)
24 548 (41 400) 702 80 +0.25 1.75
388 (37 100)
D149 550 (68 000) 636 100 +0.30 1.79
395 (32 000)
25 571 (43 500) 717 78 +0.24 1.67
410 (34 800)
26 568 (45 600) 713 49 —c —c
408 (40 500)
27 564 (42 000) 743 10 —c —c
405 (41 900)
28 550 (47 900) 727 3 —c —c
412 (48 900)
a
Measured on 1.0 105 mol dm3 of substrate in chloroform at 25 1C. b
Relative fluorescence intensity. c Not measured due to low solubility.
This journal is
Fig. 6 FTIR spectra of 20: (a) 20, (b) 20 in the presence of zinc oxide
and (c) the triethylammonium salt of 20.
529 (dichloromethane), 465 (DMSO), 453 (acetonitrile) and

464 nm (methanol)). These results indicate that the hypso-
chromic shift of 20 on zinc oxide is mainly attributed to the
formation of a bidentate complex between the carboxylate and
zinc. The polar zinc oxide surface could also be attributed to
the hypsochromic shift.
Photoelectrochemical properties
The cell performance of D131-type indoline dyes was examined.
The normalized UV-vis absorption spectra on zinc oxide
and action spectra are shown in Fig. 7. The results are also
listed in Table 2. The cell performance was improved in the
presence of cholic acid (CA), a co-adsorbate that can inhibit
the aggregation of dyes on zinc oxide due to carboxylic acid
and hydrophobic moieties. The UV-vis absorption spectra of
20 and 23 in the absence and presence of CA are depicted in
Fig. 7(a). In the case of 20, a broad absorption at around
530 nm decreased in the presence of CA, indicating the Fig. 7 (a) Normalized UV-vis absorption spectra of 20 and 23 on zinc
prevention of aggregation on zinc oxide. Meanwhile, only oxide in the absence and presence of CA, (b) normalized UV-vis
absorption spectra of D131, 20, 21, 22 and 23 on zinc oxide in the
slight differences in the absorption bands between the absence
presence of CA and (c) action spectra of D131, 20, 21, 22 and 23 in the
and presence of CA were observed for 23. The Z values of 20
presence of CA.
and 23 in the absence of CA were 3.13 and 3.30%, respectively
(Table 2, runs 3 and 7). Those in the presence of CA were 3.78
and 3.36%, respectively (Table 2, runs 2 and 6). Thus, the Z 20 (3.78%) 4 23 (3.36%), 21 (3.19%) 4 D131 (2.60%) 4 22
values of 20 and 23 were improved by 21 and 2% in the (2.08%). Thus, an improvement in cell performance was
presence of CA, respectively. These results suggest that the successfully observed for a series of D131-type thiophene-
hexyl group in 23 is very effective in inhibiting aggregation on conjugated indoline dyes. The improved cell performance of
zinc oxide. In the cases of 21 and 22, aggregation formation 20, 21 and 23, compared with D131, mainly came from the
decreased in the presence of CA, resulting in an improved cell bathochromic shift in the absorption band and a high IPCE
performance (Table 2, runs 4 and 5). The absorption bands of (470%) to increase Jsc.
20, 21, 22 and 23 on zinc oxide were more bathochromic than Next, the cell performance of D102 and 24 was examined
that of D131, as shown in Fig. 7(b). The action spectra show (Table 2, runs 8–10). The UV-vis absorption and action
the sensitization of zinc oxide by 20, 21, 22 and 23 at around spectra are shown in Fig. 8. The absorption band of 24 was
550 nm, whereas no sensitization was observed for D131 at more bathochromic than that of D102. The absorption spec-
around 550 nm, as depicted in Fig. 7(c). The incident photon- trum of 24 in the absence of CA clearly showed a broad
to-current efficiency (IPCE) in the presence of CA was in the absorption at around 600 nm, suggesting the formation of
following dye order: 20 (83.1%) 4 23 (78.2%), D131 (77.8%) aggregates. Fig. 8(b) shows the sensitization of zinc oxide by
4 21 (69.1%) 4 22 (55.5%) (Table 2, runs 1, 2, 4–6). The 24 at around 630 nm. However, the IPCE value of 24 was
short-circuit photocurrent densities (Jsc) of 21 (8.15 mA cm2), lower than that of D102 so as not to increase Jsc. The open-
20 (8.09 mA cm2), 23 (7.42 mA cm2) and 22 (6.69 mA cm2) circuit voltage (Voc) and ff of 24 were lower than those of
were higher than that of D131 (5.55 mA cm2). The fill factor D102 (Table 2, runs 8 and 9). Thus, no improvement in
(ff) was lowered by introducing a thiophene unit. Con- cell performance was observed for D102-type thiophene-
sequently, the Z value was in the following order of dyes: conjugated indoline dyes.

Table 2 Physical properties of indoline dyes
Run Compound CAa lmax/nm Abs.b IPCE (%) Jsc/mA cm2 Voc/V ff Zc (%)
1 D131 2 405 3.36 77.8 5.55 0.66 0.71 2.60
2 20 2 449 2.48 83.1 8.09 0.69 0.68 3.78
3 20 0 459 1.96 71.4 7.09 0.65 0.68 3.13
4 21 2 461 2.16 69.1 8.15 0.63 0.62 3.19
5 22 2 457 2.44 55.5 6.69 0.59 0.53 2.08
6 23 2 450 2.07 78.2 7.42 0.66 0.68 3.36
7 23 0 452 2.07 76.2 7.58 0.65 0.67 3.30
8 D102 2 476 3.20 77.1 9.00 0.65 0.66 3.88
9 24 2 514 1.94 48.6 7.33 0.62 0.63 2.83
10 24 0 539 1.54 42.4 6.44 0.59 0.58 2.20
11 D149 2 521 3.08 81.2 11.08 0.68 0.57 4.23
12 25 2 547 1.76 43.4 6.85 0.54 0.64 2.35
13 25 0 555 1.65 35.9 5.38 0.50 0.62 1.68
14 26 2 546 1.25 37.5 5.85 0.62 0.68 2.45
15 26 0 561 1.21 37.7 5.55 0.57 0.65 2.07
16 27 2 546 1.26 29.7 4.40 0.59 0.66 1.71
17 28 2 542 1.45 26.1 3.67 0.56 0.67 1.36
a b
Equivalents of cholic acid with respect to dye. Absorbance at absorption maximum on zinc oxide. c Action spectra and I–V characteristics
under AM 1.5 irradiation (100 mW cm2).
Fig. 8 (a) Normalized UV-vis absorption spectra of D102 and 24 on

zinc oxide in the absence and presence of CA, and (b) action spectra of
D102 and 24 in the presence of CA.
Finally, the cell performance of D149-type indoline dyes was

examined. The UV-vis absorption and action spectra of D149,
25, 26, 27 and 28 are shown in Fig. 9. In this case, the
difference in the UV-vis absorption bands of 25 and 26 in
the absence and presence of CA was small compared with
those in the cases of 20 and 23, as shown in Fig. 9(a). The Z
values of 25 and 26 in the presence of CA were higher than Fig. 9 (a) Normalized UV-vis absorption spectra of 25 and 26 on zinc
those in the absence of CA (Table 2, runs 12–15). Fig. 9(b) oxide in the absence and presence of CA, (b) normalized UV-vis
shows that 25, 26, 27 and 28 are more bathochromic than absorption spectra of D149, 25, 26, 27 and 28 on zinc oxide in the
D149. Fig. 9(c) indicates that though the sensitization of zinc presence of CA, and (c) action spectra of D149, 25, 26, 27 and 28 in the
oxide was observed for 25, 26, 27 and 28 at around 670 nm, presence of CA.
This journal is
their IPCE values were lower than that of D149. Thus, no (+0.25 V) and 25 (+0.24 V) was observed in solution.
improvement in cell performance was observed for the series However, their Eox level on zinc oxide could differ from that
of D149-type thiophene-conjugated indoline dyes (Table 2, in solution. As the Eox level of D131 (+0.41 V vs. Fc/Fc+ in
runs 11, 12, 14, 16 and 17). MeCN) was more positive than those of D102 (+0.37 V) and
D149 (+0.30 V) in solution, those of D131-type derivatives 20,
Relationship between IPCE and Eox, Eox E0–0 21, 22 and 23 might be more positive than those of D102- and
D149-type derivatives 24, 25, 26, 27 and 28 on zinc oxide. The
To examine why only D131-type thiophene-conjugated indo-
Eox levels of D102, 20, 21 and 22 were observed at +0.37,
line dyes showed improved cell performances, the relationship
+0.25, +0.23 and +0.22 V vs. Fc/Fc+ in acetonitrile,
between IPCE and energy levels was examined. Fig. 10(a)
respectively. This suggests that the Eox level can negatively
shows the relationship between IPCE and Eox. Indoline dyes
shift with increasing numbers of thiophene units on zinc oxide.
D131, 20, 21, 23, D102 and D149, of which the Eox levels were
Therefore, the Eox levels of D131-type mono- and dithiophene
more positive than the ca. +0.25 V vs. Fc/Fc+ in acetonitrile,
derivatives 20, 21 and 23 could be more positive than those of
showed high (470%) IPCE values. The potential level of
D102- and D149-type derivatives, and the redox potential of
I/I3 was observed at 0.04 V vs. Fc/Fc+ in acetonitrile.
I/I3 on zinc oxide could show an improved cell perfor-
Fig. 10(b) shows the relationship between IPCE and Eox
mance. As a result, indoline dyes 20, 21 and 23 could show
E0–0. It was also found that indoline dyes D131, 20, 21, 23,
better performances than D131 due to larger Jsc values. The
D102 and D149 showed high IPCE values. It is reported that
Eox levels of D102- and D149-type thiophene-conjugated
the potential levels of the conduction band of titanium oxide
indoline dyes 24, 25, 26, 27 and 28 might be too negative on
and the I/I3 redox are 0.5 and +0.4 V vs. NHE, respec-
zinc oxide, despite their bathochromic shift in the UV-vis
tively, there being an energy gap of 0.9 V.9,11 The conduction
absorption spectrum on zinc oxide. In order to improve the
band level of zinc oxide is similar to that of titanium oxide.
performance of indoline dyes, it is important to design deri-
Therefore, the level of zinc oxide is considered to be 0.94 V
vatives of them having more positive Eox level.
vs. Fc/Fc+ in acetonitrile, which is much more positive than
the Eox E0–0 levels of all the indoline dyes, the energy gap
between Eox E0–0 and the conduction band levels being Conclusion
larger than 0.7 V. It is suggested that an energy gap larger than
A series of D131-, D102- and D149-type thiophene-conjugated
0.2 V between Eox and I/I3, and Eox E0–0 and the
indoline dyes were examined as sensitizers for zinc oxide solar
conduction band levels, respectively, are required.9 Thus,
cells, prepared by the one-step cathode deposition template
though the Eox E0–0 level of all the indoline dyes are
method. Among the series of thiophene-conjugated indoline
sufficiently negative, their Eox levels are critical for the sensi-
dyes, D131-type indoline dyes improved cell performance.
tization cycle to proceed. No marked difference in the
This could have been due to their positive Eox levels. In order
Eox levels among the thiophene-conjugated derivatives 20
to improve the performance of D102- and D149-type indoline
(+0.25 V), 21 (+0.23 V), 22 (+0.22 V), 23 (+0.25 V), 24
dyes, it is important to design derivatives of them having more
positive Eox levels.
Experimental
General
Melting points were measured with a Yanagimoto MP-52
micro-melting-point apparatus. NMR spectra obtained using
a JEOL JNM-ECX 400P spectrometer. EI and FAB MS
spectra were recorded on a JEOL MStation 700 spectrometer.
UV-vis absorption and fluorescence spectra were acquired on
Hitachi U-3500 and F-4500 spectrophotometers, respectively.
Cyclic voltammetry was carried out using an EG&G Princeton
Applied Research Potentiostat/Galvanostat (Model 263A)
driven by the M270 software package. One-step cathode electro-
deposition was undertaken using a Hokuto-Denko HSV-100
potentiostat system. The photoelectrochemical measurements
of solar cells were performed on a Bunko-Keiki CEP-2000
system. The I–V curve measurements of solar cells were
performed on an EKO Instruments I–V curve tracer MP-160
and Grating spectroradiometer LS-100.
Electrochemical measurements
Fig. 10 The relationship between IPCE and energy levels: (a) IPCE The electrochemical measurements of indoline dyes D131, 20,
vs. Eox and (b) IPCE vs. Eox E0–0. 21, 22, 23, D102, 24, D149, 25, ferrocene and potassium

iodide, were performed in acetonitrile. The oxidation potential Tokyo Kasei Co. Ltd. Compound 19 was synthesized in the
(Eox) was measured by using three small-sized electrodes. similar procedure to that described for 18.12 3-Hexyl-2-
Ag/Ag+ was used as a reference electrode. Platinum wire (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene (7)13
was used as the working and counterelectrode. Acetonitrile and 3,5-(di-tert-butyl)benzylamine14 were synthesized as des-
solutions (2 ml) of dyes containing tetrabutylammonium cribed in the literature. D131, D102 and D149 were prepared
perchlorate (0.1 mol dm3) were prepared. Dry argon in a similar way, as described in the literature.5c,e
gas was introduced into the solution for 10 min. The electro-
chemical measurements were then performed at a scan rate Synthesis of 3. To a dry acetone solution (23 ml) of 1
of 100 mV s1. (980 mg, 2.37 mmol) was added NBS (423 mg, 2.38 mmol)
at 0 1C under an argon atmosphere. The mixture was stirred at
Preparation of the zinc oxide solar cell room temperature for 3 h. The reaction mixture was poured
into water (20 ml) and extracted with chloroform (3 50 ml).
An aqueous potassium chloride solution (300 ml, 0.1 mol dm3)
The extract was washed with brine (2 50 ml) and dried over
was electrolyzed at 1.0 V vs. SCE with bubbling oxygen
anhydrous sodium sulfate. The solvent was removed in vacuo.
gas at 70 1C for 30 min. Platinum was used as a counter-
The crude product was purified by silica gel column chromato-
electrode. To the pre-electrolyzed film was added an
graphy (chloroform–hexane = 1 : 3) to afford 3 as a pale
aqueous solution of zinc chloride. The concentration of zinc
yellow solid. Yield 96%, mp 81–83 1C. dH (400 MHz, CDCl3,
chloride was adjusted to 5 mmol dm3. Then, the film was
Me4Si): 1.42–1.49 (1 H, m), 1.61–1.65 (1 H, m), 1.79–1.87
again electrodeposited in the solution at 1.0 V vs. SCE at
(3 H, m), 1.96–2.02 (1 H, m), 3.76–3.79 (1 H, m), 4.65–4.69
70 1C for 20 min with bubbling oxygen gas. To the electro-
(1 H, m), 6.83 (1 H, d, J = 8.4 Hz), 6.92 (1 H, s), 6.99–7.01
deposited film was added an aqueous solution of eosin Y
(4 H, m), 7.09 (1 H, d, J = 8.4 Hz), 7.16 (1 H, s) and 7.24–7.40
(0.050 mmol dm3). The film was electrodeposited at 1.0 V
(10 H, m). m/z (EI) = 493 (M+ + 2, 100), 491 (M+, 98), 464
vs. SCE at 70 1C for 30 min with bubbling oxygen gas. The film
(69), 462 (67), 413 (55), 384 (52) and 178 (42).
was kept in a dilute aqueous potassium hydroxide solution
(pH 10.5) for 24 h to remove adsorbed eosin Y. The film was Synthesis of 8–11. To a THF solution (10 ml) of 3 (492 mg,
then dried at 100 1C for 1 h. The thin film was immersed in a 1.0 mmol) were added boronic acid esters 4–7 (1.20 mmol),
chloroform solution of dye (1 104 mol dm3) and kept at tetrakis(triphenylphosphine)palladium(0) (60 mg, 0.05 mmol)
ambient temperature for 1 h to adsorb dyes 20–28 onto the and a 2 M aqueous potassium carbonate solution (0.8 ml). The
zinc oxide. In the cases of D131, D102 and D149, the film was mixture was refluxed (8: 12 h, 9: 20 h, 10: 20 h and 11: 20 h)
immersed in an acetonitrile–tert-butyl alcohol 1 : 1 mixed under an argon atmosphere. After cooling, chloroform
solution (0.5 mmol dm3). Then, the film was washed with (100 ml) was added to the reaction mixture and it was then
chloroform. In the cases of D131, D102 and D149, the film was filtered through Celite. The filtrate was next poured into
washed with an acetonitrile–tert-butyl alcohol 1 : 1 mixed water (50 ml). The chloroform layer was washed with brine
solution. The films were dried under an air atmosphere at (3 50 ml) and dried over anhydrous sodium sulfate. The
ambient temperature. The film was used as the working solvent was removed in vacuo and the crude product purified
electrode. A platinum spattered film was used as the counter- by silica gel column chromatography (8: chloroform–hexane =
electrode. The cell size was 5.0 5.0 mm. Thermosetting resin 4 : 3 1, chloroform 1; 9: chloroform–hexane = 1 : 1 1,
was put around the cell. An acetonitrile–ethylene carbonate chloroform–hexane = 2 : 5 1; 10: chloroform–hexane =
(v/v = 1 : 4) mixed solution containing tetrabutylammonium 1 : 1 1, chloroform–hexane = 3 : 5 2; 11: chloroform–
iodide (0.5 mol dm3) and iodine (0.05 mol dm3) was used as hexane = 8 : 11 1, chloroform–hexane = 1 : 3 2) to give
the electrolyte. 8–11 as a yellow solid. The physical and spectral data are
shown below.
Photoelectrochemical measurements
Action spectra were measured under monochromatic light 8. Yield 72%, mp 204–206 1C. dH (400 MHz, CDCl3,
with a constant photon number (5 1015 photon cm2 s1). Me4Si): 1.46–1.51 (1 H, m), 1.62–1.67 (1 H, m), 1.79–1.94
I–V characteristics were measured under illumination with (3 H, m), 2.00–2.07 (1 H, m), 3.81–3.86 (1 H, m), 4.70–4.73
AM 1.5 simulated sun light (100 mW cm2) through a shading (1 H, m), 6.93 (1 H, s), 6.98–7.06 (6 H, m), 7.15 (1 H, s),
mask (5.0 4.0 mm). 7.16–7.17 (1 H, m) and 7.26–7.39 (12 H, m). m/z (EI) = 495
(M+, 100), 466 (24) and 248 (8).
Synthesis of dyes
9. Yield 49%, mp 105–107 1C. dH (400 MHz, CDCl3,
Materials. 1,2,3,3a,4,8b-Hexahydro-4-[4-(2,2-diphenylethenyl)- Me4Si): 1.39–1.47 (1 H, m), 1.55–1.59 (1 H, m), 1.69–1.84
phenyl]cyclopent[b]indole (1) was supplied from Chemicrea (3 H, m), 1.91–2.00 (1 H, m), 3.69–3.73 (1 H, m), 4.58–4.61
Co. Ltd. N-Bromosuccinimide (NBS, 2) and 2-(4,4,5,5-tetra- (1 H, m), 6.91–7.03 (8 H, m), 7.08–7.10 (3 H, m) and 7.21–7.34
methyl-1,3,2-dioxaborolan-2-yl)thiophene (4) were purchased (12 H, m). m/z (FAB) = 578 (MH+).
from Wako Pure Chemical Industries Ltd. 5-(4,4,5,5-Tetra-
methyl-1,3,2-dioxaborolan-2-yl)-2,20 -bithiophene (5), 5-(4,4,5,5- 10. Yield 53%, mp 106–109 1C. dH (400 MHz, CDCl3,
tetramethyl-1,3,2-dioxaborolan-2-yl)-2,2 0 ,5 0 ,200 -terthiophene Me4Si): 1.48–1.59 (1 H, m), 1.62–1.66 (1 H, m), 1.82–1.93
(6) and cyano acetic acid (16) were purchased from Aldrich (3 H, m), 2.03–2.06 (1 H, m), 3.80–3.88 (1 H, m), 4.67–4.78
Co. Ltd. Rhodanine-3-acetic acid (17) was purchased from (1 H, m), 6.94 (1 H, s), 6.98–7.11 (10 H, m), 7.17 (1 H, d,
This journal is
J = 3.4 Hz), 7.21 (1 H, d, J = 4.8 Hz) and 7.27–7.41 14 (107 mg, 0.16 mmol) were added cyano acetic acid (97 mg,
(12 H, m). m/z (FAB) = 660 (MH+). 1.14 mmol) and piperidine (776 mg, 9.11 mmol). The mixture
was then refluxed (20: 2 h, 21: 2 h, 22: 23 h and 23: 17 h). After
11. Yield 56%, mp 57–61 1C. dH (400 MHz, CDCl3, Me4Si):
cooling, the solvent was removed in vacuo and the residue
0.89 (3 H, t, J = 6.8 Hz), 1.30–1.34 (6 H, m), 1.42–1.52
dissolved in chloroform. To the solution was added 1 M
(1 H, m), 1.59–1.64 (3 H, m), 1.78–1.90 (3 H, m), 1.97–2.07
aqueous hydrochloric acid (0.4 ml) and water (50 ml), and
(1 H, m), 2.58 (2 H, t, J = 7.6 Hz), 3.78–3.82 (1 H, m),
the mixture stirred at room temperature for 30 min. The
4.66–4.69 (1 H, m), 6.73 (1 H, s), 6.92–7.04 (7 H, m) and
chloroform layer was separated, washed with water (3 50 ml)
7.22–7.40 (12 H, m). m/z (FAB) = 580 (MH+).
and dried over anhydrous sodium sulfate. The solvent was
Synthesis of 12–15. To DMF (4 ml) was added phosphorous removed in vacuo and the product purified by silica gel column
oxychloride (352 mg, 2.30 mmol) at 0 1C. To the solution was chromatography (20: chloroform–methanol = 8 : 1 1, 10 :
then added a DMF solution (14 ml) of 8–11 (0.84 mmol) at 1 2; 21: chloroform–methanol = 10 : 1 3; 22:
0–5 1C. The mixture was heated at 75 1C (12: 2 h, 13: 4 h, 14: chloroform–methanol = 10 : 1 1, 8 : 1 3; 23: chloroform–
20 h and 15: 2 h). After the reaction was complete, the reaction methanol = 10 : 1 3) to afford 20, 21, 22 and 23 as a purple
mixture was poured into ice–water (100 ml) and neutralized solid. The physical and spectral data are shown below.
with aqueous sodium hydroxide. The product was extracted
20. Yield 64%, mp 268–271 1C. dH (400 MHz, DMSO-d6,
with chloroform (3 50 ml). The extract was washed with
Me4Si): 1.23–1.32 (1 H, m), 1.59–1.68 (2 H, m), 1.79–1.84 (2 H,
brine (2 50 ml) and water (2 50 ml), and dried over
m), 1.99–2.08 (1 H, m), 3.82–3.86 (1 H, m), 4.86–4.90 (1 H, m),
anhydrous sodium sulfate. The solvent was removed in vacuo
6.97 (1 H, d, J = 8.7 Hz), 7.02 (2 H, d, J = 8.5 Hz), 7.07
and the product purified by silica gel column chromatography
(1 H, s), 7.11 (2 H, d, J = 8.5 Hz), 7.19–7.22 (2 H, m),
(2 chloroform) to afford 12–15 (12: orange solid, 13: red
7.28–7.36 (5 H, m), 7.41–7.48 (4 H, m), 7.57–7.59 (2 H, m),
solid, 14: red solid and 15: orange solid). The physical and
7.95 (1 H, d, J = 3.4 Hz) and 8.43 (1 H, s). m/z (FAB) =
spectral data are shown below.
591.2106 (MH+, C39H31N2O2S requires 591.2106).
Me4Si): 1.47–1.53 (1 H, m), 1.65–1.67 (1 H, m), 1.82–1.89
Me4Si): 1.28–1.35 (1 H, m), 1.58–1.69 (2 H, m), 1.81–1.86
(3 H, m), 2.07–2.11 (1 H, m), 3.81–3.85 (1 H, m), 4.76–4.79
(2 H, m), 2.00–2.07 (1 H, m), 3.81–3.85 (1 H, m), 4.81–4.84
(1 H, m), 6.94 (1 H, s), 6.96 (1 H, d, J = 8.5 Hz), 7.01 (2 H, d,
(1 H, m), 6.98 (1 H, d, J = 9.2 Hz), 7.00 (2 H, d, J = 9.1 Hz),
J = 8.8 Hz), 7.05 (2 H, d, J = 8.8 Hz), 7.23–7.39 (13 H, m),
7.06 (1 H, s), 7.09 (2 H, d, J = 9.1 Hz), 7.20–7.21 (2 H, m),
7.68 (1 H, d, J = 4.1 Hz) and 9.80 (1 H, s). m/z (EI) = 523
7.28–7.53 (13 H, m), 7.82 (1 H, br s) and 8.28 (1 H, br s). m/z
(M+, 100), 495 (56), 373 (52) and 344 (31).
(FAB) = 673.1974 (MH+, C43H33N2O2S2 requires 673.1983).
Me4Si): 1.44–1.53 (1 H, m), 1.59–1.66 (1 H, m), 1.77–1.91
Me4Si): 1.29–1.36 (1 H, m), 1.61–1.70 (2 H, m), 1.84–1.87
(3 H, m), 2.00–2.09 (1 H, m), 3.79–3.81 (1 H, m), 4.70–4.73
(2 H, m), 2.00–2.05 (1 H, m), 3.81–3.85 (1 H, m), 4.80–4.83
(1 H, m), 6.93 (1 H, s), 6.95 (1 H, d, J = 8.5 Hz), 6.99 (2 H, d,
(1 H, m), 6.98 (1 H, d, J = 6.3 Hz), 7.00 (2 H, d, J = 7.8 Hz),
J = 8.9 Hz), 7.03 (2 H, d, J = 8.9 Hz), 7.08 (1 H, d, J =
7.06 (1 H, s), 7.08 (2 H, d, J = 7.8 Hz), 7.20–7.22 (2 H, m),
3.9 Hz), 7.18 (1 H, d, J = 3.9 Hz), 7.24–7.40 (13 H, m), 7.62
7.28–7.47 (13 H, m), 7.60–7.62 (2 H, m), 7.98 (1 H, d, J = 3.4 Hz)
(1 H, d, J = 4.1 Hz) and 9.82 (1 H, s). m/z (FAB) =
and 8.49 (1 H, s). m/z (FAB) = 755.1831 (MH+,
606 (MH+).
C47H35N2O2S3 requires 755.1861).
Me4Si): 1.46–1.54 (1 H, m), 1.62–1.68 (1 H, m), 1.79–1.86
Me4Si): 0.84 (3 H, t, J = 6.0 Hz), 1.20–1.30 (7 H, m),
(3 H, m), 1.98–2.02 (1 H, m), 3.77–3.99 (1 H, m), 4.46–4.69
1.57–1.65 (4 H, m), 1.76–1.84 (2 H, m), 1.97–2.06 (1 H, m),
(1 H, m), 6.38–7.40 (23 H, m), 7.57–7.58 (1 H, m) and 9.78
2.74 (2 H, t, J = 7.2 Hz), 3.78–3.82 (1 H, m), 4.82–4.86
(1 H, s). m/z (FAB) = 688 (MH+).
(1 H, m), 6.93 (1 H, d, J = 8.2 Hz), 6.99 (2 H, d, J = 8.6 Hz),
15. Yield 96%, mp 66–68 1C. dH (400 MHz, CDCl3, Me4Si): 7.04 (1 H, s), 7.07 (2 H, d, J = 8.6 Hz), 7.17–7.19 (2 H, m),
0.89 (3 H, t, J = 7.0 Hz), 1.30–1.39 (6 H, m), 1.45–1.48 7.26–7.34 (5 H, m), 7.38–7.45 (4 H, m), 7.50 (1 H, s), 7.54
(1 H, m), 1.61–1.73 (3 H, m), 1.79–1.90 (3 H, m), 2.02–2.05 (1 H, s) and 8.25 (1 H, s). m/z (FAB) = 675.3117 (MH+,
(1 H, m), 2.91 (2 H, t, J = 7.0 Hz), 3.79–3.83 (1 H, m), C45H43N2O2S requires 675.3045).
4.73–4.77 (1 H, m), 6.93 (1 H, s), 6.94 (1 H, d, J = 8.2 Hz),
Synthesis of 24, 25, 26, 27 and 28. To an acetic acid solution
7.00 (2 H, d, J = 8.9 Hz), 7.04 (2 H, d, J = 8.9 Hz), 7.06
(4 ml) of 12–14 (0.30 mmol) was added rhodanine derivatives
(1 H, s), 7.23–7.40 (12 H, m) and 9.95 (1 H, s). m/z (FAB) =
17–19 (0.32 mmol). The mixture was heated at 120 1C and
608 (MH+).
ammonium acetate (0.88 mmol) added, after which it
Synthesis of 20, 21, 22 and 23. In the cases of 20, 21 and 23, was refluxed for 2 h. After cooling, the reaction mixture was
to an acetonitrile solution (6 ml) of 12, 13 and 14 (0.30 mmol) poured into water (20 ml). The resulting precipitate was
were added cyano acetic acid (100 mg, 1.18 mmol) filtered and washed with water, and the crude product purified
and piperidine (46 mg, 0.54 mmol). In the case of 22, to by silica gel column chromatography (24: chloroform–methanol =
an acetonitrile–chloroform (1 : 1) mixed solution (80 ml) of 8 : 1 3; 25: chloroform–methanol = 8 : 1 2; 26:

chloroform–methanol = 8 : 1 9; 27: chloroform–methanol = 109, 3907; (b) K. Hara, M. Kurashige, Y. Dan-oh, C. Kasada,
8 : 1 5; 28: chloroform–methanol = 8 : 1 3) to afford A. Shinpo, S. Suga, K. Sayama and H. Arakawa, New J.
Chem., 2003, 27, 783; (c) K. Hara, K. Sayama, Y. Ohga,
compound 24, 25, 26, 27 and 28 as a purple solid. The physical A. Shinpo, S. Suga and H. Arakawa, Chem. Commun., 2001,
and spectral data are shown below. 569.
2 (a) T. Dentani, K. Nagasaka, K. Funabiki, J.-Y. Jin, T. Yoshida,
24. Yield 89%, mp 175–178 1C. dH (400 MHz, DMSO-d6, H. Minoura and M. Matsui, Dyes Pigm., 2008, 77, 59;
Me4Si): 1.29–1.33 (1 H, m), 1.59–1.68 (2 H, m), 1.81–1.84 (b) Q.-H. Yao, L. Shan, F.-Y. Li, D.-D. Yin and C.-H. Huang,
(2 H, m), 2.00–2.05 (1 H, m), 3.81–3.85 (1 H, m), 4.69 (2 H, s), New J. Chem., 2003, 27, 1277; (c) Z.-S. Wang, F.-Y. Li and
C.-H. Huang, J. Phys. Chem. B, 2001, 105, 9210; (d) Z.-S. Wang,
4.84–4.88 (1 H, m), 6.95 (1 H, d, J = 8.5 Hz), 7.01 (2 H, d, J = F.-Y. Li, C.-H. Huang, L. Wang, M. Wei, L.-P. Jim and N.-Q. Li,
8.3 Hz), 7.06 (1 H, s), 7.09 (2 H, d, J = 8.3 Hz), 7.19–7.21 J. Phys. Chem. B, 2000, 104, 9676; (e) Z.-S. Wang, F.-Y. Li and
(2 H, m), 7.28–7.34 (5 H, m), 7.39–7.49 (4 H, m), 7.57–7.58 C.-H. Huang, Chem. Commun., 2000, 2063.
3 (a) R. Chen, X. Yang, H. Tian and L. Sun, J. Photochem. Photo-
(2 H, m), 7.77 (1 H, d, J = 3.9 Hz) and 8.10 (1 H, s). m/z
biol., A, 2007, 189, 295; (b) M. Liang, W. Xu, F. Cai, P. Chen,
(FAB) = 697.1647 (MH+, C41H33N2O3S3 requires 697.1653). B. Peng, J. Chen and Z. Li, J. Phys. Chem. C, 2007, 111, 4465;
(c) H. Choi, J.-K. Lee, K.-J. Song, K. Song, S. O. Kang and J. Ko,
25. Yield 31%, mp 4 300 1C. dH (400 MHz, DMSO-d6, Tetrahedron, 2007, 63, 1553; (d) N. Koumura, Z.-S. Wang,
Me4Si): 1.14 (3 H, t, J = 6.9 Hz), 1.25–1.37 (1 H, m), S. Mori, M. Miyashita, E. Suzuki and K. Hara, J. Am. Chem.
1.60–1.68 (2 H, m), 1.80–1.84 (2 H, m), 2.01–2.08 (1 H, m), Soc., 2006, 128, 14256; (e) S. Kim, J. K. Lee, S. O. Kang, J. Ko,
J.-H. Yum, S. Fantacci, F. D. Angelis, D. D. Censo,
3.82–3.86 (1 H, m), 3.98–4.00 (2 H, m), 4.69 (2 H, s), 4.84–4.87 M. K. Nazeeruddin and M. Grätzel, J. Am. Chem. Soc., 2006,
(1 H, m), 6.96 (1 H, d, J = 8.5 Hz), 7.00 (2 H, d, J = 9.3 Hz), 128, 16701; (f) D. P. Hagberg, T. Edvinsson, T. Marinado,
7.07 (1 H, s), 7.08 (2 H, d, J = 9.3 Hz), 7.20–7.55 (13 H, m), G. Boschloo, A. Hagfeldt and L. Sun, Chem. Commun., 2006,
7.68 (1 H, d, J = 3.9 Hz) and 8.02 (1 H, s). m/z (FAB) = 2245; (g) K. Hara, T. Sato, R. Katoh, A. Furube, T. Yoshihara,
M. Murai, M. Kurashige, S. Ito, A. Shinpo, S. Suga and
824.1757 (MH+, C46H38N3O4S4 requires 824.1745). H. Arakawa, Adv. Funct. Mater., 2005, 15, 246; (h) T. Kitamura,
M. Ikeda, K. Shigaki, T. Inoue, N. A. Anderson, X. Ai, T.-Q. Lian
26. Yield 81%, mp 4 300 1C. dH (400 MHz, DMSO-d6, and S. Yanagida, Chem. Mater., 2004, 16, 1806; (i) K. Hara,
Me4Si): 1.24–1.29 (1 H, m), 1.25 (18 H, s), 1.59–1.87 (2 H, m), M. Kurashige, S. Ito, A. Shinpo, S. Suga, K. Sayama and
1.85–1.87 (2 H, m), 2.01–2.09 (1 H, m), 3.83–3.87 (1 H, m), H. Arakawa, Chem. Commun., 2003, 252.
4.61 (2 H, s), 4.85–4.88 (1 H, m), 5.19 (2 H, s), 6.98 (1 H, d, 4 (a) D. Kim, J.-K. Lee, S. O. Kang and J. Ko, Tetrahedron, 2007,
63, 1913; (b) I. Jung, J.-K. Lee, K.-H. Song, K. Song, S. O. Kang
J = 8.5 Hz), 7.00 (2 H, d, J = 8.8 Hz), 7.07 (1 H, m), 7.10 (2 H, and J. Ko, J. Org. Chem., 2007, 72, 3652; (c) S. Kim, J.-K. Lee,
d, J = 8.8 Hz), 7.19–7.48 (14 H, m), 7.53 (1 H, s), 7.57 (1 H, d, S. O. Kang, J. Ko, J.-H. Yum, S. Fantacci, F. D. Angelis,
J = 3.9 Hz), 7.72 (1 H, d, J = 4.1 Hz) and 8.07 (1 H, s). m/z D. D. Censo, M. K. Nazeeruddin and M. Grätzel, J. Am. Chem.
Soc., 2006, 128, 16701.
(FAB) = 998.3133 (MH+, C59H56N3O4S4 requires 998.3154). 5 (a) S. Ito, S. M. Zakeeruddin, R. Humphry-Baker, P. Liska,
27. Yield 95%, mp 4 300 1C. dH (400 MHz, DMSO-d6, R. Charvet, P. Comte, M. K. Nazeeruddin, P. Pechy,
M. Takata, H. Miura, S. Uchida and M. Grätzel, Adv. Mater.,
Me4Si): 1.22–1.35 (1 H, m), 1.23 (18 H, s), 1.57–1.66 (2 H, m), 2006, 18, 1202; (b) L. Schmidt-Mende, U. Bach, R. Humphry-
1.78–1.85 (2 H, m), 1.95–2.05 (1 H, m), 3.73–3.79 (1 H, m), Baker, T. Horiuchi, H. Miura, S. Ito, S. Uchida and M. Grätzel,
4.33 (2 H, s), 4.74–4.78 (1 H, m), 5.10 (2 H, s), 6.91 (1 H, d, Adv. Mater., 2005, 17, 813; (c) T. Horiuchi, H. Miura and
S. Uchida, J. Photochem. Photobiol., A, 2004, 164, 29;
J = 8.5 Hz), 6.99 (2 H, d, J = 8.3 Hz), 7.03 (1 H, s), 7.04 (d) T. Horiuchi, H. Miura, K. Sumioka and S. Uchida, J. Am.
(2 H, d, J = 8.3 Hz), 7.17–7.54 (18 H, m), 7.62 (1 H, s) and Chem. Soc., 2004, 126, 12218; (e) T. Horiuchi, H. Miura and
7.94 (1 H, s). m/z (FAB) = 1080.3016 (MH+, C63H58N3O4S5 S. Uchida, Chem. Commun., 2003, 3036; (f) W. H. Howie,
requires 1080.3031). F. Claeyssens, H. Miura and L. M. Peter, J. Am. Chem. Soc.,
2008, 130, 1367.
28. Yield 32%, mp 4 300 1C. dH (400 MHz, DMSO-d6, 6 A. Otsuka, K. Funabiki, N. Sugiyama, T. Yoshida, H. Minoura
and M. Matsui, Chem. Lett., 2006, 35, 666.
Me4Si): 1.22–1.33 (1 H, m), 1.26 (18 H, s), 1.59–1.68 (2 H, m), 7 P. Y. Reddy, L. Giribabu, C. Lyness, H. J. Snaith, C. Vijaykumar,
1.80–1.84 (2 H, m), 1.97–2.03 (1 H, m), 3.78–3.83 (1 H, m), M. Chandrasekharam, M. Lakshmikantam, J.-H. Yum,
4.46 (2 H, s), 4.77–4.81 (1 H, m), 5.17 (2 H, s), 6.96 (1 H, d, K. Kalyanasundaram, M. Grätzel and M. K. Nazeeruddin, Angew.
Chem., Int. Ed., 2007, 46, 373.
J = 8.5 Hz), 6.98 (2 H, d, J = 9.1 Hz), 7.05 (1 H, s), 7.06 8 M. Matsui, Y. Hashimoto, K. Funabiki, J. Y. Jin, T. Yoshida and
(2 H, d, J = 9.1 Hz), 7.19–7.54 (20 H, m), 7.71 (1 H, s) and H. Minoura, Synth. Met., 2005, 148, 147.
8.02 (1 H, s). m/z (FAB) = 1162.2795 (MH+, C67H60N3O4S6 9 K. Hara, T. Sato, R. Katoh, A. Furube, Y. Ohga, A. Shinpo,
requires 1162.2908). S. Suga, K. Sayama, H. Sugihara and H. Arakawa, J. Phys. Chem.
B, 2003, 107, 597.
10 T. Yoshida, M. Iwaya, H. Ando, T. Oekermann, K. Nonomura,
Acknowledgements D. Schlettwein, D. Wöhrle and H. Minoura, Chem. Commun.,
2004, 400.
This work was financially supported in part by Grants-in-Aid 11 R. Katoh, A. Furube, T. Yoshihara, K. Hara, G. Fujihashi,
for Science Research (no. 19550185) from the Japan Society S. Takano, S. Murata, H. Arakawa and M. Tachiya, J. Phys.
for the Promotion of Science (JSPS). Chem. B, 2004, 108, 4818.
12 J. D. Mee, US Pat., 5679795, 1997.
References 13 G. Bidan, A. De Nicola, V. Enée and S. Guilerez, Chem. Mater.,
1998, 10, 1052.
1 (a) Z.-S. Wang, K. Hara, Y. Dan-oh, C. Kasada, A. Shinpo, 14 M. Matsui, M. Wang, K. Funabiki, Y. Hayakawa and
S. Suga, H. Arakawa and H. Sugihara, J. Phys. Chem. B, 2005, T. Kitaguchi, Dyes Pigm., 2007, 74, 169.
This journal is
Gold imidazolium-based ionic liquids, efficient catalysts for

cycloisomerization of c-acetylenic carboxylic acids
Florentina Neat-u,a Vasile I. Pârvulescu,a Véronique Michelet,b Jean-Pierre Gênet,b
Alexandre Goguetc and Christopher Hardacrecd
Received (in Durham, UK) 22nd July 2008, Accepted 8th September 2008
DOI: 10.1039/b812580e
Ionic liquid stabilized gold(III) chloride is shown to be a very active catalyst in the cyclization
of sterically hindered and unhindered acetylenic carboxylic acid substrates even in the absence
of a base.
Introduction enhance the stability are extremely important for practical

applications.20 These can be in the form of the solvent used or
Ionic liquids (ILs) have received significant attention recently the nature of the support.21 For example, stabilization of gold
because they exhibit several advantages over molecular in the form of nanoparticles in ionic liquids by imidazolium
solvents with respect to their environmental impact.1 Catalytic derivatives has been reported.22–25
reactions in ILs have been examined for at least 20 years and In this report the behavior of a 4 wt% Au/beta catalyst and
have been used for a wide variety of carbon–carbon bond a series of 1,3-dialkylimidazolium tetrachloroaurate salts in
forming reactions, which were the first to be undertaken in this ionic liquids as catalysts for the cyclization of acetylenic
media, and a number of good reviews cover the area of ILs.2–6 substrates has been studied. Gold has recently been reported
The extensive interest stems from the fact that the properties as a catalyst in ionic liquids in the hydration of phenyl-
of ionic liquids may be tuned in order to suit a particular acetylene26,27 and the syntheses of substituted 3(2H)-furanones,27
application by varying the cation–anion combination system- 2,5-dihydrofurans28 and substituted indoles.29 However, with
atically and thereby are useful engineering solvents. In addi- the exception of the Co2(CO)8-catalyzed intramolecular and
tion, for chemical reactions, the ionic liquid provides an ionic intermolecular Pauson–Khand annelation using 1-butyl-3-
environment which can significantly alter the reactivity and methylimidazolium hexafluorophosphate ([C4mim][PF6]) and
selectivity of processes compared with molecular solvents.7 tetrafluoroborate ([C4mim][BF4]) ionic liquids as solvents, no
The transition metal-catalyzed cyclization of 4-alkynoic other related reactions to the cyclization of acetylenic sub-
acids constitutes a major route8 for the construction of strates have been reported in ILs, to date.30
5-membered exocyclic lactones and has been the subject of a
large number of investigations.9–14 Recently, a very attractive
route to perform this reaction under mild conditions in the Experimental
presence of gold was reported.15,16 In our laboratory, the Catalysts preparation
catalytic properties of AuCl and AuCl3 for gem-substituted
substrates, in the absence of base, was described15 as well as 1. Au-beta catalyst. The catalyst was prepared by stirring
the use of two heterogeneous systems Au2O317 and Au/beta.18 1 g of beta zeolite (PQ Corporation) for 3 h with 100 cm3 of 1 M
These systems were found to be active for both substituted and NH4NO3 at 353 K.22 The slurry was filtered off and carefully
unsubstituted substrates. In addition, the optimized hetero- washed with deionized water, dried for 6 h at 333 K and
geneously catalyzed system was found to be recyclable.22 calcined for 24 h at 773 K. Deposition of gold was performed
Whilst gold has been shown to be highly active, it commonly using the deposition–precipitation method. The support
undergoes significant deactivation due to the ease by which it (1 g) was added to 100 cm3 of an aqueous solution of HAuCl4
may change its oxidation state and, in the case of nanoparti- (2.1 103 M) at 343 K which had previously adjusted to a
cles, the catalyst particle size leading to instability in the form pH = 8.5 with 0.2 M NaOH. The temperature of the slurry
of the active catalyst.19 Therefore, modalities which can was maintained at 343 K under vigorous stirring for 3 h.
Thereafter, the sample was filtered off, washed with deionized
a
Department of Chemical Technology and Catalysis, University of water to remove the free chloride and then dried under
Bucharest, B-dul Regina Elisabeta 4-12, 030016 Bucharest, Romania. vacuum at 333 K for 24 h. The resultant catalyst contained
E-mail: v_parvulescu@chem.unibuc.ro; Fax: +40 21 4010241 4 wt% Au as determined by ICP-AES analysis. This catalyst
b
Laboratoire de Synthèse Se´lective Organique et Produits Naturels,
ENSCP, UMR 7573, 11 rue P. et M. Curie, F-725231 Paris Cedex 05, has been used as a reference material in these experiments.
France. E-mail: veronique-michelet@enscp.fr; Fax: +33 1 44071062
c
CenTACat School of Chemistry and Chemical Engineering, Queen’s 2. Ionic liquids synthesis. Gold ionic liquids were
University, Stranmillis Road, Belfast, Northern Ireland, synthesized using the method reported previously by Hasan
UK BT9 5AG et al.25 Four 1-alkyl-3-methylimidazolium tetrachloroaurate
d
QUILL School of Chemistry and Chemical Engineering, Queen’s
University, Stranmillis Road, Belfast, Northern Ireland, UK BT9 5AG. ([Cnmim][AuCl4], n = 2, 4, 6, 18) ionic liquids were prepared
E-mail: c.hardacre@qub.ac.uk; Fax: +44 28 90974687 by adding a 10% molar excess of [Cnmim]Cl to tetrachloroauric

3-phenyl-5-methylene-g-butyrolactone (2a), 3-n-butyl-3-ethoxy-
carbonyl-5-methylene-g-butyrolactone (2b), 3-methoxycarbonyl-
5-methylene-3-(3 0 -phenylprop-2 0 -enyl)-g-butyrolactone (2c),
3-allyl-3-methoxycarbonyl-5-methylene-g-butyrolactone (2d), 3-
benzyl-3-ethoxycarbonyl-5-methylene-g-butyrolactone (2e) and
Fig. 1 Schematic of the cation of the basic ionic liquid (BIL) used as 3-methoxycarbonyl-5-methylene-g-butyrolactone (2f) were in
solvent for the cyclization of the functionalized acetylenic substrates good agreement were those reported previously.19–21 In all
1a and 1b. cases, no cyclization is observed in the absence of any of the
gold catalysts irrespective of the solvent used.
acid (HAuCl44H2O, Alfa Aesar) resulting in the rapid
formation of a yellow solid. Following heating to above
its melting points with stirring for 0.5 h, the product was
purified by recrystallization from benzene–acetonitrile in the Results and discussion
volume ratio of 4 : 1. [Cnmim]Cl were prepared in house using
Catalysts characterization
standard literature methods.31 Trihexyltetradecylphospho-
nium hydrogen sulfate ([P66614][HSO4]) was supplied by Cytec. The beta zeolite used in these experiments had a surface area
1-Butyl-3-methylimidazolium bis{(trifluoromethyl)sulfonyl}- of 464 m2 g1 and a pore volume of 0.96 cm3 g1. After the
imide ([C4mim][NTf2]) and trihexyltetradecylphosphonium deposition of gold (4 wt%) the surface area decreased to
bis{(trifluoromethyl)sulfonyl}imide ([P66614][NTf2]) were 383 m2 g1 and the pore volume to 0.80 cm3 g1. TEM
formed by metathesis from [C4mim]Cl and [P66614]Cl (Cytec), analysis of this material shown an uniform size distribution
respectively, according to literature methods.32 The base func- with an average of 3 nm. The characterization of IL-stabilized
tionalized ionic liquid 5-diisopropylamino-3-oxapentyl)- gold(III) chloride was examined using TEM, XPS and
dimethylethylammonium bis{(trifluoromethyl)sulfonyl}imide EXAFS. Fig. 2 shows the XPS spectra of the Au 4f photo-
(BIL) shown in Fig. 1 was synthesized as previously re- electron emission corresponding to the mixture of the catalyst
ported.33 In all cases prior to reaction the ionic liquids were ([C6mim][AuCl4]) with the ionic liquid [C6mim]Cl after the
dried under vacuum at 50 1C overnight. All ionic liquids reaction. The binding energies of Au 4f7/2 and Au 4f5/2 levels
contained o0.16 wt% water determined by Karl–Fischer were located at 90.0 eV and 86.3 eV, respectively. EXAFS of
analysis and o5 ppm halide by suppressed ion chromato- [C6mim][AuCl4] dissolved in [C6mim]Cl showed a single peak
graphy. All other reagents were used as received. at 0.22 nm associated with 4 chlorine atoms in the first
coordination shell. During reaction, this peak decreases
Catalyst characterization slightly and a small decrease in the white line of the XANES
is observed. This variation may indicate that chlorine is being
The solid catalysts were characterized by nitrogen adsorption–
replaced by a lighter element such as coordination by the
desorption isotherms at 77 K (Micromeritics ASAP 2000) after
substrate during reaction, as would be expected. TEM analysis
out-gassing the samples at 393 K for 12 h.
is in agreement with the XPS and EXAFS measurements and
The XPS spectra were recorded using a Kratos Axis
showed no nanoparticle formation. These observations are
UltraDLD spectrometer with monochromatic Al-Ka radia-
tion. The data were analyzed using Casa-XPS (v2.3.13)
employing a Shirley-background subtraction prior to fitting.
EXAFS data were collected at the Synchrotron Radiation
Source in Daresbury, UK, using station 9.3. The spectra were
recorded at the Au LIII edge using a double crystal Si(111)
monochromator. Scans were collected and averaged. Data
were processed using EXCALIB which was also used to
convert raw data into energy vs. absorption data. EXBROOK
was used to remove the background. The analysis of the
EXAFS was performed using EXCURV98.34 The gold con-
centration was determined by ICP-AES.
Catalytic tests
Typically 0.26 mmol of acetylenic acid was stirred with 2.5 mol%
[Cnmim][AuCl4] dissolved in 0.5 g [Cnmim]Cl in air at
room temperature, until completion of the reaction. After
the completion of the reaction, the reaction products
were extracted three times with diethyl ether and the
solvent completely removed under vacuum to give the
corresponding lactone. 1H and 13C NMR were recorded
on a Bruker AV 300 instrument operating at 300 Hz to Fig. 2 The XPS spectra in the Au 4f region of the [C6mim][AuCl4]
identify the products. The measured NMR spectra for after reaction.
This journal is
consistent with the presence of a dissolved Au(III) species with Table 2 Au-catalyzed cyclization of functionalized carboxylic acids
B4 chlorines in the first coordination sphere.35
Catalytic tests
Table 1 shows the activity of Au/beta in a range of ionic
liquids for the cyclization of the functionalized acetylenic
substrates 1a and 1b.
Although cycloisomerization of substrate 1a did occur in the
BIL and [P66614][HSO4] with conversions of 75 and 70%,
respectively, (Table 1, entries 1, 2), the ILs could not be Entry R1 R2 Product Temp./1C Time/h Yielda (%)
separated from the reaction products due to the high solubility
of the ionic liquid–substrate mixture in diethyl ether. In the 1 CO2Et n-Bu 2b RT 1 96
2 CO2Me Cinnamyl 2c 40 2 90
case of the reaction performed in [C4mim][NTf2] and 3 CO2Me Allyl 2d RT 2 91
[P66614][NTf2], the ionic liquid could only be partially sepa- 4 CO2Et Bn 2e RT 1 85
rated from the reactants and products and showed conversion 5 CO2Et Bn 2e RT 2 95
6 CO2Me H 2f RT 1 84
of the substrate of 80% and 70%, respectively (Table 1, entries 7 Ph H 2a RT 1 96
3, 4). In each case, the conversions were obtained from NMR a
Isolated yield.
determination in the ionic liquid. [C6mim]Cl was found to
separate efficiently from diethyl ether and the cycloisomeriza-
tion of 1a (Table 1, entry 5) resulted in the desired compound
were cleanly transformed to the corresponding g-alkylidene
2a in 79% isolated yield.
g-butyrolactones. Moreover, similar activity and selectivity
Due to the ease of workup [C6mim]Cl was also examined as
was found for the ionic liquid catalyst compared with
a medium for the cyclization of 1b over Au/beta. From an
the homogeneous AuCl catalysts system in acetonitrile.15
analysis of the 1H NMR, a conversion of 91% was obtained
Irrespective of the alkenyl side chain length the lactones were
with an isolated yield of the lactone of 58% (Table 1,
isolated in 85–96% yields (Table 2, entries 1–5) even at room
entry 6). Similar activities and selectivities were also found in
temperature. In all cases, the catalytic amount of gold ionic
conventional molecular solvents, such as acetonitrile (Table 1,
liquid used in these reactions was equivalent to the amount
entry 7).
used under heterogeneous conditions. No side reactions were
The heterogeneously catalyzed reaction results were com-
observed on the alkenyl side chains during the course of the
pared with the use of the ionic liquid as a catalyst in the form
reaction.
of the tetrachloroaurate based ionic liquids. Since [C6mim]-
Using the gold based ionic liquid system, complete trans-
[AuCl4] is a solid at room temperature, [C6mim]Cl was used as
formations of 2-prop-2-ynylmalonic acid monomethyl ester 1f
solvent. The results are summarised in Table 2.
with an 84% isolated yield (Table 2, entry 6) and of 2-phenyl-
To date, it has only been possible to exclude a base from the
pent-4-ynoic acid 1a with an 96% isolated yield (Table 2, entry 7)
homogeneous reaction conditions if the two substituents on a
after 1 h at room temperature were obtained. Similar results
tetrahedral centre were of a significant size, as understood by
were found for the reaction of 1a in the presence of [C2mim]-
the Thorpe–Ingold effect.36 In the case of the ionic liquid
[AuCl4], [C4mim][AuCl4] and [C18mim][AuCl4] at room
catalyst system, all the g-acetylenic carboxylic acids examined
temperature. These results for unsubstituted substrates are
comparable with those obtained under heterogeneous Au2O3
Table 1 Cyclization of functionalized acetylenic substrate over conditions (3 h),21 or homogeneous AuCl/K2CO3 conditions
Au/beta in a range of ionic liquids (2 h)20 and show significant advantages over other homo-
geneous gold chloride based catalysts.19 In the case of the
homogeneous catalysts, the formation of degradation pro-
ducts or the corresponding methylketone was observed for
the sterically unhindered substrates and the reaction only
occurred in the presence of a base. In the ionic liquid catalyzed
reactions, excellent reactivity was found without the need for
additives. Furthermore, the IL-catalysts were recycled three
times without any loss in conversion or yields.
Entry R1 R2 Solvent Product Yielda (Conv.) (%) A comparison of the homogeneous reaction (Table 2, entries
7 and 1) with that of the heterogeneous reaction (Table 1,
1 Ph H BIL 2a (75)b
2 Ph H [P66614][HSO4] 2a (70)b entries 5 and 6) indicates that the former is more active
3 Ph H [P66614][NTf2] 2a (70)b requiring a lower temperature and resulting in a higher con-
4 Ph H [C4mim][NTf2] 2a (80)b version/yield after 1 h. This is reflected in the turnover
5 Ph H [C6mim]Cl 2a 79 (83)
frequencies (TOF) for the homogeneous catalysts compared
6 CO2Et n-Bu [C6mim]Cl 2b 58 (91)
7 CO2Et n-Bu CH3CN 2b 60 (90) with the supported catalysts which are B19.8 h1 (at RT) and
a b B1.3 h1 (at 40 1C), respectively, for the formation of 2b, for
Isolated yield. IL inseparable from the system.
example. The lower rate is unlikely to be due to mass transfer

a Portfolio partnership from the EPSRC and an EU transna-
tional grant. CCLRC are thanked for providing EXAFS
beamtime.
References
1 J. A. Boon, J. A. Levinsky, J. I Pflug and J. S. Wilkes, J. Org.
Chem., 1986, 51, 480.
2 Ionic Liquids IIIA and B: Fundamentals, Progress Challenges and
Opportunities–Properties and Structure, eds. R. D. Rogers and
K. R. Seddon, American Chemical Society, Washington DC, 2005.
Scheme 1 The mechanism of cyclization of acetylenic carboxylic acid 3 J. S. Wilkes, J. Mol. Catal., A: Chem., 2004, 214, 11.
using Au3+ derived catalysts. It should be noted that representation of 4 Ionic Liquids in Synthesis, eds. P. Wasserscheid and T. Welton,
Wiley-VCH, Weinheim, 2007.
the gold as [Au] is for illustrative purposes only and will exist in the
5 C. Hardacre, Annu. Rev. Mater. Res., 2005, 35, 29.
form of a [AuClx]y+ complex. 6 V. Pârvulescu and C. Hardacre, Chem. Rev., 2007, 106, 2615.
7 C. Hardacre, J. D. Holbrey, M. Nieuwenhuyzen and T. G. A.
limitations in the heterogenous case which has been observed Youngs, Acc. Chem. Res., 2007, 40, 1146.
8 (a) F. Alonso, I. P. Beletskaya and M. Yus, Chem. Rev., 2004, 104,
in other solid catalyzed reactions in ionic liquids37 as the
3079; (b) M. Beller, J. Seayad, A. Tillack and H. Jiao, Angew.
acetonitrile reaction (Table 1, entries 6 and 7) also shows Chem., Int. Ed., 2004, 43, 3368; (c) I. Nakamura and Y.
reduced activity. The higher TOF may be expected due to the Yamamoto, Chem. Rev., 2004, 104, 2127; (d) for Ru-catalyzed
inaccessibility of the bulk gold atoms; however, even taking intermolecular reactions, see C. Bruneau and P. H. Dixneuf, Acc.
Chem. Res., 1999, 32, 311.
into account the lower dispersion of the heterogeneous cata- 9 H. Imagawa, Y. Fujikawa, A. Tsuchihiro, A. Kinoshita,
lyst, which contains 3 nm gold particles, the homogeneous T. Yoshinaga, H. Takao and N. Nishizawa, Synlett, 2006, 639.
catalyst has a higher intrinsic activity compared with the 10 C. H. Oh, H. J. Yi and J. H. Lee, New J. Chem., 2007, 31, 835.
heterogeneous system. 11 R. W. Spencer, T. F. Tam, E. Thomas, V. J. Robinson and
A. Krantz, J. Am. Chem. Soc., 1986, 108, 5589.
Scheme 1 shows a proposed mechanism for the gold based 12 Z. Huo, N. T. Patil, T. Jin, N. K. Pahadi and Y. Yamamoto, Adv.
ionic liquid catalyzed reaction. From the XPS and EXAFS, Synth. Catal., 2007, 349, 680; Z. Ahmed, U. Albrecht and
the active catalyst is thought to be Au3+ which activates the P. Langer, Eur. J. Org. Chem., 2005, 3469; A. Duchêne, J. Thibonnet,
J.-L. Parrain, E. Anselmi and M. Abarbri, Synthesis, 2007, 597.
acetylenic group.20 The ionic liquid provides a medium which 13 M. Jimenez-Tenotio, M. C. Puerta, P. Valerga, F. J. Moreno-
eliminates the use of a base. This role of the ionic liquid may Dorado, F. M. Guerra and G. M. Massanet, Chem. Commun.,
be to shift the acid equilibrium of the starting material to 2001, 2324.
favour the carboxylate anion, either by hydrogen bonding 14 S. Elgafi, L. D. Field and B. A. Messerle, J. Organomet. Chem.,
2000, 607, 97.
with the chloride, for example, or via stabilizing the anion in 15 (a) E. Genin, P. Y. Toullec, S. Antoniotti, C. Brancour, J.-P. Genêt
the ionic environment. This increase in concentration of the and V. Michelet, J. Am. Chem. Soc., 2006, 128, 3112; (b) E. Genin,
active intermediate allows reaction and activation of the P. Y. Toullec, S. Antoniotti, C. Brancour, J.-P. Genêt and
V. Michelet, ARKIVOC, 2007, v, 67.
carbon–carbon triple bond by the Au3+ centre and nucleo-
16 H. Harkat, J.-M. Weibel and P. Pale, Tetrahedron Lett., 2006, 47,
philic addition to the alkyne. After the cyclization a hydrogen 6273; for a recent Au-catalyzed cyclization of g- and d-acetylenic
mediated demetalation ends the catalytic cycle. It should be acids, see: E. Marchal, P. Uriac, B. Legoin, L. Toupet and P. van
noted that the scheme does not preclude the possibility that the de Weghe, Tetrahedron, 2007, 63, 9979.
17 P. Y. Toullec, E. Genin, S. Antoniotti, J.-P. Genêt and
cation of the ionic liquid may play an important role in V. Michelet, Synlett, 2008, 707.
creating the active catalyst. For example, imidazolium based 18 F. Neat-u, Z. Li, R. Richards, P. Y. Toullec, J.-P. Genêt,
ionic liquids have been shown to form carbenes with homo- K. Dumbuya, J. M. Gottfried, H.-P. Steinrück, V. I. Pârvulescu
geneous catalysts in C–C bond forming reactions.10 and V. Michelet, Chem.–Eur. J., 2008, 14, 9412.
19 A. Abad, A. Corma and H. Garcia, Chem.–Eur. J., 2008, 14, 212
and references therein.
20 R. J. David, Science, 2003, 301, 926, and references therein.
Conclusions 21 (a) Z.-R. Tang, J. K. Edwards, J. K. Bartley, S. H. Taylor,
A. F. Carley, A. A. Herzing, C. J. Kiely and G. J. Hutchings,
Gold chloride based ionic liquids have been shown to be very
J. Catal., 2007, 249, 208; (b) S. Carrettin, A. Corma, M. Iglesias
active catalysts in the cyclization of acetylenic substrates. The and F. Sanchez, Appl. Catal., A, 2005, 291, 247.
ionic liquid medium prevents nanoparticle formation via 22 K.-S. Kim, D. Demberelnyamba and H. Lee, Langmuir, 2004, 20,
stabilization of the gold in the form of isolated species by 556.
23 H. Itoh, K. Naka and Y. Chujo, J. Am. Chem. Soc., 2004, 126, 3026.
chlorine coordination. The ionic liquid also allows activation 24 R. Tatumi and H. Fujihara, Chem. Commun., 2005, 83.
of the carboxylic acid in the starting material and provides a 25 M. Hasan, I. V. Kozhevikov, M. R. H. Siddiqui, A. Steiner and
medium which eliminates the need for added base in order to N. Winterton, Inorg. Chem., 1999, 38, 5637.
cyclize unhindered acetylenic carboxylic acid. 26 M. Deetlefs, H. G. Raubenheimer and M. W. Esterhuysen, Catal.
Today, 2002, 72, 29.
27 Y. Liu, M. Liu, S. Guo, H. Tu, Y. Zhou and H. Gao, Org. Lett.,
Acknowledgements 2006, 8, 3445.
28 O. Aksin and N. Krause, Adv. Synth. Catal., 2008, 350, 1106.
This work was financially supported by the Consiliul National 29 I. Ambrogio, A. Arcadi, S. Cacchi, G. Fabrizi and F. Marinelli,
Synlett, 2007, 1775.
al Cercetarii Stiintifice din Invatamantul Support (CNCSIS) 30 P. Mastrorilli, C. F. Nobile, R. Paolillo and G. P. Suranna, J. Mol.
and the Centre National de la Recherche Scientifique (CNRS), Catal., A: Chem., 2004, 214, 103.
This journal is
31 C. M. Gordon, J. D. Holbrey, A. R. Kennedy and K. R. Seddon, H. Q. N. Gunaratne, A. McKeown, V. I. Pârvulescu and C. Hardacre,
J. Mater. Chem., 1998, 8, 2627; J. D. Holbrey and K. R. Seddon, J. Mol. Catal., A: Chem., 2007, 269, 64.
J. Chem. Soc., Dalton Trans., 1999, 2133; A. Downard, M. J. Earle, 34 N. Binstead, EXCURV98: CCLRC Daresbury Laboratory com-
C. Hardacre, S. E. J. McMath, M. Nieuwenhuyzen and S. J. Teat, puter program, 1998.
Chem. Mater., 2004, 16, 43. 35 H. Kitagawa, N. Kojima and T. Nakajima, J. Chem. Soc., Dalton
32 P. Bonhôte, A. P. Dias, N. Papageorgiou, K. Kalyanasundram and Trans., 1991, 3121.
M. Grätzel, Inorg. Chem., 1996, 5, 1168. 36 C. K. Ingold and J. F. Thorpe, J. Chem. Soc., Trans., 1915, 107, 1080.
33 U. Fröhlich, PhD Thesis, Queens University, Belfast, 2005U. Fröhlich, 37 P. N. Davey, S. A. Forsyth, H. Q. N. Gunaratne, C. Hardacre,
P. Goodrich, H. Q. N. Gunaratne, C. Hardacre, A. McKeown and A. McKeown, S. E. J. McMath, D. W. Rooney and K. R. Seddon,
K. R. Seddon, to be published; C. Paun, J. Barklie, P. Goodrich, Green Chem., 2005, 7, 224.

Magnetically moveable bimetallic (nickel/silver) nanoparticle/carbon

nanotube composites for methanol oxidationw
Guan-Ping Jin,*ab Ronan Baron,a Neil V. Rees,a Lei Xiaoa
and Richard G. Compton*a
Received (in Durham, UK) 22nd August 2008, Accepted 18th September 2008
First published as an Advance Article on the web 31st October 2008
DOI: 10.1039/b814630f
Multi-walled carbon nanotubes (CNTs) functionalized both by nickel and silver nanoparticles
were obtained using a single step chemical deposition method in an ultrasonic bath. The new
composite material was characterized by means of scanning electron microscopy (SEM), X-ray
diffraction (XRD) and cyclic voltammetry (CV). The electroactivity of the bi-functionalized CNTs
multi-walled carbon nanotubes was assessed in respect to the electrooxidation of methanol. It was
found that the carbon nanotube supported silver nanoparticles have significantly higher catalytic
properties than the bulk metal of the same surface area. Furthermore, it was shown that the
presence of only a very small proportion of magnetic nickel nanoparticles (1.5% of the total
number of metallic nanoparticles) allows the bi-functionalized carbon nanotubes to be moved
magnetically in solution, making them easily recoverable after use whilst keeping an optimal
electrocatalytic surface area.
1. Introduction silver nanoparticles are known to be efficient electrocatalysts

for methanol oxidation in alkaline solutions17,18 with less
The synthesis of magnetic nanomaterials has attracted con- poisoning observed than at platinum materials.19 However,
siderable attention in the last few years. One of the reasons for even though silver is much less expensive than platinum its
that interest is that magnetic material can be moved using a cost remains an issue.
magnet and which makes the considered material recoverable In order to get the benefits of both the magnetic properties
both for economical and environmental issues.1–4 Nanomater- of magnetic nanoparticles and the catalytic properties of
ials that can be magnetically driven are also very promising AgNPs we designed a hybrid material, which contains both.
for medical applications, such as drug delivery5 or complex NiNPs and AgNPs were synthesized on CNTs using a one-
biomanipulations.6 pot chemical deposition in an ultrasonic bath using a
The functionalization of carbon materials with magnetic methodology recently developed in our laboratory for the
particles is particularly attractive due to the properties and synthesis of NiNPs on glassy carbon microspheres.20 To
wide use of carbon materials. In particular, magnetic nano- date, this publication is the first report of the bi-functionaliza-
particles have been synthesized on the surface of carbon tion of CNT with NiNPs and AgNPs. In addition, the
nanotubes using various different methodologies.6–10 electrocatalytic oxidation of methanol at the new hybrid
As far as the use of magnetic nanomaterials in electro- material was studied.
chemistry is concerned, there have been only a limited number
of reports on the matter. Most notably Willner et al. studied
the use of hydrophobic magnetic nanoparticles capable of 2. Experimental
blocking an electrode surface11–13 and Wang et al. addressed
the use of magnetic nickel nanoparticles both for on-demand 2.1 Reagents and equipment
control of electrocatalytic processes and to reduce electrode Bamboo-like multi-walled carbon nanotubes (CNTs, diameter
surface fouling.14–16 30 10 nm, 5–20 mm length, o95% purity) were purchased
A lot of interest is devoted to methanol electrocatalytic from NanoLab (Brighton, MA, USA). Nickel(II) chloride
oxidation as it can be used in fuel cells and both bulk silver and (NiCl2, 99.9%) was obtained from Alfa Aesar (Heysham,
UK). L-Ascorbic acid (99.7%) and silver nitrate were supplied
a
Department of Chemistry, Physical and Theoretical Chemistry by BDH (Poole, UK). Nafion was purchased from Aldrich
Laboratory, Oxford University, South Parks Road, Oxford, (Poole, UK). Acetonitrile (ACN) was supplied by Sigma-
UK OX1 3QZ. E-mail: richard.compton@chem.ox.ac.uk; Aldrich (Gillingham, UK). All the reagents were used without
Fax: 0044-1-865 275410; Tel: 0044-1-1865 275413
b
Anhui Key Laboratory of Controllable Chemistry Reaction & further purification. All solutions were prepared using purified
Material Chemical Engineering, School of Chemical Engineering, water from Vivendi UHQ grade water system with a resistivity
Hefei University of Technology, Hefei, 230009, P. R. China. of not less than 18.2 MO cm.
E-mail: jgp@hfut.edu.cn; Fax: 0086-0551-2902450; Electrochemical measurements were recorded using an
Tel: 0086-551-2901450
w Electronic supplementary information (ESI) available: Videos S1–3. Autolab PGSTAT 30 computer-controlled potentiostat with
See DOI: 10.1039/b814630f a standard three-electrode setup. Either a home-made 4 mm
This journal is
diameter disc paraffin-impregnated graphite electrode21 or a 2.4 Movement of the AgNPs,NiNPs/CNTs composite
0.08 mm diameter disk bulk silver served as working electro- material
des. Paraffin-impregnated graphite electrodes have similar
The AgNPs,NiNPs/CNTs (AgNPs/CNTs, NiNPs/CNTs)
behaviour than other common graphite electrodes and have
composite materials were pipetted onto a 1.0 mm thick glass
been chosen here because they are easy to fabricate and it is
surface with some water. A magnet (NdFeB alloy rod magnet,
easy to renew their surface by a polishing step. A platinum
purchased from e-magnets UK Ltd, Sheffield, UK) was posi-
wire was used as a counter electrode, and a silver wire used as
tioned directly below the glass surface and moved by an
the reference electrode completed the cell assembly. The
electronic motor. The directed movement of the nanocom-
paraffin-impregnated graphite electrode surface was renewed
posites was observed and recorded using an optical microscope
by successive mechanical polishing steps on alumina powders
with a Bressler Visiomar video camera (160 magnification
(Micropolish II, Buehler) of 1 to 0.3 mm in diameter. The
using a 320 240 pixel frame).
electrode was sonicated for 5 min in deionized water after each
polishing step. All experiments were carried at a temperature
of 20 1 1C. All the solutions were degassed with nitrogen 3. Results and discussion
prior to the electrochemical recordings.
Scanning electron microscopy (FEG-SEM, tungsten fila- 3.1 Synthesis and microscopic characterization of the
ment as electron source, acceleration voltage 20 keV) images nanoparticle-modified CNTs
and energy dispersion X-ray spectra analysis were performed The synthesis of the silver and nickel nanoparticles on the
using a JEOL 6300 F instrument. X-Ray diffraction patterns surface of the CNTs was obtained following the steps noted in
(XRD) were collected on a PANalytical X’Pert instrument Scheme 1. First the CNTs are treated with concentrated nitric
with 40 kV and 40 mA settings. and perchloric acids to generate carboxylic groups on their
Sonication was obtained using a D-78224 Singen/Htw edges and defects. The negatively charged sites chelate silver
sonicator (50/60 Hz, 80 W, UK). and nickel cations added to the solution. It is then expected
that the addition of ascorbic acid as a mild reducing agent in
2.2 Ultrasonic synthesis of silver and nickel nanoparticles the presence of ultrasound results in the production of small
on CNTs nickel and silver nanostructures on the surface of the CNTs.
Similar experimental routes were followed for the synthesis of
The nickel and silver nanoparticles were synthesized onto nickel or silver nanoparticles separately on the CNTs.
the surface of CNTs using the following protocol: The CNTs A scanning electronic microscopy analysis of the samples
were sonicated in conc. HClO4 + HNO3 (3:7, v:v) for reveals that silver and nickel nanoparticles of 100 nm in
7 h in order to oxidize their surface, they were then filtered diameter in average are obtained on the CNTs (Fig. 1). The
and extensively washed with deionized water to pH 7, and EDX (Fig. 2) and XRD spectra of the samples (Fig. 3) confirm
dried in air. Then, 2.9 mg NiCl2, 1.7 mg AgNO3 and 2.0 mg the presence of both silver and nickel nanoparticles. It can be
oxidized CNTs were added to 60 mL of acetonitrile in an noticed that the peaks for Ni (111) and Ag (111) are larger
airtight glass flask. The mixture was sonicated for one hour. than the other peaks, which reveals that the most common
4.0 mg of L-ascorbic was then added in the flask and the pH nanoparticles on the CNTs are face-centered cubic (fcc)
was adjusted to 5.2 using 1 M NaOH. The reaction was nickel and silver. The average crystallite size calculated using
allowed to proceed for 5 min at 65 1C under sonication. Scherrer’s equation from the width at half peak maximum for
Finally, the products were separated by centrifugation, the NiNPs is 30 25, and 25 15 nm, respectively for the
washed with acetonitrile and deionized water to remove any
unreacted species. The multi-walled carbon nanotubes deco-
rated with silver and nickel nanoparticles (AgNPs,NiNPs/
CNTs) were allowed to air-dry for 24 h prior to use. Multi-
walled carbon nanotubes decorated only with silver (AgNPs/
CNTs) or nickel nanoparticles (NiNPs/CNTs) were obtained
using the same method.
2.3 Modification of the paraffin-impregnated graphite

electrodes with CNTs
Films of CNTs on the surface of paraffin-impregnated
graphite electrodes were obtained as follows: 2 mg of CNTs
decorated with nanoparticles was suspended in 2 mL of
Nafion (0.05%) and acetonitrile solution to form a ‘‘casting’’
suspension. The casting suspension was then briefly sonicated
for 2 min in order to disperse the CNTs decorated with Scheme 1 Preparation of multi-walled carbon nanotubes (CNTs)
nanoparticles. Some of the suspension was then pipetted onto functionalized both by nickel and silver nanoparticles using a single
the surface of a freshly polished paraffin-impregnated graphite step chemical deposition method in an ultrasonic bath and subsequent
electrodes and let to dry in air. immobilization of the new composite material on an electrode surface.

Fig. 1 SEM images of the multi-walled carbon nanotubes functionalized both by nickel and silver nanoparticles (AgNPs,NiNPs/CNTs). The
square on Fig. 1(A) indicates where the EDX spectrum in Fig. 2 was obtained.
Experimental section. The electrode surfaces can be charac-

terized electrochemically by oxidizing the metallic nanoparti-
cles. Some metal oxides have a well-defined and specific
reduction potential and the corresponding reduction peak
can be used to estimate the surface area of specific metals.
Fig. 4 shows the cyclic voltammograms that were obtained in
0.1 M NaOH for the various modified electrodes. It can
be observed that the voltammogram corresponding to the
AgNPs,NiNPs/CNTs modified electrode corresponds to the
superposition of the characteristic features of both the AgNPs/
CNTs and the NiNPs/CNTs modified electrodes. Using the
Fig. 2 EDX spectra of (A) AgNPs,NiNPs/CNTs, (B) NiNPs/CNTs literature values of 790 and 270 mC cm 2 for the charge passed
and (C) AgNPs/CNTs. per unit area of surface area of nickel and silver,23–25 we can
estimate the total surface area of each of the metals for the
AgNPs,NiNPs/CNTs/Nafion material. The average loading
of the nickel and silver nanostructures on the CNTs were
estimated to be, respectively in the order of 3.4 10 2 and
2.2 cm2 mg 1. Which then shows that, for nanoparticles of
about the same size, the NiNPs represent only 1.5% of the
total number of nanoparticles.
3.3 Electrocatalysis
The electroactivity of the mono- and bi-functionalized multi-
walled carbon nanotubes was assessed and compared with the
Fig. 3 XRD spectra of (a) Ni/CNTs, (b) AgNPs/CNTs and (c)

AgNPsNi/CNTs.
NiNPs/CNTs and the AgNPs,NiNPs/CNTs and 20 10 nm

for the AgNPs of the AgNPs/CNTs and the AgNPs,NiNPs/
CNTs. It can be further stated on the nature of the silver and
nickel nanoparticles that those particles are distinct and do not
crystallise in the form of alloys, as it is well known that Ni and
Ag are immiscible in both the solid and liquid phases.22
Fig. 4 Cyclic voltammetry (30th cycle) in 0.1 M NaOH at a 4 mm
3.2 Electrode modification and characterization diameter paraffin-impregnated graphite electrode modified with
(a) 20 mL CNTs/Nafion, (b) 20 mL NiNPs/CNTs/Nafion, (c) 20 mL
The electrode surfaces were modified by the decorated CNTs AgNPs/CNTs/Nafion and (d) 80 mL AgNPs,NiNPs/CNTs/Nafion
in a Nafion film by following the protocol described in the casting solutions. Scan rate: 50 mV s 1.
This journal is
Table 1 Catalytic performance for methanol oxidation of various
electrode architectures; A is the metal total surface area estimated by
electrochemical oxidation of the surface, Ip is the peak current value
measured for a voltammetric scan obtained at 50 mV s 1 in 0.56 M
methanol and 0.1 M NaOH and Jp is the corresponding current
density in respect to the total surface of silver
Electrode A/cm2 Ip/mA Jp/mA cm 2
2
Ag bulk 0.16 0.05 9.28 10 0.58 0.2
NiNPs/CNTs/Nafion 0.29 0.1 3.00 10.3 2
AgNPs/CNTs/Nafion 0.30 0.1 3.3 11.0 2
AgNPs,NiNPs/CNTs/Nafion 0.56 0.2 4.14 7.4 2
3.4 Characterization of magnetically driven movement of the

AgNPs,NiNPs/CNTs composites
Fig. 5 Second cycle cyclic voltammetric curves obtained in 0.56 M The possibility of magnetically recovering the electrocatalytic
methanol and 0.1 M NaOH at a 0.08 mm diameter silver electrode nanomaterial was explored by assessing the possibility to move
(curve a) and at a 4 mm diameter paraffin-impregnated graphite it with a magnet using the setup described in the Experimental
electrode modified with casting solutions made of 80 mL CNTs/Nafion section. As it can be seen in Fig. 6 and Video S1 (ESIw), with
(curve b), 80 mL NiNPs/CNTs/Nafion (curve c), 80 mL AgNPs/CNTs/ the shift of a magnet positioned directly below the glass
Nafion (curve d) and 120 mL AgNPs,NiNPs/CNTs/Nafion (curve e). surface, the AgNPs,NiNPs/CNTs composites move from right
Scan rate: 50 mV s 1.
bottom to middle, then, to left up in the video screen,
suggesting an obvious movement for AgNPs,NiNPs/CNTs
composites on the surface of glass. The same test was
electroactivity of bulk silver macroelectrodes in respect
undertaken for the NiNPs/CNTs and AgNPs/CNTs nano-
to the electrooxidation of methanol. The cyclic voltam-
composites. A similar response can be seen for NiNPs/CNTs
mograms obtained for the second cycle are shown in Fig. 5.
composites (Video S2, ESIw). However, no move was observed
We choose to present the second cycle as a non-negligable
for AgNPs/CNTs nanocomposites (Video S3, ESIw). It is then
decrease in intensity (ca. 25%) is observed from the first cycle
possible to conclude that the bifunctionalisation of the CNTs
to the second one. Measurements show a decrease of less
provides the possibility to magnetically drive them to a specific
than 10% is then observed between the second and the
location in a solution. This added property to the new
twentieth cycle. The electrochemical characterization of the
electroactive nanomaterial allows, for example, the recovery
modified electrode surfaces, conducted independently as
of the catalyst once the reaction has taken place.
described above, provides valuable data to compare the
electrocatalytic efficiency of the different materials. Indeed,
the catalytic currents obtained can be normalized with the
4. Conclusions
total metal surface area to provide the current density per unit
of electroactive surface (Table 1). The data reported in Table 1 Multi-walled carbon nanotubes functionalized either by nickel or
show that the AgNPs/CNTs/Nafion- and AgNiNPs/CNTs/ silver nanoparticles or by both were obtained using a single step
Nafion-modified electrodes have similar properties, with a chemical deposition method in an ultrasonic bath. The electro-
current density about more than ten times higher than the activity of the bi-functionalized CNT multi-walled carbon nano-
current density obtained at the bulk silver macroelectrode. tubes was assessed in respect to the electrooxidation of methanol.
Such a higher electrocatalytic property can partially be It was found that they have significantly higher catalytic proper-
explained by the higher substrate diffusion that we expect to ties than the bulk silver of the same surface area. Furthermore, it
observe at dispersed nanoparticles.26–31 Furthermore it has to was shown that the addition of a minute fraction (1.5%) of
be said from the results reported in Table 1 that the experi- NiNPs in respect to the total number of nanoparticles adds to
mental results show that NiNPs and AgNPs have similar their electrocatalytic properties the possibility to easily move
electrocatalytic properties towards the electrooxidation of them in solution using a magnet. The bi-functionalized carbon
methanol. nanotubes are then easily recoverable after use.
Fig. 6 Optical microscopy images of the AgNPs,NiNPs/CNTs material, taken at 10 s time-intervals and following the movement of a magnet
going forward (images (A) to (C)) and then going backward (images (D) to (F)). These pictures were extracted from Video S1 (ESIw).

Acknowledgements 13 E. Katz, R. Baron and I. Willner, J. Am. Chem. Soc., 2005, 127,
4060.
G.-P. J. gratefully acknowledges financial support from 14 J. Wang, M. Musameh and R. Laocharoensuk, Electrochem.
Commun., 2005, 7, 652.
Natural Science Foundation of Anhui Province of China
15 J. Wang, M. Musameh, R. Laocharoensuk, O. Gonzalez-Garcia,
(No. 070415210), Science and Technology Program Founda- J. Oni and D. Gervasio, Electrochem. Commun., 2006, 8, 1106.
tion of Hefei City (No. 20071032), and Doctor Foundation of 16 R. Laocharoensuk, A. Bulbarello, S. B. Hocevar, S. Mannino,
Hefei University of Technology (2005). R. B. and N. V. R. are B. Ogorevc and J. Wang, J. Am. Chem. Soc., 2007, 129, 7774.
17 D. J. Guo and H. L. Li, Carbon, 2005, 43, 1259.
grateful to EPSRC for funding. 18 M. Avramov-Ivic, S. Strbac and V. Mitrovic, Electrochim. Acta,
2001, 46, 3175.
19 R. Baron, F. W. Campbell, I. Streeter, L. Xiao and
References R. G. Compton, Int. J. Electrochem. Sci., 2008, 3, 556.
20 G.-P. Jin, R. Baron, L. Xiao and R. G. Compton, J. Nanosci.
1 M. J. Jacinto, P. K. Masunaga, H. Sueli, R. F. Jardim and Nanotechnol., DOI: 10.1166/jnn.2008.462.
L. M. Rossi, Appl. Catal., A, 2008, 338, 52. 21 G.-P. Jin and X. Q. Lin, Electrochim. Acta, 2005, 50, 3556.
2 B. Baruwati, D. Guin and S. W. Manorama, Org. Lett., 2007, 9, 22 J. Xu, U. Herr, T. Klassen and R. S. Averback, J. Appl. Phys.,
5377. 2006, 79, 3935.
3 G. Chouhan, D. Wang and H. Alper, Chem. Commun., 2007, 4809. 23 L. M. Abrantes, M. C. Oliveira, J. P. Bellver and J. Lecoeur,
4 C. O. Dalaigh, S. A. Corr, Y. Gun’ko and S. J. Connon, Angew. Electrochim. Acta, 1994, 39, 1915.
Chem., Int. Ed., 2007, 46, 4329. 24 K. A. Soliman 1 and L. A. Kibler, Electrochim. Acta, 2007, 52, 5654.
5 F. Yang, D. L. Fu, J. Long and Q. X. Ni, Med. Hypotheses, 2008, 25 M. J. Esplandiu, M. A. Schneeweiss and D. M. Kolb, Phys. Chem.
70, 765. Chem. Phys., 1999, 1, 4847.
6 C. Gao, W. Li, H. Morimoto, Y. Nagaoka and T. Maekawa, 26 R. G. Compton, G. G. Wildgoose, N. V. Rees, I. Streeter and
J. Phys. Chem. B, 2006, 110, 7213. R. Baron, Chem. Phys. Lett., 2008, 459, 1.
7 S. Qu, J. Wang, J. Kong, P. Yang and G. Chen, Talanta, 2007, 71, 27 I. Streeter, R. Baron and R. G. Compton, J. Phys. Chem. C, 2007,
1096. 111, 17008.
8 H. Cao, M. Zhu, Y. Li, J. Liu, Z. Ni and Z. Qin, J. Solid State 28 R. Baron, B. Sljukic, C. Salter, A. Crossley and R. G. Compton,
Chem., 2007, 180, 3218. Electroanalysis, 2007, 19, 1062.
9 A. Reyhani, S. Z. Mortazavi, O. Akhavan, A. Z. Moshfegh and 29 R. Baron, G. G. Wildgoose and R. G. Compton, J. Nanosci.
S. Lahooti, Appl. Surf. Sci., 2007, 253, 8458. Nanotechnol., DOI: 10.1166/jnn.2008.470.
10 B. Jia, L. Gao and J. Sun, Carbon, 2007, 45, 1476. 30 B. Šljukić, R. Baron, C. Salter, A. Crossley and R. G. Compton,
11 I. Willner and E. Katz, Langmuir, 2006, 22, 1409. Anal. Chim. Acta, 2007, 590, 67.
12 E. Katz, L. Sheeney-Haj-Ichia, B. Basnar, I. Felner and I. Willner, 31 R. Baron, B. Šljukić, C. Salter, A. Crossley and R. G. Compton,
Langmuir, 2004, 20, 9714. Russ. J. Phys. Chem., 2007, 81, 1443.
This journal is
Microwave-assisted facile synthesis of discotic liquid crystalline

symmetrical donor–acceptor–donor triads
Satyam Kumar Gupta, V. A. Raghunathan and Sandeep Kumar*
Received (in Durham, UK) 23rd May 2008, Accepted 11th July 2008
First published as an Advance Article on the web 8th September 2008
DOI: 10.1039/b808750d
We report the synthesis and characterization of two series of novel triphenylene–anthraquinone-

based symmetric discotic liquid crystalline trimers. These triads were prepared using microwave
dielectric heating. Conventional heating under similar reaction conditions failed to produce
desired products. To the best of our knowledge, these are the first donor–acceptor–donor triads
in which all the three components represent discotic mesogenic moieties. Chemical structures of
these discotic oligomers have been characterized by spectral techniques and elemental analysis.
The thermotropic liquid crystalline properties of these donor–acceptor–donor triads were
investigated by polarizing optical microscopy and differential scanning calorimetry. They exhibit
a columnar mesophase over a wide range of temperature. The columnar hexagonal mesophase
structure of these discotic oligomers has been elucidated with the help of X-ray diffraction studies.
Introduction organic electronic devices such as photovoltaic solar cells, light

emitting diodes and field effect transistors.2
The notable improvement in the performance of electronic Microwave-assisted high-speed chemical synthesis has
devices based on organic semiconductors has attracted great attracted a considerable amount of attention in the past decade.
interest in recent years.1 The improved efficiency of organic Almost all types of organic reactions have been performed
devices has origins ranging from appropriate molecular design using the efficiency of microwave-flash heating. This is not
to well-defined structured layers essential for effective charge only due to the fact that reactions proceed significantly faster
transport. Recently there have been tremendous efforts to and more selectively than under conventional thermal condi-
achieve both p-type (hole conducting) and n-type (electron tions but also because of the operational simplicity, high yield
conducting) properties in organic semiconducting materials of products and cleaner reactions with easier work-up. A large
which are crucial for molecular electronics. One elegant number of review articles provide extensive coverage of the
approach for such materials is to covalently link electron subject.3 Recently we and others have reported the synthesis
donor and electron acceptor components at molecular level. of a variety of liquid crystalline materials using microwave
These kinds of materials are expected to behave as intrinsic, dielectric heating.4
non-composite p/n-type semiconductors. Such chemical tailor- Very recently a great deal of attention is being paid to liquid
ing could lead to the development of other molecular archi- crystal oligomers.5 The physical properties of liquid crystalline
tectures and it is envisaged that the combination of covalent oligomers are significantly different from those of conven-
chemistry and self-assembly will be crucial for the develop- tional low molar mass liquid crystals. Their purification and
ment of nano-engineered functional materials for electronic characterization are simple, and due to the restricted motion
applications.1 Among the diverse semiconductors, discotic of their components liquid crystal oligomers provide and
liquid crystals (DLCs) play an important role in the design stabilize a variety of fluid phases with fascinating functions.
of electronic devices.2 Discotic liquid crystals are unique Further, an oligomeric approach provides a wide flexibility in
nanostructures with remarkable electronic and optoelectronic molecular design towards multifunctional liquid crystals.
properties. Due to the co-facial stacking of aromatic cores, However, compared to the number of calamitic oligomers,
disc-like molecules self organize into one dimensional colum- discotic oligomers are rare. In this context we are interested in
nar wire and these columns in turn arrange themselves in the design and synthesis of novel functional discotic oligo-
various two-dimensional lattices. The transport along the meric materials and their mesophase behavior. Our molecular
columnar axis is much faster than between the columns. Due design is such that it contains the well studied electron rich
to their relatively high charge carrier mobility, tendency to triphenylene moiety6 and electron deficient anthraquinone7 as
form highly order films of various thickness and self healing of the hole and electron transporting components, respectively.
defects owing to their dynamic nature, discotic mesogens have These molecular double-cables, owing to their incommensu-
been considered as attractive candidates for applications in rate core sizes, may stack one on top of the other in the
columns to give columnar versions of double cable polymers,8
which could eventually provide side-by-side percolation
pathways for electrons and holes in solar cells. Here, we
Raman Research Institute, C.V. Raman Avenue, Sadashivanagar,
Bangalore, 560 080, India. E-mail: skumar@rri.res.in; report the synthesis and mesomorphism of novel triphenylene–
Fax: +91 80 23610492; Tel: +91 80 23610122 anthraquinone–triphenylene discotic liquid crystalline symmetric

trimers. To the best of our knowledge, these are the first monitoring). The cooled reaction mixture was then poured
donor–acceptor–donor triads in which all the three compo- into an excess of distilled water and extracted with chloroform.
nents represent discotic mesogenic moiety. The organic extract was dried over anhydrous sodium sulfate,
concentrated and the product was purified by repeated column
chromatography over silica gel (eluent: 4% ethyl acetate in
Experimental hexane). Solvent was then removed in rotary evaporator. The
General information residue was then dissolved in dichloromethane and the result-
ing solution was added to cold methanol to afford 7a10
Chemicals and solvents (AR quality) were used as received (34 mg, 25%). 1H NMR (400 MHz, CDCl3): d 7.83 (s, 12 H),
without any further purification. Microwave irradiation was 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz,
performed in an unmodified household microwave oven. 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H), 1.77 (q, J = 7.5 Hz,
(LG, MS-192W). However, commercial microwave reactors 4 H), 0.8–1.6 (m, 190 H). 13C NMR (100 MHz, CDCl3):
for organic reactions are now available which provides d 181.2, 157.5, 153.9, 149.1, 147, 132.7, 123.7, 107.6, 107.1,
adequate mixing and control of reaction parameters such as 77.3, 77, 76.7, 75.9, 74.7, 74.1, 69.8, 69.2, 31.9, 31.7, 30.4, 29.5,
temperature and pressure. Column chromatographic separa- 29.4, 26.1, 25.9, 22.7, 21.3, 18.5, 15.9, 14.0. Elemental analysis:
tions were performed on silica gel (230–400 mesh). Thin layer Calc. for C174H276O20, C 77.75, H 10.35. Found: C 77.32,
chromatography (TLC) was performed on aluminum sheets H 10.53%. All other compounds give satisfactory spectral and
precoated with silica gel (Merck, Kieselgel 60, F254). Chemi- elemental analysis data in accordance with their chemical
cal structure characterization of the compounds was carried structure. Selected data for compound 7a6: 1H NMR: d 7.83
out through a combination of 1H NMR, 13C NMR (Bruker (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J =
AMX 400 spectrometer) and elemental analysis (Carlo-Erba 6.4 Hz, 4 H), 4.06 (t, J = 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77
EA1112 analyzer). 1H NMR spectra were recorded using (q, J = 7.5 Hz, 4 H), 0.8–1.6 (m, 158 H). Elemental analysis:
deuterated chloroform (CDCl3) as solvent. Tetramethylsilane Calc. for C158H244O20, C 77.03, H 9.98. Found: C 76.63,
(TMS) was used as an internal standard. The transition H 9.98%. 7a7: 1H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23
temperatures and associated enthalpy values were determined (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz, 4 H), 4.06 (t, J =
using a differential scanning calorimeter (DSC; Perkin-Elmer, 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J = 7.8 Hz, 4 H), 0.8–1.6
Model Pyris 1D) which was operated at a scanning rate of (m, 166 H). Elemental analysis: Calc. for C162H252O20, C
5 1C min1 both on heating and cooling cycles. The apparatus 77.22, H 10.08; Found C 76.91, H 10.04%. 7a8: 1H NMR:
was calibrated using indium (156.6 1C) as a standard. The d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14
textural observations of the mesophase were carried out using (t, J = 6.5 Hz, 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H),
polarizing light microscopy (Olympus BX51) provided with a 1.78 (q, J = 6.9 Hz, 4 H), 0.8–1.6 (m, 174 H). Elemental
heating stage (Mettler FP82HT) and a central processor analysis: Calc. for C166H260O20, C 77.40, H 10.17. Found: C
(Mettler FP90). X-Ray diffraction studies (XRD) were carried 77.13, H 9.82%. 7a10 0 : 1H NMR: d 7.83 (s, 12 H), 7.61
out on unoriented samples using Cu-Ka (l = 1.54 Å) radia- (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.5 Hz,
tion from a Rigaku Ultrax 18 rotating anode generator 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J =
(5.4 kW) monochromated with a graphite crystal. The samples 6.9 Hz, 4 H), 0.8–1.6 (m, 190 H). Elemental analysis: Calc. for
were held in sealed Lindemann capillary tubes (0.7 mm C174H276O20, C 77.75, H 10.35. Found: C 77.32, H 10.89%.
diameter) and the diffraction patterns were collected on a 7a14: 1H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz,
two-dimensional Marresearch image plate. 24 H), 4.14 (t, J = 6.3 Hz, 4 H), 4.06 (t, J = 5.6 Hz, 8 H), 1.94
(m, 32 H), 1.77 (q, J = 7.8 Hz, 4 H), 0.8–1.6 (m, 222 H).
Synthesis of trimers
Elemental analysis: Calc. for C190H308O20, C 78.35, H 10.66.
Rufigallol 2, 1,5-dihydroxy-2,3,6,7-tetraalkoxy-9,10-anthra- Found: C 77.96, H 10.71%. 7b6: 1H NMR: d 7.83 (s, 12 H),
quinone 3, hexaalkoxytriphenylene 4, monohydroxypenta- 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.15 (t, J = 6.4 Hz,
alkoxytriphenylene 5 and o-bromo-substituted triphenylene 4 H), 4.06 (t, J = 6.4 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J =
6 were prepared as reported by us previously.9 All the trimers 7.8 Hz, 4 H), 0.8–1.6 (m, 150 H). Elemental analysis: Calc. for
were prepared following same method which involves alkyla- C154H236O20, C 76.83, H 9.88. Found: C 76.37, H 9.89%. 7b7:
1
tion of 1,5-dihydroxy-2,3,6,7-tetraalkoxy-9,10-anthraquinone H NMR: d 7.83 (s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz,
3 with terminal bromo-substituted triphenylene 6 using micro- 24 H), 4.14 (t, J = 6.8 Hz, 4 H), 4.06 (t, J = 6.3 Hz, 8 H),
wave dielectric heating. A typical procedure for the synthesis 1.94 (m, 32 H), 1.78 (q, J = 7.4 Hz, 4 H), 0.8–1.6 (m, 158 H).
of a representative example 7a10 is given below. The suffix Elemental analysis: Calc. for C158H244O20, C 77.03, H 9.98.
number in the series 7a and 7b, represents the number of Found: C 76.62, H 10.36%. 7b10: 1H NMR: d 7.83 (s, 12 H),
carbon atoms in the peripheral chains attached with central 7.59 (s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.3 Hz,
anthraquinone moiety (R in the structure 7, Scheme 1). 4 H), 4.06 (t, J = 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77 (q, J =
A mixture of compound 6a (n = 9) (300 mg, 0.30 mmol), 7.8 Hz, 4 H), 0.8–1.6 (m, 182 H). Elemental analysis: Calc. for
3 (R = C10H21) (43 mg, 0.05 mmol) and Cs2CO3 (200 mg, 0.61 C170H268O20, C 77.58, H 10.26. Found: C 77.31, H 10.23%.
mmol) in NMP (0.5 mL) was irradiated in a microwave oven 7b10 0 : 1H NMR: d 7.84 (s, 12H, Ar–H), 7.59 (s, 2 H), 4.23
for 30 s. The vial was removed from the oven and left to stand (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.3 Hz, 4 H), 4.06 (t, J =
for about 1 min and again irradiated for 30 s. This process was 6.5 Hz, 8 H), 1.94 (m, 32 H), 1.77 (q, J = 7.8 Hz, 4 H), 0.8–1.6
repeated for 20 times until the reaction was complete (TLC (m, 182 H). Elemental analysis: Calc. for C170H268O20, C 77.58,
This journal is
Scheme 1 Synthetic route of triphenylene–anthraquinone trimers. 7a Series: OR = H (7a0); R = n-C6H13 (7a6); R = n-C7H15 (7a7); R =
n-C8H17 (7a8); R = n-C10H21 (7a10); R = 3,7-dimethyloctyl (7a10 0 ); R = n-C14H29 (7a14); 7b Series: R = n-C6H13 (7b6); R = n-C7H15 (7b7);
R = n-C10H21 (7b10); R = 3,7-dimethyloctyl (7a10 0 ); R = n-C12H25 (7a12); R = n-C14H29 (7a14).
H 10.26. Found: C 77.14, H 10.00%. 7b12: 1H NMR: d 7.84 o-bromo-substituted triphenylene failed under classical
(s, 12 H), 7.59 (s, 2 H), 4.23 (t, J = 6.3 Hz, 24 H), 4.14 (t, J = thermal heating conditions even by using strong basic condi-
6.3 Hz, 4 H), 4.06 (t, J = 6.2 Hz, 8 H), 1.94 (m, 32 H), 1.77 tions and prolonged reaction times (24 h). For instance,
(q, J = 7.8 Hz, 4 H), 0.8–1.6 (m, 190 H). Elemental analysis: heating the same reaction mixture in DMF at 100 1C for
Calc. for C178H284O20, C 77.91, H 10.43. Found: C 77.78, 48 h or heating a mixture of 3 and 6 in DMF and NaOH or
H 10.30%. 7b14: 1H NMR: d 7.83 (s, 12 H), 7.59 K2CO3 for 48 h did not furnish any product.
(s, 2 H), 4.23 (t, J = 6.5 Hz, 24 H), 4.14 (t, J = 6.4 Hz,
4 H), 4.06 (t, J = 6.3 Hz, 8 H), 1.94 (m, 32 H), 1.78 (q, J = Thermal behavior
7.6 Hz, 4 H), 0.8–1.6 (m, 198 H). Elemental analysis: Calc. for
The thermal behavior of all the compounds was investigated
C186H300O20, C 78.21, H 10.59. Found: C 78.16, H 10.53%.
by polarizing optical microscopy (POM) and differential scan-
ning calorimetry (DSC). In the case of materials which were
Results and discussion mesomorphic, classical textures of discotic columnar meso-
phases appeared upon cooling from the isotropic liquid as
Synthesis
shown in Fig. 1. These textures are similar to the known
The synthesis of the novel symmetrical trimers was achieved as textures for Colh phases. All the trimers contain two identical
shown in Scheme 1. The unequal reactivity of the six phenolic triphenylenes substituted with five hexyloxy peripheral chains
groups of rufigallol 2, two of which are less reactive by virtue linked to the central anthraquinone moiety through a
of being intramolecularly hydrogen bonded to the adjacent 12- (7a series) or a 10- (7b series) methylene spacer. In both
quinone carbonyls, was exploited. Etherification of rufigallol 2 the series the peripheral alkyl chain lengths around the
under mild conditions produced 1,5-dihydroxy-2,3,6,7-tetra- anthraquinone core varies from hexyloxy to tetradecyloxy.
alkoxy-9,10-anthraquinone 3 without alkylating the hydrogen The transition temperature and associated enthalpy data
bonded C-1 and C-5 positions. These tetraalkoxy derivatives obtained from the heating and cooling cycles of DSC are
were further alkylated by o-bromo-substituted triphenylenes collected in Table 1. The peak temperatures are given in 1C
with the help of microwave dielectric heating as shown in and the numbers in parentheses indicate the transition en-
the Scheme 1, under mild basic conditions to furnish the thalpy (DH) in J g1. The compound 7a0, without any
symmetrical trimers within 10 min, which is simple, efficient, peripheral alkyl chains (OR = H) around the central core of
rapid and economic. All attempts to etherify the intramolecu- the trimer, does not exhibit any liquid crystalline property. It
larly hydrogen bonded C-1 and C-5 positions with bulky melts from crystalline solid state to isotropic liquid state at

Fig. 1 Optical micrograph of 7a6 at 80 1C on cooling from the
isotropic liquid (crossed polarizer, magnification 200)
Fig. 2 DSC thermogram of the trimer 7a6 on heating and cooling
cycles (scan rate 10 1C min1).
39.7 1C on heating and on cooling it crystallizes slowly over a
period of time at room temperature. This could be because the
absence of alkyl chains around the core does not provide the
space filling effect of alkyl chains which is crucial for exhibiting
mesophase behavior in discotic liquid crystals. The highest
homologue of the series 7a14 also does not display any liquid
crystalline property, it passes from crystalline solid state to
isotropic liquid state at 47 1C on heating and on cooling the
isotropic liquid crystallizes at 18.4 1C. This could be because
the longer alkyl chains around the central anthraquinone core
may hinder the self-assembly of molecules. All other members
of the 7a series 7a6, 7a7, 7a8, 7a10 and 7a10 0 display enantio-
tropic mesophase behavior. In their DSC thermograms, they
display a soft solid to mesophase transition followed by
mesophase to isotropic transition on heating. Upon cooling
they show only isotropic to mesophase transition and the
mesophase remains stable down to room temperature or
partially solidified at low temperature. As a typical example Fig. 3 Variation of phase transition temperatures of 7a6–7a10
the DSC thermogram of compound 7a6 is shown in Fig. 2. On with number of carbon atoms in the peripheral alkyl chains of
increasing the alkyl chain length around the anthraquinone anthraquinone.
core the mesophase to isotropic transition temperatures of the
trimers decrease as shown in the Fig. 3. This could be because 7b10 0 shows monotropic phase behavior. Other trimers 7b10,
the longer alkyl chains introduce more intracolumnar disorder 7b12 and 7b14 of the series do not exhibit any liquid crystalline
and hence core–core unstacking becomes easier. property. They show only crystalline to isotropic and isotropic
In series 7b only two trimers 7b6 and 7b7 were found to to crystalline transitions on heating and cooling, respectively.
display enantiotropic liquid crystalline properties. Compound This is not surprising as the spacer connecting the donor with
Table 1 Phase transition temperatures (peak, 1C) and associated enthalpy changes (J g1 in parentheses) of novel symmetrical trimers
Compounda First heating scan First cooling scan

7a6 ss 59.1 (1.6) Colh 104.1(6.0) I I 99.3 (6.4) Colh
7a7 ss 37 (1.9) g 0 67.4 (1.5) Colh 89.6 (2.4) I I 81.4 (2.4) Colh 6.4 (0.9) ss
7a8 ss 47.3 (8.6) Colh 83.0 (2.5) I I 72.1 (3.1) Colh
7a10 ss 51.2 (8.6) Colh 59.1 (0.9) I I 53 (2.6) Colh 32.6 (0.9) ss
7a10 0 ss 45.6 (10.6) Colh 69 (2.3) I I 57 (2.6) Colh
7a14 Cr 47 (34.2) I I 18.4 (23.0) Cr
7b6 ss 41.5 (9.6) Colh 69.3 (1.2) I I 59.7 (1.4) Colh
7b7 ss 45 (20.4) Colh 65.8 (2.6) I I 58.6 (2.8) Colh
7b10 Cr 47(2.4) Cr 0 63 (31.1) I I 31.4 (1.0) Cr 0 21.4(0.4) Cr
7b10 0 Cr 70.7 (36.5) I I 45.4 (6.9) Colh
7b12 Cr 44.4 (18.1) I I 8.6 (11.2) Cr
7b14 Cr 60.1 (33.1) I I 29.7 (28.4) Cr
a
See Scheme 1 for chemical structures. ss: semisolid; Cr: crystal; Colh: hexagonal columnar phase; I: isotropic phase.
This journal is
the acceptor is short, and so long peripheral substitution
around the central core can disturb their packing. The absence
of a mesophase in compounds 7a14, 7b10, 7b12 and 7b14
clearly indicates that, when the peripheral chain lengths of the
central core are either equal to or longer than the spacer
length, then these symmetrical trimers do not exhibit any
liquid crystalline property. Shorter alkyl chains around the
central core stabilize the mesophase in these discotic trimers. If
we compare the mesophase stability between compound 7a10
and 7a10 0 having the same mass unit around the central core,
the compound 7a10 0 shows a wider mesophase range of
23.4 1C compared to 7.9 1C of compound 7a10. Similarly on
comparing 7b10 and 7b10 0 we find that compound 7b10 does
not exhibit any liquid crystalline property but compound
7b10 0 displays a monotropic phase behavior. The above
trimers contain the same mass units around the central core
but the alkyl chain lengths around the central core are
different. Both 7a10 0 and 7b10 0 contain shorter chain lengths
i.e. 3,7-dimethyloctyl as compared to 7a10 and 7b10 with
longer decyl chains.
X-Ray diffraction studies

In order to reveal the mesophase structure and hence the
supramolecular organization of these compounds, X-ray dif- Fig. 4 X-Ray diffraction pattern of the trimer 7a6 at 85 1C and its
fraction experiments were carried out using unoriented sam- intensity vs. y profile.
ples. X-Ray diffraction patterns for all the trimers were
recorded in the columnar phase 10 1C below the clearing
temperature while cooling from the isotropic phase. The Table 2 Values of d-spacings, and of inter- (dinter) and intracolumnar
X-ray diffraction patterns of the mesophase exhibited by all (dintra) distances (Å) of the trimers derived from their diffraction
patterns
the samples belonging to both the series is supportive of a
discotic hexagonal columnar arrangement. As a typical exam- Compound d-Spacing/Å dinter/Å dintra/Å
ple, the X-ray diffraction pattern of compound 7a6 and its
7a6 17.71 20.45 3.58
one-dimensional intensity vs. theta (y) graph derived from the 7a7 17.80 20.56 3.65
pattern are shown in the Fig. 4. Qualitatively all the com- 7a8 18.15 20.96 3.66
pounds show similar X-ray diffraction patterns. As can be seen 7a10 18.59 21.47 3.66
7a10 0 18.13 20.93 3.73
from the figure, in the small angle region, two sharp peaks, one 7b6 17.33 20.01 3.66
very strong and one weak reflection are seen whose d-spacings 7b7 17.43 20.13 3.65
are in the ratio of 1 : 1/O3, consistent with a two-dimensional H6TP 19.5 22.52 3.56
hexagonal lattice. In the wide-angle region two diffuse reflec- H6AQ 18.19 21.0 3.6
tions are seen. The broad one centered at 4.62 Å corresponds
to the liquid-like order of the aliphatic chains. The reflection at
higher y value and well separated from the previous one is due
to the stacking of the molecular cores one on the top of the
other. The diffuse nature of this peak implies that the stacking
of the discs within each column is correlated over short
distances only. The average stacking distance (core–core
separation) was found to be 3.66 Å and falls in the range
observed for a number of materials exhibiting a discotic
columnar phase. The discotic molecules stack one on top of
the other to form the columns and these columns in turn
arrange themselves on a two-dimensional hexagonal lattice for
both the series of compounds. The intercolumnar distances, a,
calculated using the relation a = d10/cos301, where d10 is the
spacing corresponding to the strong peak in the small angle
region, for all the compounds, are listed in Table 2. In both
the series it is evident that as alkyl chain lengths increase
the diameter of the cylindrical columns formed by the
discotic molecules also increases, as shown in Fig. 5. The Fig. 5 Variation of d-spacing value with respect to side chain length.

intercolumnar distances varies from 20.5–21.5 Å, whereas the that there is no or very weak charge transfer interaction
intracolumnar distance is constant at around 3.7 Å, which is between donor and acceptor units. Similar behaviour has
usually observed for discotic columnar mesophases. In these previously been reported for other non-liquid crystalline as
unoriented samples, we do not observe any additional small well as liquid crystalline donor–acceptor dimers.9a,12
angle peak for the formation of a superlattice arising from the
ideal top-on-top stacking of the trimer molecules which could
lead to the formation of columnar double cables. Therefore, it Conclusions
was concluded that the triphenylene and anthraquinone sub- In conclusion, we have synthesized two series of novel symme-
units arrange themselves statistically to form a columnar trical liquid crystalline trimers based on anthraquinone and
hexagonal phase. The intercolumnar distance for hexahexyl- triphenylene moieties using microwave irradiation. The etheri-
oxytriphenylene (H6TP) and hexahexyloxyanthraquinone fication of H-bonded hydroxyl groups of tetraalkoxyanthra-
(H6AQ) is 22.52 Å,10 and 21.0 Å,11 respectively, but the quinones with bulky o-bromo-substituted triphenylenes failed
intercolumnar distance of the symmetrical trimer 7a6 is to produce the desired triads under classical reaction condi-
20.45 Å, which is less than the corresponding monomers. This tions. The mesophase behavior of the symmetrical trimers was
minor shrinkage of the intercolumnar distance in the trimer is studied by polarizing optical microscopy and differential
expected upon covalent linking the two molecules. On com- scanning calorimetry and they exhibit a columnar mesophase
paring the X-ray diffraction results of 7a6 with 7b6 and 7a7 over a wide range of temperature. Hexagonal columnar struc-
with 7b7 (Table 2), it is evident that the intercolumnar distance ture of the mesophase of these donor–acceptor–donor triads
is decreasing with decreasing spacer length. This is due to was established by X-ray diffraction studies. Longer spacer
shortening of hexagonal lattice with decreasing the length of length, smaller peripheral alkyl chain length and branching in
spacer linking the discotic moieties. As expected, the inter- peripheral alkyl chains of the anthraquinone favor liquid
columnar distance of 7a10 is larger than that of 7a10 0 , since crystalline property in these symmetrical trimers.
7a10 contains longer alkyl chains around the central anthra-
quinone core than 7a10 0 , although they contain the same mass
units around the anthraquinone core. However, the intra- References
columnar distance of 7a10 is less than 7a10 0 because of the 1 (a) M. Mas-Torrent and C. Rovira, Chem. Soc. Rev., 2008, 37,
steric effect exerted by the branched alkyl chains around the 827–838; (b) B. C. Thompson and J. M. J. Frechet, Angew. Chem.,
central core of 7a10 0 , which will hinder the discotic cores Int. Ed., 2008, 47, 58–77; (c) E. Menard, M. A. Meitl, Y. Sun,
J.-U. Park, D. Jay-Lee, Y.-S. Nam, S. Jeon and J. A. Rogers,
coming closer in columns. Chem. Rev., 2007, 107, 1117–1160; (d) M. Berggren, D. Nilsson
and N. D. Robinson, Nat. Mater., 2007, 6, 3–5; (e) N. Koch,
Absorption spectra ChemPhysChem, 2007, 8, 1438–1455; (f) Y. Sun, Y. Liu and
D. Zhu, J. Mater. Chem., 2005, 15, 53–65; (g) H. E. Katz, Chem.
As the trimers contain both electron donor and acceptor Mater., 2004, 16, 4748–4756; (h) S. R. Forrest, Nature, 2004, 428,
moieties, it is expected that they may show charge transfer 911–918; (i) C. D. Dimitrakopoulos and P. R. L. Malenfant, Adv.
Mater., 2002, 14, 99–117.
absorption. However, the UV-vis spectrum of the trimer 7a10 2 (a) S. Kumar, Chem. Soc. Rev., 2006, 35, 83–109; (b) S. Laschat,
(Fig. 6) does not show any additional absorption band as A. Baro, N. Steinke, F. Giesselmann, C. Hagele, G. Scalia, R. Judele,
compared to the separate hexaalkoxytriphenylene 4 and hexa- E. Kapatsina, S. Sauer, A. Schreivogel and M. Tosoni, Angew.
Chem., Int. Ed., 2007, 46, 4832–4887; (c) S. Sergeyev, W. Pisula
alkoxyanthraquinone (RF6C4) and is essentially a sum of
and Y. H. Geerts, Chem. Soc. Rev., 2007, 36, 1902–1929; (d) J. Wu,
donor and acceptor units. The colour of the trimer 7a10 also W. Pisula and K. Mullen, Chem. Rev., 2007, 107, 718–747;
almost matches with the colour of the acceptor. This implies (e) Y. Shimizu, K. Oikawa, K. Nakayama and D. Guillon,
J. Mater. Chem., 2007, 17, 4223–4229; (f) N. Boden, R. J. Bushby,
J. Clements and B. Movaghar, J. Mater. Chem., 1999, 9, 2081–2086;
(g) R. J. Bushby and O. R. Lozman, Curr. Opin. Solid State Mater.
Sci., 2002, 6, 569–578; (h) R. J. Bushby and O. R. Lozman, Curr.
Opin. Colloid Interface Sci., 2002, 7, 343–354; (i) H. Takezoe,
K. Kishikawa and E. Gorecka, J. Mater. Chem., 2006, 16,
2412–2416; (j) K. Ohta, K. Hatsusaka, M. Sugibayashi,
M. Ariyoshi, K. Ban, F. Maeda, R. Naito, K. Nishizawa,
A. M. van de Craats and J. M. Warman, Mol. Cryst. Liq. Cryst.,
2003, 397, 25–45; (k) M. Manickam, G. Cooke, S. Kumar,
R. Ashton, J. A. Preece and N. Spencer, Mol. Cryst. Liq. Cryst.,
2003, 397, 99–116; (l) A. N. Cammidge and R. J. Bushby, in
Handbook of Liquid Crystals, ed. D. Demus, J. Goodby,
G. W. Gray and H.-W. Spiess, V. Vill, Wiley-VCH, Weinheim,
1998, ch. VII, vol. 2B, pp. 693–748.
3 For recent reviews on microwave-assisted organic synthesis, see:
(a) M. A. Herrero, J. M. Kremsner and C. O. Kappe, J. Org.
Chem., 2008, 73, 36–47; (b) F. Wiesbrock, R. Hoogenboom and
U. S. Schubert, Macromol. Rapid Commun., 2004, 25, 1739–1764;
(c) M. Nuchter, B. Ondruschka, W. Bonrath and A. Gum, Green
Chem., 2004, 6, 128–141; (d) A. K. Bose, M. S. Manhas,
S. N. Ganguly, A. H. Sharma and B. K. Banik, Synthesis, 2002,
Fig. 6 UV-vis spectra of a chloroform solution of 7a10 and of its 1578–1591; (e) A. de la Hoz, A. Diaz-Ortiz and A. Moreno, Chem.
individual monomers (hexaalkoxyanthraquinone (RF6C4) and hexa- Soc. Rev., 2005, 34, 164–178; (f) V. Molteni and D. A. Ellis, Curr.
alkoxytriphenylene). Org. Synth., 2005, 2, 333–375; (g) M. Larhed, C. Moberg and
This journal is
A. Hallberg, Acc. Chem. Res., 2002, 35, 717–727; (h) D. Bogdal, 6 S. Kumar, Liq. Cryst., 2004, 31, 1037–1059.
Microwave-Assisted Organic Synthesis — One Hundred Reaction 7 S. Kumar, Phase Transitions, 2008, 81, 113–128.
Procedures, Elsevier, Amsterdam, 2005. 8 A. Cravino and N. S. Sariciftci, J. Mater. Chem., 2002, 12,
4 (a) K. Ooi, F. Maeda, K. Ohta, T. Takizawa and T. Matsuse, 1931–1943.
J. Porphyrins Phthalocyanines, 2005, 9, 544–553; (b) S. K. Pal, 9 (a) S. Kumar, J. J. Naidu and S. K. Varshney, Mol. Cryst. Liq.
H. K. Bisoyi and S. Kumar, Tetrahedron, 2007, 63, 6874–6878; Cryst., 2004, 411, 355–362; (b) S. Kumar and M. Manickam, Chem.
(c) S. K. Pal and S. Kumar, Tetrahedron Lett., 2006, 47, Commun., 1997, 1615–1616; (c) S. Kumar and M. Manickam,
8993–8997; (d) S. Kumar and H. K. Bisoyi, Phase Transitions, Synthesis, 1998, 1119–1122.
2006, 79, 285–292; (e) H. K. Bisoyi and S. Kumar, Tetrahedron 10 E. O. Arikainen, N. Boden, R. J. Bushby, J. Clements,
Lett., 2007, 48, 4399–4402; (f) H. K. Bisoyi and S. Kumar, J. Phys. B. Movaghar and A. Wood, J. Mater. Chem., 1995, 12, 2161–2165.
Org. Chem., 2008, 21, 47–52. 11 C. Carfagna, P. Iannelli, A. Roviello and A. Sirigu, Liq. Cyst.,
5 (a) S. Kumar, Liq. Cryst., 2005, 32, 1089–1113; (b) C. T. Imrie and 1987, 5, 611–616.
P. A. Henderson, Chem. Soc. Rev., 2007, 36, 2096–2124; 12 (a) G. Cooke, N. Kaushal, N. Boden, R. J. Bushby, Z. Lu and
(c) C. T. Imrie and G. R. Luckhurst, in Handbook of Liquid Crystals, O. Lozman, Tetrahedron Lett., 2000, 41, 7955–7959; (b) A. Schultz,
ed. D. Demus, J. Goodby, G. W. Gray, H.-W. Spiess and V. Vill, S. Laschat, A. P. Abbott, M. Langner and T. B. Reeve, J. Chem.
Wiley-VCH, Weinheim, 1998, ch. X, vol. 2B, pp. 801–833. Soc., Perkin Trans. 1, 2000, 3356–3361.

Synthesis, crystal structures and luminescence properties of lanthanide

oxalatophosphonates with a three-dimensional framework structurew
Yanyu Zhu, Zhengang Sun,* Yan Zhao, Jing Zhang, Xin Lu, Na Zhang,
Lei Liu and Fei Tong
Received (in Montpellier, France) 20th August 2008, Accepted 3rd October 2008
DOI: 10.1039/b814400a
Six new three-dimensional (3D) lanthanide oxalatophosphonates, [Ln(HL)(C2O4)0.5(H2O)2]H2O

(Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6); H3L = H2O3PCH(OH)CO2H), have been
synthesized under hydrothermal conditions and structurally characterized by single-crystal X-ray
diffraction as well as by infrared spectroscopy, elemental analysis and thermogravimetric analysis.
Compounds 1–6 are isomorphous and they exhibit a complex three-dimensional (3D) open-
framework structure with a one-dimensional channel system along the c-axis. The interconnection
of the lanthanide(III) ions by phosphonate ligands results in a lanthanide phosphonate layer, and
these layers are further bridged by oxalate anions to form a 3D open-framework. Compound 6
shows strong red luminescence in the solid state at room temperature.
Introduction preparation, such as a phosphonic acid and a carboxylic acid,

has been found to be another effective method for the
Metal phosphonates as a class of inorganic–organic hybrid exploration of hybrid open-frameworks. Among these studies,
materials have attracted a great deal of research interest as a the oxalate moiety, C2O42 , was found to be a good candidate
result of their ability to form interesting structures with and has been successfully incorporated into phosphonate
potential applications as catalysts, ion exchangers, sorbents, frameworks with transition metals and main group ele-
meso-/microporous materials, or intercalation chemistry.1–5 ments.27–30 Although some progress has been made in the
Usually, the metal phosphonates adopt layered or pillared construction of metal oxalatophosphonates as mentioned
layered structures, with the organic groups filling in between above, less progress has been achieved in the synthesis of
the inorganic layers.6–10 Other structural types have also been lanthanide oxalatophosphonates.31–33 Lanthanide phospho-
observed in some phosphonates, among which the open- nates normally have low solubility in water and other organic
framework and porous structures are of particular inter- solvents, hence introducing a second ligand such as C2O42
est.11–16 The strategy of attaching functional groups such as into the lanthanide phosphonate system can improve the
amine, hydroxyl and carboxylate groups to the phosphonic solubility and crystallinity of the lanthanide phosphonate. In
acid has proven to be effective for the isolation of a variety addition, the coordination of two types of ligands with the
of metal phosphonates with open-framework and micro- lanthanide ion may reduce or eliminate water molecules from
porosity.17–21 Based on 2-hydroxyphosphonoacetic acid, proline- the coordination sphere of the lanthanide(III) ion, hence
N-methylphosphonic acid and DL-(a-aminoethyl)phosphonic increasing the luminescent intensity and lifetime of the
acid, a series of metal phosphonates with two-dimensional materials.34 In this paper, we selected 2-hydroxyphosphono-
(2D) layer and three-dimensional (3D) open-framework struc- acetic acid (H3L) as the phosphonate ligands and oxalate
tures have also been isolated in our laboratory.22 as the second metal linker. Hydrothermal reactions of the
Recently, many research activities have focused on the above two ligands with lanthanide(III) chlorides afforded six
synthesis of inorganic–organic hybrid compounds by incor- new lanthanide oxalatophosphonate hybrids with 3D open-
porating organic ligands in the structures of metal phospho- framework structures, namely, [Ln(HL)(C2O4)0.5(H2O)2]H2O
nates.23–26 The direct use of two types of ligands in the (Ln = La (1), Ce (2), Pr (3), Nd (4), Sm (5), Eu (6); H3L =
H2O3PCH(OH)CO2H). The luminescent property of com-
pound 6 has also been studied.
Institute of Chemistry for Functionalized Materials, Faculty of
Chemistry and Chemical Engineering, Liaoning Normal University,
Dalian, 116029, P. R. China. E-mail: szg188@163.com;
Fax: +86 411 82156858 Results and discussion
w Electronic supplementary information (ESI) available: Fig. S1:
Simulated XRD pattern of compound 1 and experimental powder Synthesis
XRD patterns of compounds 1–6. Fig. S2: Experimental powder XRD
pattern of compound 1 and of dehydrated samples after calcination at By using 2-hydroxyphosphonoacetic acid as the phosphonate
150 and 180 1C. Table S1: Selected bond lengths (Å) for compounds ligand and oxalate as the second metal linker, six new lantha-
1–6. Table S2: Selected bond angles (1) for compounds 1–6. CCDC nide(III) oxalatophosphonates have been synthesized under
reference numbers 670477–670481 (1–5) and 686602 (6). For ESI
and crystallographic data in CIF or other electronic format see hydrothermal conditions. The compounds 1–6 were obtained
DOI: 10.1039/b814400a as a pure phase materials by adjusting the synthetic conditions.
This journal is
The molar ratio of the starting materials and the pH of the
reaction mixture play an important role in the formation of
these six compounds. NaOH was employed as the inorganic
base to adjust the pH of the reaction mixture. It was found
that pure phases of compounds 1–6 can be obtained with good
yields when the molar ratio of LnCl36H2O, H3L, H2C2O4
2H2O, NaOH, H2O and the pH are 1 : 4 : 4 : 4 : 888 and
1.5–2.5. In addition, the reaction temperature was very
important for the formation of suitable single crystals for
X-ray diffraction. The compounds 1–6 were obtained at
120–140 1C under hydrothermal conditions. The powder
XRD patterns of compounds 1–6 and the simulated XRD
patterns of compound 1 are shown in the supplementary
material (Fig. S1, ESIw). The diffraction peaks on the patterns
correspond well in position, confirming these six compounds
are isomorphous, and showing their phase purity. The differ-
ences in reflection intensities are probably due to preferred
orientation in the powder samples.
Description of the crystal structures

Compounds 1–6 are isomorphous and feature three-dimen-
sional open frameworks, hence only the structure of 3 will be
discussed in detail as a representation. The ORTEP diagram Fig. 2 (a) 1D chain {Pr(HL)}+ and (b) A 2D praseodymium(III)
for compound 3 is shown in Fig. 1. Crystallographic data and phosphonate layer in compound 3.
structural refinements for compounds 1–6 are summarized in
Table 1.
As shown in Fig. 1, the Pr(III) ion is nine-coordinated by two five-membered chelating rings. The pentadentate HL2 ligand
phosphonate oxygen atoms, two carboxylate oxygen atoms, is bidentate with Pr1 and Pr1D and monodentate with Pr1B.
and one hydroxyl oxygen atoms from three HL2 anions, two Each HL2 anion chelates with Pr1D ion by using its one
oxygen atoms from one oxalate anion as well as two aqua carboxylate oxygen atom (O6) and one hydroxyl oxygen
ligands. The Pr–O distances range from 2.372(3) to 2.573(3) Å, atom (O4), and one carboxylate oxygen atom (O5) and one
which are comparable to those reported for other praseo- phosphonate oxygen atom (O2) chelate with Pr1 ion.
dymium(III) phosphonates.23,33 The asymmetric unit contains One phosphonate oxygen atom (O3) is unidentate, whereas
half of an oxalate ion which lies about an inversion centre. the remaining one (O1) is protonated and noncoordinated.
The oxalate anion is bidentate, and it chelates with Such configuration is favorable because of the formation of
two different Pr(III) ions by using its four carboxylate stable six-atom rings (P–O–Pr–O–C–C) and five-atom rings
oxygen atoms. Each oxalate anion forms two Pr–O–C–C–O (O–Pr–O–C–C). It is noted that the Ln–O (hydroxyl oxygen)
distances are longer than the other Ln–O distances in com-
pounds 1–6, attributed to the presence of the hydroxyl proton
(Table S1, ESIw).
The HL2 anion acts as a bridging ligand to link Pr(III) ions
into a 1D chain of {Pr(HL)}+ along the b axis (Fig. 2(a)).
The dihedral angle between two chelating rings sharing a
common Pr(III) ion is 74.61(10)1. These chains are cross-linked
by bridging HL2 anions to form a praseodymium phosphonate
layer in the bc plane (Fig. 2(b)), the layers are interconnected
by sharing Pr(III) ions into a pillared-layered architecture with
the oxalate groups acting as pillars (Fig. 3). The result of
connections in this manner is the formation of a 1D channel
system along the c axis (Fig. 4(a)). The channel is formed by
21-atom rings composed of five Pr(III) ions, three HL2 anions
and two oxalate anions (Fig. 4(b)). The dimensions of the
Fig. 1 ORTEP representation of a selected unit of compound 3. The
channels are estimated to be 11.2 Å (Pr1a–P1e) 10.2 Å
thermal ellipsoids are drawn at the 30% probability level. All H atoms
(Pr1–C3c) based on the structural data. The oxygen atoms
and lattice water molecules are omitted for clarity: Pr(1)–O(3)B,
2.372(3) Å; Pr(1)–O(2), 2.481(3) Å; Pr(1)–O(7), 2.493(3) Å; from coordinated water molecules are oriented toward the
Pr(1)–O(6)A, 2.522(3) Å; Pr(1)–O(5), 2.559(3) Å; Pr(1)–O(9), 2.537(4) channel center, and lattice water molecules are located inside
Å; Pr(1)–O(8)C, 2.571(3) Å; Pr(1)–O(10), 2.542(4) Å; Pr(1)–O(4)A, the channels. The structure of 3 can be viewed as the praseo-
2.573(3) Å. Symmetry codes: A: x + 2, y + 1/2, z + 3/2; B: x + dymium phosphonate layer being connected via oxalate anions
2, y, z + 2; C: x + 1, y, z + 1; D: x + 2, y 1/2, z + 3/2. to form a complex 3D open-framework structure.

Table 1 Crystal data and structure refinements for compounds 1–6
1 2 3 4 5 6
Empirical formula C3H9O11PLa C3H9O11PCe C3H9O11PPr C3H9O11PNd C3H9O11PSm C3H9O11PEu
M 390.98 392.19 392.98 396.31 402.42 404.03
Crystal system Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic Monoclinic
Space group P21/c P21/c P21/c P21/c P21/c P21/c
a/Å 7.1991(6) 7.2260(7) 7.2300(7) 7.2326(6) 7.2351(6) 7.2293(9)
b/Å 13.3838(11) 13.2918(13) 13.2239(13) 13.1558(11) 13.0550(10) 13.0429(16)
c/Å 10.2926(8) 10.2745(10) 10.2535(10) 10.2337(8) 10.1999(8) 10.1980(13)
b/1 98.8980(10) 99.4930(10) 99.8690(10) 100.1070(10) 100.4270(10) 100.541(2)
V/Å3 979.77(14) 973.32(16) 965.82(16) 958.63(14) 947.51(13) 945.4(2)
Z 4 4 4 4 4 4
Dc/g cm 3 2.651 2.676 2.703 2.746 2.821 2.839
m/mm 1 4.576 4.894 5.263 5.636 6.420 6.858
GOF on F2 1.017 1.063 1.074 1.039 1.090 1.099
a
R1 [I 4 2s(I)] 0.0210 0.0239 0.0278 0.0220 0.0206 0.0243
wR2 [I 4 2s(I)]a 0.0547 0.0526 0.0726 0.0543 0.0512 0.0589
R1 (All data)a 0.0233 0.0296 0.0318 0.0242 0.0226 0.0255
wR2 (All data)a 0.0560 0.0555 0.0753 0.0557 0.0523 0.0595
P P P P
a
R1 = (||Fo| |Fc|)/ |Fo|; wR2 = [ w(|Fo| |Fc|)2/ wFo2]1/2.
spectrum of compound 3 will be discussed (Fig. 5). The

IR spectrum for compound 3 was recorded in the region
4000–400 cm 1. The broad band in the range 3550–3000 cm 1
corresponds to the O–H stretching vibrations of water mole-
cules, hydroxyl groups and phosphonate groups. There are
two strong bands centered at 1650 and 1575 cm 1, which are
assigned to the asymmetrical and symmetrical stretching
vibrations of C–O groups when present as COO moieties.35
Strong bands between 1200 and 900 cm 1 are due to stretching
vibrations of the tetrahedral CPO3 groups, as expected.36
Additional intense and sharp bands at low energy (617, 572
and 430 cm 1 etc) are found. These bands are probably due to
bending vibrations of the tetrahedral CPO3 groups.
Fig. 3 A ball-and-stick and polyhedral view of compound 3 along the Thermal properties
b axis.
Except for the final weight loss temperature and total weight
losses, the TGA curves of compounds 1–6 are very similar,
IR spectra
with three main continuous weight losses. Herein, we use
The IR spectra of the six compounds have many similar compound 1 as an example to illuminate the weight losses in
features corresponding to the common groups, thus only the detail. As shown in Fig. 6, the first step corresponds to the loss
Fig. 4 (a) View of the framework for compound 3 along the c-axis showing the voids in the structure. (b) A 21-atom rings in compound 3.
All H atoms and lattice water molecules are omitted for clarity. Symmetry codes: a: x + 2, y 1/2, z + 3/2; b: x, y 1/2, z 1/2; c: x + 1,
y 1/2, z + 1/2; d: x + 1, y, z + 1; e: x 1, y, z 1.
This journal is
structure of these six compounds can be kept after dehydra-
tion process (Fig. S2, ESIw).
Photoluminescent properties
It is well-known that the lanthanides, especially europium and
terbium, can absorb ultraviolet radiation efficiently through an
allowed electronic transition to convert to the excited state
5
D4, and these excited states are deactivated to the multiplet
7
FJ states radiatively via emission of visible radiation as
luminescence. The solid-state luminescence property of com-
pound 6 was investigated at room temperature. Compound 6
emits red light upon excitation at 396 nm, and its luminescence
spectrum is depicted in Fig. 7. These emission bands arise from
5
D0 - 7FJ (J = 1, 2 and 4) transitions, typical of Eu(III)
ions.34,37 The 5D0 - 7F1 transition (593 nm) corresponds to a
magnetic dipole transition, and the intensity of this emission
for 6 is medium-strong. The most intense emission in
the luminescent spectrum is the 5D0 - 7F2 transitions at
Fig. 5 IR spectra of compounds 1–6. 617 nm, which are the so-called hypersensitive transitions
and are responsible for the brilliant-red emission of compound
6.38 The emission spectrum of 6 shows a weak emission band
at 695 nm, which can be attributed to the 5D0 - 7F4
transition. The results indicate that compound 6 is a good
candidate as a red-light luminescent material.
Fig. 6 TGA curves of compounds 1–6. Fig. 7 Solid-state emission spectrum of compound 6 at room
temperature.
of one lattice water molecule and two aqua ligands. The

Conclusions
weight loss started at 50 1C and was completed at 145 1C.
The observed weight loss of 14.0% is close to the calculated By using 2-hydroxyphosphonoacetic acid as the phosphonate
value (13.8%). The second step between 345 and 430 1C can be ligand and oxalate as the second metal linker, six new
attributed to decomposition of oxalate and phosphonate units. lanthanide(III) oxalatophosphonates with a general formula
The third step corresponds to the further decomposition of the [Ln(HL)(C2O4)0.5(H2O)2]H2O (Ln = La (1), Ce (2), Pr (3),
phosphonate group. The observed total weight loss at 735 1C Nd (4), Sm (5), Eu (6); H3L = H2O3PCH(OH)CO2H) have
is about 41.5%, and the final products are not identified. been synthesized and structurally characterized. Compounds
However, we suspect they are mainly LaPO4. The total weight 1–6 are isomorphous and the structure of these compounds
loss of 41.5% is close to the calculated value (40.2%) if the features a 3D open-framework with a one-dimensional
final product is assumed to be LaPO4. The observed total channel system along the c-axis. The interconnection of the
weight losses of compounds 2–6 are 41.4, 39.0, 37.0, 38.6, lanthanide(III) ions by phosphonate ligands results in a lantha-
40.3%, respectively. Considering the thermal stability of the nide phosphonate layer, and these layers are further bridged
compounds, X-ray powder diffraction studies were performed by oxalate anions to form 3D open-frameworks. Compound 6
for the as-synthesized compound 1 and the samples calcined at is a new example of luminescent rare-earth oxalatophospho-
150 and 180 1C. The XRD patterns for the calcined samples fit nates characterized by a significant red luminescence. The
well with that of the as-synthesized samples, indicating that the results of our study indicate that by introduction of oxalate

as the second ligand, we can obtain lanthanide oxalatophos- C3H9O11PPr (392.98): calc.: C 9.16, H 2.29, P 7.89, Pr 35.86;
phonates with well characterized crystal structures as well as found: C 9.23, H 2.20, P 7.96, Pr 35.94%. IR (KBr) data: 3473
strong luminescence. (br), 2915 (w), 1650 (m), 1575 (s), 1432 (m), 1371 (m), 1363
(m), 1317 (m), 1214 (s), 1064 (s), 927 (m), 831 (w), 777 (w), 696
Experimental (w), 617 (w), 572 (w), 516 (w) cm 1.
Materials [Nd(HL)(C2O4)0.5(H2O)2]H2O (4). The procedure was the

same as that for 1 except that LaCl36H2O was replaced by
2-Hydroxylphosphonoacetric acid (H3L) solution was NdCl36H2O (0.18 g, 0.50 mmol). Yield: 55.0% (based on Nd).
obtained from Taihe Chemical Factory (48.0 wt%). The C3H9O11PNd (396.31): calc.: C 9.08, H 2.27, P 7.82, Nd 36.40;
lanthanide(III) chlorides were prepared by the dissolving found: C 9.15, H 2.35, P 7.91, Nd 36.49%. IR (KBr) data:
corresponding lanthanide oxides (General Research Institute 3484 (br), 2915 (w), 1652 (s), 1577 (s), 1432 (m), 1369 (m), 1319
for Nonferrous Metals, 99.99%) in hydrochloric acid followed (m), 1209 (s), 1064 (s), 968 (w), 931 (m), 835 (w), 786 (w), 781
by recrystallization and drying. All other chemicals were used (w), 694 (w), 619 (m), 580 (m), 520 (m) cm 1.
as received without further purification.
[Sm(HL)(C2O4)0.5(H2O)2]H2O (5). A mixture of SmCl3
Physical measurements
6H2O (0.19 g, 0.50 mmol), H3L (0.50 ml, 2.00 mmol),
Elemental analyses (carbon and hydrogen) were performed H2C2O42H2O (0.25 g, 2.00 mmol), and NaOH (0.08 g,
using a PE-2400 elemental analyzer. La, Ce, Pr, Nd, Sm, Eu 2.00 mmol) in 8 mL distilled water was sealed in an autoclave
and P were determined by using an inductively coupled plasma equipped with a 20 mL Teflon liner, and then heated at 120 1C
(ICP) atomic absorption spectrometer. IR spectra were for 4 days. After the mixture was cooled slowly to room
recorded on a Bruker AXS TENSOR-27 FT-IR spectrometer temperature, pale yellow block crystals were obtained in ca.
with KBr pellets in the range 4000–400 cm 1. The X-ray 86.0% yield based on Sm. C3H9O11PSm (402.42): calc.: C 8.95,
powder diffraction data were collected on a Bruker AXS D8 H 2.25, P 7.69, Sm 37.36; found: C 9.03, H 2.33, P 7.63, Sm
Advance diffractometer using Cu-Ka radiation (l = 1.5418 Å) 37.28%. IR (KBr) data: 3477 (br), 3290 (br), 2925 (w), 1660
in the 2y range of 9–601 with a step size of 0.021. The (s), 1575 (s), 1433 (m), 1366 (m), 1318 (m), 1212 (s), 1072 (s),
luminescence analysis was performed on a JASCO FP-6500 930 (m), 783 (w), 704 (w), 617 (m), 524 (m) cm 1.
spectrofluorimeter (solid). TG analysis was performed on a
Perkin–Elmer Pyris Diamond TG–DTA thermal analysis [Eu(HL)(C2O4)0.5(H2O)2]H2O (6). The procedure was the
system in static air with a heating rate of 10 K min 1 from same as that for 5 except that SmCl36H2O was replaced by
50 to 800 1C. EuCl36H2O (0.19 g, 0.50 mmol). Yield: 45.0% (based on Eu).
C3H9O11PEu (404.03): calc.: C 8.92, H 2.24, P 7.67, Eu 37.61;
Synthesis found: C 8.98, H 2.31, P 7.58, Eu 37.69%. IR (KBr) data: 3475
[La(HL)(C2O4)0.5(H2O)2]H2O (1). A mixture of LaCl3 (br), 3292 (br), 2920 (w), 1670 (s), 1579 (s), 1435 (m), 1361 (m),
6H2O (0.18 g, 0.50 mmol), H3L (0.50 ml, 2.00 mmol), 1317 (m), 1217 (s), 1180 (m), 1070 (s), 974 (w), 921 (m), 783
H2C2O42H2O (0.25 g, 2.00 mmol), and NaOH (0.08 g, (w), 707 (w), 621 (m), 580 (w), 526 (w), 482 (m) cm 1.
2.00 mmol) was dissolved in 8 mL distilled water. The resulting
Crystallographic determinations
solution was stirred for about 1 h at room temperature, sealed
in a 20 mL Teflon-lined stainless steel autoclave, and heated at Data collections for compounds 1–6 were performed on the
140 1C for 4 days under autogenous pressure. After the Bruker Smart APEX II X-diffractometer equipped with
mixture was cooled slowly to room temperature, colorless graphite-monochromated Mo-Ka radiation (l = 0.71073 Å)
block crystals were obtained in ca. 40.0% yield based on La. at 293 2 K. An empirical absorption correction was applied
C3H9O11PLa (390.98): calc.: C 9.21, H 2.30, P 7.93, La 35.53; using the SADABS program. All structures were solved by
found: C 9.28, H 2.22, P 7.85, La 35.45%. IR (KBr) data: 3540 direct methods and refined by full-matrix least squares fitting
(br), 1644 (m), 1581 (s), 1432 (w), 1373 (w), 1309 (w), 1209 (s), on F2 by SHELXS-97.39 All non-hydrogen atoms were refined
1178 (w), 1070 (s), 935 (m), 781 (w), 719 (w), 619 (w), 580 (w), anisotropically. Hydrogen atoms of organic ligands were
526 (w) cm 1. generated geometrically with fixed isotropic thermal para-
meters, and included in the structure factor calculations.
[Ce(HL)(C2O4)0.5(H2O)2]H2O (2). The procedure was the
same as that for 1 except that LaCl36H2O was replaced by
CeCl37H2O (0.19 g, 0.50 mmol). Yield: 81.0% (based on Ce). Acknowledgements
C3H9O11PCe (392.19): calc.: C 9.18, H 2.29, P 7.90, Ce, 35.73; This research was supported by grants from the Natural
found: C 9.11, H 2.21, P 7.95, Ce 35.65%. IR (KBr) data: 3465 Science Foundation of Liaoning Province of China
(br), 2221 (w), 1648 (m), 1583 (s), 1425 (w), 1373 (w), 1311 (w), (20062140).
1213 (s), 1074 (s), 937 (w), 781 (w), 721 (w), 615 (w), 588 (w),
524 (w) cm 1.
References
[Pr(HL)(C2O4)0.5(H2O)2]H2O (3). The procedure was the
1 (a) S. Cheng, G.-Z. Peng and A. Clearfield, Ind. Eng. Chem. Prod.
same as that for 1 except that LaCl36H2O was replaced by Res. Dev., 1984, 23, 2; (b) G. Cao, H. G. Hong and T. E. Mallouk,
PrCl36H2O (0.18 g, 0.50 mmol). Yield: 76.0% (based on Pr). Acc. Chem. Res., 1992, 25, 420; (c) G. E. Fanucci, J. Krzystek,
This journal is
M. W. Meisel, L.-C. Brunel and D. R. Talham, J. Am. Chem. Soc., 22 (a) J. Li, L. Meng, Z.-G. Sun, Z.-M. Liu, Y. Zhao, J. Zhang,
1998, 120, 5469. Y.-Y. Zhu, X. Lu, L. Liu and N. Zhang, Inorg. Chem. Commun.,
2 (a) J. D. Wang, A. Clearfield and G.-Z. Peng, Mater. Chem. Phys., 2008, 11, 211; (b) D.-P. Dong, J. Li, Z.-G. Sun, X.-F. Zheng,
1993, 35, 208; (b) C. Y. Ortiz-Avila, C. Bhardwaj and A. Clearfield, H. Chen, L. Meng, Y.-Y. Zhu, Y. Zhao and J. Zhang, Inorg. Chem.
Inorg. Chem., 1994, 33, 2499. Commun., 2007, 10, 1109; (c) Z.-G. Sun, L.-Y. Cui, Z.-M. Liu,
3 (a) K. Maeda, Y. Kiyozumi and F. Mizukami, J. Phys. Chem. B, D.-P. Dong, L. Meng, H. Chen, L.-C. Zhang, Z.-M. Zhu and
1997, 101, 4402; (b) F. Odobel, B. Bujoli and D. Massiot, Chem. W.-S. You, Inorg. Chem. Commun., 2006, 9, 1121; (d) L.-Y. Cui,
Mater., 2001, 13, 163. Z.-G. Sun, Z.-M. Liu, W.-S. You, Z.-M. Zhu, L. Meng, H. Chen and
4 (a) T. E. Mallouk and J. A. Gavin, Acc. Chem. Res., 1998, 31, 209; D.-P. Dong, Inorg. Chem. Commun., 2006, 9, 1232.
(b) A. Clearfield, Chem. Mater., 1998, 10, 2801; (c) T. Kimura, 23 J.-L. Song, C. Lei and J.-G. Mao, Inorg. Chem., 2004, 43, 5630.
Chem. Mater., 2003, 15, 3742. 24 J.-L. Song, J.-G. Mao, Y.-Q. Sun and A. Clearfield, Eur. J. Inorg.
5 G. Alberti and U. Costantino, in Comprehensive Supramolecular Chem., 2003, 4218.
Chemistry, ed. J. M. Lehn, Pergamon-Elsevier Science Ltd, 25 J. Zhu, X. Bu, P. Feng and G. D. Stucky, J. Am. Chem. Soc., 2000,
London, 1996, p. 1. 122, 11563.
6 Z.-M. Sun, J.-G. Mao, Y.-Q. Sun, H.-Y. Zeng and A. Clearfield, 26 B.-P. Yang and J.-G. Mao, Inorg. Chem., 2005, 44, 566.
New J. Chem., 2003, 27, 1326. 27 B. Adair, S. Natarajan and A. K. Cheetham, J. Mater. Chem.,
7 H.-H. Song, L.-M. Zheng, Z. Wang, C.-H. Yan and X.-Q. Xin, 1998, 8, 1477.
Inorg. Chem., 2001, 40, 5024. 28 N. Stock, G. D. Stucky and A. K. Cheetham, Chem. Commun.,
8 J.-L. Song, H.-H. Zhao, J.-G. Mao and K. R. Dunbar, Chem. 2000, 2277.
Mater., 2004, 16, 1884. 29 C.-H. Lin and K.-H. Lii, Inorg. Chem., 2004, 43, 6403.
9 D.-K. Cao, J. Xiao, J.-W. Tong, Y.-Z. Li and L.-M. Zheng, Inorg. 30 C.-P. Tsao, C.-Y. Sheu, N. Nguyen and K.-H. Lii, Inorg. Chem.,
Chem., 2007, 46, 428. 2006, 45, 6361.
10 S. Bauer, J. Marrot, T. Devic, G. Férey and N. Stock, Inorg. 31 J.-L. Song and J.-G. Mao, Chem.–Eur. J., 2005, 11, 1417.
Chem., 2007, 46, 9998. 32 S.-M. Ying and J.-G. Mao, Cryst. Growth Des., 2006, 6, 964.
11 O. R. Evans, H. L. Ngo and W. B. Lin, J. Am. Chem. Soc., 2001, 33 Y.-L. Huang, M.-Y. Huang, T.-H. Chan, B.-C. Chang and
123, 10395. K.-H. Lii, Chem. Mater., 2007, 19, 3232.
12 J. A. Groves, P. A. Wright and P. Lightfoot, Dalton Trans., 2005, 34 J.-G. Mao, Coord. Chem. Rev., 2007, 251, 1493.
2007. 35 A. Cabeza, M. A. G. Aranda and S. Bruque, J. Mater. Chem.,
13 J. A. Groves, S. R. Miller, S. J. Warrender, C. M. Draznieks, 1998, 8, 2479.
P. Lightfoot and P. A. Wright, Chem. Commun., 2006, 3305. 36 (a) A. Cabeza, X. Ouyang, C. V. K. Sharma, M. A. G. Aranda,
14 G. B. Hix, A. Turner, L. Vahter and B. M. Kariuki, Microporous S. Bruque and A. Clearfield, Inorg. Chem., 2002, 41, 2325;
Mesoporous Mater., 2007, 99, 62. (b) Z.-M. Sun, J.-G. Mao, B.-P. Yang and S.-M. Ying, Solid State
15 Z.-Y. Du, A. V. Prosvirin and J.-G. Mao, Inorg. Chem., 2007, 46, Sci., 2004, 6, 295.
9884. 37 (a) P. Lenaerts, K. Driesen, R. V. Deun and K. Binnemans, Chem.
16 Y.-Q. Guo, B.-P. Yang, J.-L. Song and J.-G. Mao, Cryst. Growth Mater., 2005, 17, 2148; (b) Z. He, E.-Q. Gao, Z.-M. Wang,
Des., 2008, 8, 600. C.-H. Yan and M. Kurmoo, Inorg. Chem., 2005, 44, 862;
17 P. Yin, S. Gao, L.-M. Zheng and X.-Q. Xin, Chem. Mater., 2003, (c) Y. Wang, X. Zheng, W. Zhuang and L. Jin, Eur. J. Inorg.
15, 3233. Chem., 2003, 3572.
18 J.-L. Song and J.-G. Mao, J. Solid State Chem., 2005, 178, 3514. 38 (a) A. de Bettencourt-Dias, Inorg. Chem., 2005, 44, 2737;
19 N. Stock and T. Bein, J. Mater. Chem., 2005, 15, 1384. (b) G. L. Law, K. L. Wong, X. Zhou, W. T. Wong and
20 D. Kong and A. Clearfield, Cryst. Growth Des., 2005, 5, 1263. P. A. Tanner, Inorg. Chem., 2005, 44, 4142.
21 B.-P. Yang, A. V. Prosvirin, Y.-Q. Guo and J.-G. Mao, Inorg. 39 G. M. Sheldrick, SHELXS-97, Program for the solution of crystal
Chem., 2008, 47, 1453. structures, University of Göttingen, Germany, 1997.

The annular tautomerism of the curcuminoid NH-pyrazolesw

Pilar Cornago,*a Pilar Cabildo,a Rosa M. Claramunt,a Latifa Bouissane,a
Elena Pinilla,b M. Rosario Torresb and José Elgueroc
Received (in Montpellier, France) 16th July 2008, Accepted 10th October 2008
First published as an Advance Article on the web 2nd December 2008
DOI: 10.1039/b812018h
The structures of four NH-pyrazoles, (E)-3,5-bis[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-1H-

pyrazole (3), (E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-methyl-1H-pyrazole (4),
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-4,5(3)-dimethyl-1H-pyrazole (5) and (E)-3(5)-
[b-(3,4-dimethoxyphenyl)-ethenyl]-4-methyl-5(3)-phenyl-1H-pyrazole (8), have been determined by
X-ray crystallography. Compounds that have a phenol residue crystallize forming sheets that are
stabilized by a complex pattern of hydrogen bonds between a unique tautomer (4), or by a 2 : 1
mixture of both tautomers (5) (these tautomers being identical in the case of 3). Pyrazole 8, which
lacks OH groups, crystallizes in cyclic dimers that are stabilized by N–H N hydrogen bonds.
The tautomerism in solution and in the solid state was determined by 13C and 15N CPMAS NMR
spectroscopy. For compounds 4, 5 and 8, the solid state results agree with those observed by
crystallography; the most abundant tautomer in solution coincides with the tautomer present in
the solid state (4 and 8) or with the most abundant tautomer in the crystal (5).
Introduction
Turmeric is a spice derived from the rhizomes of Curcuma
longa, which is a member of the ginger family.1 The bright
yellow color of turmeric comes mainly from polyphenolic
pigments known as curcuminoids. Curcumin (1) (Scheme 1)
is the principal curcuminoid found in turmeric, and is gen-
Scheme 1 The structure of curcumin (1) and the tautomerism of
erally considered to be its most active constituent. In addition pyrazoles 2.
to its use as a spice and a pigment, turmeric has been used in
India for medicinal purposes for centuries. More recently,
cancer in animal models of oral, stomach, liver and colon
evidence that 1 may have anti-inflammatory and anti-cancer
cancer.
activities has renewed scientific interest in its potential to
We have devoted a series of papers to the annular tauto-
prevent and treat disease. 1 is also an effective scavenger of
merism of NH-pyrazoles 2 (2a vs. 2b),3,4 and decided to study
reactive oxygen and nitrogen species in vitro. In addition to its
those derived from 1 and related b-diketones.
direct antioxidant activity, 1 has been found to inhibit PLA2,
Pyrazole 3, which is derived from 1, has been prepared many
COX-2 and 5-LOX activity in cultured cells. It has also been
times since 1991.5–11 It has been described as a pale yellow
found to inhibit NF-kB-dependent gene transcription, and to
solid that melts at 211–2145 or 2157 1C.
inhibit the induction of COX-2 and iNOS in cell culture and
The activity of the curcuminoid pyrazoles covers domains
animal studies.2 1 has been found to induce cell cycle arrest
such as anti-inflammatory (5-lipooxygenase and cyclooxygen-
and apoptosis in a variety of cancer cell lines grown in
ase inhibitors)5,8 and anti-tumoral (anti-angiogenic)6–8 agents,
cultures. The ability of 1 to induce apoptosis in cultured
and drugs for the treatment of Alzheimer’s disease (AD;
cancer cells has generated scientific interest in its potential to
potent g-secretase inhibitors, potent ligands for fibrillar
prevent some types of cancer. Oral administration of 1 has
Ab42 aggregates, tau aggregation inhibitors and depolymeriz-
been found to inhibit the development of chemically-induced
ing agents for tau aggregates).10,11 Particularly promising for
treating reduced cognitive functions is 4,4 0 -[(1-phenyl-1H-
pyrazole-3,5-diyl)di-(1E)-2,1-ethenediyl]bis(2-methoxyphenol)
a
Departamento de Quı´mica Orgánica y Bio-Orgánica, Facultad de (CNB-001), the product obtained by reacting 1 with phenyl-
Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain. hydrazine.12 In the last of these applications, curcumin-
E-mail: mcornago@ccia.uned.es; Fax: +34 913988372; derived pyrazoles were synthesized in order to minimize
Tel: +34 913987323
b
Departamento de Quı´mica Inorgánica I, Facultad de Ciencias the metal chelation properties of 1. The reduced rotational
Quı´micas, Universidad Complutense de Madrid (UCM), 28040 freedom and the absence of stereoisomers were anticipated
Madrid, Spain to enhance the inhibition of g-secretase. Accordingly, the
c
Instituto de Quı´mica Me´dica, CSIC, Juan de la Cierva 3, E-28006 replacement of the 1,3-dicarbonyl moiety by isosteric hetero-
Madrid, Spain
w CCDC reference numbers 690489–690492. For crystallographic data cycles, such as pyrazoles, turned these compounds into very
in CIF or other electronic format see DOI: 10.1039/b812018h interesting candidates for AD research.
This journal is
The aim of this paper is to determine and discuss the Table 1 The bond lengths (Å) and angles (1) for compounds 3, 4, 8
structure, tautomerism and possible proton transfer in the and the three crystallographically-independent molecules of 5
solid state (SSPT) of six NH-pyrazoles by using a combination 3 4 5(1) 5(2) 5(3) 8
of X-ray crystallography and 13C/15N NMR spectroscopy.
The nomenclature used in the text and in the experimental is N1–N2 1.354(3) 1.365(3) 1.349(4) 1.352(4) 1.359(3) 1.351(3)
N2–C3 1.347(4) 1.339(3) 1.341(5) 1.348(5) 1.349(5) 1.339(4)
not in accordance with IUPAC rules. For all of the com- C3–C4 1.399(4) 1.398(4) 1.388(6) 1.410(5) 1.401(6) 1.415(4)
pounds with phenolic hydroxyl groups, 3–6, the phenol system C4–C5 1.373(4) 1.369(3) 1.381(6) 1.366(5) 1.374(6) 1.379(4)
has the highest priority; however, using IUPAC nomenclature C5–N1 1.353(4) 1.340(3) 1.332(6) 1.346(5) 1.331(5) 1.360(4)
C3–C6 1.445(4) 1.453(3) — 1.463(5) 1.450(6) 1.377(3)
here would be at the expense of comparability and clearness.
C5–C6 — — 1.446(7) — — 1.444(4)
For instance, compound 4 would be 2-methoxy-4-[(E)-2- C6–C7 1.327(4) 1.325(3) 1.309(1) 1.310(6) 1.304(4) 1.333(4)
(5-methyl-1H-pyrazol-3-yl)vinyl]phenol under IUPAC rules, C7–C8 1.467(4) 1.472(3) 1.460(1) 1.457(5) 1.475(6) 1.460(4)
rather than (E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)ethenyl]- C3–C15 — — 1.484(6) — — —
C5–C15 1.450(4) 1.484(2) — 1.490(5) 1.509(6) —
5(3)-methyl-1H-pyrazole. In order to prioritize comparability C15–C16 1.322(4) — — — — —
over correct nomenclature, we have named all of the com- C16–C17 1.463(4) — — — — —
pounds as pyrazole derivatives. C10–O2 1.376(4) 1.367(3) 1.359(6) 1.367(4) 1.372(5) 1.372(3)
O2–C14 1.433(4) 1.419(3) 1.424(6) 1.430(5) 1.442(5) 1.416(4)
C11–O1 1.368(4) 1.369(3) 1.372(5) 1.361(5) 1.363(5) 1.371(3)
C15–O1 — — — — — 1.418(4)
Results and discussion C19–O4 1.366(4) — — — — —
O4–C23 1.416(4) — — — — —
Synthesis C20–O3 1.382(4) — — — — —
N2–N1–C5 112.2(3) 112.7(2) 112.2(4) 111.8(3) 111.6(3) 112.4(2)
All of the compounds discussed in this work (Scheme 2) are N1–N2–C3 105.3(2) 104.4(2) 104.4(3) 105.2(3) 104.7(3) 105.3(2)
reported in the experimental section. They were prepared by
the reaction of hydrazine with the corresponding b-diketone,
the most common method of synthesizing pyrazoles,13 which Crystals of sufficient quality for X-ray diffraction analysis
in the case of 3 was 1.14 were obtained for compounds 3 (1 : 1 H2O/EtOH), 4 (1 : 1 : 1
CH2Cl2/hexane/EtOH), 5 (1 : 1 : 1 CH2Cl2/hexane/EtOH) and
X-Ray structure determination 8 (1 : 1 : 1 CH2Cl2/hexane/EtOH) from their respective solvent
The structures of pyrazoles 3 (derived from 1), 4, 5 and 8 have mixtures. Table 1 shows selected bond lengths and angles for
been determined by X-ray crystallography. each of these compounds, and Table 2 shows the distances and
Concerning tautomerism, in the case of 3, tautomers 3a and angles of the intermolecular hydrogen bonds.
3b are identical. In the case of 4, the only tautomer present One crystallographically-independent molecule was identi-
is 3-(3-methoxy)-4-hydroxy-styryl-5-methyl-1H-pyrazole (4a). fied in the structural determination of 3, where the pyrazole
In the case of 5, there is a 2 : 1 mixture of 3-(3-methoxy)-4- and phenyl rings were co-planar, with bond distances and
hydroxy-styryl-4,5-dimethyl-1H-pyrazole (5a) and 3,4-di- angles within normal ranges (Fig. 1). The intermolecular
methyl-5-(3-methoxy)-4-hydroxy-styryl-1H-pyrazole (5b). In hydrogen bonds led to layers parallel to (1 0 1), as shown in
the case of 8, the only observed tautomer is 3-phenyl-4- Fig. 2.
methyl-5-(3-methoxy)-4-hydroxy-styryl-1H-pyrazole (8b). The
main data are collected in Table 1 and Table 2. A charac- Table 2 The bond lengths (Å) and angles (1) for the hydrogen bonds
teristic feature of the geometry of NH-pyrazoles is that the in compounds 3, 4, 5 and 8
angle centered at N1 (the atom bearing the NH proton) is
Compound D–H A dD–H dH A dD A +D–H A
always larger than that centered at N2, about 112 and 1041,
respectively.15 3 O3–H3 O4 1.10 1.98 2.647(4) 115.1
N1–H1B O3a 1.06 1.93 2.864(4) 144.7
O1–H1A N2b 1.17 1.79 2.811(4) 142.7
O3–H3 O1c 1.10 2.26 2.825(4) 108.7
4 O1–H1A N2d 0.99 1.86 2.832(3) 167.5

N1–H1B O2e 1.07 2.17 2.962(3) 128.6
5 O13–H113 N21 1.16 1.81 2.782(5) 137.3

N12–H12 N23 1.10 1.82 2.914(5) 175.6
O11–H111 O13f 0.92 2.03 2.813(4) 141.3
O12–H112 N22g 1.14 1.57 2.673(4) 159.4
N11–H11 O11g 1.08 2.01 2.951(5) 144.3
N13–H13 O12i 1.02 1.93 2.853(4) 148.6
8 N1–H1 N2j 0.90(4) 2.07(4) 2.872(3) 147(4)

Symmetry transformations used to generate equivalent atoms: a x +
2, y 12, z + 12. b x + 1, y + 12, z + 32. c x + 1, y, z 1. d x + 1,
y + 2, z + 1. e x, y + 32, z 12. f x + 4, y 12, z + 32. g x +
1, y 12, z + 12. h x + 4, y + 12, z + 32. i x + 1, y + 12, z +
1 j
Scheme 2 The structures of the NH-pyrazoles. 2. x + 2, y, z + 1.

Fig. 1 The X-ray molecular structure of compound 3 (ORTEP plot,
35% probability for the ellipsoids).
Fig. 4 The view along the b axis of 4, showing the formation of layers
due the intermolecular hydrogen bonds.
(N1–H1B–O2) led to layers parallel to (1 0 0), as shown in

Fig. 4.
The asymmetric unit of compound 5 is presented in Fig. 5.
The crystal consists of three crystallographically-independent,
almost planar molecules, held together by hydrogen bonds
that form a trimer, which, through additional hydrogen
bonding, forms layers parallel to (–1 0 3), as shown in Fig. 6.
Fig. 7 shows the non-planar molecule of compound 8, with
a dihedral angle of 15.7(1)1 between the pyrazole and
the phenyl ring at the 3-position, and 36.5(1)1 between the
pyrazole and the phenyl ring of the styryl group at the
5-position. Molecules of 8 are centrosymmetrically linked by
Fig. 2 The view along the a axis of 3, showing the formation of layers hydrogen bonds (Table 2), giving rise to dimers, and these
due the intermolecular hydrogen bonds. species are within van der Waals distances (Fig. 8).
The cyclic N–H N hydrogen-bonded motifs (cyclamers) of
Fig. 3 shows an ORTEP representation of the asymmetric NH-pyrazoles have been studied on several occasions.4d,16,17
unit of compound 4, a non-planar molecule with a dihedral These motifs are characteristic of NH-pyrazoles lacking sub-
angle of 19.0(1)1 between the pyrazole and phenyl rings. stituents that bear hydrogen bonding functional groups, such
Dimers (O1–H1A–N2) linked by hydrogen bonds as –OH or –CO2H. These groups, as well as solvent molecules
like H2O and ROH, participate in the hydrogen bonding
network that determines the secondary structure of the crys-
tals, destroying the (N–H N)n hydrogen bonds.18–20 In three
of the compounds described in the present paper, those
bearing phenol groups (3, 4 and 5) form several hydrogen
bonds involving the OH group: 3 (O–H N, N–H O,
O–H O), 4 (O–H N, N–H O) and 5 (O–H N,
N–H O, O–H O, N–H N; present as two molecules of
tautomer 5a and one molecule of tautomer 5b). In the case of
8, which lacks phenol groups, the compound crystallizes as a
dimer. This kind of cyclamer is characteristic of NH-pyrazoles
Fig. 3 The X-ray molecular structure of compound 4 (ORTEP plot, that are substituted with phenyl groups at the 3- and 5-posi-
35% probability for the ellipsoids). tions,16 to which compound 8 is clearly related.
This journal is
Fig. 5 The X-ray molecular structure of compound 5 (ORTEP plot, 40% probability for the ellipsoids).
Fig. 8 The view along the a axis of 8, showing the formation of

dimers.
These data have been collected with the aim of determining the
tautomeric equilibrium constants by simple integration.
Although it has been pointed out that only 1H NMR signal
intensities are reliable for the determination of populations, in
our experience, 13C and 15N signals can also been used in
connection with signals related by tautomerism, i.e. carbon or
nitrogen atoms linked to the same substituents.3c The assign-
Fig. 6 The view along the a axis of 5, showing the formation of layers ments of the signals were based on standard 2D experiments,
due the intermolecular hydrogen bonds. on the values of coupling constants (auto-consistency) and by
comparison with other NH-pyrazoles where tautomerization
is blocked.21
We have illustrated with one example the kind of spectra
that we obtained (Fig. 9). The spectrum corresponds to
compound 5 in HMPA-d18, concentration 0.10 M and tem-
perature 268 K (Table 4). The region of the methyl groups
shows two narrow signals corresponding to the most abundant
tautomer, and two broad signals corresponding to the less
abundant one, as expected by simple consideration of the
energy profile.
For compounds whose structure had not been determined
Fig. 7 The X-ray molecular structure of compound 8 (ORTEP plot,
by crystallography, we relied on CPMAS NMR results: 6b and
35% probability for the ellipsoids).
7b were the only tautomers present in the solid state
(see Table 4 and Table 5). We are aware that solid state
NMR study
NMR and single crystal X-ray diffraction do not show exactly
We have reported the 1H, 13C and 15N NMR results concerning the same properties, for instance, static vs. dynamic disorder.3b
compounds 3–8 in Table 3, Table 4 and Table 5, respectively. To avoid further complications, we used fine powders for

This journal is
Table 3 The 1H NMR chemical shifts (d) and 1H–1H coupling constants of compounds 3–8 (J/Hz) in DMSO-d6 and HMPA-d18 solutionsa
c

Compound R1 R2 R3 Solvent Conc./M T/K NH R2 H3 H4 H6 OMe OR3 H7 H8 R1 Tautomerism
3 * H H DMSO 0.12 300 12.80 6.61 (H) 6.76 6.93 7.13 3.82 9.17 (H) 7.03 6.91 — Average
4 CH3 H H DMSO 0.07 300 12.40 6.20 (H) 6.74 6.91 7.12 3.81 9.15 (H) 6.95 6.88 2.19 (Me) Average
HMPA 0.07 300 13.26 6.11 (H) 6.85/7.16 3.80 10.26 (H) 6.85/7.16 2.23 (Me) B50% a
HMPA 0.07 300 13.20 6.11 (H) 6.85/7.16 3.80 10.24 (H) 6.85/7.16 2.15 (Me) B50% b
HMPA 0.10 276 13.34 6.19 (H) 6.85 6.85 7.06 3.80 10.42 (H) 7.20 6.87 2.25 (Me) B50% a
HMPA 0.10 276 13.27 6.11 (H) 6.85 6.85 7.06 3.80 10.34 (H) 6.92 6.83 2.14 (Me) B50% b
5 CH3 CH3 H DMSO 0.07 300 12.29 2.03 (Me) 6.75 6.91 7.13 3.83 9.08 (H) 6.95 6.86 2.10 (Me) Average
HMPA 0.10 300 13.16 2.04 (Me) 6.87 6.92 6.97 3.80 10.28 (H) 7.21 6.82 2.04 (Me) 35% a
HMPA 0.10 300 13.10 2.04 (Me) 6.87 6.92 6.97 3.80 10.20 (H) 7.21 6.82 2.07 (Me) 65% b
HMPA 0.10 268 13.25 2.05 (Me) 6.87 6.96 7.00 3.81 10.44 (H) 7.25 6.88 2.05 (Me) 35% a
HMPA 0.10 268 13.20 2.05 (Me) 6.87 6.96 7.00 3.81 10.38 (H) 7.25 6.88 2.07 (Me) 65% b
6 C6H5 H H DMSO 0.11 300 12.96 6.88 (H) 6.78 6.96 7.15 3.84 9.10 (H) 7.10 6.95 7.80 (o) 36% a
7.43 (m)
7.31 (p)
DMSO 0.11 300 13.18 6.88 (H) 6.78 6.96 7.15 3.84 9.21 (H) 7.10 6.95 7.80 (o) 64% b
7.43 (m)
7.31 (p)
The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2009
7 C6H5 H CH3 DMSO 0.06 300 13.00 6.87 (H) 6.96 7.06 7.19 3.83 3.78 (Me) 7.14 7.03 7.80 (o) 40% a
7.43 (m)
7.32 (p)
DMSO 0.06 300 13.21 6.87 (H) 6.96 7.06 7.19 3.83 3.78 (Me) 7.14 7.03 7.80 (o) 60% b
7.43 (m)
7.32 (p)
8 C6H5 CH3 CH3 DMSO 0.05 300 12.94 2.29 (Me) 6.95 7.07 7.25 3.84 3.77 (Me) 7.14 7.06 7.65 (o) Rich in b
7.45 (m)
7.34 (p)
HMPA 0.06 268 13.94 2.34 (Me) 7.09 7.09 7.25 3.88 3.84 (Me) 7.45 7.13 7.70 (o) b
7.45 (m)
7.31 (p)
a
The coupling constants were, on average: 3JH3–H4 = 8.0 Hz, 4JH4–H6 = 2.0 Hz (not always observed) and 3JH7–H8trans = 16.5 Hz.
New J. Chem., 2009, 33, 125–135 | 129

13
Table 4 The C NMR chemical shifts (d) and 1H–13C coupling constants (J/Hz) in DMSO-d6 and HMPA-d18 solutions, and under CPMAS
conditionsa
Ca Cb Cc R2 C1 C2 C3
Compound R1 R2 R3 Solvent Conc./M T/K C4 C5 C6 C7 C8 OCH3 R1 Tautomerism
3 * H H DMSO 0.12 300 151.0 99.3 142.0 — (H) 147.9 146.8 115.6 No tautomerism
120.1 128.4 109.5 129.8 112.9 (C8) 55.6
118.4 (C8 0 )
CPMAS — 300 150.2 95.5 142.8 — (H) 147.4 145.1 114.5 No tautomerism
N.o.b 127.1 106.3 129.9 111.9 53.5
56.5
4 CH3 H H DMSO 0.36 300 149.6 101.3 140.5 — (H) 147.9 146.6 115.7 Average
119.9 128.6 109.5 129.0 117.4 55.6 11.6 (Me)
HMPA 0.10 276 150.9 100.0 142.4 — (H) 148.7 148.6 115.7 B50% a
119.4 128.4 110.5 128.7 113.2 55.9 10.8 (Me-5)
138.4 101.6 148.9 — (H) 148.7 146.9 115.7 B50% b
119.6 128.4 110.5 129.4 119.3 55.9 13.9 (Me-3)
CPMAS — 300 151.5 101.1 142.4 — (H) 148.8 143.3 115.3 a
120.5 129.9 113.2 129.9 113.2 55.9 9.9 (Me-5)
115.3
5 CH3 CH3 H DMSO 0.07 300 141.6 110.4 141.6 8.1 (Me) 147.9 146.6 115.6 Average
119.8 128.8 109.6 127.9 114.9 55.7 10.6
HMPA 0.08 300 147.5 109.9 135.7 8.4 (Me) 149.0 148.7 116.1 35% a
119.6 129.0 111.5 127.7 118.7 56.3 11.9 (br)
HMPA 0.08 300 138.3 109.9 145.8 8.4 (Me) 149.0 148.7 116.1 65% b
119.6 129.0 111.5 128.4 112.7 56.3 11.9 (br)
HMPA 0.10 268 147.5 110.0 135.7 8.8 (br, Me) 148.8 148.6 115.8 35% a
119.5 128.8 110.7 127.6 118.5 55.9 9.1 (br)
HMPA 0.10 268 138.3 109.9 145.8 8.4 (Me) 148.8 148.6 115.8 65% b
119.5 128.8 110.7 128.3 112.4 55.9 12.1
CPMAS — 300 145.9 110.2 138.6 9.8 (Me) 148.8 146.6 121.8 66% a
123.4 130.9 105.5 128.9 117.0 55.3 11.2 (br)
137.5 112.0 146.6 9.8 (Me) 148.8 146.6 121.8 34% b
123.4 130.9 105.5 128.9 119.0 55.3 11.2 (br)
6 C6H5 H H DMSO 0.11 300 151.4 100.4 140.3 — (H) 147.9 146.6 115.3 36% a
122.1 128.1 109.5 130.1 118.4 55.5 132.0 (i)
125.0 (o)
128.7 (m)
127.5 (p)
DMSO 0.11 300 142.6 99.5 151.0 — (H) 147.9 147.1 115.6 64% b
120.2 128.1 109.5 130.1 112.7 55.6 133.6 (i)
125.1 (o)
128.7 (m)
127.5 (p)
6b C6H5 H H CPMAS — 300 144.0 103.5 152.6 — (H) 148.3 116.0

116.0 129.0 112.3 129.0 113.5 54.0 133.2 (i)
126.4 (o)
129.0 (m)
129.0 (p)
7 C6H5 H CH3 DMSO 0.11 300 151.3 99.2 142.8 — (H) 149.0 149.0 111.9 40% a
119.4 129.4 108.9 128.9 113.6 55.51 (C1) 133.7 (i)
55.45 (C2) 125.0 (o)
128.6 (m)
127.4 (p)
DMSO 0.11 300 142.4 99.8 150.9 — (H) 149.0 149.0 111.9 60% b
119.9 129.4 108.9 129.7 113.6 55.51 (C1) 133.7 (i)
55.45 (C2) 125.0 (o)
128.6 (m)
127.4 (p)

Table 4 (continued )
Ca Cb Cc R2 C1 C2 C3
Compound R1 R2 R3 Solvent Conc./M T/K C4 C5 C6 C7 C8 OCH3 R1 Tautomerism
7b C6H5 H CH3 CPMAS — 300 143.1 96.3 149.8 — (H) 148.8 148.8 110.6
120.9 129.1 108.0 129.1 110.6 53.5 (C1*) 132.1 (i)
56.1 (C2*) 125.2 (o)
129.1 (m)
126.2 (p)
8 C6H5 CH3 CH3 DMSO 0.31 300 141.7 110.7 147.1 9.4 (Me) 149.1 148.8 111.9 Aver.
119.9 130.0 109.1 128.4 114.5 55.6 (C1) 133.2 (i) Rich in b
55.5 (C2) 127.1 (o)
128.5 (m)
127.3 (p)
HMPA 0.06 268 139.7 110.4 149.5 10.1 (Me) 149.8 149.3 112.1 b
120.2 130.9 109.1 128.8 113.2 55.9 (C1) 135.9 (i)
55.9 (C2) 127.2 (o)
128.6 (m)
126.9 (p)
CPMAS — 300 140.7 112.5 148.8 9.2 (Me) 148.8 148.8 112.5 b
124.7 130.2 110.7 130.2 117.1 54.7 134.6 (i)
128.5 (o)
130.2 (m)
126.7 (p)
a
The 1J coupling constants are not reported; their average values are: pyrazole C4–Hb = 175 Hz; phenyl CH = 159 Hz except C4–H and
C6–H = 156 Hz; olefin C–H = 155 Hz; OCH3 = 144 Hz; C–Me substituents: 126.5 Hz. The other couplings (Hz) are: 2J = 2.2 (C1), 2J = 4.5
(C7), 2J = 5.9 (Cb–Me4); 3J = 8.4 (C1), 3J = 7.3 (C2), 3J = 5.8 (C4), 3J = 6.8 (C5), 3J = 6.0 (C6), 3J = 4.5 (C7), 3J = 2.4 (Cb–H).
b
Not observed.
CPMAS NMR, obtained by grinding the same batch of cyclamers, linked by N–H N hydrogen bonds. Compound 3
crystals that we used for X-ray crystallography. has the same substituent at both positions (tautomer 3a is
identical to tautomer 3b), but crystallizes in a complex
Percentages of tautomers and equilibrium constants network of hydrogen bonds involving the OH groups. Com-
Although some exceptions are known, the assumption of the pound 8 crystallizes as a dimer, but with only one tautomer
identical nature of the most stable tautomer in solution and present (8a). Thus, none of the compounds of Table 6 display
the tautomer present in the crystal is one of the most basic SSPT. Finally, compound 5 is the only known example of an
tenets in tautomerism.3b,3c,17b The results in Table 6 confirm NH-pyrazole that crystallizes as a 2 : 1 mixture of two
this principle for compounds 4, 5 and 8, and allow us tautomers (there are examples of 2 : 2 and 3 : 1 mixtures,
to conclude that in the solid state, 6 should crystallize as but in cyclic tetramers17b,22).
6b and 7 as 7b, or at least in cyclamers where 6b and 7b are
predominant. Experimental
Compound 5 exists in the solid state as a 66% 5a/34% 5b
mixture and in HMPA as a 35% 5a/65% 5b mixture, thus The melting points of pyrazoles 3–8 were determined by
being an exception to the rule of similarity between solution differential scanning calorimetry (DSC) on a Seiko DSC
and solid state. However, the difference in energy at 300 K 220C connected to a Model SSC5200H Disk Station; for the
between the two situations is only of 3.2 kJ mol1. other compounds, a hot stage microscope was used. Thermo-
grams (sample size 0.003–0.0010 g) were recorded at a scan-
ning rate of 2.0 1C min1. Thin-layer chromatography
Conclusions
(TLC) was performed using Merck silica gel (60 F254) and
The structure, tautomerism and absence of SSPT have been compounds were detected with a 254 nm UV lamp. Silica gel
determined for six NH-pyrazoles by a combination of X-ray (60–320 mesh) was employed for routine column chromato-
crystallography and 13C/15N NMR spectroscopy. Two of the graphy separations. Elemental analyses for carbon, hydrogen
conditions required to observe SSPT in NH-pyrazoles are the and nitrogen were carried out by the Microanalytical Service
identity (or, at least, strong similarity) of the substituents at of the Universidad Complutense of Madrid on a Perkin-Elmer
the 3- and 5-positions, and the formation of cyclic structures, 240 analyzer.
This journal is
PTa
No
No
No
No
No
No
No
No
B50
%b
100
100
100
70
50
34
0
B50
%a
100
30
50
66
0
0
0
103.6 (major)
100.6
100.9
111.2
105.3
98.7
–N=
N.o.b
N.o.
N.o.
13
Fig. 9 The methyl group region of the C NMR spectrum of 5.
185.6 (major)
172.0 (major)
General procedure for the preparation of pyrazole derivatives

(3–8)
180.8
180.5
173.6
177.7
175.9
187.8
–181.5
–182.2
–181.3
Compounds 3–8 were prepared by reacting the corresponding

N–H
b-diketones23 (1 mmol) with hydrazine hydrate 98% (1.5 mmol)

N NMR chemical shifts (d) in DMSO-d6 and HMPA-d18 solutions, and under CPMAS conditions
in acetic acid (5 mL). After heating at reflux for 2 h, the

reaction mixture was poured into water, and the precipitate
filtered off, washed with water and dried. The solid was
T/K
purified by column chromatography using ethyl acetate as

300
276
300
300
300
300
268
300
the eluent.
(E)-3,5-Bis[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-1H-
Conc./M
pyrazole (3)
0.10
0.08
0.06
3 was prepared from purified commercially available 1. The

—
compound was obtained as a colourless solid after recrystalli-

zation from H2O/EtOH (1 g, 2.74 mmol, 63%). Mp: 217.1 1C,
lit.: 211–214 1C5 or 215 1C.8 Anal. calc. for C21H20N2O4
CPMAS
CPMAS
CPMAS
CPMAS
CPMAS
Solvent
HMPA
HMPA
HMPA
(364.14): C, 69.22; H, 5.53; N, 7.69; found: C, 68.79; H,

5.53; N, 7.70%.
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-methyl-
1H-pyrazole (4)
CH3
R3
H
H
H
H
4 was prepared from (E)-6-(4-hydroxy-3-methoxyphenyl)hex-

5-ene-2,4-dione.23 The compound was obtained as a colourless
solid after recrystallization from CH2Cl2/hexane/EtOH
(251 mg, 1.1 mmol, 85%). Mp: 141.6 1C. Anal. calc. for
CH3
CH3
R2
C13H14N2O2 (230.11): C, 67.26; H, 6.44; N, 12.11; found: C,

H
H
67.81; H, 6.13; N, 12.17%.

Not observed
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-4,5(3)-
C6H5
C6H5
CH3
CH3
CH3
R1
dimethyl-1H-pyrazole (5)
*
5 was prepared from (E)-6-(4-hydroxy-3-methoxyphenyl)-3-

Proton transfer
15
methylhex-5-ene-2,4-dione.23 The compound was obtained as

Table 5 The
a colourless solid after recrystallization from CH2Cl2/hexane/

Compound
EtOH (180 mg, 0.73 mmol, 61%). Mp: 176.1 1C. Anal. calc.
for C14H16N2O2 (244.12): C, 68.46; H, 6.61; N, 11.35; found:
8b
6b
4a
C, 68.83; H, 6.60; N, 11.47%.

3
4

Table 6 The tautomeric composition of 3–8 (Sty: Ar–CHQCH–)a
Compound Tautomers X-Ray CPMAS DMSO HMPA

b
3 a, b: 3,5-BisSty 3a = 3b 3a = 3b 3a = 3b No PT N. M.
4 a: 3-Sty-5-Me 4a 4a Average rich in 4a B50% 4a
b: 3-Me-5-Sty B50% 4b
5 a: 3-Sty-5-Me 66% 5a 66% 5a Average rich in 5b 35% 5a
b: 3-Me-5-Sty 34% 5b 34% 5b 65% 5b
6 a: 3-Sty-5-Ph N. M. 6b 36% 6a N. M.
b: 3-Ph-5-Sty 64% 6b
7 a: 3-Sty-5-Ph N. M. 7b 40% 7a N. M.
b: 3-Ph-5-Sty 60% 7b
8 a: 3-Sty-5-Ph 8b 8b Average rich in 8b 8b
b: 3-Ph-5-Sty
a b
N. M. means not measured. Proton transfer
Table 7 The crystal and structure refinement data for compounds 3, 4, 5 and 8
Crystal data 3 4 5 8
Empirical formula C21H20N2O4 C13H14N2O2 C14H16N2O2 C20H20N2O2
Formula weight 364.39 230.26 244.29 320.38
Crystal system Monoclinic Orthorhombic Monoclinic Orthorhombic
Space group P2(1)/c Pbca P2(1)/c Pbca
Unit cell dimensions a/Å 8.2394(10) 13.2563(15) 8.519(2) 13.2363(13)
b/Å 14.0198(17) 7.6962(9) 12.964(4) 8.2769(8)
c/Å 16.306(2) 22.855(3) 34.615(10) 30.673(3)
b (1) 101.060(3) — 94.607(7) —
3
Volume/Å 1848.7(4) 2331.7(5) 3810.6(19) 3360.4(6)
Z 4 8 12 8
Density (calculated)/Mg m3 1.309 1.312 1.277 1.267
Absorption coefficient/mm1 0.092 0.090 0.087 0.083
Scan technique o and j o and j o and j o and j
F(000) 768 976 1560 1360
Range for data collection (1) 1.93 to 25.00 1.78 to 27.00 1.18 to 25.00 1.33 to 25.00
Index ranges 9, 16, 18 to 9, 16, 19 13, 9, 29 to 16, 9, 29 9, 15, 41 to 10, 15, 41 15, 9, 36 to 10, 9, 32
Reflections collected 13 998 19 397 28 784 16 484
Independent reflections 3244 2541 6720 2954
Observed reflections [I 4 2s(I)] 1418 1248 2855 1655
Rint 0.1198 0.0889 0.0905 0.0708
Completeness to y (%) 99.6 100.0 100.0 99.9
Data/restraints/parameters 3244/0/245 2541/0/156 6720/2/497 2954/0/224
Goodness-of-fit on F2 0.912 1.034 0.984 1.074
R1a 0.0539 0.0508 0.0769 0.0507
wR2b (all data) 0.1808 0.1768 0.2486 0.1848
Largest differential peak and 0.232 and 0.278 0.214 and 0.247 0.950 and 0.377 0.193 and 0.192
hole/eÅ3
P P P P
a
R1 = ||Fo| |Fc||/ |Fo|. b wR2 = [w(Fo2 Fc2)2]/ [w(Fo2).
(E)-3(5)-[b-(4-hydroxy-3-methoxyphenyl)-ethenyl]-5(3)-phenyl- for C19H18N2O2 (306.37): C, 74.48; H, 5.92; N, 9.14; found: C,

1H-pyrazole (6) 74.21; H, 5.82; N, 9.16%.
6 was prepared from (E)-5-(4-hydroxy-3-methoxyphenyl)-1- (E)-3(5)-[b-(3,4-dimethoxyphenyl)-ethenyl]-4-methyl-5(3)-
phenylpent-4-ene-1,3-dione.23 The compound was obtained as phenyl-1H-pyrazole (8)
a colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (228 mg, 0.78 mmol, 77%). Mp: 142.9 1C. Anal. calc. 8 was prepared from (E)-5-(3,4-dimethoxyphenyl)-2-methyl-1-
for C18H16N2O2 (292.12): C, 73.95; H, 5.54; N, 10.11; found: phenylpent-4-ene-1,3-dione.23 The compound was obtained as
C, 73.95; H, 5.54; N, 10.11%. a colourless solid after recrystallization from CH2Cl2/hexane/
EtOH (170 mg, 0.53 mmol, 58%). Mp: 182.0 1C. Anal. calc.
for C20H20N2O2 (320.39): C, 74.97; H, 6.29; N, 8.74; found: C,
(E)-3(5)-[b-(3,4-dimethoxyphenyl)-ethenyl]-5(3)-phenyl-1H- 74.28; H, 6.14; N, 8.77%.
pyrazole (7)
X-Ray data collection and structure refinement (compounds 3, 4,
7 was prepared from (E)-5-(3,4-dimethoxyphenyl)-1-phenyl-
5 and 8)
pent-4-ene-1,3-dione.23 The compound was obtained as a
colourless solid after recrystallization from CH2Cl2/hexane/ Data collection for all of the compounds was carried out at
EtOH (196 mg, 1.27 mmol, 51%). Mp: 173.4 1C. Anal. calc. room temperature on a Bruker Smart CCD diffractometer
This journal is
using graphite-monochromated Mo-Ka radiation (l = In the gs-HMQC experiments, GARP modulation of 13C was
0.71073 Å) operating at 50 kV and 30 mA. In all cases, the used for decoupling. 15N NMR spectra were acquired using
data were collected over a hemisphere of the reciprocal space 2D inverse proton detected heteronuclear shift correlation
by the combination of three exposure sets. Each frame ex- spectroscopy. Typical parameters for the gs-HMQC
posure time was either 10 or 20 s, covering 0.31 in o. The cell (1H–15N) spectra were: a spectral width of 5787 Hz for 1H
parameters were determined and refined by a least-squares fit and 12.5 kHz for 15N, a 1024 256 data set, number of
of all reflections collected. The first 100 frames were re- scans = 4, a relaxation delay of 1 s and a 7 ms delay for the
collected at the end of the data collection to monitor crystal evolution of the 15N–1H coupling. The FIDs were processed
decay, and no appreciable decay was observed. A summary of using zero filling in the F1 domain, and a sine-bell window
the fundamental crystal and refinement data is given in function in both dimensions was applied prior to Fourier
Table 7. The structures of all the compounds were solved by transformation. A Bruker BVT 3000 temperature unit was
direct methods and conventional Fourier synthesis, and re- used to control the temperature of the cooling gas stream and
fined by full matrix least-squares on F2 (SHELXL-97).24 All an exchanger was used to achieve low temperatures.
non-hydrogen atoms were refined anisotropically.
In all cases, the hydrogen atoms were calculated, included Solid state. Solid state 13C (100.73 MHz) and 15N (40.60 MHz)
and refined as riding on their respective carbon-bonded atom CPMAS NMR spectra were recorded on a Bruker WB 400
with a common anisotropic displacement. The rest of the spectrometer at 300 K using a 4 mm DVT probe head.
hydrogen atoms, i.e. those bonded to nitrogen or oxygen Samples were carefully packed in 4 mm diameter cylindrical
atoms, were located in a Fourier difference synthesis, and in zirconia rotors with Kel-F caps. Operating conditions in-
all cases were included and refined as riding on their respective volved 90 3.2 ms 1H pulses and a decoupling field strength of
bonded atoms for 3, 4 and 5, while for 8, its coordinates were 78.1 kHz in a TPPM sequence. The non-quaternary suppres-
refined and the thermal factors kept constant. The longer O–H sion (NQS) technique to observe only the quaternary carbon
bond distances in some of the hydroxyl groups are due to the atoms was employed. 13C spectra were initially referenced
formation of hydrogen bonds.25 to a glycine sample and then the chemical shifts were recalcu-
The largest peaks and holes in the final difference map were lated to Me4Si (for the carbonyl atom, dglycine = 176.1).
0.232 and 0.278, 0.214 and 0.247, 0.950 and 0.377, and Similarly, 15N spectra were initially referenced to 15NH4Cl
0.193 and 0.192 eÅ3 for 3, 4, 5 and 8, respectively. The final and then recalculated to nitromethane, using the relationship:
R1 and wR2 values were 0.0539 and 0.1808, 0.0508 and 0.1768, d 15Nnitromethane = d 15NNH4Cl 338.1. Typical acquisition
0.0769 and 0.2486, and 0.0507 and 0.1848 for 3, 4, 5 and 8, parameters for the 13C CPMAS were: a spectral width of
respectively. 40 kHz, a recycle delay of 15–75 s, an acquisition time of
30 ms, a contact time of 2 ms and a spin rate of 12 kHz.
Typical parameters for the 15N CPMAS were: a spectral width
NMR spectroscopy of 40 kHz, a recycle delay of 15–75 s, an acquisition time of 35
Solution NMR spectra. Solution NMR spectra were re- ms, a contact time of 7–8 ms and spin rate of 6 kHz.
corded on a Bruker DRX 400 (9.4 T; 400.13 MHz for 1H,
100.62 MHz for 13C and 40.56 MHz for 15N) spectrometer Acknowledgements
fitted with a 5 mm inverse detection H–X probe and equipped
with a z-gradient coil at 300 K. 1H and 13C NMR chemical This work has been financed by the Spanish MEC (CTQ2006-
shifts (d) are referenced to Me4Si; for 15N NMR, nitromethane 02586 and CTQ2007-62113).
(0.00) was used as an external standard. Typical parameters
for the 1H NMR spectra were: a spectral width of 5787 Hz, a References
pulse width of 7.5 ms, an attenuation level of 0 dB and a
1 J. Higdon, Curcumin, Linus Pauling Institute, Oregon State Uni-
resolution of 0.34 Hz per point. Typical parameters for the 13C versity, Oregon, USA (http://lpi.oregonstate.edu/infocenter/phyto
NMR spectra were: a spectral width of 21 kHz, a pulse width chemicals/curcumin/).
of 10.6 ms, an attenuation level of 6 dB, a relaxation delay of 2 (a) R. M. Claramunt, D. Sanz del Castillo, J. Elguero, P. Nioche,
2 s and a resolution of 0.63 Hz per point; WALTZ-16 was used C. S. Raman, P. Martasek and B. S. S. Masters, XVIIth Interna-
tional Symposium on Medicinal Chemistry, Poster P101, Drugs
for broadband proton decoupling and the FIDs were multi- Future, 2002, 27(Suppl. A), 177; (b) C. Pérez-Medina, M. Pérez-
plied by an exponential weighting (lb = 1 Hz) before Fourier Torralba, C. López, R. M. Claramunt, P. Nioche and
transformation. 2D inverse proton detected heteronuclear C. S. Raman, XIV Congreso Nacional de la Sociedad Española de
Quı´mica Terapeútica, Bilbao, Spain, 2005.
shift correlation spectra, gs-HMQC (1H–13C) and gs-HMBC
3 (a) J. Elguero, C. Marzin, A. R. Katritzky and P. Linda, The
(1H–13C), were acquired and processed using standard Bruker Tautomerism of Heterocycles, Academic Press, New York, 1976,
NMR software. Typical parameters for these spectra were: pp. 655; (b) V. I. Minkin, A. D. Garnosvskii, J. Elguero,
a spectral width of 5787 Hz for 1H and 20.5 kHz for 13C, a A. R. Katritzky and O. V. Denisko, Adv. Heterocycl. Chem.,
2000, 76, 157–323; (c) R. M. Claramunt, C. López, M. D. Santa
1024 256 data set, number of scans = 2 (gs-HMQC) or 4 Marı́a, D. Sanz and J. Elguero, Prog. Nucl. Magn. Reson. Spec-
(gs-HMBC), a relaxation delay of 1 s, and a delay for the trosc., 2006, 49, 169–206.
evolution of 13C–1H coupling constants of 3 ms (gs-HMQC) 4 (a) J. Quiroga Puello, B. Insuasty Obando, C. Foces-Foces,
or 60 ms (gs-HMBC). The FIDs were processed using zero L. Infantes, R. M. Claramunt, P. Cabildo, J. A. Jimenez and
J. Elguero, Tetrahedron, 1997, 53, 10783–10802; (b) M. H.
filling in the F1 domain, and a sine-bell window function in Holschbach, D. Sanz, R. M. Claramunt, L. Infantes,
both dimensions was applied prior to Fourier transformation. S. Motherwell, P. R. Raithby, M. L. Jimeno, D. Herrero,

I. Alkorta, N. Jagerovic and J. Elguero, J. Org. Chem., 2003, 68, D. Bagchi and H. G. Preuss, CRC Press, Boca Raton, 2005,
8831–8837; (c) R. M. Claramunt, M. Á. Garcı́a, C. López, pp. 349–387.
S. Trofimenko, G. P. A. Yap, I. Alkorta and J. Elguero, Magn. 15 I. Alkorta, J. Elguero, B. Donnadieu, M. Etienne, J. Jaffart,
Reson. Chem., 2005, 43, 89–91; (d) S. Trofimenko, G. P. A. Yap, D. Schagen and H.-H. Limbach, New J. Chem., 1999, 23, 1231–1237.
F. A. Jove, R. M. Claramunt, M. Á. Garcı́a, M. D. Santa Marı́a, 16 (a) C. Foces-Foces, I. Alkorta and J. Elguero, Acta Crystallogr.,
I. Alkorta and J. Elguero, Tetrahedron, 2007, 63, 8104–8111. Sect. B: Struct. Sci., 2000, 56, 1018–1028; (b) I. Alkorta,
5 D. L. Flynn, T. R. Belliotti, A. M. Boctor, D. Connor, C. Kostlan, J. Elguero, C. Foces-Foces and L. Infantes, ARKIVOC (Gaines-
D. E. Nies, D. F. Ortwine, D. J. Schrier and J. C. Sircar, J. Med. ville, FL, U. S.), 2006, ii, 15–30.
Chem., 1991, 34, 518–525. 17 (a) R. M. Claramunt, P. Cornago, V. Torres, E. Pinilla,
6 J. S. Shim, D. H. Kim, H. J. Jung, J. H. Kim, D. Lim, S.-K. Lee, M. R. Torres, A. Samat, V. Lokshin, M. Valés and J. Elguero,
K.-W. Kim, J. W. Ahn, J.-S. Yoo, J.-R. Rho, J. Shin and J. Org. Chem., 2006, 71, 6881–6891; (b) R. M. Claramunt,
H. J. Kwon, Bioorg. Med. Chem., 2002, 10, 2439–2444. P. Cornago, M. D. Santa Marı́a, V. Torres, E. Pinilla,
7 J. Ishida, H. Ohtsu, Y. Tachibana, Y. Nakanishi, K. F. Bastow, M. R. Torres and J. Elguero, Supramol. Chem., 2006, 18, 349–356.
M. Nagai, H.-K. Wang, H. Itokawa and K.-H. Lee, Bioorg. Med. 18 C. Foces-Foces, C. Cativiela, J. L. Serrano, M. M. Zurbano,
Chem., 2002, 10, 3481–3487. N. Jagerovic and J. Elguero, J. Chem. Crystallogr., 1996, 26, 127–131.
8 H. Ohtsu, Z. Xiao, J. Ishida, M. Nagai, H.-K. Wang, H. Itogawa, 19 (a) A. M. S. Silva, L. M. P. M. Almeida, J. A. S. Cavaleiro,
C.-Y. Su, C. Shih, T. Chiang, E. Chang, Y. Lee, M.-Y. Tsai, C. Foces-Foces, A. L. Llamas-Saiz, C. Fontenas, N. Jagerovic and
C. Chang and K.-H. Lee, J. Med. Chem., 2002, 45, 5037–5042. J. Elguero, Tetrahedron, 1997, 53, 11645–11658; (b) D. C. G. A.
9 C. Selvam, S. M. Jachak, R. Thilagavathi and A. K. Chakraborti, Pinto, A. M. S. Silva, J. A. S. Cavaleiro, C. Foces-Foces,
Bioorg. Med. Chem.Lett., 2005, 15, 1793–1797. A. L. Llamas-Saiz, N. Jagerovic and J. Elguero, Tetrahedron,
10 R. Narlawar, K. Baumann, R. Schubenel and B. Schmidt, 1999, 55, 10187–10200.
Neurodegener. Dis., 2007, 4, 88–93. 20 C. Foces-Foces, A. Echevarrı́a, N. Jagerovic, I. Alkorta,
11 R. Narlawar, M. Pickhardt, S. Leuchtenberger, K. Baumann, J. Elguero, U. Langer, O. Klein, M. Minguet-Bonvehı́ and
S. Krause, T. Dyrks, S. Weggen, E. Mandelkow and B. Schmidt, H.-H. Limbach, J. Am. Chem. Soc., 2001, 123, 7898–7906.
ChemMedChem, 2008, 3, 165–172. 21 M. Begtrup, G. Boyer, P. Cabildo, C. Cativiela, R. M. Claramunt,
12 P. Maher, T. Akaishi, D. Schubert and K. Abe, Neurobiol. Aging, J. Elguero, J. I. Garcı́a, C. Toiron and P. Vedsø, Magn. Reson.
2008, DOI: 10.1016/j.neurobiolaging.2008.05.020. Chem., 1993, 31, 107–168.
13 (a) J. Elguero, in Comprehensive Heterocyclic Chemistry, ed. 22 J. Elguero, N. Jagerovic, C. Foces-Foces, F. H. Cano, M. V. Roux,
A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, F. Aguilar-Parrilla and H.-H. Limbach, J. Heterocycl. Chem.,
vol. 5, pp. 167; (b) J. Elguero, in Comprehensive Heterocyclic 1995, 32, 451–456.
Chemistry II, ed. A. R. Katritzky, C. W. Rees and E. F. Scriven, 23 P. Cornago, R. M. Claramunt, L. Bouissane, I. Alkorta and
Pergamon Press, Oxford, 1996, vol. 3, pp. 1; (c) B. Stanovnik and J. Elguero, Tetrahedron, 2008, 64, 8089–8094.
J. Svete, in Science of Synthesis, ed. R. Neier, Thieme, Stuttgart, 24 G. M. Sheldrick, SHELXL-97, Program for refinement of crystal
2002, vol. 12, ch. 12.1. structures, University of Göttingen, Germany, 1997.
14 B. B. Aggarwal, A. Kumar, M. S. Aggarwal and S. Shishodia, 25 G. R. Desiraju and T. Steiner, The Weak Hydrogen Bond in
Curcumin Derived from Tumeric (Curcuma longa): a Spice for All Structural Chemistry and Biology, Oxford University Press, Ox-
Seasons, in Phytopharmaceuticals in Cancer Chemoprevention, ed. ford, 1999.
This journal is
Neutral 5-nitrotetrazoles: easy initiation with low pollutionw

Thomas M. Klapötke,* Carles Miró Sabaté and Jörg Stierstorfer
Received (in Durham. UK) 21st July 2008, Accepted 8th September 2008
DOI: 10.1039/b812529e
5-Nitro-2H-tetrazole (1), 1-methyl-5-nitrotetrazole (2) and 2-methyl-5-nitrotetrazole (3) were

synthesized starting from the corresponding 5-amino-substituted tetrazoles in good yields and
purities. The compounds were fully characterized by analytical and spectroscopic methods and
their solid state structures were determined by low temperature X-ray diffraction techniques. Due
to the potential of tetrazoles as energetic materials an extensive computational study (CBS-4M)
was performed in order to estimate the energies of formation (DfU1) of the molecules, which are
highly endothermic (1, 2527 kJ kg1; 2, 2253 kJ kg1 and 3, 2006 kJ kg1). The EXPLO5
software was used to calculated the corresponding detonation velocities (Ddet) and detonation
pressures (pdet) (1, Ddet = 9457 m s1 and pdet = 390 kbar; 2, Ddet = 8085 m s1 and
pdet = 257 kbar and 3, Ddet = 8109 m s1 and pdet = 262 kbar) by combining the DfU1 values
of the materials with the (X-ray calculated) densities and molecular formulas, giving performances
comparable to commonly used secondary explosives (e.g., RDX). Lastly, all three neutral
compounds can be easily initiated by impact (o2 J) and with high detonation velocities and
excellent combined oxygen and nitrogen contents offer a more powerful and environmentally
friendly alternative to commonly used primary explosives in initiating devices.
Introduction
In the continuous search for novel green energetic materials1
with high nitrogen but low carbon content,2,3 several groups
around the world are currently investigating HEDMs (High
Energy Dense Materials) based on tetrazoles.4 These energetic
materials have variable application such as in low-smoke
producing pyrotechnic compositions,5 gas generators,6 pro-
pellants,7 high explosives8 and primers in primer charges
(PC).9 Tetrazole derivatives,10,11 tetrazolate12,13 and tetra-
zolium14,15 salts are of special interest. One of the most
promising class of molecules in this regard are 5-substituted
tetrazoles16 (Fig. 1) due to the fact that their properties can be
controlled by selection of the substituent at the carbon atom.
While electron donating groups (EDGs) such as NH217 or
OH18 yield rather stable compounds, electron withdrawing
Fig. 1 Structural formulas of neutral 5-substituted tetrazoles.
groups (EWGs) such as NO219 and CN20 destabilize the ring
system and increase the sensitivity of the materials. Also
the azide and nitramine groups rather than based on the
protonation/alkylation of the tetrazole ring is directed by the
electronic influence of these groups on the ring system.
electronegativity of the substituent. While EWGs direct the
The combination of a tetrazole ring with energetic groups
protonation/alkylation to the nitrogen atom labelled as N2 of
containing oxygen such as nitro groups (R–NO2),26 nitrate
the tetrazole ring (see crystal structure labels),21 EDGs favor
esters (R–O–NO2)27 or nitramines (R2N–NO2)28 is of parti-
substitution at N1.22 However, there are other factors that
cular interest. Energetic materials based on tetrazoles show the
contribute to the explosivity of tetrazoles. For example, the
desirable compromise in properties with high nitrogen con-
high sensitivity of 5-azidotetrazole (C)23 and 5-nitriminotetra-
tents on the one hand, and surprising kinetic and thermal
zole (D)24,25 is better explained due to the energetic nature of
stabilities due to aromaticity on the other.
The interesting energetic properties of tetrazole-based
Prof. Dr. Thomas M. Klapötke, Energetic Materials Research,
energetic materials have been mainly investigated in view of
Department of Chemistry and Biochemistry, University of Munich the properties of such compounds for use as propellants and/
(LMU), Butenandtstr. 5-13, D-81377 Munich, Germany. or secondary explosives1,29 and it has only been until recent
E-mail: tmk@cup.uni-muenchen.de; Fax: +49 89 2180 77492 times that metal salts with 5-substituted tetrazole ligands have
w CCDC reference numbers 689202 (1), 689201 (2) and 689203 (3). For
crystallographic data in CIF or other electronic format see DOI: been studied as prospective primary explosives.30,31 Primary
10.1039/b812529e explosives are characterized by easy initiation when submitted

to heat or shock and have the ability to transmit the detona- 5-aminotetrazolate using dimethyl sulfate22 yields a separable
tion to less sensitive (secondary) explosives. For these reasons, mixture of the two (1-methyl and 2-methyl) isomers.35
they are used in initiating devices. Typical detonation Both compounds can be treated similarly and diazotization
velocities for this class of compounds are in the range with two equivalents of sodium nitrite in the presence of a
3500–5500 m s1, much lower than those of secondary non-nucleophilic acid (e.g., sulfuric acid) yields 1-methyl-5-
explosives (5500–9000 m s1).32 Commonly used primary nitrotetrazole (2) and 2-methyl-5-nitrotetrazole (3) as crystal-
explosives are based on lead (e.g., lead azide or styphnate) line compounds. Similar reactions are also found in the
with the accompanying environmental impact and thus, recent literature by using N2O5.36 2 and 3 are extracted from the
efforts have focused on the development of more environmen- reaction mixture using CH2Cl2. The selection of the acid for
tally friendly metal-based alternatives.30,31 the diazotation process is of utmost importance since it affects
In this work we would like to present the syntheses, full the yield of the nitro-compound. For example using hydro-
analytical, spectroscopic and structural characterization of chloric acid 1- or 2-methyl-5-chlorotetrazoles are obtained as
neutral 5-nitrotetrazoles. In addition, the energetic properties the main product.
of the compounds were assessed revealing easy initiation by Lastly, 1 is readily soluble in most common solvents such as
impact and detonation velocities, which are almost twice as ether, THF, MeCN, acetone, water, DMSO and DMF
high as those of commonly used primary explosives.5 whereas 2 and 3 show also good solubility in MeOH, EtOH,
acetone, MeCN, ethyl acetate, THF, CH2Cl2 and DMSO
and DMF.
Syntheses NMR spectroscopy
5-Nitro-2H-tetrazole (1) was prepared starting from 5-amino- All three neutral 5-nitrotetrazoles were characterized by ana-
1H-tetrazole (5-At) by a modified literature procedure accord- lytical and spectroscopic methods. The elemental analysis of 1
ing to Scheme 1.33 5-At was diazotized according to a was omitted due to the risk of explosion found in similar
previously published procedure in our group34 to yield ammo- compounds with a high sensitivity30 on the one hand and to
nium 5-nitrotetrazolate. ‘‘In situ’’ formation of the potassium the hygroscopicity of the material on the other. The 1H NMR
salt by reaction with potassium hydroxide in ethanol and spectra of 1–3 measured in DMSO-d6 show two signals
subsequent treatment with diluted hydrochloric acid and corresponding to the ring proton (1, broad, d = 6.29 ppm)
extraction with ether yields the desired compound. The solvent and to the methyl group protons (2, d = 3.68 ppm and 3,
needs to be removed using vacuum since the product (1) d = 4.50 ppm). The electron withdrawing character of the
absorbs water on time and the compound needs to be stored –NO2 group shifts the proton resonances to low field in
under nitrogen. On the other hand, methylation of sodium comparison to 5-amino-1H-tetrazole and 1-methyl- and
2-methyl-5-amino-1H-tetrazole (i.e., –NH2 group).37 Table 1
contains summarized the 13C and 15N NMR chemical shifts
and the 15N–1H coupling constants for all three compounds.
The proton coupled as well as the proton decoupled 15N NMR
spectra (with full NOE) were also recorded. As already
observed in the 1H NMR spectra, the methyl group resonance
(in this case carbon resonance) of the 1-methyl isomer (2, d =
33.1 ppm) is shifted to higher field in comparison with that of
the 2-methyl isomer (3, d = 41.9 ppm). Similarly, the ring
carbon atom signal is also to be found at higher field for
2 (d = 157.6 ppm) than for 3 (d = 166.4 ppm). This carbon
Scheme 1 Syntheses of neutral 5-nitrotetrazoles: a = ref. 34; atom shows the lowest field resonance for 1 (d = 168.4 ppm),
b = (i) KOH, (ii) HCl (2 M); (c) (i) NaOH, (ii) Me2SO4; d = 2 eq. which is in keeping with salts containing the 5-nitrotetrazolate
NaNO2, H2SO4. anion.30,34
Table 1 15N and 13C NMR resonances of compounds 1–3 with protonation (1, PIS) and methylation (2 and 3, MIS) induced shiftsa and coupling
constantsb
Compound N1 N2 N3 N4 N5 C1 C2
1 69.6 [3.4] 19.6 [5.2] 19.6 [5.2] 69.6 [3.4] 29.8 [4.5] 168.4 —
2 155.7 [89.5] 0.7 [15.1] 6.7 [7.7] 54.8 [11.4] 37.6 [12.3] 157.6 33.1
2 3
J(N–H) = 2.1 J(NH) = 1.8
3 97.9 [31.7] 76.6 [91.0] 5.3 [9.1] 55.1 [11.1] 33.5 [8.2] 166.4 41.9
3 2 3
J(N–H) = 1.7 J(N–H) = 2.1 J(NH) = 1.7
NaNTc 66.2 14.4 14.4 66.2 25.3 169.2 —
a b
PIS and MIS values are shown in square [] brackets and given in ppm. Coupling constants (J) are given in Hz. c NaNT = Sodium
5-nitrotetrazolate (see ref. 30).
This journal is
Table 2 Crystallographic data and refinements
1 2 3
Formula CHN5O2 C2H3N5O2 C2H3N5O2
Mr/g mol1 115.07 129.09 129.09
Crystal system Monoclinic Monoclinic Monoclinic
Space group P21 (No. 4) P21/n (No. 14) P21/c (No. 14)
Color/habit Colorless plates Colorless rods Colorless rods
Size/mm 0.03 0.18 0.04 0.08 0.100.03 0.18
0.27 0.27
a/Å 5.3358(4) 10.0578(4) 6.331(1)
b/Å 9.4799(7) 9.7055(4) 4.993(1)
c/Å 8.3190(8) 16.5331(6) 16.388(3)
b/1 106.989(9) 101.701(4) 97.13(3)
V/Å3 402.44(6) 1580.36(11) 514.0(2)
Z 4 12 4
Dc/g cm3 1.899 1.628 1.668
Fig. 2 15
N NMR spectra of compounds 1–3. m/mm1 0.174 0.143 0.146
F(000) 232 792 264
lMoKa/Å 0.71073 0.71073 0.71073
The quadrupolar moment of the 14N nucleus results in T/K 123 200 200
signals at approximately +14 (N2/3), 24 (NO2) and 66 y Range/1 4.0, 32.5 3.9, 25.0 3.2, 26.0
(N1/4) in the 14N NMR spectrum of compound 1, which are Data set 7: 7; 14: 14; 11: 10; 11: 11; 7: 7; 6: 6;
12:12 19: 15 20: 19
broad (n1/2 B 300 Hz, B60 Hz and B320 Hz, respectively). Reflections 5975 7250 3454
The 15N NMR spectra show comparable resonances to those collected
observed in the 14N NMR spectra but much sharper (Fig. 2). Independent 1452 2766 1003
The proton induced shifts (PIS, 1) and methyl induced shifts reflections
Rint 0.059 0.064 0.037
(MIS, 2 and 3)37 are useful for identifying the protonation/ Observed 742 1139 862
alkylation site as well as assigning the resonances of the reflections
nitrogen atoms and are also tabulated in Table 1. Comparison No. parameters 153 258 94
R1 (obs) 0.0274 0.0664 0.0364
of the resonances observed for the 5-nitrotetrazolate anion in
wR2 (all data) 0.0497 0.2102 0.0946
sodium 5-nitrotetrazolate with those of the compounds in this GooF 0.83 0.91 1.08
study shows unexpected shifts. The nitrogen atoms labelled as Dr/e Å3 0.23, 0.21 0.27, 0.85 0.22, 0.14
N2 and N3, which are equivalent due to fast exchange in the CCDC 689202 689201 689203
NMR in solution of 1, show the largest (positive) PIS value,
indicative of protonation taking place on these two nitrogen Bruker ‘‘Collect’’ and the ‘‘HKL Denzo and Scalepack’’
atoms as observed (in the solid state) in the crystal structure of software.40 The structures were solved with SIR-92 (2, 3),41
the compound (see X-ray discussion). The remainder of the and SHELXS-97 (1),42 refined with SHELXL-9743 and finally
PIS values are small in value and negative. The MIS effect in checked using the PLATON software.44 The non-hydrogen
compounds 2 and 3 is much more unexpected and the methyl- atoms were refined anisotropically and the hydrogen atoms
ated nitrogen atoms (N1 for 2 and N2 for 3) show the largest were located and freely refined. The absorptions of 1 and 2
(negative) MIS values (B90 ppm for both). The next nitrogen were corrected by a SCALE3 ABSPACK multi-scan
atom close to the methyl group (i.e., at two bonds) feels the method.45 All relevant data and parameters of the X-ray
effect of the alkyl group much more weakly (MIS = 31.7 ppm measurements and refinements are given in Table 2.46
for N1 in 3) but can still be used to assign the resonances of One of the two crystallographically independent formula
this atom. Lastly, the fast exchange of the proton in 1 results in units found in the crystal structure of compound 1 is repre-
broadening of the resonance corresponding to the protonated sented in Fig. 3. Protonation of the NT anion occurs at N3,
nitrogen atom, whereas 2 and 3 show coupling constants to the
methyl groups, which are slightly larger for the nitrogen atoms
directly attached to the methyl group (2J(NH) = 2.1 Hz)
than for those at three bonds of the methyl group protons
(3J(NH) = 1.7–1.8 Hz).
Molecular structures
Suitable single crystals of 1 and 2 were picked from the
crystallization mixture and mounted in Kel-F oil and trans-
ferred to the N2 stream of an Oxford Xcalibur3 diffractometer
with a Spellman generator (voltage 50 kV, current 40 mA) and
a KappaCCD detector. The data collections were performed
using the CrysAlis CCD software,38 the data reduction with
the CrysAlis RED software.39 The data for compound 3 were Fig. 3 Formula unit of 1 with the labelling scheme. Hydrogen atoms
collected on a Nonius Kappa CCD diffractometer under an N2 shown as spheres of arbitrary radius and thermal displacements set at
stream as well. Data collection and reduction was done by the 50% probability.

Table 3 Selected bond lengths [Å] and angles [1] for compounds 1–3
1 (A) 1 (B) 2 (A) 2 (B) 2 (C) 3

O1–N5 1.229(3) 1.227(3) 1.208(6) 1.194(6) 1.196(5) 1.223(2)
O2–N5 1.221(3) 1.215(3) 1.191(6) 1.202(5) 1.185(5) 1.222(2)
N5–C1 1.440(4) 1.450(4) 1.450(7) 1.481(7) 1.438(6) 1.445(2)
N1–C1 1.319(4) 1.310(4) 1.326(6) 1.316(6) 1.342(6) 1.321(2)
N1–N2 1.323(4) 1.319(4) 1.336(6) 1.345(5) 1.354(6) 1.319(2)
N2–N3 1.318(3) 1.322(3) 1.297(6) 1.317(6) 1.325(6) 1.329(2)
N3–N4 1.324(4) 1.318(3) 1.356(7) 1.363(6) 1.317(7) 1.317(2)
N4–C1 1.333(4) 1.336(4) 1.303(6) 1.291(6) 1.295(6) 1.331(2)
N1(2)–C2 1.461(6) 1.478(7) 1.487(6) 1.461(2)
O2–N5–O1 125.5(3) 126.0(3) 127.6(6) 127.2(5) 125.6(5) 125.1(1)

O1–N5–C1 117.9(3) 117.2(3) 115.8(5) 117.2(5) 117.4(5) 117.4(1)
O2–N5–C1 116.6(3) 116.7(3) 116.6(5) 115.7(5) 117.0(5) 117.5(1)
N1–C1–N5 123.2(3) 122.3(3) 125.9(5) 123.2(5) 124.8(4) 121.9(1)
C1–N1–N2 100.1(3) 99.0(3) 106.8(4) 106.5(4) 107.3(4) 99.9(1)
N3–N2–N1 114.7(3) 115.4(3) 106.6(5) 106.2(4) 104.9(4) 114.3(1)
N2–N3–N4 105.7(2) 105.5(2) 111.4(5) 110.8(4) 111.5(5) 106.1(1)
N3–N4–C1 105.0(2) 104.3(3) 103.6(5) 103.5(4) 106.6(5) 104.6(1)
N4–C1–N5 122.1(3) 121.9(3) 122.5(5) 123.5(5) 125.4(5) 123.0(1)
N1–C1–N4 114.5(3) 115.8(3) 111.6(5) 113.1(5) 109.7(5) 115.1(1)
C1–N1–C2 106.8(4) 131.9(5) 131.4(5)
N1–N2–C2 123.6(1)
N2–N1–C2 121.1(5) 121.5(5) 121.3(5)
N3–N2–C2 122.1(1)
which is in contrast with 5-amino-46 or 5-azidotetrazole.23 In oxygen atoms (O3). A report of hydrogen-bridges is given in
Table 3 there are summarized the angles and distances of the Table 4. The interaction between N7 and O3 (N7 O3i =
two 5-nitrotetrazolate rings, which, within the limits of error, 3.015(4) Å; symmetry code: (i) x, 0.5 + y, z) ‘‘fixes’’ the
are not significantly different. The main difference is observed nitro group in such a way that it is coplanar to the tetrazole
in the twist of the nitro groups in respect to the tetrazole rings. ring and forms the C1,1(6) motifs represented in Fig. 4
Whereas in one of the two molecules the nitro group is almost (at the primary level) (Table 5). Similarly, the dimer
coplanar to the ring (O4–N10–C1–N6 = 178.2(3)1), in the pairs formed by two crystallographically related rings
other, this is significantly deviated (O2–N5–C1–N1 =
164.9(3)1). So, one of the formula units is similar to metal
NT salts, which show small torsion angles between 2 and 51,30
whereas the other one is more similar to NT salts with
nitrogen-rich bases (0–101).34 A plausible explanation for this
could be that in NT salts, there is a negative charge, which is
delocalized all around the tetrazole ring and over the nitro
group, making them virtually coplanar. Proof for this is the
relatively longer C1–N1 distances (B1.445(4) Å) in 1. There-
fore one would expect larger torsion angles due to the lack of
delocalization in both formula units. The smaller torsion angle
for one of the two units can be explained by hydrogen-bonding
effects (see discussion below).
Regardless of the expected planarity of 1 the presence of a
proton surrounded by many electronegative atoms forces the
compound to form hydrogen bonds, which prohibits layering.
These hydrogen bonds are formed by the protonated nitrogen
atom (N2 or N7) as the donor atom and either tetrazole ring
nitrogen atoms or, in one instance with one of the nitro groups
Table 4 Geometry for selected hydrogen bonds in the structure of 1
D–H A D–H (Å) H A (Å) D A (Å) D–H A (1)

1
N2–H1 N4 0.97(4) 1.88(4) 2.837(4) 171.(3)
N7–H2 O3a 0.85(4) 2.22(4) 3.015(4) 158.(3) Fig. 4 View of the unit cell of 1 along the a-axis showing the graph-
N7–H2 N3b 0.85(4) 2.53(4) 3.057(4) 121.(3) sets in the structure (dotted lines). Symmetry codes: (ii) 1 x, 0.5 + y,
a b 1 z; (iii) 1 + x, y, 1 + z; (iv) 1 x, 0.5 + y, 1 z; (v) 2 x, 0.5 +
Symmetry codes for 1: x, 0.5 + y, z. 1 x, 0.5 + y, 1 z.
y, 1 z; (vi) 1 x, 0.5 + y, z; (vii) x, 1 + y, z; (viii) 1 + x, y, z.
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Table 5 Graph-set matrix for medium to strong hydrogen bonds in only one molecule of the asymmetric unit is shown in Fig. 5.
the crystal structure of 1. First level motifs on-diagonal and second Since hydrogen bonds are not present in the structures
level graph sets off-diagonal
of 2 and 3, the densities (2: 1.628, 3: 1.668 g cm3) are
H-Bond N2–H1 N4 N7–H2 O3a N7–H2 N3b significantly lower than that observed for 1 (1.899 g cm3).
3, (in Fig. 6), crystallizes monoclinic in the space group P21/c
N2–H1 N4 D1,1(2)
N7–H2 O3a D3,3(9) C1,1(6) with four molecules in the unit cell. The molecular geometry
N7–H2 N3b D3,3(7) C1,1(4) of 2 as well as of 3 is particularly comparable to that of
a
Symmetry codes for 1: x, 0.5 + y, z. b
1 x, 0.5 + y, 1 z. 1 and other 5-substituted tetrazoles. All C–N and N–N bond
lengths lie between single and double bonds, whereby the
shortest distance (1.30–1.33 Å) is observed between the
(N7 N3ii = 3.057(4) Å; symmetry code: (ii) 1 x, 0.5 + y, nitrogen atoms N2 and N3. In both cases the NO2
1 z) yield a C1,1(4) graph-set. Lastly, the third hydrogen group is co-planar with the tetrazole ring, which confirms
bond found in the structure forms only finite patterns of the previously published assumptions.47 The distances between
type D1,1(2) at the primary level, which combine with the the atoms C1 and N5 are between 1.43 and 1.48 Å, which
other two hydrogen bonds yielding larger dimeric interactions are in the range of typical C–N single bonds. The same trend
with the label D3,3(X) (X = 7, 9) at the secondary level. This can be found for the N1–C2 and N2–C2 bond lengths
results in a highly efficient packing as can be deduced from the (1.46–1.49 Å).
high density of the compound (1.899 g cm3).
The unit cell of 2, which crystallizes in the monoclinic space Thermal and energetic properties
group P21/c contains twelve molecules. For better clearness
In order to assess the thermal and energetic properties of
neutral 5-nitrotetrazoles 1–3 the thermal stability (decomposi-
tion points from DSC measurements), as well as the sensitivi-
ties to friction, impact, electrostatic discharge and thermal
shock of all three compounds were experimentally assessed
(Tables 6 and 7) using standard BAM tests.50–55 In addition,
for all three CHNO compounds the constant volume energies
Table 6 Physico-chemical properties, initial safety data and predicted

performance of compounds 1–3
1 2 3
Formula CHN5O2 C2H3N5O2 C2H3N5O2
Molecular mass/ 115.05 129.08 129.08
g mol1
Impact sensitivitya/J o1 2 1
Friction sensitivityb/N o5 82 40
Electrical dischargec/J — 0.50 0.20
N (%)d 60.9 54.3 54.3
N + O (%)e 88.6 79.0 79.0
O (%)f 7.0 43.4 43.4
Fig. 5 Formula unit of 2 with the labelling scheme. Hydrogen atoms Thermal shockg
shown as spheres of arbitrary radius and thermal displacements set at Deflagration Combustion Combustion
30% probability. Combustion Very good Good Good
Smokeless + + +
DSCh/1C 98 (mp), 130 45 (mp), 155 75 (mp), 150
(decomp.) (decomp.) (decomp.)
Densityi/g cm3 1.899 1.628 1.668
DfHm1 j/kJ mol1 281 278 247
DfU1 k/kJ kg1 +2527 +2253 +2006
Calculated values using EXPLO5

DEUm1 l/J g1 5744 5588 5368
TEm/K 4804 4226 4071
n
p /kbar 390 257 262
o 1
D /m s 9457 8085 8109
Gas vol.p/L kg1 779 766 763
a
BAM methods, see ref. 50–55. b BAM methods, see ref. 50–55. c OZM
electric spark tester, see ref. 57–59. d Nitrogen content. e Nitrogen +
oxygen content. f Oxygen balance.60 g Fast heating behavior. h Decom-
position temperature from DSC (b = 5 1C). i Estimated from X-ray
diffraction. j Calculated molar enthalpy of formation. k Energy of
formation. l Energy of explosion, EXPLO5 V5.02. m Explosion tempera-
Fig. 6 Formula unit of 3 with the labelling scheme. Hydrogen atoms
ture. n Detonation pressure. o Detonation velocity. p Assuming only
shown as spheres of arbitrary radius and thermal displacements set at
gaseous products.
50% probability.

Table 7 Comparison of energetic properties of compounds 1–3 with decomposition points. The presence of the ring proton in 1
RDX results in a higher melting point than for 2 and 3 due to the
1 2 3 RDX possibility of forming classical hydrogen bonds in 1, however,
3
the compound is much more sensitive (i.e., less stable) and
Density/g cm r 1.899 1.630 1.670 1.820 decomposes at lower temperatures. The substitution pattern of
Oxygen balance (%) O 7.0 43.4 43.4 21.6
Energy of formation/kJ kg1 DfU +2527 +2253 +2006 +67 the methyl group in 2 and 3 also accounts for the lower
Heat of detonation/kJ kg1 Qv 5744 5588 5368 5902 melting point of 2 in comparison to 3 due to the formation
Detonation temperature/K Tex. 4804 4226 4071 3986 of a less effective packing, as suggested by the lower crystal
Detonation pressure/kbar P 390 257 262 299
Detonation velocity/m s1 D 9457 8085 8109 8796
density of 2 (1.628 g cm3) in comparison to 3 (1.668 g cm3).
Volume of detonation gases/L kg1 V0 779 766 763 932 Furthermore, the presence of the methyl group results in
an increase (20–25 K) of the decomposition temperatures
(B150 1C) as observed for methylated 5-aminotetrazoles.37
Further studies on the decomposition of 3 can be found in
literature.48 In addition to DSC analysis, the response to thermal
shock of 1–3 was tested by placing a small sample (B0.5–1.0 mg)
of compound in the flame. This resulted in an vigorous reaction
(deflagration) in the case of 1 and normal burning in the case of
2 and 3, in all cases smokeless. By comparison with typical
primary explosives such as lead azide or styphnate, which both
explode in the flame, the compounds studied here are less
sensitive to thermal shock and show a similar response to
classical secondary explosives such as TNT or RDX.
Data collected for initial safety testing of compounds 1–3
are summarized in Table 6. The impact and friction sensiti-
vities as well as the electrostatic sensitivity were determined.49
The impact sensitivity tests were carried out according to
STANAG 448950 modified according to instruction51 using a
BAM (Bundesanstalt für Materialforschung)52 drophammer.53
The friction sensitivity tests were carried out according to
Fig. 7 DSC thermographs of 5-nitrotetrazoles 1–3 at a heating rate STANAG 448754 modified according to instruction55 using
b = 5 1C min1. the BAM friction tester. Compound 1 is very sensitive towards
impact (o1 J) and extremely friction sensitive (o5 N). 2 and 3
of combustion were calculated using quantum chemical are also very sensitive towards impact (2, 2 J and 3, 1 J) but
methods (see Computational Methods section). Initially, we less sensitive towards friction (2, 82 N and 3, 40 N). Grinding
measured experimentally the combustion data for 3 using of the compounds in a mortar results in rattling and (in some
oxygen bomb calorimetry, however the high sensitivity of instances) a loud explosion. According to the ‘‘UN Recom-
the compound did not allow reproducible values to be ob- mendations on the transport of dangerous goods’’,56
tained. The material explodes rather than burning in the compounds 1–3 are classified as ‘‘very sensitive’’ regarding
aerobic conditions of the measurements leading to erroneous the impact sensitivity values. The compounds in this study
values. The heats and energies of formation of 1–3 were back- are significantly more sensitive to friction and impact than
calculated from the combustion data and subsequently used in nitrogen-rich salts of 5-nitro-2H-tetrazole34 and the impact
conjunction with the molecular formula and density (from sensitivity approaches that of alkali metal salts of 5-nitro-2H-
X-ray) to predict the performance (detonation pressure and tetrazole.30 Comparison of the energetic compounds of the
velocity) for each compound using the EXPLO5 computer materials in this study with those of commonly used high
code.61 explosives are useful to assess the potential of the materials
Fig. 7 shows typical DSC thermographs of compounds described here. All three materials have impact sensitivity
1–3. Slow heating in a DSC apparatus (b = 5 1C min1) of values, which are comparable to lead azide (2.5–4.0 J, pure
samples of B1.5 mg of each energetic material gives rapid product). As for the friction sensitivity, 1 has a value between
decomposition at temperatures above 130 1C for all three that of the primary explosives lead azide (0.1–1.0 N, pure
compounds. All three materials show highly exothermic product) and tetrazene (7 N), whereas 2 and 3 have similar
decompositions following to endothermic peaks at 98 (1), 45 (2) sensitivity to the secondary explosive PETN (60 N).5 In
and 75 (3) 1C corresponding to the melting of the compounds. addition, the sensitivity towards electrostatic discharge of 2
The difference in area between endothermic and exothermic and 3 was tested using an electric spark tester ESD 2010EN
peaks gives a feeling for the energy released upon decomposi- (OZM Research) operating with the ‘‘Winspark 1.15 software
tion. For all 1–3 the decomposition releases much more energy package’’.57 Due to the hygroscopicity of compound 1, this
than that required for melting. Particularly, compound 1 compound was omitted from this study. The electrical spark
shows only a small melting endotherm followed by highly sensitivities of microcrystalline materials (5–100 mm)58 were
energetic decomposition. It is interesting to note the effect determined to be 0.50 0.05 (2) and 0.20 (3) 0.04 J. These
of the substituent in the tetrazole ring in the melting and values can be compared to those of commonly used secondary
This journal is
explosives, e.g. RDX (0.15 J), PETN (0.19) and TNT (0.57). equations (see below), Hess’s Law, the known standard heats
However, the ESD sensitivities determined are higher of formation for water and carbon dioxide and a correction
than those of modern insensitive explosives such as TATB for change in gas volume during combustion. No corrections
(1,3,5-triamino-2,4,6-trinitrobenzene).59 Lastly, the high for the non-ideal formation of nitric acid (typically B5% of
sensitivities of 1–3 can be attributed not only to the high the nitrogen content reacts to form HNO3) were made.
endothermicity of the materials (see discussion below) but also As pointed out above, all three compounds are highly en-
to the only slightly negative oxygen balance, in particular in dothermic with energies of formation above +2000 kJ kg1.
the case of compound 1. 1 has the most positive value of all at +2527 kJ kg1 and all
In addition to safety considerations, performance of three compounds show similar endothermicities to nitrogen-
HEDMs is of utmost importance. Using the molecular for- rich salts with the 5,5 0 -azotetrazolate anion ([N4C–N =
mula, density (from X-ray) and energy of formation, the N–CN4]2).12,63
EXPLO5 computer code61 can be used to calculate the deto-
nation velocity and pressure of CHNO-based explosive 1: CHN5O2 (s) + 0.25 O2 (g) - CO2 (g) + 0.5 H2O (l)
materials. The program is based on the chemical equilibrium, + 2.5 N2 (g) (1)
steady-state model of detonation. It uses the Becker– 2, 3: C2H3N5O2 (s) + 1.75 O2 (g) - 2 CO2 (g) + 1.5
Kistiakowsky–Wilson’s equation of state (BKW EOS) for H2O (l) + 2.5 N2 (g) (2)
gaseous detonation products and Cowan–Fickett’s equation
of state for solid carbon.61,62 The calculation of the equili- The methylated derivatives 2 and 3 have calculated detonation
brium composition of the detonation products is done by velocities of B8100 m s1, higher than TNT (6900 m s1),
applying modified White, Johnson and Dantzig’s free energy lower than RDX (8800 m s1) and similar to 5,5 0 -azotetrazole
minimization technique. The program is designed to enable salts,12,63 regardless of the high sensitivity of the compounds.
the calculation of detonation parameters at the CJ point. The On the other hand, 1 although being very sensitive to impact
BKW equation in the following form was used with the and friction and thus classifying as a primary explosive has an
BKWN set of parameters (a, b, k, y) as stated below the astonishingly high calculated detonation velocity of 9457 m s1,
equations and Xi being the mol fraction of ith gaseous which is comparable to some of the highest performing
product, ki is the molar covolume of the ith gaseous pro- secondary explosives known to date such as HMX (octogen,
duct.40,41 The results of the EXPLO5 calculations for neutral 9100 m s1), CL-20 and octanitrocubane (B10 000 m s1)5
5-nitrotetrazoles 1–3 are presented in Tables 6 and 7, with the and also higher than the primary explosive 5-azido-1H-tetra-
corresponding values for commonly used RDX for compari- zole regardless of the lower endothermicity of the –NO2 group
son purposes. in comparison to the –N3 substituent.21 Here it is necessary to
P mention that the previous study of Koldobskii and coworkers
pV/RT = 1 + xebxx = (k Xiki)/[V (T + y)]a; a = 0.5, on compound 1, reports a experimental density value of
b = 0.176, k = 14.71, y = 6620. 1.73 g cm3,33 which is much lower than our calculated value
Further physico-chemical properties of all three compounds of 1.899 g cm3 and therefore affects strongly the detonation
are tabulated in Table 7. Compounds 1–3 have high nitrogen parameters. The detonation pressures have accordingly high
contents in the range between B50 and 60%, excellent com- values (390 kbar for 1 and B260 kbar for 2 and 3), which are
bined oxygen and nitrogen balances in the range between comparable to HMX (octogen) (pdet. = 384 kbar) and RDX
B80 and 90% and slightly negative oxygen balances approxi- (hexogen) (pdet. = 299 kbar) respectively.5
mately in the range between that of dinitroglycol (C2H4N2O6,
Decomposition gases
O = 0.0%) and that of nitromethane (CH3NO2, O =
39.3%). As expected, the densities, calculated from the Using the calculated heats of formation, the calculated density
X-ray measurements, are lower in the case of the methylated (from X-ray) and the molecular formula the ICT code64 was
derivatives 2 and 3 (B1.65 g cm3) but still comparable to used to predict the heats of explosion as well as the decom-
TNT (1.654 g cm3), while 1 has an exceptionally high density position gases formed upon explosion/decomposition of com-
of 1.899 g cm3 comparable to b-HMX (1.900 g cm3).5 The pounds 1–3. Table 8 contains tabulated results of these
energies of formation of 1–3 were back-calculated from the calculations together with the predicted values for two com-
energies of combustion on the basis of their combustion monly used high explosives, namely lead azide (primary
Table 8 Predicted decomposition gases and heats of explosion of compounds 1–3 and comparison with commonly used high explosives (using the
ICT code)
Compoundab CO2 H2O N2 CO H2 NH3 CH4 HCN C Pb DHexc

1 276.61 75.54 607.47 17.11 0.05 1.34 — — 21.40 — 1621
2 100.72 185.39 533.13 17.25 0.47 11.16 0.80 0.44 150.35 — 1558
3 100.45 186.28 533.22 16.21 0.43 11.06 0.66 0.43 150.97 — 1512
Pb(N3)2 — — 288.56 — — — — — — 711.44 391
RDXd 292.09 232.40 373.83 22.90 0.21 5.26 0.16 0.30 72.28 — 1592
a
The amount of gases formed at 298 K is given in g kg1 (i.e., grams of gas per kilogram of energetic compound). b
—, the decomposition product
was not predicted by the code. c Heat of explosion in cal g1. d Measured at a density of 1.76 g cm3.

explosive) and RDX (secondary explosive), for comparative Table 9 CBS-4M results
purposes.
Pt. Gp. H298/a.u. G298/a.u. NIMAG
As expected from the high nitrogen content of the materials
molecular nitrogen is predicted to be the major product of the 5-Nitro-1H-tetrazole Cs 462.190261 462.227578 0
decomposition of compounds 1–3 (B500–600 g kg1). By 5-Nitro-2H-tetrazole Cs 462.195276 462.232789 0
1-Methyl-5-nitrotetrazole Cs 501.427898 501.468919 0
comparison, the decomposition of RDX is expected to pro- 2-Methyl-5-nitrotetrazole Cs 501.437871 501.479892 0
duce much lower amounts of environmentally-friendly nitro- H 0.500991 0.514005
gen (374 g kg1), which is however still the main expected C 37.786156 37.803062
N 54.522462 54.539858
product followed by the formation of carbon dioxide (292 g O 74.991202 75.008515
kg1). In keeping with the logic that RDX derives its energy
from both oxidation of the carbon backbone and the forma-
tion of nitrogen. The second main product predicted upon Table 10 Literature values for atomic DH1f298/kcal mol1
decomposition of 1 is also carbon dioxide (277 g kg1), which
ref. 69 NIST70
is anticipated to form in larger amounts than for compounds 2
and 3 (B100 g kg1) fitting with the better oxygen balance of H 52.6 52.1
1. 2 and 3 are nevertheless expected to generate larger amounts C 170.2 171.3
N 113.5 113.0
of water than 1 (B185 vs. 75 g kg1). Apart from carbon soot, O 60.0 59.6
which is predicted to form in relatively large amounts for 2 and
3 (B150 g kg1), the rest of the decomposition gases (CO, H2,
NH3, CH4 and HCN) are foreseen to form in marginally low Table 11 Enthalpies of the gas-phase species M
quantities (o20 g kg1). The amount of highly toxic gases
M M DfH1(g)/kcal mol1
(i.e., CO and HCN) expected from the explosion of 1–3 are
then comparable to those formed upon explosion of RDX and 5-Nitro-1H-tetrazole CHN5O2 +87.1
in contrast with the large amounts of highly toxic lead powder 5-Nitro-2H-tetrazole CHN5O2 +84.0
1-Methyl-5-nitrotetrazole C2H3N5O2 +80.7
predicted for the explosion of lead azide (711 g kg1). Lastly, 2-Methyl-5-nitrotetrazole C2H3N5O2 +74.5
the heats of explosion have all values above 1500 cal g1, is
larger for the more energetic compound 1, are comparable to
the secondary explosive RDX and much larger than the Table 12 Enthalpies of sublimation of compounds 1–371
primary explosive lead azide (391 cal g1).
Tm/K DHsub/kcal mol1
1 374 16.8
Computational methods. Due to the high sensitivity of all 2 318 14.3
compounds studied here, bomb calorimetric measurements 3 348 15.6
could only be performed with small amounts of the materials
and doubtful combustion data was obtained. Therefore we
From the gas-phase enthalpies of formation DfH1(g) the
decided to estimate the thermodynamic data by quantum
enthalpies of the solid state were calculated using the enthal-
chemical methods. All calculations were carried out using
pies of sublimation by the equation:
the Gaussian G03W (revision B.03) program package.65 The
enthalpies (H) and free energies (G) were calculated using the DfH1(s) = DfH1(g) (DsubH) (4)
complete basis set (CBS) method described by Petersson and
coworkers in order to obtain very accurate values. The CBS For a solid compound the enthalpy of sublimation (DsubH) can
models use the known asymptotic convergence of pair natural be approximated on the basis of TROUTON’s rule 72 if the
orbital expressions to extrapolate from calculations using a melting temperature (Tm in K) is known:
finite basis set to the estimated complete basis set limit. CBS-4 DsubH [J mol1] = 188 Tm [K] (5)
begins with a HF/3-21G(d) geometry optimization; the zero
point energy is computed at the same level. It then uses a large With the known enthalpies of formation of carbon
basis set SCF calculation as a base energy, and a MP2/ dioxide (DfH1298(CO2(g)) = 393.8 kJ mol1) and water
6-31+G calculation with a CBS extrapolation to correct (DfH1298(H2O(g)) = 241.9 kJ mol1) the enthalpies of
the energy through second order. A MP4(SDQ)/6-31+(d,p) formation of 1–3 can now be calculated. From these values,
calculation is used to approximate higher order contributions. the energy of formation (DfU1298) can easily be obtained from
In this study we applied the modified CBS-4M method the combustion eqns (1)–(3) according to eqn (6) with Dn
(M referring to the use of minimal population localization) being the change of moles of the gaseous components
which is a re-parametrized version of the original CBS-4 (Dn: 1 = 3.25; 2, 3 = 2.75) in eqns (7) and (8).
method and also includes some additional empirical correc-
DUm = DHm DnRT (6)
tions.66,67 The enthalpies of the gas-phase species M were
computed according to the atomization energy method 1: C (s) + 0.5 H2 (g) + 2.5 N2 (g) + O2 (g)
(eqn (3)) (Tables 9–12).68 - CHN5O2 (s) (7)
P
DfH1(g, M, 298) = H(Molecule, 298) H1(Atoms, 298) 2, 3: 2 C (s) + 1.5 H2 (g) + 2.5 N2 (g) + O2 (g)
P
+ DfH1(Atoms, 298) (3) - C2H3N5O2 (s) (8)
This journal is
Table 13 Solid state enthalpies (DfH1) and energies of formation 3.7 mL water. The solution was stirred at reflux until no more
(DfU1) ammonia gas was evolved. At this point, the reaction mixture
DfH1(s)/kcal DfH1(s)/kJ DfU1(s)/kcal M/g DfU1(s)/kJ was cooled by means of an ice-bath and cold B25% sulfuric
mol1 mol1 Dn mol1 mol1 kg1 acid (2 mL) was added dropwise using a plastic syringe. The
solution was then extracted with ether (4 6 mL) and the
1 +67.2 +281.4 4 +69.5 115.07 +2527.1
2 +66.5 +278.4 5 +69.5 129.08 +2252.8 ether extracts were combined and washed to remove the excess
3 +58.9 +246.6 5 +61.9 129.08 +2006.4 of acid with water (6 mL). The organic phase was then dried
with magnesium sulfate and filtered and the solvent was
stripped under high vacuum (B103 mbar) yielding the pure
As can be seen from Table 13 compounds 1–3 are formed product as a slightly yellow semicrystalline solid (0.27 g, 72%),
strongly endothermically (1: 281, 2: 278, 3: 247 kJ mol1). which was carefully (!!) scratched out using a plastic spatula
These values are slightly higher than that of 5-amino-1H- and analyzed. DSC (5 1C min1, 1C): 98 (mp), 4130 (de-
tetrazole (DfH1(s) = 208 kJ mol1) and in the same range comp.); IR n~/cm1 (KBr, rel. int.): 3443 (s), 2013 (w), 1629
observed for 5-nitriminotetrazole (264 kJ mol1) and (m), 1565 (vs), 1443 (m), 1401 (m), 1320 (s), 1262 (vw), 1192
1-methyl-5-nitriminotetrazole (260 kJ mol1). The enthalpy (w), 1103 (w), 1047 (m), 1022 (m), 840 (s), 666 (w), 534 (vw);
of formation of energetic materials are governed by the Raman n~/cm1 (rel. int.): 3316 (2), 3261 (2), 1572 (14), 1492
molecular structure of the compound. Therefore, heterocycles (9), 1446 (100), 1433 (90), 1396 (15), 1358 (7), 1317 (13), 1200
with a higher nitrogen content (e.g. imidazole (DfH1(s) = 58.6 (13), 1186 (14), 1142 (30), 1094 (42), 1069 (13), 1043 (11), 1027
kJ mol1),72 1,2,4-triazole (DfH1(s) = 109.3 kJ mol1),73 1H- (26), 837 (22), 775 (13), 736 (4), 592 (3), 532 (11), 444 (22), 256
1,2,3,4-tetrazole (DfH1(s) = 237.4 kJ mol1))74 show trends in (17), 240 (16), 154 (6); 1H NMR (DMSO-d6, 400.18 MHz, 25
increasing heats of formation. 1C, TMS) d/ppm: 6.29 (1H, NH); 13C{1H} NMR (DMSO-d6,
100.63 MHz, 25 1C, TMS) d/ppm: 168.4 (1C, C–NO2); 14N
Experimental NMR (DMSO-d6, 40.55 MHz, 25 1C, MeNO2) d/ppm: +14
(2 N, n1/2 B300 Hz, N2/3), 24 (1 N, n1/2 B60 Hz, NO2), 66
CAUTION! The 5-nitrotetrazoles described here are energetic (2 N, n1/2 B320 Hz, N1/4); 15N NMR (DMSO-d6, 40.55 MHz,
compounds, which are sensitive towards heat, impact, friction 25 1C, MeNO2) d/ppm: +19.6 (2 N, s, N2/N3), 29.8 (1 N, s,
and electrostatic discharge. Although we experienced no diffi- NO2), 69.6 (2 N, s, N1/4); m/z (FAB, xenon, 6 keV, m-NBA
culties in the synthesis of these materials, proper protective matrix): 113.9 (100, CN5O2); EA (CHN5O2, 115.07): calc. C
measures (safety glasses, face shield, leather coat, earthened 10.44, H 0.88, N 60.87; found: not determinable due to high
equipment and shoes, Kevlars gloves and ear plugs) should be sensitivity; BAM drophammer: o1 J, friction tester: o5 N,
used when undertaking work involving 1–3 on small and in flame: deflagration.
particular on larger scales.
General method Synthesis of 1-methyl-5-nitrotetrazole (2)

All reagents and solvents were used as received (Sigma- A suspension of 1-methyl-5-aminotetrazole (2.00 g, 20 mmol)
Aldrich, Fluka, Acros Organics) unless stated otherwise. in 1 M sulfuric acid (10 mL) and 30 mL of water was added at
Melting points were measured with a Linseis PT10 DSC75 0 1C to 30 mL water containing sodium nitrite (2.76 g,
and checked with a Büchi Melting Point B-450 apparatus 40 mmol). After stirring at room temperature for 12 h and
(uncorrected). DSC measurements were performed at a heat- filtration of the precipitated bis(1-methyltetrazolyl)triazene,
ing rate of 5 1C min1 in closed aluminum sample pans with a the solvent was evaporated. Dry acetone (80 mL) was added
1 mm hole in the top for gas release under a nitrogen flow of to this and the precipitated Na2SO4 was removed by filtration.
20 mL min1 with an empty identical aluminum sample pan as After evaporating the acetone the crude product was recrys-
a reference. NMR spectra were recorded with a Jeol Eclipse tallized from a small amount of ethanol (1.52 g, yield 59%);
270, Jeol EX 400 or a Jeol Eclipse 400 instrument. All chemical DSC (5 1C min1, 1C): 45 1C (mp), 155 1C (decomp.); IR
shifts are quoted in ppm relative to TMS (1H, 13C) and (KBr, cm1): n~ = 3038 (w), 2860 (w), 1550 (vs), 1481 (s), 1467
MeNO2 (14N, 15N). Infrared (IR) spectra were recorded using (m), 1408 (s), 1364 (s), 1328 (vs), 1280 (w), 1209 (m), 1073 (m),
a Perkin-Elmer Spektrum One FT-IR instrument.76 Transmit- 1025 (w), 846 (s), 720 (s), 535 (w), 430 (m); Raman (1064 nm,
tance values are qualitatively described as ‘‘very strong’’ (vs), 200 mW, 25 1C, cm1): n~ = 3054 )2), 2978 (6), 2964 (6), 1530
‘‘strong’’ (s), ‘‘medium’’ (m) and ‘‘weak’’ (w). Raman spectra (20), 1508 (9), 1469 (100), 1463 (44), 1447 (44), 1425 (15), 1412
were measured using a Perkin-Elmer Spektrum 2000R NIR (11), 1329 (24), 1261 (10), 1208 (13), 1103 (11), 1085 (23), 1028
FT-Raman instrument equipped with a Nd:YAG laser (21), 923 (7), 779 (2), 740 (2), 709 (3), 679 (4); 1H NMR ([d6]-
(1064 nm). The intensities are reported as percentages of the DMSO, 25 1C, ppm) d: 3.68 (s, 3H, CH3); 13C NMR ([d6]-
most intense peak and are given in parentheses. Elemental DMSO, 25 1C, ppm) d: 157.6 (CN4), 33.1 (CH3); 14N NMR
analyses were performed with a Netsch Simultaneous Thermal (DMSO-d6, 40.55 MHz, 25 1C, MeNO2) d/ppm: 37 (1 N,
Analyzer STA 429. n1/2 B60 Hz, NO2), 15N NMR ([d6]-DMSO, 25 1C) d = 4. 5
(N3), 14.1 (N6), 18.29 (N2, t, 3JNH = 1.9 Hz), 71.15
Synthesis of 5-nitro-2H-tetrazole (1)
(N4), 157.16 (N5), 168.38 (N1, d, 2JNH = 2.2 Hz), –289.13
Anhydrous ammonium 5-nitrotetrazolate (0.44 g, 3.32 mmol) (N7, 1JNH = 102.7 Hz), 329.66 (N8, 1JNH = 69.4 Hz); m/z
and potassium hydroxide (0.19 g, 3.32 mmol) were dissolved in (DEI+): 130 (19) [M + H]+, 129 (65) [M]+, 100 (1), 83 (8), 55

(15), 54 (17), 53 (100), 46 (38), 43 (28), 40 (7), 39 (5), 28 (45), 18 (e.g., lead azide) and puts it first in the list of high performing
(8), 15 (4); EA (C2H3N5O2, 129.08): calcd.: C 18.61, H 2.34, N primers. Unfortunately, 1 absorbs water, which limits its
54.26; found: C 18.39, H 2.28, N 52.80; BAM drophammer: application. Furthermore 1–3 are thermally too unstable for
2 J; friction tester: 82 N, ESD: 0.50 0.05 J, flame: combustion. use as conventional high explosives. The predicted products
(ICT code) formed upon explosion of 1–3 are expected to be
Synthesis of 2-methyl-5-nitrotetrazole (3) less harmful than those expected from the decomposition of
To 20 mL of an aqueous sodium nitrite (2.76 g, 0.04 mol) commonly used high explosives, which suggest their potential
solution, a solution of 2-methyl-5-aminotetrazole (2.00 g, 0.02 mol) (2 and 3) as environmentally friendly alternatives with high
in 20 mL 1N sulfuric acid was added at 0 1C. The reaction performance and low initiation barriers (by impact) for use in
mixture was stirred for 8 h and the precipitated bis(2-methyl- energetic applications (e.g., as ingredients for energetic fillers
tetrazolyl)triazene precipitated was removed by filtration. in high explosive compositions).
Afterwards the product was extracted three times with 20 mL
of CH2Cl2. The organic phases were combined, dried over Acknowledgements
MgSO4 and evaporated. The crude product was recrystallized
from acetone yielding single crystals suitable for XRD ana- Financial support of this work by the Ludwig-Maximilian
lysis. (1.68 g, yield 65%); DSC (5 1C min1, 1C): 75 1C (mp), University of Munich (LMU), the Fonds der Chemischen
150 1C (decomp.); IR (KBr, cm1): n~ = 3022 (m), 1610 (m), Industrie (FCI), the European Research Office (ERO) of the
1565 (s), 1510 (m), 1468 (m), 1412 (s), 1285 (s), 1160 (m), 1001 U.S. Army Research Laboratory (ARL) under contract nos.
(w), 880 (m), 788 (m), 750 (m), 670 (w), 610 (w), 530 (w); N-62558-05-C-0027, 9939-AN-01 and W911NF-07-1-0569
Raman (1064 nm, 200 mW, 25 1C, cm1): n~ = 3052 (12), 2967 and the Bundeswehr Research Institute for Materials, Explo-
(60), 1555 (28), 1486 (40), 1468 (26), 1418 (100), 1369 (11), sives, Fuels and Lubricants (WIWEB) under contract nos.
1335 (8), 1322 (14), 1287 (12), 1209 (30), 1075 (12), 1043 (40), E/E210/4D004/X5143 and E/E210/7D002/4F088 is gratefully
1026 (44), 841 (16), 776 (17), 715 (46), 547 (10), 436 (30), 378 acknowledged. The authors are indebted to and thank
(18), 307 (16), 218 (16); 1H NMR ([d6]-DMSO, 25 1C, ppm) d: Dr Betsy Rice and Dr Gary Chen for many helpful discussions
4.50 (s, 3H, CH3); 13C NMR ([d6]-DMSO, 25 1C, ppm) d: and support of our work. We also acknowledge Mr. Stefan
166.4 (CN4), 41.9 (CH3); 14N NMR (DMSO-d6, 40.55 MHz, Huber for help with the sensitivity tests. The authors acknowl-
25 1C, MeNO2) d/ppm: 34 (1 N, n1/2 B50 Hz, NO2); 15N edge collaborations with Dr M. Krupka (OZM Research,
NMR ([d6]-DMSO, 25 1C) d = 5.3 (N3), 33.5 (N5), 55.1 Czech Republic) in the development of new testing and
(N4), 76.6 (N2, 2JNH = 2.1 Hz), –97.9 (N1, 3JNH = 1.7 Hz); evaluation methods for energetic materials and with
m/z (DEI+): 130 (2) [M + H]+, 129 (2) [M]+, 115 (1) [M + H Dr M. Sućesca (Brodarski Institute, Croatia) in the develop-
CH 3]+, 101 (15), 58 (89), 43 (100) [HN3]+, 42 (6), 28 (3) ment of new computational codes to predict the detonation
[N2]+, 18 (29); EA (C2H3N5O2, 129.08): calcd.: C 18.61, parameters of high-nitrogen explosives.
H 2.34, N 54.26; found: C 18.88, H 2.35, N 52.99; BAM
drophammer: 1 J; friction tester: 40 N, ESD: 0.20 0.04 J, References
flame: combustion.
1 T. M. Klapötke, in ‘Moderne Anorganische Chemie’, ed. E. Riedel
(Hrsg.), Walter de Gruyter, Berlin, New York, 2003, 2nd edn,
Conclusions pp. 95–100; T. M. Klapötke, in High Energy Density Materials, ed.
T. M. Klapötke (Hrsg.), Springer, Berlin, Heidelberg, 2007,
pp. 85–122.
From this combined experimental and theoretical study the
2 A. Hammerl, G. Holl, T. M. Klapötke, P. Mayer, H. Nöth,
following conclusions can be drawn: H. Piotrowski and M. Warchhold, Eur. J. Inorg. Chem., 2002, 4,
Convenient procedures for the synthesis of three highly 834.
energetic neutral 5-nitrotetrazoles (1–3) are presented, which 3 T. M. Klapötke, P. Mayer, A. Schulz and J. J. Weigand, J. Am.
Chem. Soc., 2005, 127, 2032.
allow the materials to be obtained at low cost using facile 4 R. P. Singh, H. Gao, D. T. Meshri and J. M. Shreeve, in High
routes, good yields and excellent purities. The full characteri- Energy Density Materials, ed. T. M. Klapötke (Hrsg.), Springer,
zation of the compounds by analytical and spectroscopic Berlin, Heidelberg, 2007, pp. 35–84.
methods is described in detail. In addition we determined the 5 A. Köhler and R. Mayer, ‘Explosivstoffe’, Wiley-VCH, D-Wein-
heim, 9nd edn, 1998; D. M. Badgujar, M. B. Talawar, S. N. Asthana
molecular structure of the compounds in the solid state by and P. P. Mahulikar, J. Hazard. Mater., 2008, 151, 289–305.
X-ray diffraction methods. The energetic properties of the 6 S. Oga, Jpn. Kokai Tokkyo Koho, JP2006249061, p. A20060921,
compounds were assessed by means of standard tests and 2006.
7 T. M. Klapötke, G. Holl. J. Geith, A. Hammerl and J. J. Weigand,
quantum chemical calculations (CBS-4M). 1–3 are calculated
New Trends in Research of Energetic Materials, Proceedings of the
to be strongly endothermic with heats of formation between Seminar, Pardubice, 7th, Czech Republic, 2004.
247 and 282 kJ mol1. The compounds show highly exother- 8 T. M. Stierstorfer and J. Stierstorfer, Phys. Chem. Chem. Phys.,
mic decomposition peaks (DSC) and are easily initiated by 2008, 10, 4340–4346; T. M. Klapötke and J. Stierstorfer, Eur. J.
Inorg. Chem., 2008, 26, 4055–4062; T. M. Klapötke, J. Stierstorfer
impact. Furthermore, 1–3 have high performances (EXPLO5 and A. U. Wallek, Chem. Mater., 2008, 20(13), 4519–4530.
code) comparable to commonly used secondary explosives 9 G. Geisberger, T. M. Klapötke and J. Stierstorfer, Eur. J. Inorg.
regardless of their ease of initiation and 1 classifies as a Chem., 2007, 30, 4743–4750.
primary explosive in regard to its impact and friction sensitivity 10 R. P. Singh, R. D. Verma, D. T. Meshri and J. M. Shreeve, Angew.
Chem., Int. Ed., 2006, 45(22), 3584.
values and still has a calculated detonation velocity, which is 11 T. M. Klapötke, P. Mayer, A. Schulz and J. J. Weigand, Propel-
almost twice as large as that of common primary explosives lants, Explos., Pyrotech., 2004, 29(6), 325.
This journal is
12 A. Hammerl, M. A. Hiskey, G. Holl, T. M. Klapötke, K. Polborn, V. A. Ostrovskii, Russ. J. Org. Chem. (Engl. Transl.), 1997, 33,
J. Stierstorfer and J. J. Weigand, Chem. Mater., 2005, 17, 3784. 1771–1783.
13 C. Ye, J. C. Xiao, B. Twamley and J. M. Shreeve, Chem. Commun., 34 T. M. Klapötke, P. Mayer, C. Miró Sabaté, J. M. Welch and
2005, 2750. N. Wiegand, Inorg. Chem., 2008, 47, 6014–6027.
14 J. C. Galvez-Ruiz, G. Holl, K. Karaghiosoff, T. M. Klapötke, 35 R. A. Henry and W. G. Finnegan, J. Am. Chem. Soc., 1954, 76,
K. Loehnwitz, P. Mayer, H. Noeth, K. Polborn, C. J. Rohbogner, 923–926.
M. Suter and J. J. Weigand, Inorg. Chem., 2005, 44(14), 5192. 36 A. M. Churakov, S. E. Semenov, S. L. loffe, Y. A. Strelenko and
15 H. Xue, B. Twamley and J. M. Shreeve, Inorg. Chem., 2004, 43(25), V. A. Tartakovskii, Mendeleev Commun., 1995, 5(3), 102–103.
7972. 37 K. Karaghiosoff, T. M. Klapötke, P. Mayer, C. Miró Sabaté,
16 Z. P. Demko and K. B. Sharpless, J. Org. Chem., 2001, 66(24), A. Penger and J. M. Welch, Inorg. Chem., 2008, 47, 1007–1019.
7945–7950. 38 CrysAlis CCD, Oxford Diffraction Ltd., Version 1.171.27p5 beta
17 J. Thiele, Liebigs Ann., 1892, 270, 1–2. (release 01-04-2005 CrysAlis171 .NET) (compiled Apr 1 2005,
18 K. Hattori, E. Lieber and J. P. Horwitz, J. Am. Chem. Soc., 1956, 17:53:34).
78, 411–415. 39 CrysAlis RED, Oxford Diffraction Ltd., Version 1.171.27p5 beta
19 G. I. Koldobskii, D. S. Soldatenko, E. S. Gerasimova, (release 01-04-2005 CrysAlis171 .NET) (compiled Apr 1 2005,17:53:34).
N. R. Khokhryakova, M. B. Shcherbinin, V. P. Lebedev and 40 Z. Otwinowski and W. Minor, in ‘‘Processing of X-ray Diffraction
V. A. Ostrovskii, Russ. J. Org. Chem. (Engl. Transl.), 1997, Data Collected in Oscillation Mode’’, Methods in Enzymology,
33(12), 1771–1783. Volume 276 Macromolecular Crystallography, Part A, eds.
20 E. Oliveri-Mandala and T. Passalaqua, Gazz. Chim. Ital., 1912, C. W. Carter Jr and R. M. Sweet, Academic Press, New York,
41(II), 430–435. 1997, pp. 307–326,.
21 G. F. Holland and J. N. Pereira, J. Med. Chem., 1967, 10(2), 41 SIR-92, A program for crystal structure solution A. Altomare,
149–154; S. V. Voitekhovich, P. N. Gaponik and A. O. Koren, G. Cascarano, C. Giacovazzo and A. Guagliardi, J. Appl. Crystallogr.,
Mendeleev Commun., 1997, 1, 41–42; P. N. Gaponik, 1993, 26, 343.
S. V. Voitekhovich and B. G. Klyaus, Russ. J. Org. Chem., 2004, 42 G. M. Sheldrick, SHELXS-97, Program for Crystal Structure
40(4), 598–600; M. D. Cullen, B. L. Deng, T. L. Hartman, Solution, Universität Göttingen, 1997.
K. M. Watson, R. W. Buckheit, Jr, C. Pannecouque, E. De Clercq 43 G. M. Sheldrick, SHELXL-97, Program for the Refinement of
and M. Cushman, J. Med. Chem., 2007, 50(20), 4854–4867. Crystal Structures, University of Göttingen, Germany, 1997.
22 R. A. Henry, W. G. Finnegan and E. Lieber, J. Am. Chem. Soc., 44 A. L. Spek, PLATON, A Multipurpose Crystallographic Tool,
1954, 76, 2894–2898; C. Stadler, J. Daub, J. Köhler, Utrecht University, Utrecht, The Netherlands, 1999.
R. W. Saalfrank, V. Coropceanu, V. Schuenemann, C. Ober, 45 SCALE3 ABSPACK-An Oxford Diffraction program
A. X. Trautwein, S. F. Parker, M. Poyraz, T. Inomata and (1.0.4,gui:1.0.3), r 2005 Oxford Diffraction Ltd.
R. D. Cannon, Dalton Trans., 2001, 3373–3383; S. Achamlale, 46 D. D. Bray and J. G. White, Acta Crystallogr., Sect. B, 1979, 35, 3039.
A. Elachqar, A. El Hallaoui, A. Alami, S. Elhajji, 47 M. M. Sokolova, V. V. Mel’nikov, A. A. Mel’nikov and
M. L. Roumestant and P. Viallefont, Phosphorus, Sulfur Silicon B. V. Gidaspov, Chem. Heterocycl. Compd., 1977, 6, 689–692.
Relat. Elem., 1998, 140, 103–111; A. O. Koren, P. N. Gaponik, 48 V. I. Kolesov, V. P. Sinditskii, V. Y. Egorshev, B. A. Lurie and
O. A. Ivashkevich and T. B. Kovalyova, Mendeleev Commun., M. Y. Soloviev, International Annual Conference of ICT, 32nd,
1995, 1, 10–11. 2001, 117/1-117/12.
23 J. Stierstorfer, T. M. Klapötke, A. Hammerl and B. Chapman, 49 M. Sućeska, Test Methods for Explosives, Springer, New York,
Z. Anorg. Allg. Chem., 2008, 634, 1051–1057; A. Hammerl and 1995, p. 21 (impact), p. 27 (friction).
T. M. Klapötke, Inorg. Chem., 2002, 41(4), 906–912; A. Hammerl, 50 NATO standardization agreement (STANAG) on explosives,
T. M. Klapötke, P. Mayer and J. J. Weigand, Propellants, Explos., impact sensitivity tests, no. 4489, Ed. 1, Sept. 17, 1999.
Pyrotech., 2005, 30(1), 17–26. 51 WIWEB-Standardarbeitsanweisung 4-5.1.02, Ermittlung der
24 T. M. Klapötke and J. Stierstorfer, Helv. Chim. Acta, 2007, 90, Explosionshier der Schlagempfindlichkeit mit dem Fallhammer,
2132–2150; T. M. Klapötke and J. Stierstorfer, New Trends in Nov. 8, 2002.
Research of Energetic Materials, Proceedings of the Seminar, 52 http://www.bam.de.
Pardubice, Czech Republic, 2007, 10th, vol. 2, pp. 674–690. 53 http://www.reichel-partner.de/.
25 A. M. Astakhov, R. S. Stepanov, L. A. Kruglyakova and 54 NATO standardization agreement (STANAG) on explosive, fric-
A. A. Nefedov, Russ. J. Org. Chem., 2001, 37(4), 577–582. tion sensitivity tests, no. 4487, Ed. 1, Aug. 22, 2002.
26 D. Adam, K. Karaghiosoff, G. Holl, M. Kaiser and T. M. 55 WIWEB-Standardarbeitsanweisung 4-5.1.03, Ermittlung der
Klapötke, Propellants, Explos., Pyrotech., 2002, 27(1), 7. Explosionsgefährlichoder der Reibeempfindlichkeit mit dem
27 K. Karaghiosoff, T. M. Klapötke, A. Michailovski, H. Nöth and Reibeapparat, Nov. 8, 2002.
M. Suter, Propellants, Explos., Pyrotech., 2003, 28(1), 1. 56 Impact: Insensitive 440 J, less sensitive Z 35 J, sensitive Z 4, very
28 T. M. Klapötke, P. Mayer and V. Verma, Propellants, Explos., sensitive r3 J. Friction: Insensitive 4 360 N, less sensitive =
Pyrotech., 2006, 31(4), 263. 360 N, sensitive o360 N and 480 N, very sensitive r80 N,
29 H. Xue, S. W. Arritt, B. Twamley and J. M. Shreeve, Inorg. Chem., extremely sensitive r10 N. According to the UN Recommenda-
2004, 43, 7972–7977; H. Xue, Y. Gao, B. Twamley and tions on the Transport of Dangerous Goods.
J. M. Shreeve, Chem. Mater., 2005, 17, 191–198; H. Xue, 57 http://www.ozm.cz/testing-instruments/small-scale-electrostatic-
Y. Gao, B. Twamley and J. M. Shreeve, Inorg. Chem., 2005, 44, discharge-tester.htm.
5068–5072; Y. Gao, B. Twamley and J. M. Shreeve, Chem. Eur. J., 58 S. Zeman, V. Pelikán and J. Majzlı́k, Cent. Eur. J. Energ. Mater.,
2006, 12, 9010–9018; J. C. Gálvez-Ruiz, G. Holl, K. Karaghiosoff, 2006, 3(3), 45–51.
T. M. Klapötke, K. Löhnwitz, P. Mayer, H. Nöth, K. Polborn, 59 D. Skinner, D. Olson and A. Block-Bolten, Propellants, Explos.,
C. J. Rohbogner, M. Suter and J. J. Weigand, Inorg. Chem., 2005, Pyrotech., 1997, 23, 34–42.
44(12), 4237–4253; T. M. Klapötke and C. Miró Sabaté, Z. Anorg. 60 Calculation of the oxygen balance: O (%) = (wO 2xC 1/2yH
Allg. Chem., 2007, 633, 2671–2677; C. Darwich, T. M. Klapötke 2zS)1600/M. (w: number of oxygen atoms, x: number of carbon
and C. Miró Sabaté, Chem. Eur. J., 2008, 14, 5756–5771. atoms, y: number of hydrogen atoms, z: number of sulfur atoms,
30 T. M. Klapötke, C. Miró Sabaté and J. M. Welch, Dalton Trans., M: molecular weight).
2008, DOI: 10.1039/b811410b. 61 M. Sućeska, Mater. Sci. Forum, 2004, 465–466, 325–330;
31 M. H. V. Huynh, M. D. Coburn, T. J. Meyer and M. Wetzler, M. Sućeska, Propellants, Explos., Pyrotech., 1991, 16, 197–202;
Proc. Natl. Acad. Sci. USA, 2006, 103(27), 10322–10327; M. H. M. Sućeska, Propellants, Explos., Pyrotech., 1999, 24, 280–285.
V. Huynh, M. A. Hiskey, T. J. Meyer and M. Wetzler, Proc. Natl. 62 M. L. Hobbs and M. R. Baer, Calibration of the BKW-EOS With
Acad. Sci. USA, 2006, 103(14), 5409–5412. a Large Product Species Data Base and Measured C–J, Properties
32 J. Akhavan, in The Chemistry of Explosives, RSC Paperbacks, Proc. of the 10th Symp. (International) on Detonation, ONR
Cambridge, UK, 2nd edn, 2004. 33395-12, Boston, MA, July 12–16, 1993, p. 409.
33 G. I. Koldobskii, D. S. Solyearnko, E. S. Gerasimova, 63 T. M. Klapötke and C. Miró Sabaté, Chem. Mater., 2008, 20(5),
N. R. Khokhryakova, M. B. Shcherbinin, V. P. Lebedev and 1750–1763.

64 ICT-Thermodynamic Code, version 1.0, Fraunhofer-Institut für 66 J. W. Ochterski, G. A. Petersson and J. A. Montgomery, Jr,
Chemische Technologie (ICT): Pfinztal/Berghausen, Germany, J. Chem. Phys., 1996, 104, 2598.
1988–2000; R. Webb and M. van Rooijen, Proceedings of the 67 J. A. Montgomery, Jr, M. J. Frisch, J. W. Ochterski and
29th International Pyrotechnics Seminar, 2002, 823–828; G. A. Petersson, J. Chem. Phys., 2000, 112, 6532.
H. Bathelt and F. Volk, 27th International Annual Conference of 68 E. F. Byrd and B. M. Rice, J. Phys. Chem., 2006, 110(3),
ICT, 1996, 92, 1–16. 1005–1013; B. M. Rice, S. V. Pai and J. Hare, Combust. Flame,
65 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, 1999, 118(3), 445–458.
M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr, T. Vreven, 69 L. A. Curtiss, K. Raghavachari, P. C. Redfern and J. A. Pople,
K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, J. Chem. Phys., 1997, 106(3), 1063.
V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, 70 P. J. Linstrom and W. G. Mallard, NIST Chemistry WebBook,
G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, NIST Standard Reference Database Number 69, National Insti-
R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, tute of Standards and Technology, Gaithersburg, MD, June 2005,
O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, 20899, http://webbook.nist.gov.
J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann, 71 M. S. Westwell, M. S. Searle, D. J. Wales and D. H. Williams,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, J. Am. Chem. Soc., 1995, 117, 5013.
P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, 72 R. C. West and S. M. Selby, Handbook of Chemistry and Physics,
V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, The Chemical Rubber Co., Cleveland, OH, 48th edn, 1967–1968,
D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, pp. D22–D51.
J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, 73 V. A. Ostrovskii, M. S. Pevzner, T. P. Kofman and I. V. Tselinskii,
B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, Targets Heterocycl. Syst., 1999, 3, 467.
R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, 74 W. S. McEwan and M. W. Rigg, J. Am. Chem. Soc., 1951, 73,
A. Nanayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, 4725–4727.
W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 75 http://www.linseis.com/.
03 (Revision B0.4), Gaussian, Inc., Pittsburgh, PA, 2004. 76 http://www.perkin-elmer.com/.
This journal is
Probing multivalency for the inhibition of an enzyme: glycogen

phosphorylase as a case studyw
Samy Cecioni,a Oana-Andreea Argintaru,a Tibor Docsa,b Pál Gergely,b
Jean-Pierre Pralya and Sébastien Vidal*a
Received (in Montpellier, France) 22nd July 2008, Accepted 21st August 2008
First published as an Advance Article on the web 23rd October 2008
DOI: 10.1039/b812540f
Glycogen phosphorylase is involved in the hepatic glucose production and appears an emerging
biological target for the treatment of type 2 diabetes. Two distinct trivalent inhibitors of GP were
synthesized either through Cu(I)-assisted 1,3-dipolar cycloaddition or through formation of a tris-
oxadiazole derivative. A biological study of the inhibiting properties of these trivalent inhibitors
of GP have shown that the valency of the molecules influences slightly the inhibition of the
enzyme whereas the presence of a spacer arm between the core and the pharmacophore moieties
does not. The possible modes of binding of these multivalent inhibitors to the enzyme are
discussed.
Introduction displaying a large number of sites for the inhibition of this

enzyme.8 A series of GP inhibitors have been described pre-
Glycogen phosphorylase and diabetes viously with various heterocyclic structures9 but our work10 is
Diabetus mellitus affects about 3% of the world population focusing on carbohydrate-based inhibitors of GP7b,c,f which
and up to 6% for the adult population of developed countries. are capable of binding selectively at the catalytic site of GP.
Diabetes, one of the major causes of death worldwide, is These glycomimetic approaches are based on structural modi-
characterized by elevated glycaemia causing heart and kidney fications at the molecular level for improving the binding to
failures as well as visual impairment problems.1 Type 2 the enzyme and therefore affording valuable GP inhibitors.
diabetes is non-insulino-dependent and arises from insulin
signalling inefficiency resulting in insufficient or even late Multivalency and inhibition of enzymes
insulin secretion. A series of biological targets have been
identified for anti-diabetic therapy2 such as peroxisome Another approach for the inhibition of GP could take advan-
proliferator-activated receptors a/g (PPARs a/g),3 glucagon- tage of multivalency. This strategy may provide additional
like peptide-1 (GLP-1),4 dipeptidyl peptidase IV (DPP-IV)5 or opportunities in the field of drug discovery for the design of
protein tyrosine phosphatase 1B (PTP 1B).6 Glycogen phos- potent enzyme inhibitors particularly by reaching higher
phorylase (GP) has recently appeared as an enzyme of interest affinities and probably better selectivities. A few examples of
for the treatment of type 2 diabetes.7 This enzyme catalyses multivalent inhibition of an enzyme are reported in the
glycogen depolymerisation to release glucose-1-phosphate literature where multimeric species of a specific drug are
according to the schematic equation: capable of improving the inhibition in comparison to the
monomeric molecule.11 The binding of one ligand subunit
(Glucose)n - (Glucose)n1 + Glucose-1-phosphate from the multivalent molecule to the enzyme generates an
increase in local concentration of ligands, thus creating an
The inhibition of GP is expected to slow down glycogenolysis apparent cooperativity causing an enhancement in inhibition.
and to lower the production of glucose from the liver therefore Dimeric inhibitors of influenza virus neuraminidase have been
allowing for a better control over hyperglycaemia. GP has developed by MacDonald et al.12 and displayed up to a
been extensively studied and crystallographic data analyses are 100-fold increase in inhibition along with improved pharmaco-
kinetic properties. In an additional study of the same
a
Universite´ de Lyon, Lyon, Universite´ Lyon 1, Villeurbanne, CNRS, group,13 a set of trimeric and tetrameric inhibitors displayed
UMR5246, Institut de Chimie et Biochimie Molećulaires et
Supramolećulaires, Laboratoire de Chimie Organique
improved antiviral activities and long-lasting protective activ-
2 - Glycochimie, 43 Boulevard du 11 Novembre 1918, F-69622 ities against influenza virus. More recently, the group of
Villeurbanne, France. E-mail: sebastien.vidal@univ-lyon1.fr; J. Gervay-Hague has described the synthesis of a series of
Fax: +33 472 448 349; Tel: +33 472 448 349 trivalent zanamivir derivatives via click chemistry although no
b
Cell Biology and Signalling Research Group of the Hungarian
Academy of Sciences, Department of Medical Chemistry, Research biological activity has been reported yet.14 Inhibition of
Centre for Molecular Medicine, University of Debrecen, Nagyerdei acetylcholinesterase by dimeric molecules resulted in up to
krt. 98, Debrecen, H-4032, Hungary. E-mail: gpal@dote.hu; 3000-fold increases in potency and selectivity compared to
Fax: +36 52 412 566; Tel: +36 52 412 345 the monomeric inhibitor.15 Glycosidases inhibition16 with
w Electronic supplementary information (ESI) available: Determina-
tion of Ki values and detailed atom numbering of molecules. See DOI: tethered dimeric azasugars was investigated and the molecules
10.1039/b812540f displayed interesting inhibitions of these enzymes but more

importantly a selectivity for two enzymes out of the seven effect is observed and the IC50 value observed will be similar to
tested.16a However, tetravalent 1-azafagomine inhibitors dis- 1/3 IC50mono (Fig. 1, Case 1). Nevertheless, the IC50 measured
played no improved inhibition compared to the monovalent can be improved with a lower value in comparison to 1/3
structure but rather a strong decrease in activity.16b Finally, IC50mo (Fig. 1, Case 2). If each binding site of the enzyme is
bivalent inhibitors of tetrameric b-tryptase constructed on a occupied by a ligand of the multivalent inhibitor, the forma-
cyclodextrin scaffold have shown increased inhibitions for this tion of 3:1 complexes would afford aggregates of proteins. If
enzyme.17 the size of the aggregates remains small enough to maintain a
Inspired by the above mentioned results for the multivalent good solubility of the complex, the IC50 observed will be
neuraminidase inhibition and by the fact that a multimeric similar to 1/3 IC50mono (Fig. 1, Case 3). Nevertheless, if the
enzyme offers additional possibilities for improved inhibition size of the multivalent inhibitor-enzyme clusters becomes large
through multivalency, we have designed synthetic routes to enough to cause their precipitation, the quantity of enzyme
trivalent carbohydrate-based GP inhibitors. A single case of a present in the solution will diminish and therefore the IC50
dimeric inhibitor of GP has been reported with a bis(5- value measured will be lower than 1/3 IC50mono (Fig. 1, Case
chloroindole-2-carboxamide) derivative inhibiting human liver 4). In this case, the IC50 value measured will be a ‘‘virtual’’
GPa (HLGPa) with an IC50 value of 6 nM compared to 12.5 mM value because of the lower quantity of the enzyme available in
for the parent monovalent inhibitor (2000-fold increase).18 solution.
This result highlights a productive and cooperative binding
of both ends of the bivalent inhibitor to two binding sites. The
co-crystallization of HLGPa with the divalent inhibitor Results and discussion
demonstrated that a single molecule of inhibitor was capable Synthesis of trivalent inhibitors
of interacting with each monomeric unit of GP by linking the
two binding sites across the interface of GP homodimeric We have recently reported the preparation of 3-C-glycosyl-
structure. This result encouraged us to further investigate this 5-aryl-1,2,4-oxadiazoles which displayed good inhibition
approach for the design of multivalent inhibitors of GP. towards GP.10b In this context, we synthesized an alkyne-
A closer look at the modes of binding of multivalent terminated 3-C-glycosylated 1,2,4-oxadiazole which could then
inhibitors to an enzyme reveals several possibilities as depicted be involved in a 1,3-dipolar cycloaddition with a tris-azido-
in Fig. 1. A dimeric enzyme such as GP can interact with two functionalized derivative to obtain a multivalent GP inhibitor
monomeric molecules of inhibitor in a 1:1 complex (2:2 at the candidate. A more condensed trimeric inhibitor was also
molecular level) providing a reference IC50mono value for prepared by direct coupling of an amidoxime with a tris-acyl
monovalent inhibitors. When considering the same inhibitor chloride and subsequent dehydrative cyclization to the corres-
repeated three times on a molecular scaffold, four main ponding trivalent C-glycosylated oxadiazole. These inhibitors
possible cases can then be envisaged. The inhibition of a were designed in order to determine the influence of a spacer
trivalent inhibitor must be divided by three in order to arm between the core and the pharmocophore ligands on the
consider the contribution of each residue in its comparison inhibition of the enzyme.
to a monovalent inhibitor. If a 1:1 complex is formed in
Synthesis of the trivalent inhibitor with a spacer arm
solution, a simple statistical effect can be invoked if no positive
The perbenzoylated glucosyl cyanide 119 was reacted with
hydroxylamine hydrochloride in pyridine to afford the desired
amidoxime 2 (Scheme 1). In our previous work,10b the crude
product obtained was rather difficult to purify by silica gel
column chromatography. The amidoxime 2 could be obtained
pure without chromatography simply by diluting the crude
product in ethyl acetate and then washing the organic layer
with 1 M aqueous HCl to remove pyridine and excess of
hydroxylamine, followed by saturated aqueous NaHCO3 and
brine. This simple chromatography-free purification process
afforded the expected amidoxime 2 in 99% yield and high
purity. The formation of the O-acyl-amidoxime 3 was
achieved with 4-pentynoic acid in the presence of EDCI/HOBt
as coupling agents.
We previously observed that reactions times lasting from a
few hours to a few days were required for the thermal
cyclodehydration of O-acyl-amidoximes. In order to optimize
both time and yield, we performed this reaction under TBAF
catalysis20 and/or microwaves activation21 (Table 1). We
observed that the use of TBAF catalysis at room temperature
provided the cyclic oxadiazole 4 within 1 day (entry 1) while
Fig. 1 Possible modes of binding for a mono- and trivalent inhibitors thermal activation combined with TBAF catalysis drastically
with a dimeric enzyme. shortened the reaction time to 10 minutes (entry 2). No
This journal is
Scheme 1 Reagents and conditions: (a) NH2OHHCl, C5H5N, 50 1C, 5 h, 99%; (b) HCRC(CH2)2CO2H, EDCI, HOBt, CH2Cl2/DMF (9:1), 8 1C
then r.t., 16 h, 67%; (c) PhMe, TBAF 10 mol%, mW (150 1C, 200 W, 5 min), 97%; (d) NaOMe, MeOH then Amberlite IR-120 (H+ form);
(e) PhCH2N3, CuI, Et3N, mW (110 1C, 150 W, 15 min), 88%; (f) C6H3(CH2N3)3, CuI, Et3N, mW (110 1C, 150 W, 15 min), 98%.
Table 1 Cyclodehydration of O-acyl-amidoxime 3 to the 1,2,4-oxadiazole 4 in toluene
Entry Catalyst T/1C Microwave condition Time Yield (%)

1 10% TBAF 25 None 24 h 99
2 10% TBAF 110 None 10 min 97
3 None 150 100 W 1h No reaction
4 None 175 200 W 2h Decomposition
5 10% TBAF 150 200 W 5 min 97
6 10% TBAF 150 200 W 30 min 66
reaction or decomposition of the starting material was ob- by mass spectrometry (m/z = 2035.4 [M + H]+). Interest-
served when applying microwaves activation without TBAF ingly, molecular ions could be observed neither for compound
catalysis (entries 3 and 4). Nevertheless, the association of 13 nor the mono-oxadiazole intermediate. Saponification of
TBAF catalysis and microwaves activation performed on a the ester groups of 11 resulted in the concomitant cleavage of
short timescale (entry 5 and 6) provided a result comparable to the O-acyl amidoxime function and afforded the benzoic acid
that observed under conventional heating (entry 2). These derivative 12 whose structure was clearly demonstrated by
results underline the beneficial influence of TBAF catalysis. mass spectrometry (m/z = 581 [M H]) and NMR analyses.
The alkyne-terminated oxadiazole 4 was then engaged in a The triple thermal cyclodehydration of 10 was then performed
Huisgen’s Cu(I)-catalyzed 1,3-dipolar cycloaddition22 reaction under microwaves activation and TBAF catalysis for
under microwaves activation with benzyl azide to afford the 40 minutes. The tris-oxadiazole derivative 13 was isolated in
desired 1,4-disubstituted 1,2,3-triazole 6 in excellent yield. 72% yield as the only product of the reaction highlighting
Debenzoylation of compounds 4 and 6 afforded two hydro- again the positive influence of TBAF catalysis and microwaves
xylated GP inhibitor candidates 5 and 7. Similarly, the reac- activation for this cyclodehydration process. Deprotection
tion of 1,3,5-tris(azidomethyl)benzene23 with the alkyne under Zemplén conditions afforded the expected hydroxylated
derivative 4 under microwaves activation and Cu(I) catalysis trivalent GP inhibitor candidate 14.
afforded the cycloadduct 8. The saponification of the benzoate
esters provided the fully hydroxylated macromolecule 9. Inhibition of glycogen phosphorylase
The inhibition of GP was determined, as previously repor-
Synthesis of the trivalent inhibitor without spacer arm
ted,10b for the three monovalent C-glycosylated oxadiazoles
We next prepared a more condensed trifunctional macro- (5, 7 and 1510b) and the two trivalent derivatives 9 and 14
molecule were the C-glucosyl-oxadiazole moiety was directly (Fig. 2, Table 2). The enzymatic assays were performed at two
attached to a benzene ring (Scheme 2). Condensation of concentrations and most molecules displayed poor inhibition
amidoxime 2 with 1,3,5-benzenetricarbonyl trichloride af- properties at a concentration of 625 mM and moderate to good
forded the corresponding triester 10 in 73% yield. At first, inhibition at higher concentration (2.5 mM). In addition,
compound 10 was subjected to cyclodehydration under Ki values could be estimated only for trivalent derivatives 9
thermal conditions (reflux in 1,4-dioxane). The product obtained and 14 (see ESIw).
was not the expected tris-oxadiazole 13 but the bis-oxadiazole The alkyne-terminated C-glycosylated oxadiazole derivative
11 with one unreacted O-acyl amidoxime moiety as evidenced 5 displayed no inhibition at 625 mM and poor activity at

Scheme 2 Reagents and conditions: (a) C6H3(COCl)3, 1,4-dioxane, r.t., 24 h, 73%; (b) 1,4-dioxane, 100 1C, 4 days; (c) NaOMe, MeOH then
Amberlite IR-120 (H+ form); (d) PhMe, TBAF 30 mol%, mW (150 1C, 200 W, 40 min), 72%.
Table 2 Inhibition of GP observed for monovalent and trivalent

inhibitors at two concentrations
Inhibition (%)
Inhibitor Valency At 625 mM At 2.5 mM Ki/mM
5 1 0 22 4 n.d.a
7 1 0 0 n.d.a
15 1 10 n.d.a n.d.a
9 3 30 5 56 5 480 45b
14 3 35 5 62 5 535 50b
a b
n.d. = not determined. Estimated.
2.5 mM. The inhibition properties disappeared completely

when a spacer arm was added such as in the structure of 7.
Interestingly, the trivalent analogue 9 of the non-active deri-
vative 7 was now inhibiting GP with values of 30% at 625 mM
and 56% at 2.5 mM. The valency of the molecule is therefore
responsible for an increase in inhibition from 0 to 56% when
comparing 7 and 9 at 2.5 mM. The C-glycosylated oxadiazole
derivative 15 bearing a phenyl group on the 5-position of the
oxadiazole ring displayed 10% inhibition at 625 mM.10b The
inhibition was again increased to 35% at 625 mM for trivalent
analogue 14. We anticipated that the distance between the core
and the carbohydrate moiety would influence for the binding
to the enzyme. Nevertheless, this was not the case based on the
inhibition measured for 9 and 14.
The increase of valency from monovalent to trivalent species
is responsible for an increase in inhibition of GP. The inhibi-
Fig. 2 Structure of monovalent and trivalent GP inhibitors tested. tion per residue for trivalent molecules is always similar the
This journal is
corresponding monovalent analogue in accordance with the were inspected by UV light (l = 254 nm) and developed by
statistical effect model proposed (Fig. 1, Case 1). The 3:1 treatment with a mixture of 10% H2SO4 in EtOH/H2O
complex non soluble mode of binding (Fig. 1, Case 4) can be (1:1 v/v) followed by heating. Silica gel column chromato-
ruled out for these trivalent inhibitors of GP to the dimeric graphy was performed with Gedurans silica gel Si 60 (40–63 mm)
enzyme since no precipitate was observed under the concen- purchased from Merck (Darmstadt, Germany). Reactions
trations of trivalent inhibitors and enzyme used for the under microwave activation were performed on a CEM
inhibition studies. The inhibition observed for the trivalent Discover system. HRMS (LSIMS) mass spectra were recorded
species was never better than 1/3 of the inhibition (in %) in the positive mode using a Thermo Finnigan Mat 95 XL
observed for the corresponding monovalent molecules. In spectrometer. MS (ESI) mass spectra were recorded in the
conclusion, two modes of binding are possible with either positive mode using a Thermo Finnigan LCQ spectrometer.
1
1:1 or 3:1 complexes (Fig. 1, Case 1 or Case 3, respectively) H and 13C NMR spectra were recorded at 23 1C using Brüker
resulting in an observed inhibition close to 1/3 of the inhibition Advance DRX300 or DRX500 spectrometers with the residual
for the parent monovalent inhibitor. solvent as the internal standard. The following abbreviations
In the present study, the expected binding sites of these are used to explain the observed multiplicities: s, singlet; d,
glucose-based multivalent inhibitors are the catalytic site of doublet; dd, doublet of doublet; ddd, doublet of doublet of
GP homodimer which are separated from each other by a long doublet; t, triplet; td, triplet of doublet; q, quadruplet; m,
distance and pointing into opposite directions.8d The structure multiplet; br, broad; p, pseudo. Structure elucidation was
of the trivalent inhibitors tested did not permit such an intra- deduced from 1D and 2D NMR spectroscopy which allowed,
molecular interaction with both catalytic sites on the same in most cases, complete signal assignments based on COSY,
GP dimer, but rather an interaction with two independent HSQC, and HMBC correlations. NMR solvents were
GP dimers. In comparison, the bis(5-chloroindole-2-carboxamide) purchased from Euriso-Top (Saint Aubin, France). Atom
derivative is binding simultaneously at each indole binding site numbering of the molecules is presented in the ESI.w
near the interface between the monomeric units of the GP
dimer.17 The linker is composed of 12 atoms between two Syntheses
indole aromatic units which are therefore available for inter- 1,3,5-Tris(azidomethyl)benzene. A solution of 1,3,5-tris(bro-
acting with the binding site of each monomer of GP. momethyl)benzene (3.07 g, 8.6 mmol) and sodium azide
The designed trivalent molecules could also bind to the enzyme (3.36 g, 51.6 mmol) in DMF (100 mL) was stirred at 65 1C
on a different site. The large aromatic appendage present in the for 24 hours. The solution was cooled to room temperature
aglycon, composed of oxadiazole, phenyl and triazole rings, then poured into water (400 mL). The aqueous layer was
might interact with the surface of the protein through hydro- extracted with Et2O (3 250 mL). The combined organic
phobic interactions. The stability of the inhibitor-protein com- layers were washed with water (2 400 mL) and brine
plex would therefore be lower than complex involving an internal (300 mL). The organic layer was dried (Na2SO4), filtered
binding site such as the catalytic site. The observed inhibitions and evaporated with extreme care (water-bath at room tem-
would therefore be weak as currently observed in the present perature, reduced pressure and Plexiglas shield) to afford 1,3,5-
study. Nevertheless, we do not possess any experimental data tris(azidomethyl)benzene (2.05 g, 98%) as a colorless oil. Rf =
confirming or denying such a mode of interaction. 0.83 (PE/EtOAc, 8:2). 1H NMR (300 MHz, CDCl3) d = 4.39
(s, 6H, CH2N3), 7.25 (s, 3H, H-ar).
Conclusions C-(2,3,4,6-Tetra-O-benzoyl-b-D-glucopyranosyl)-formami-
In conclusion, we have designed two kinds of multivalent doxime (2). A solution of 2,3,4,6-tetra-O-benzoyl-b-D-gluco-
inhibitors of GP based on the acylation of an amidoxime pyranosyl cyanide 1 (3.00 g, 4.96 mmol) and hydroxylamine
intermediate followed by thermal dehydrative cyclization to hydrochloride (0.86 g, 12.4 mmol) in pyridine (10 mL) was
the corresponding oxadiazole. The introduction of an alkyne stirred at 50 1C for 5 hours. The mixture was diluted with
residue at the 5-position of the oxadiazole ring allowed the EtOAc (250 mL) and washed with 100 mL portions of water,
coupling to a trivalent azido-functionalized benzene ring 1 M HCl, saturated NaHCO3, water and brine successively.
leading to an extended trivalent inhibitor candidate. The The organic layer was dried (MgSO4), filtered and evaporated
enzyme inhibition assays revealed poor to moderate inhibitory to obtain the pure amidoxime 2 (3.24 g, 99%) as a white foam.
effect of these analogues. But, more important was the fact Rf = 0.48 (PE/EtOAc, 1:1). 1H NMR (300 MHz, CDCl3)
that multivalent inhibitors were always superior to their d 4.21 (ddd, 1H, J = 9.7 Hz, J = 5.1 Hz, J = 2.7 Hz, H-5),
monovalent counterparts. This study provides one of the few 4.31 (d, 1H, J = 9.8 Hz, H-1), 4.47 (dd, 1H, J = 5.1 Hz, J =
examples of multivalent inhibition for an enzyme, even though 12.4 Hz, H-6a), 4.62 (dd, 1H, J = 2.7 Hz, J = 12.4 Hz, H-6b),
the inhibitions observed remain modest. 4.76 (bs, 2H, NH2), 5.69 (t, 1H, J = 9.8 Hz, H-2), 5.73 (t, 1H,
J = 9.8 Hz, H-4), 5.96 (t, 1H, J = 9.8 Hz, H-3), 7.24–7.43
(m, 10H, H-ar), 7.47–7.57 (m, 2H, H-ar), 7.81–8.04 (m, 8H, H-ar).
Experimental
O-(Pent-4 0 -ynoyl)-3-C-(2,3,4,6-tetra-O-benzoyl-b-D-gluco-
General methods
pyranosyl)-formamidoxime (3). A solution of 4-pentynoic acid
Thin-layer chromatography (TLC) was carried out on aluminum (27 mg, 0.27 mmol) in CH2Cl2/DMF (4 mL, 9:1) was cooled to
sheets coated with silica gel 60 F254 (Merck). TLC plates 8 1C before addition of 1-hydroxybenzotriazole (HOBt)

(36.5 mg, 0.27 mmol), 1-(3-dimethylaminopropyl)-3-ethyl- was stirred at room temperature for 4 hours. The solution
carbodiimide hydrochloride (EDCI) (52 mg, 0.27 mmol) and was neutralized with a cation exchange resin (Amberlite IR-120,
amidoxime 2 (146 mg, 0.23 mmol). The mixture was kept at H+ form) and the resin washed with MeOH (3 5 mL).
8 1C for 30 minutes then stirred at room temperature for The filtrate was evaporated off and the residue was dissolved in
16 hours. The solvents were evaporated off and the crude MeOH then precipitated with CH2Cl2. The resulting solid was
product was purified by flash silica gel column chromato- washed with CH2Cl2 (2 5 mL) and dried under vacuum
graphy (PE then PE/EtOAc, 1:1) to afford the O-acylamidoxime to afford the hydroxylated oxadiazole 5 (103 mg, 98%) as a
3 (110 mg, 67%) as a white foam. Rf = 0.53 (PE/EtOAc, 1:1). white foam. Rf = 0.26 (CH2Cl2/MeOH, 9:1). [a]D = +9.6
[a]D = 2.9 (c = 1.00/CH2Cl2). 1H NMR (300 MHz, CDCl3) (c = 0.51/H2O). 1H NMR (300 MHz, CD3OD) d 2.36 (t, 1H,
d 1.94 (t, 1H, J = 2.5 Hz, H-5 0 ), 2.40–2.63 (m, 4H, H-2 0 H-3 0 ), J = 2.6 Hz, H-100 ), 2.73 (td, 2H, J = 2.6 Hz, J = 7.3 Hz, H-300 ),
4.31 (ddd, 1H, J = 2.7 Hz, J = 5.1 Hz, J = 9.8 Hz, H-5), 4.54 3.18 (t, 2H, J = 7.3 Hz, H-400 ), 3.42–3.53 (m, 3H, H-30 H-40 H-50 ),
(d, 1H, J = 9.8 Hz, H-1), 4.53–4.59 (m, 1H, H-6a), 4.67 3.65–3.73 (m, 2H, H-20 H-60 a), 3.87 (dd, 1H, J o1.0 Hz, J = 12.0
(dd, 1H, J = 2.7 Hz, J = 9.5 Hz, H-6b), 5.36 (s, 2H, NH2), Hz, H-60 b), 4.44 (d, 1H, J = 9.7 Hz, H-10 ). 13C NMR (75 MHz,
5.76 (t, 1H, J = 9.8 Hz, H-4), 5.80 (t, 1H, J = 9.8 Hz, H-2), CD3OD) d 16.6 (C-300 ), 27.1 (C-400 ), 62.8 (C-60 ), 71.2 (C-40 ), 71.3
6.01 (t, 1H, J = 9.8 Hz, H-3), 7.25–7.57 (m, 12H, H-ar), (C-100 ), 73.3 (C-20 ), 74.8 (C-10 ), 79.2 (C-30 ), 82.3 (C-200 ), 82.6 (C-50 ),
7.83–8.07 (m, 8H, H-ar). 13C NMR (75 MHz, CDCl3) d 14.3 169.2 (C-3), 180.5 (C-5). ESI-MS (positive mode) m/z: 285.0
(C-3 0 ), 32.1 (C-2 0 ), 63.0 (C-6), 69.2 (C-4), 69.3 (C-5 0 ), 70.0 [M + H]+, 307.1 [M + Na]+, 590.9 [2M + Na]+. HR-ESI-MS
(C-2), 73.7 (C-3), 75.6 (C-1), 76.7 (C-5), 82.5 (C-4 0 ), 128.40, (positive mode) m/z: calcd. for C12H16N2O6Na [M + Na]+
128.45, 128.5 (3s, 8C, CH-ar), 128.77, 128.82, 129.4 (3s, 4C, 307.0906, found 307.0907.
CIV-ar), 129.8, 129.9, 130.00, 130.04 (4s, 8C, CH-ar), 133.4,
133.5, 133.7 (3s, 4C, CH-ar), 153.7 (NQCR–NH2), 165.3, 5-[200 -(1 0 0 0 -Benzyl-1 0 0 0 ,2 0 0 0 ,3 0 0 0 -triazol-4 0 0 0 -yl)ethyl]-3-C-
165.6, 165.7, 166.3 (4s, 4C, COPh), 169.0 (C-1 0 ). ESI-MS (2 ,3 0 ,4 0 ,6 0 -tetra-O-benzoyl-b-D-glucopyranosyl)-1,2,4-oxa-
0
(positive mode) m/z: 719.2 [M + H]+, 741.3 [M + Na]+, diazole (6). In a CEM Discover 5 mL vial was introduced a
786.9 [M + HCOOH + Na]+, 1436.9 [2M + H]+, 1458.9 solution of benzyl azide (110 mg, 0.828 mmol), alkyne 4
[2M + Na]+, 1504.5 [2M + HCOOH + Na]+. HR-ESI-MS (193 mg, 0.276 mmol), copper iodide (26 mg, 0.138 mmol)
(positive mode) m/z: calcd. for C40H34N2O11 [M + H]+ and DIPEA (240 mL, 1.38 mmol) in toluene (5 mL). The
719.2241, found 719.2244. solution was sonicated for 1 min then heated at 110 1C for 15
min upon microwave irradiation (150 W). The solvent was
5-(But-100 -yn-400 -yl)-3-C-(2 0 ,30 ,4 0 ,6 0 -tetra-O-benzoyl-b-D-gluco- evaporated off and the residue purified by flash silica gel
pyranosyl)-1,2,4-oxadiazole (4). In a CEM Discover 5 mL vial column chromatography (PE/EtOAc, 1:1) to afford the cyclo-
was introduced a solution of O-acylamidoxime 3 (369 mg, adduct 6 (202 mg, 88%) as a colorless oil. Rf = 0.24
0.5 mmol) and TBAF (50 mL, 50 mmol, 1 M in THF) in toluene (PE/EtOAc, 1:1). [a]D = +1.4 (c = 1.02/CH2Cl2). 1H NMR
(5 mL). The reaction vial was heated at 150 1C for 5 min upon (500 MHz, CDCl3) d 3.22 (bs, 2H, H-200 ), 3.28 (bs, 2H, H-100 ),
microwave irradiation (200 W). The solvent was evaporated 4.37 (ddd, 1H, J = 3.0 Hz, J = 5.3 Hz, J = 9.7 Hz, H-5 0 ), 4.56
and the residue purified by flash silica gel column chromato- (dd, 1H, J = 5.3 Hz, J = 12.4 Hz, H-6 0 a), 4.68 (dd, 1H, J =
graphy (PE then PE/EtOAc, 1:1) to afford the oxadiazole 4 3.0 Hz, J = 12.4 Hz, H-6 0 b), 5.10 (d, 1H, J = 9.7 Hz, H-1 0 ),
(348 mg, 97%) as a white foam. Rf = 0.65 (PE/EtOAc, 7:3). 5.48 (s, 2H, NCH2Ph), 5.86 (t, 1H, J = 9.7 Hz, H-4 0 ), 5.97
[a]D = +8.3 (c = 1.12/CH2Cl2). 1H NMR (300 MHz, CDCl3) (t, 1H, J = 9.7 Hz, H-2 0 ), 6.06 (t, 1H, J = 9.7 Hz, H-3 0 ),
d 1.84 (t, 1H, J = 2.6 Hz, H-100 ), 2.65 (td, 2H, J = 2.6 Hz, J = 7.24–7.56 (m, 18H, H-5 0 0 0 H-ar), 7.80–8.03 (m, 8H, H-ar). 13C
7.5 Hz, H-300 ), 3.10 (t, 2H, J = 7.5 Hz, H-400 ), 4.33 (ddd, 1H, NMR (125 MHz, CDCl3) d 21.8 (C-200 ), 26.6 (C-100 ), 53.6
J = 3.4 Hz, J = 5.1 Hz, J = 9.8 Hz, H-5 0 ), 4.53 (dd, 1H, J = (NCH2Ph), 62.9 (C-6 0 ), 68.1 (C-4 0 ), 69.8 (C-2 0 ), 71.7 (C-1 0 ),
5.2 Hz, J = 12.4 Hz, H-6 0 a), 4.65 (dd, 1H, J = 3.0 Hz, J = 73.4 (C-3 0 ), 76.5 (C-5 0 ), 122.2 (C-5 0 0 0 ), 127.8, 127.9, 128.0,
12.4 Hz, H-6 0 b), 5.09 (d, 1H, J = 9.5 Hz, H-1 0 ), 5.82 (t, 1H, 128.4, 128.5, 128.9, 129.7, 129.8 (8s, 25C, CH-ar), 133.4, 133.6,
J = 9.5 Hz, H-4 0 ), 6.00 (m, 2H, H-2 0 H-3 0 ), 7.29–7.58 (m, 12 H, 133.8, 133.9 (4s, 4C, CIV-ar), 134.7 (CIV-ar), 145.3 (C-4 0 0 0 ),
H-ar), 7.81–8.02 (m, 8H, H-ar). 13C NMR (75 MHz, CDCl3) d 164.7, 165.0, 165.6, 165.3 (4s, 4C, COPh), 165.6 (C-3), 180.1
16.0 (C-300 ), 26.2 (C-400 ), 63.3 (C-6 0 ), 69.4 (C-4 0 ), 70.2 (C-100 ), (C-5). ESI-MS (positive mode) m/z: 834.1 [M + H]+, 856.1
70.6 (C-2 0 ), 72.4 (C-1 0 ), 74.1 (C-3 0 ), 77.0 (C-5 0 ), 80.8 (C-200 ), [M + Na]+, 1666.4 [2M + H]+. HR-ESI-MS (positive mode)
128.3 (s, 2C, CH-ar), 128.4 (s, 4C, CH-ar), 128.5 (s, 2C, CH- m/z: calcd. for C47H40N5O10 [M + H]+ 834.2775, found
ar), 128.7, 128.7, 128.8, 129.5 (4s, 4C, CIV-ar), 129.7, 129.8, 834.2781.
129.8, 129.9 (4s, 8C, CH-ar), 133.2, 133.3, 133.4, 133.5 (4s, 4C,
CH-ar), 164.6, 165.2, 165.8, 166.3 (s, 4C, COPh), 166.2 (C-3), 5-[200 -(1 0 0 0 -Benzyl-1 0 0 0 ,2 0 0 0 ,3 0 0 0 -triazol-4 0 0 0 -yl)-ethyl]-3-C-(b-D-
179.0 (C-5). ESI-MS (positive mode) m/z: 701.1 [M + H]+, glucopyranosyl)-1,2,4-oxadiazole (7). A solution of benzoy-
723.2 [M + Na]+, 1400.9 [2M + H]+, 1422.9 [2M + Na]+. lated cycloadduct 6 (128 mg, 0.153 mmol) and NaOMe
HR-ESI-MS (positive mode) m/z: calcd. for C40H32N2O10Na (5 mg, 0.09 mmol) in CH2Cl2/MeOH (5.5 mL, 10:1) was
[M + Na]+ 723.1955, found 723.1954. stirred at room temperature for 4 hours. The solution was
neutralized with a cation exchange resin (Amberlite IR-120,
3-C-(b-D-Glucopyranosyl)-5-(but-100 -yn-400 -yl)-1,2,4-oxadiazole (5). H+ form) and resin washed with MeOH (3 5 mL). The
A solution of benzoylated oxadiazole 4 (261 mg, 0.37 mmol) filtrate was evaporated off and the residue purified by
and NaOMe (5 mg, 0.09 mmol) in CH2Cl2/MeOH (5 mL, 2:3) flash silica gel column chromatography (CH2Cl2 then
This journal is
CH2Cl2/MeOH, 8:2 then EtOAc/MeOH, 8:2) to afford the (45 mg, 84%) as a white foam. 1H NMR (300 MHz, D2O) d
hydroxylated cycloadduct 7 (63 mg, 98%) as a white foam. 3.02–3.19 (m, 6H, H-100 ), 3.20–3.30 (m, 6H, H-200 ), 3.51–3.86
0000 0000 0000 0000 0000 0000
Rf = 0.68 (EtOAc/MeOH, 4:1). [a]D = +5.5 (c = 0.95/ (m, 18H, H-2 H-3 H-4 H-5 H-6 a H-6 b), 4.54
0000
MeOH). 1H NMR (300 MHz, CD3OD) d 3.18–3.23 (m, 2H, (d, 3H, J = 8.8 Hz, H-1 ), 5.39 (s, 6H, NCH2C6H3), 6.98
H-200 ), 3.24–3.36 (m, 2H, H-100 ), 3.44–3.52 (m, 3H, H-3 0 H-4 0 (s, 3H, H-2 H-4 H-6), 7.73 (s, 3H, H-5 0 ). 13C NMR (125 MHz,
H-5 0 ), 3.68–3.74 (m, 2H, H-2 0 H-6 0 a), 3.88 (dd, 1H, J o1.0 Hz, D2O) d 22.0 (s, 3C, C-100 ), 26.3 (s, 3C, C-200 ), 53.4 (s, 3C,
0000 0000
J = 11.4 Hz, H-6 0 b), 4.44 (d, 1H, J = 9.7 Hz, H-1 0 ), 5.55 NCH2C6H3), 61.1 (s, 3C, C-6 ), 72.1 (s, 3C, C-2 ), 73.2
0000 0000 0000 0000
(s, 2H, NCH2Ph), 7.28–7.38 (m, 5H, H-ar), 7.79 (s, 1H, H-5 0 0 0 ). (s, 3C, C-1 ), 69.6, 77.1, 80.6 (3s, 9C, C-3 C-4 C-5 ),
13
C NMR (75 MHz, CD3OD) d 23.3 (C-200 ), 27.2 (C-100 ), 54.9 124.2 (s, 3C, C-5 0 ), 127.3 (s, 3C, C-2 C-4 C-6), 137.2 (s, 3C, C-1
(NCH2Ph), 62.8 (C-6 0 ), 71.3, 79.2, 82.6 (3s, 3C, C-3 0 C-4 0 C-3 C-5), 146.5 (s, 3C, C-4 0 ), 167.5 (s, 3C, C-3 0 0 0 ), 181.0 (s, 3C,
C-5 0 ), 73.4 (C-2 0 ), 74.9 (C-1 0 ), 123.9 (C-5 0 0 0 ), 129.1, 129.5, C-5 0 0 0 ). ESI-MS (positive mode) m/z: 1118.2 [M + Na]+.
130.0 (3s, 5C, CH-ar), 136.8 (CIV-ar), 146.9 (C-4 0 0 0 ), 169.2 HR-ESI-MS (positive mode) m/z: calcd. for C45H57N15NaO18
(C-3), 180.9 (C-5). ESI-MS (positive mode) m/z: 418.1 [M + [M + Na]+ 1118.3904, found 1118.3918.
H]+, 440.1 [M + Na]+, 856.6 [2M + Na]+. HR-ESI-MS
(positive mode) m/z: calcd. for C19H23N5NaO6 [M + Na]+ N,N0 ,N00 -1,3,5-Tris(benzoyloxy)-C-(2 0 ,3 0 ,4 0 ,6 0 -tetra-O-benzoyl-
440.1546, found 440.1549. b-D-glucopyranosyl)tricarboximidamide (10). A solution of
1,3,5-benzenetricarbonyl trichloride (102 mg, 0.38 mmol) and
0000 0000 0000 0000
1,3,5-Tris-4 0 -200 -[3 0 0 0 -C-(2 ,3 ,4 ,6 -tetra-O-benzoyl-b- amidoxime 2 (794 mg, 1.24 mmol) in 1,4-dioxane (15 mL) was
000 000 000 000 0 0 0
D-glucopyranosyl)-1 ,2 ,4 -oxadiazol-5 -yl]-ethyl-1 ,2 ,3 - stirred at room temperature for 24 hours. The solvent was then
triazol-1 0 -ylmethylbenzene (8). In a CEM Discover 5 mL vial evaporated off and the mixture was diluted with EtOAc (150 mL).
was introduced a solution of 1,3,5-tris(azidomethyl)benzene The organic layer was washed by 100 mL portions of saturated
(POTENTIALLY EXPLOSIVE, 4.9 mg, 20 mmol), alkyne 4 NaHCO3, water and brine successively. The organic layer was
(63 mg, 90 mmol), copper iodide (1.9 mg, 10 mmol) and DIPEA dried (MgSO4), filtered and evaporated. The crude product was
(17 mL, 100 mmol) in toluene (6 mL). The solution was purified by flash silica gel column chromatography (EtOAc) to
sonicated for 1 min then heated at 110 1C for 15 min upon afford the O-acylamidoxime 10 (571 mg, 73%) as a white foam.
microwave irradiation (150 W). The solvent was evaporated Rf = 0.75 (PE/EtOAc, 3:7). [a]D = 48.6 (c = 1/CH2Cl2). 1H
off and the residue purified by flash silica gel column chromato- NMR (300 MHz, CDCl3) d 4.23–4.33 (m, 3H, H-50 ), 4.49–4.57
graphy (PE/EtOAc, 1:1 then EtOAc) to afford the tris- (m, 6H, H-1 0 H-6 0 a), 4.58–4.65 (m, 3H, H-60 b), 5.46 (bs, 6H,
cycloadduct 8 (46 mg, 98%) as a colorless oil. Rf = 0.67 NH2), 5.70 (t, 3H, J = 9.6 Hz, H-2 0 ), 5.76 (t, 3H, J = 9.6 Hz,
(EtOAc). 1H NMR (300 MHz, CDCl3) d 3.10–3.32 (m, 12H, H-40 ), 5.98 (t, 3H, J = 9.6 Hz, H-3 0 ), 7.22–7.58 (m, 36H, H-ar),
0000
H-100 H-200 ), 4.34–4.40 (m, 3H, H-5 ), 4.51 (dd, 3H, J = 5.1 7.80–8.04 (m, 24H, H-ar), 8.52 (s, 3H, H-2 H-4 H-6). 13C NMR
0000
Hz, J = 12.4 Hz, H-6 a), 4.66 (dd, 3H, J = 2.7 Hz, J = 12.4 (75 MHz, CDCl3) d 62.9 (C-6 0 ), 69.0 (C-4 0 ), 70.0 (C-2 0 ), 73.5
0000 0000
Hz, H-6 b), 5.12 (d, 3H, J = 9.4 Hz, H-1 ), 5.31 (s, 6H, (C-3 0 ), 75.6 (C-10 ), 76.8 (C-5 0 ), 128.3, 128.4, 128.5, 128.7, 129.3,
0000
NCH2C6H3), 5.87 (t, 3H, J = 9.4 Hz, H-4 ), 5.97 (t, 3H, J = 129.7, 129.8, 129.90, 129.94, 130.2 (10s, 20C, CH-ar), 133.3,
0000 0000
9.4 Hz, H-2 ), 6.05 (t, 3H, J = 9.4 Hz, H-3 ), 6.93 (s, 3H, 133.4, 133.6, 134.1 (4s, 4C, C-ar), 154.5 (H2NCQNO), 161.5
H-2 H-4 H-6), 7.23–7.50 (m, 36H, H-ar), 7.74–8.00 (m, 24H, (NOCQO), 165.2, 165.58, 165.63, 166.1 (4s, 4C, COPh). LSIMS
H-ar). 13C NMR (75 MHz, CDCl3) d 22.5 (s, 3C, C-100 ), 26.6 (positive mode, thioglycerol) m/z: 2071.6 [M + H]+. HR-ESI-
0000
(s, 3C, C-200 ), 53.1 (NCH2C6H3), 63.3 (s, 3C, C-6 ), 69.3 MS (positive mode) m/z: calcd. for C114H91N6O33 [M + H]+
0000 0000 0000
(s, 3C, C-4 ), 70.7 (s, 3C, C-2 ), 72.3 (s, 3C, C-1 ), 74.1 2071.5627, found 2071.5651.
0000 0000
(s, 3C, C-3 ), 77.0 (s, 3C, C-5 ), 122.2 (s, 3C, C-5 0 ), 127.0
(s, 3C, C-2, C-4, C-6), 128.39, 128.43, 128.5 (3s, 24C, CH-ar), 3,5-Bis[3 0 -C-(b-D-glucopyranosyl)-1 0 ,2 0 ,4 0 -oxadiazol-5 0 -yl]-
128.69, 128.71, 128.8, 129.5 (4s, 12C, CIV-ar), 129.7, 129.78, benzoic acid (12). A solution of tris-O-acylamidoxime 10
129.82, 129.9 (4s, 24C, CH-ar), 133.2, 133.4, 133.6 (3s, 12C, (532 mg, 256 mmol) in 1,4-dioxane (12 mL) was stirred at
CH-ar), 137.0 (s, 3C, C-1, C-3, C-5), 145.6 (s, 3C, C-4 0 ), 164.9, 100 1C for 4 days. The reaction was then cooled to room
165.2, 165.8, 166.2 (4s, 12C, COPh), 166.4 (s, 3C, C-3 0 0 0 ), temperature and the solvent evaporated off. The crude pro-
180.0 (s, 3C, C-5 0 0 0 ). ESI-MS (positive mode) m/z: 1173.5 duct 11 was used without further purification. A solution of
[M + 2H]2+. crude 11 (239 mg) and NaOMe (10 mg) in CH2Cl2/MeOH
(5 mL, 1:1) was stirred at room temperature for 5 hours. The
1,3,5-Tris-4 0 -200 -[30 0 0 -C-(b-D-glucopyranosyl)-1 0 0 0 ,2 0 0 0 ,40 0 0 -oxa- solvent was evaporated off and the crude mixture was purified
diazol-5 0 0 0 -yl]ethyl-1 0 ,2 0 ,3 0 -triazol-1 0 -ylmethylbenzene (9). A by flash reverse-phase silica gel chromatography (H2O then
solution of benzoylated tris-cycloadduct 8 (114 mg, 49 mmol) H2O/MeOH 7:3) to afford the benzoic acid derivative 12
and NaOMe (5 mg, 92 mmol) in CH2Cl2/MeOH (5.5 mL, 10:1) (95 mg, 58% over two steps) as a white foam. Rf = 0.20
was stirred at room temperature for 6 hours. The solution was (EtOAc/MeOH 1:1). [a]D = +7.1 (c = 0.41/MeOH). 1H
neutralized with a cation exchange resin (Amberlite IR-120, NMR (300 MHz, CDCl3) d 3.62–3.76 (m, 3H, H-300 , H-400 ,
H+ form) and resin washed with MeOH (3 5 mL). The H-500 ), 3.81–3.89 (m, 2H, H-200 , H-600 a), 3.99 (m, 1H, H-600 b),
filtrate was evaporated off and the residue was dissolved in 4.75 (m, 1H, H-100 ), 8.77 (s, 2H, H-ar), 8.87 (s, 1H, H-ar). 13C
MeOH then precipitated with PE. The resulting solid was NMR (75 MHz, CDCl3) d 61.2 (C-600 ), 69.7, 77.1, 80.8 (3s, 3C,
washed with PE (5 5 mL), dissolved into pure water and C-300 , C-400 , C-500 ), 72.1 (C-200 ), 73.4 (C-100 ), 124.7 (s, 2C,
freeze-dried to afford the hydroxylated tris-cycloadduct 9 CIV-ar), 126.9 (CIV-ar), 129.8 (CH-ar), 133.0 (s, 2C, CH-ar),

139.5 (CO2H), 168.4 (C-3 0 ), 175.8 (C-5 0 ). ESI-MS (negative glycogen phosphorylase were collected using different concen-
mode) m/z: 581 [M H]. HR-ESI-MS (negative mode) m/z: trations of a-D-glucose-1-phosphate (2–20 mM), constant
calcd for C23H25N4O14 [M H] 581.1367, found 581.1369. concentrations of glycogen (1% w/v) and AMP (1 mM), and
various concentrations of inhibitors. Inhibitors were dissolved
1,3,5-Tris[3 0 -C-(200 ,300 ,400 ,600 -tetra-O-benzoyl-b-D-glucopyra- in dimethyl sulfoxide (DMSO) and diluted in the assay buffer
nosyl)-1 0 ,2 0 ,4 0 -oxadiazol-5 0 -yl]benzene (13). In a CEM Discover (50 mM triethanolamine, 1 mM EDTA and 1 mM dithio-
5 mL vial was introduced a solution of O-acylamidoxime threitol) so that the DMSO concentration in the assay should
10 (454 mg, 0.22 mmol) and TBAF (70 mL, 70 mmol, 1 M in be lower than 5%. The enzymatic activities were presented in
THF) in toluene (5 mL). The reaction vial was heated the form of double-reciprocal plots (Lineweaver–Burk) apply-
at 150 1C for 40 min upon microwave irradiation (200 W). ing a nonlinear data analysis program. The inhibitor constants
The solvent was evaporated and the residue purified by (Ki) were determined by Dixon plots, by replotting the
flash silica gel column chromatography (PE then PE/EtOAc, slopes from the Lineweaver–Burk plots against the inhibitor
1:1) to afford the trivalent oxadiazole 13 (317 mg, 72%) as a concentrations.26,27 The means of standard errors for all
white foam. Rf = 0.79 (PE/EtOAc, 1:1). [a]D = 35.1 (c = calculated kinetic parameters averaged to less than 10%.
1.00/CH2Cl2). 1H NMR (300 MHz, CDCl3) d 4.41 (ddd, 3H, Ki values for compounds 9 and 14 were also estimated and
J = 3.1 Hz, J = 5.1 Hz, J = 9.5 Hz, H-500 ), 4.59 (dd, 3H, found to be 490 45 mM and 535 50 mM, respectively.
J = 5.2 Hz, J = 12.5 Hz, H-600 a), 4.71 (dd, 3H, J = 2.9 Hz, The poor solubility of inhibitors 5, 7 and 15 limited the
J = 12.5 Hz, H-600 b), 5.22 (d, 3H, J = 9.5 Hz, H-100 ), 5.91 concentrations used in the kinetic studies. The inhibition of
(t, 3H, J = 9.7 Hz, H-400 ), 6.04–6.15 (m, 6H, H-200 H-300 ), glycogen phosphorylase was therefore determined at 625 mM
7.26–7.52 (m, 36H, H-ar), 7.82–8.02 (m, 24H, H-ar), 8.96 and 2.5 mM concentrations of these inhibitors and given in
(s, 3H, H-2). 13C NMR (75 MHz, CDCl3) d 63.3 (s, 3C, Table 2.
C-600 ), 69.4 (s, 3C, C-400 ), 70.8 (s, 3C, C-200 ), 72.6 (s, 3C, C-100 ),
74.1 (s, 3C, C-300 ), 77.4 (s, 3C, C-500 ), 126.2 (s, 3C, C-1 C-3
C-5), 128.5, 128.5, 128.6 (3s, 24C, CH-ar), 129.9, 130.0 Acknowledgements
(2s, 24C, CH-ar), 131.3 (s, 3C, C-2 C-4 C-6), 133.3, 133.4, The authors wish to thank Université Claude Bernard Lyon 1
133.6, 133.6 (4s, 12C, CH-ar), 164.9, 165.2, 165.9, 166.3 and CNRS for financial support. A stipend to S. C. and
(4s, 12C, COPh), 167.6 (s, 3C, C-3 0 ), 174.1 (s, 3C, C-5 0 ). financial support from Région Rhône-Alpes )Cluster de
ESI-MS (positive mode) m/z: 2039.6 [M + Na]+. Recherche Chimie* are gratefully acknowledged. CNRS is
also thanked for additional funding through )Programme
1,3,5-Tris[3 0 -C-b-D-glucopyranosyl)-1 0 ,2 0 ,4 0 -oxadiazol-5 0 -yl]- Interdisciplinaire: Chimie pour le Développement Durable*.
benzene (14). A solution of benzoylated tris-oxadiazole 13 (296 This work was also supported by grants from the Hungarian
mg, 0.15 mmol) and NaOMe (15 mg, 0.3 mmol) in CH2Cl2/ Science Research Fund (OTKA K60620) and the Hungarian
MeOH (8 mL, 3:5) was stirred at room temperature for 3 Ministry of Health (ETT 083/2006).
hours. The solution was neutralized with a cation exchange
resin (Amberlite IR-120, H+ form) and the resin washed with
MeOH (3 5 mL). The filtrate was evaporated off and the References
residue was dissolved in MeOH then precipitated with 1 (a) S. Wild, G. Roglic, A. Green, R. Sicree and H. King, Diabetes
CH2Cl2. The resulting solid was washed with CH2Cl2 (2 Care, 2004, 27, 1047; (b) P. Zimmet, K. G. M. M. Alberti and
5 mL) and dried under vacuum to afford the hydroxylated tris- J. Shaw, Nature, 2001, 414, 782.
2 (a) D. E. Moller, Nature, 2001, 414, 821; (b) N. Morral, Trends
oxadiazole 14 (114 mg, 99%) as a white foam. Rf = 0.63
Endocrinol. Metab., 2003, 14, 169; (c) L. Agius, Best Pract. Res.
(CH2Cl2/MeOH, 9:1). [a]D = +10.6 (c = 1.00/H2O). 1H Clin. Metab., 2007, 21, 587.
NMR (300 MHz, D2O) d 3.61–3.84 (m, 15H, H-200 H-300 3 (a) B. R. Henke, J. Med. Chem., 2004, 47, 4118; (b) C. Fievet,
H-400 H-500 H-600 a), 3.97 (d, 3H, J = 11.9 Hz, H-600 b), 4.67 J.-C. Fruchart and B. Staels, Curr. Opin. Pharmacol., 2006, 6, 606.
4 (a) L. B. Knudsen, J. Med. Chem., 2004, 47, 4128; (b) M. A. Nauck
(d, 3H, J = 9.4 Hz, H-100 ), 8.74 (s, 3H, H-2 H-4 H-6). 13C and J. J. Meier, Regul. Pept., 2005, 128, 135.
NMR (75 MHz, D2O) d 59.0 (s, 3C, C-600 ), 71.0 (s, 3C, C-100 ), 5 (a) A. E. Weber, J. Med. Chem., 2004, 47, 4135; (b) A. Barnett, Int.
67.4, 69.9, 74.9, 78.6 (4s, 12C, C-200 C-300 C-400 C-500 ), 123.5 J. Clin. Pract., 2006, 60, 1454; (c) D. J. Drucker, Diabetes Care,
(s, 3C, C-1 C-3 C-5), 129.2 (s, 3C, C-2 C-4 C-6), 166.5 (s, 3C, 2007, 30, 1335.
6 (a) B. J. Goldstein, J. Clin. Endocrinol. Metab., 2002, 87, 2474;
C-3 0 ), 172.0 (s, 3C, C-5 0 ). ESI-MS (negative mode) m/z: (b) R. Hooft van Huijsduijnen, W. H. B. Sauer, A. Bombrun and
812.9 [M + HCO2]. ESI-MS (positive mode) m/z: 791.7 D. Swinnen, J. Med. Chem., 2004, 47, 4142; (c) L. Bialy and
[M + Na]+. HR-ESI-MS (positive mode) m/z: calcd. for H. Waldmann, Angew. Chem., Int. Ed., 2005, 44, 3814.
7 (a) J. L. Treadway, P. Mendys and D. J. Hoover, Exp. Opin. Invest.
C30H36N6NaO18 [M + Na]+ 791.1984, found 791.1981. Drugs, 2001, 10, 439; (b) N. G. Oikonomakos, Curr. Protein Pept.
Sci., 2002, 3, 561; (c) L. Somsak, V. Nagy, Z. Hadady, T. Docsa
Glycogen phosphorylase inhibition measurements and P. Gergely, Curr. Pharm. Des., 2003, 9, 1177; (d) D. J. Baker,
J. A. Timmons and P. L. Greenhaff, Diabetes, 2005, 54, 2453;
Glycogen phosphorylase b was prepared from rabbit skeletal (e) L. Somsák, V. Nagy, Z. Hadady, N. Felfoldi, T. Docsa and
muscle according to the method of Fischer and Krebs,24 using P. Gergely, Front. Med. Chem., 2005, 2, 253; (f) N. G.
dithiothreitol instead of L-cysteine, and recrystallized at least Oikonomakos and L. Somsák, Curr. Opin. Invest. Drugs, 2008,
three times before use. Kinetic experiments were performed in 9, 379.
8 (a) R. J. Fletterick and S. R. Sprang, Acc. Chem. Res., 1982, 15,
the direction of glycogen synthesis as described previously.25 361; (b) S. R. Sprang, K. R. Acharya, E. J. Goldsmith, D. I. Stuart,
Kinetic data for the inhibition of rabbit skeletal muscle K. Varvill, R. J. Fletterick, N. B. Madsen and L. N. Johnson,
This journal is
Nature, 1988, 336, 215; (c) D. Barford and L. N. Johnson, Nature, 13 K. G. Watson, R. Cameron, R. J. Fenton, D. Gower, S. Hamilton,
1989, 340, 609; (d) N. G. Oikonomakos, V. T. Skamnaki, B. Jin, G. Y. Krippner, A. Luttick, D. McConnell, S. J. F.
K. E. Tsitsanou, N. G Gavalas and L. N. Johnson, Structure, MacDonald, A. M. Mason, V. Nguyen, S. P. Tucker and
2000, 8, 575. W.-Y. Wu, Bioorg. Med. Chem. Lett., 2004, 14, 1589–1592.
9 (a) N. G. Oikonomakos, J. B. Schnier, S. E. Zographos, 14 Y. Lu and J. Gervay-Hague, Carbohydr. Res., 2007, 342,
V. T. Skamnaki, K. E. Tsitsanou and L. N. Johnson, J. Biol. Chem., 1636–1650.
2000, 275, 34566; (b) M. N. Kosmopoulou, D. D. Leonidas, 15 Y. F. Han, C. P.-L. Li, E. Chow, H. Wang, Y.-P. Pang and
E. D. Chrysina, N. Bischler, G. Eisenbrand, C. E. Sakarellos, P. R. Carlier, Bioorg. Med. Chem., 1999, 7, 2569–2575.
R. Pauptit and N. G. Oikonomakos, Eur. J. Biochem., 2004, 16 (a) B. A. Johns and C. R. Johnson, Tetrahedron Lett., 1998, 39,
271, 2280; (c) T. Klabunde, K. U. Wendt, D. Kadereit, 749; (b) A. Lohse, K. B. Jensen, K. Lundgren and M. Bols, Bioorg.
V. Brachvogel, H. J. Burger, A. W. Herling, N. G. Oikonomakos, Med. Chem., 1999, 7, 1965.
M. N. Kosmopoulou, D. Schmoll, E. Sarubbi, E. von Roedern, 17 N. Schaschke, G. Matschinerb, F. Zettlb, U. Marquardta,
K. Schonafinger and E. Defossa, J. Med. Chem., 2005, 48, 6178; A. Bergnera, W. Bodea, C. P. Sommerhoff and L. Moroder, Chem.
(d) B. R. Henke and S. M. Sparks, Mini-Rev. Med. Chem., 2006, 6, 845; Biol., 2001, 8, 313–327.
(e) D. J. Baker, P. L. Greenhaff and J. A. Timmons, Exp. Opin. Ther. 18 V. L. Rath, M. Ammirati, D. E. Danley, J. L. Ekstrom,
Pat., 2006, 16, 459; (f) A. M. Birch, P. W. Kenny, N. G. Oikonomakos, E. M. Gibbs, T. R. Hynes, A. M. Mathiowetz, R. K. McPherson,
L. Otterbein, P. Schofield, P. R. O. Whittamore and D. P. Whalley, T. V. Olson, J. L. Treadway and D. J. Hoover, Chem. Biol., 2000, 7,
Bioorg. Med. Chem. Lett., 2007, 17, 394. 677–682.
10 (a) N. G. Oikonomakos, M. N. Kosmopoulou, S. E. Zographos, 19 L. Somsak and V. Nagy, Tetrahedron: Asymmetry, 2000, 11,
D. D. Leonidas, E. D. Chrysina, L. Somsak, V. Nagy, J.-P. Praly, 1719–1727.
T. Docsa, B. Toth and P. Gergely, Eur. J. Biochem., 2002, 269, 20 A. R. Gangloff, J. Litvak, E. J. Shelton, D. Sperandio, V. R. Wang
1684; (b) M. Benltifa, S. Vidal, B. Fenet, M. Msaddek, and K. D. Rice, Tetrahedron Lett., 2001, 42, 1441–1443.
P. G. Goekjian, J.-P. Praly, A. Brunyánszki, T. Docsa and 21 Y. Wang, R. L. Miller, D. R. Sauer and S. W. Djuric, Org. Lett.,
P. Gergely, Eur. J. Org. Chem., 2006, 4242; (c) M. Benltifa, 2005, 7, 925–928.
S. Vidal, D. Gueyrard, P. G. Goekjian, M. Msaddek and 22 (a) R. Huisgen, R. Knorr, L. Möbius and G. Szeimies, Chem. Ber.,
J.-P. Praly, Tetrahedron Lett., 2006, 47, 6143; (d) L. He, 1965, 98, 4014; (b) R. Huisgen, G. Szeimies and L. Möbius, Chem.
Y. Z. Zhang, M. Tanoh, G.-R. Chen, J.-P. Praly, Ber., 1967, 100, 2494; (c) R. Huisgen, K. Fraunberg and
E. D. Chrysina, C. Tiraidis, M. Kosmopoulou, D. D. Leonidas H. J. Sturm, Tetrahedron Lett., 1969, 10, 2589; (d) V. V.
and N. G. Oikonomakos, Eur. J. Org. Chem., 2007, 596. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew.
11 H. L. Handl, J. Vagner, H. Han, E. Mash, V. J. Hruby and Chem., Int. Ed., 2002, 41, 2596; (e) C. W. Tornoe, C. Christensen
R. J. Gillies, Exp. Opin. Ther. Targets, 2004, 8, 565–586. and M. Meldal, J. Org. Chem., 2002, 67, 3057.
12 (a) S. J. F. Macdonald, K. G. Watson, R. Cameron, 23 T. M. Garrett, T. J. McMurry, M. W. Hosseini, Z. E. Reyes,
D. K. Chalmers, D. A. Demaine, R. J. Fenton, D. Gower, F. E. Hahn and K. N. Raymond, J. Am. Chem. Soc., 1991, 113,
J. N. Hamblin, S. Hamilton, G. J. Hart, G. G. A. Inglis, B. Jin, 2965–2977.
H. T. Jones, D. B. McConnell, A. M. Mason, V. Nguyen, 24 E. H. Fischer and E. G. Krebs, Methods Enzymol., 1962, 5, 369.
I. J. Owens, N. Parry, P. A. Reece, S. E. Shanahan, D. Smith, 25 N. G. Oikonomakos, V. T. Skamnaki, E. Osz, + L. Szilágyi,
W.-Y. Wu and S. P. Tucker, Antimicrob. Agents Chemother., 2004, L. Somsák, T. Docsa, B. Tóth and P. Gergely, Bioorg. Med.
48, 4542; (b) S. J. F. MacDonald, R. Cameron, D. A. Demaine, Chem., 2002, 10, 261.
R. J. Fenton, G. Foster, D. Gower, J. N. Hamblin, S. Hamilton, +
26 E. Osz, L. Somsák, L. Szilágyi, L. Kovács, T. Docsa, B. Tóth and
G. J. Hart, A. P. Hill, G. G. A. Inglis, B. Jin, H. T. Jones, P. Gergely, Bioorg. Med. Chem. Lett., 1999, 9, 1385.
D. McConnell, J. McKimm-Breschkin, G. Mills, V. Nguyen, 27 L. Somsák, L. Kovács, M. Tóth, E. Osz, + L. Szilágyi,
I. J. Owens, N. Parry, S. E. Shanahan, D. Smith, K. G. Watson, Z. Györgydeák, Z. Dinya, T. Docsa, B. Tóth and P. Gergely,
W.-Y. Wu and S. P. Tucker, J. Med. Chem., 2005, 48, 2694. J. Med. Chem., 2001, 44, 2843.

The formation of silver nanofibres by liquid/liquid interfacial reactions:

mechanistic aspects
Kun Luo and Robert A. W. Dryfe*
Received (in Montpellier, France) 9th June 2008, Accepted 22nd August 2008
First published as an Advance Article on the web 23rd October 2008
DOI: 10.1039/b809654f
The liquid/liquid interfacial reaction (LLIR) between silver nitrate in aqueous solution and
ferrocene in organic solution has been investigated: the resultant silver deposit is found to contain
long, well-defined nanometre scale fibres, together with thin silver nanowire networks. In situ
optical microscopy and ex situ scanning electron microscopy indicate that the 1D growth of the
interfacial deposits is due to recrystallisation of the structure formed initially. Geometric factors
are found to exert a larger effect on the 1D growth of silver by LLIRs compared to the
electrochemical mechanism previously suggested by Scholz et al.
1. Introduction disulfide boundary. In this case, particles can either be formed,

or pre-formed particles can be assembled,17 at the L/L inter-
Nanostructures (i.e. structures with at least one dimension in face. A surprising variation in particle morphology has been
the range of 1 to 100 nm) have attracted increasing attention reported at the L/L interface. Most interfacial deposits appear
because of their unusual chemical and physical properties. to consist of spherical NPs, which assemble to form films, or
There has been particular interest in methods of forming aggregate into larger structures if no stabilising ligands are
one dimensional (1D) nanostructures, including nanowires, present.18,19 The intrinsic difficulty in studying the larger-scale
because such structures provide a better model system for structure is in finding an appropriate microscopic technique to
investigating the dependence of electronic transport, optical probe particle morphology in situ. Recent studies have des-
and mechanical properties on size confinement and dimen- cribed the preparation of well-defined metal and metal oxide
sionality.1 Strategies for achieving 1D growth have been NPs at the toluene/water interface, with X-ray scattering being
summarized by Xia et al.,2 these include: (i) use of the used to study the nanometre-scale assembly of Au NPs into an
intrinsically anisotropic crystallographic structure of a solid;3 ordered interfacial film.20,21 Silver deposition by LLIR, the
(ii) introduction of a liquid/solid interface to reduce the focus of this manuscript, has been described in a number of
symmetry of a seed;4 or use of supersaturation control to previous reports. Silver assembly (as opposed to formation) in
modify the growth habit of a seed;5 (iii) use of various the presence of surfactants at the water/dichloromethane
templates with 1D morphologies to direct the formation of interface produces a ‘‘metal liquid-like film’’,22 whose struc-
nanostructures6–9 (iv) assembly of zero dimensional nano- ture has been described as micron-scale flocs of silver NPs.23,24
structures (i.e. nanoparticles);10 (v) use of appropriate capping Assembly of silver NPs at an aqueous/chloroform interface in
reagent(s) to kinetically control the growth rates of various the presence of thiol species has also been described.25 Other
facets of a seed.11,12 Another interface, the liquid/liquid (L/L) reports have suggested that more unusual structures are ob-
interface, can also be used to limit the growth of materials, as served for Ag assembly and/or deposition at the L/L interface.
in (ii) above, or to assemble the symmetry of nanoparticles Agitation of aqueous silver hydrosols, during their assembly at
(NPs), as in (iv) above, where liquid/liquid interfacial reactions the water/toluene interface, has been reported to form
(LLIRs) are involved. ‘‘2D networks of uniform diameter nanowires’’.26 The forma-
Metal NPs can be grown at the L/L interface either electro- tion of silver deposits, by interfacial reduction with an organic
chemically, by applying a voltage across the L/L interface phase electron donor, gives rise to intergrown ‘‘whisker’’
when sufficient electrolytes are present in each phase,13 or by structures, although in this case the geometry is not uniform.27
spontaneous chemical reaction where the electron exchange The latter article noted that a transition between 1D and 2D
between redox couples present in the oil and water phases is growth could be tuned according to the experimental condi-
normally accompanied with biphasic ion exchange. Using the tions of the spontaneous LLIR. By choosing appropriate
former approach, gold NPs,14 platinum NPs15 and pyrrole organic solvents and concentrations of the reagents in the
oligomers16 have been prepared electrochemically at the inter- two phases, either silver whiskers (with radii from about 50 nm
face between immiscible electrolyte solutions. The second to 50 microns) or ultrathin Ag films were observed. Herein, we
approach, using spontaneous deposition, can be traced back present further investigations into the spontaneous LLIR
to Faraday’s formation of colloidal gold at the water/carbon between Fc in various organic solvents and aqueous AgNO3
solutions, where long and well-defined Ag nanofibres were
found under appropriate reaction conditions. The morpholo-
School of Chemistry, University of Manchester, Oxford Road,
Manchester, UK M13 9PL. E-mail: robert.dryfe@manchester.ac.uk; gical evolution and reaction mechanism are also discussed,
Fax: +44 (0)161 275 4734 based on the micrographic observations.
This journal is
2. Experimental
Silver nitrate (AgNO3, BDH Chemicals, GPR), ferrocene
(Fc, 99%, Alfa Aesar), 1,2-dichoroethane (DCE, Rathburn,
HPLC), nitrobenzene (NB, 99%, Sigma) and toluene
(99%, Fisher Scientific) were used directly without further
treatment. Typically, 3.3 mM of silver nitrate solution was
prepared with deionised water from an Elga ‘‘Purelab Ultra’’
(Elga, Marlow, UK) system. Ferrocene was dissolved in DCE,
or other organic solvents, as the organic phase for the inter-
facial reactions. The aqueous solution of AgNO3 and one of
the organic Fc solutions were placed together in a glass tube
with dimensions 75 mm (height) 25 mm (diameter), follow-
ing the sequence that the higher density phase was added prior
to the light one. The mixture was then kept still at ambient
temperature. The interfacial deposit was collected after 48 h of
reaction, and transferred onto glass slides and dried in air. It Fig. 1 Optical micrographs recorded during the formation of Ag
was then washed with acetone and deionised water separately, interfacial deposits by LLIR: (a) at ca. 1 min, (b) at 5 min, (c) at
25 min, (d) at 1 h, (e) at 24 h, (f) at 48 h. The length of the scale bars in
and dried at ambient temperature before further analysis.
the figure is 50 microns.
Copper grids with holey carbon films (S147-4, Agar Scientific)
were employed to collect samples for analysis via transmission
electron microscopy (TEM) and high resolution transmission bit denser compared to Fig. 1(e) when the reaction time was
microscopy (HRTEM). The samples were rinsed with both extended to 48 h (shown in Fig. 1(f)), but no visible fibre-like
acetone and deionised water, and were dried in air in order to deposit was found under the optical microscopy. The process
remove the remained contaminants. was also investigated ex situ by SEM, and the morphological
In situ optical microscopy was performed by a Leica DMIL evolution of the Ag deposit is illustrated by Fig. 2, although an
optical microscope fitted with a Sony CCD-IRIS camera on important point to note here is that the extraction and drying
an anti-vibration system (Active vibration isolation system of the sample could induce changes in morphology. The
TS-200, HWL Scientific Instruments GmbH). The X-ray interfacial deposit seen after twenty five minutes of reaction
diffraction (XRD) analysis was carried out using an Oxford appeared as micron-scale ‘‘flakes’’ with a few nuclei on the
Diffraction System (Xcalibur 2, Mo-Ka = 0.7093 Å), and XL surface as displayed in Fig. 2(a), indicative of a possible
30 FEG Philips and ESEM XL30 Philips electron microscopes destruction of an originally compact 2D interfacial layer
were employed at 15 kV for scanning electron microscopy during the sample collection. After 1 h of the reaction, some
(SEM). TEM and HRTEM were performed with a Tecnai F30 1D Ag deposits can be differentiated from others (see
FEG-TEM system operating at 300 kV. Fig. 2(b)). After 4 h of reaction (Fig. 2(c)), some of the
‘‘microflakes’’ are found with holes and irregular edges in
3. Results the background and co-exist with the 1D Ag nanostructures,
which are not seen at shorter or longer reaction times. After 48
The deposition of Ag resulting from the LLIR between h, long Ag nano-scale fibres are observed, as illustrated in
AgNO3 in water and Fc in organic solvent can be written as:27 Fig. 2(d), together with some short 1D nanostructures and
‘‘microflakes’’. The inset shows that the nanofibre is rather
Fc(o) + Ag+(w) + X(w) - Fc+(o) + X(o) + Ag(s) (1)
smooth and well-defined at a larger magnification. The Ag
where the subscripts ‘‘s’’, ‘‘w’’, and ‘‘o’’ in the reactions nanofibres shown in Fig. 2(d) are measured and give an
represent interfacial, aqueous and organic phases, respectively, average diameter of 171 4 nm (N = 13) with a mean aspect
and the anion X is added to balance the charge since no Fc+ ratio of ca. 174, where the largest aspect ratio from the other
transfer to the aqueous phase was believed to occur (in the micrographs is observed to be ca. 450. Fig. 2(e) further reveals
experiments reported herein, X is nitrate). The reaction was that the growth of the nanofibres originates from defects, such
monitored in situ by an optical microscope placed on the active as independent nuclei or the edges of the ‘‘microflakes’’ etc.
anti-vibration system. As shown in Fig. 1(a), at the beginning TEM and HRTEM micrographs offer the means of observa-
of the reaction (ca. 1 min), only separate particles were tion under higher magnification. Fig. 3(a) suggests that some
observed at the L/L interface. Many particles were rapidly of the ‘‘microflakes’’ observed under SEM are actually com-
generated, and started aggregating, after about five minutes of posed of networks of thinner 1D nanostructures, termed
contact between the two phases (Fig. 1(b)). After 10 min, ‘‘nanowires’’ in the following text, with an average diameter
fractal-like aggregates appeared at the interface, as illustrated of 14.8 3.7 nm (N = 163), where the distribution of the
by Fig. 1(c), and the fluidity at the interface became obstructed diameter values visible in Fig. 3(a) is shown in Fig. 3(b).
after 25 min of reaction, owing to the appearance of large Ag Fig. 3(a) also illustrates the evolution from the 2D film to
agglomerates (see Fig. 1(d)). After 24 h of reaction (Fig. 1(e)), 1D nanostructures, where a few branches of nanowires are
the L/L interface became somewhat solidified, and a grey observed to extend from a piece of film higlighted by the circle
coloured deposit was seen. The interfacial deposits became a in the figure. The triangular highlights in Fig. 3(c) suggest that

Fig. 2 SEM micrographs of the Ag interfacial deposits collected at different times during the LLIR process: (a) at 25 min, (b) at 1 h, (c) at 4 h,
(d) at 48 h, the inset shows the diameter of the nanowire is around 100–200 nm; (e) at 48 h, 1D growth stems from the defects of the interfacial deposit.
fringes under TEM (circular highlight). The HRTEM image in

Fig. 3(d) indicates that the wires are nanocrystalline. From the
micrographs presented in Fig. 2 and 3, one can summarize that
the microflakes (the 2D growth owing to the presence of the
L/L interface) are formed in the early stages of the LLIR, a
process followed by 1D growth at the active sites of the
interfacial layer after a long-term LLIR, such as the edge of
the layer or the tips of triangular nuclei. The intermediate
stage (holey microflakes with irregular edges displayed in
Fig. 2(c)) at 4 h of the LLIR, suggests the appearance of a
parallel process which might be either the dissolution of the
as-formed microflakes; alternatively the secondary aggrega-
tion or growth of the nuclei may occur, to form thin nanowire
networks shown in Fig. 3(a). Considering that complete
microflakes and nanofibres are seen in the SEM micrographs
at 48 h of the LLIR, and the nanowire networks can only be
seen under TEM, the visible networks in Fig. 3(c) would
appear to arise from the dissolution of the as-formed 2D
layers. The LLIR process is therefore viewed as involving:
(i) formation of Ag nuclei at the L/L interface; (ii) agglomera-
tion of the as-prepared Ag nuclei to form 2D flakes due to the
Fig. 3 TEM and HRTEM micrographs of the Ag interfacial deposit
constraint of the L/L interface; (iii) dissolution of some of the
of the LLIR reaction between 3.3 mM AgNO3 aqueous solution and
initial Ag nuclei while secondary nucleation or growth occurs
5 mM Fc in DCE at 48 h: (a) nanowire networks in the deposit, the
highlighted part shows the 1D growth from a piece of a 2D thin film, elsewhere. Some of the larger 2D structures can even be
(b) distribution of the diameter of the nanowires, (c) the connection of dissolved if the nuclei are depleted; (iv) the structural defects,
the nanowires, the parts highlighted with ‘‘&’’ indicate that nanowires including the tips of the triangular nuclei, independent nuclei
protrude from portions that were originally nanoparticulate. The and the edges of the microflakes, offer active sites for new
other parts highlighted with ‘‘J’’ denote the ‘‘welding’’ positions of nucleation, leading to 1D growth. The diameter of the 1D
the nanowires; (d) HRTEM image of the nanowires, which indicates nanostructures is normally dependant on the size of the
the nanowires are composed of crystalline silver. protuberance of the defects, for example larger nuclei for the
nanofibres, compared to the corner of the smaller triangular
the growth of the nanowires originates from the triangular nuclei for the nanowires.
nuclei, and the 1D extension from the nuclei is ‘‘welded’’ on Different organic solvents, such as NB and toluene, were
meeting other wires as shown by the appearance of lattice used instead of DCE in the LLIR process. A thin and
This journal is
structures are observed with the presence of ‘‘microflakes’’.
In contrast, no 1D growth is seen after the LLIR between
3.3 mM AgNO3 solution and 5 mM Fc in toluene, but only
smoother ‘‘microflakes’’ are shown in Fig. 5(b) under SEM.
The X-ray diffraction patterns of the Ag interfacial deposits
formed by the LLIRs between 3.3 mM AgNO3 solution and
5 mM Fc in DCE, NB and toluene are presented in Fig. 6.
Reflections assigned to Ag (111), (200), (220), (311), (222)
planes are marked in the plot (Fm3m, a = 4.08 Å, JCPDF No.
02-1167). The crystallite size is estimated from the broadening
of X-ray diffraction peaks by Scherrer’s equation:28
Bcrystallite = kl/(L cos y) (2)
where l is the wavelength of the X-ray, y is the Bragg angle,
L is the average crystallite size measured in a direction
perpendicular to the surface of the specimen, and k is a
constant taken to be 0.9. The crystallite size calculated from
the (111) reflection of the interfacial deposit of DCE/water
system is 2.2 nm, which is the same as that in the toluene/water
system. The crystallite size for the interfacial deposit from the
Fig. 4 The Ag film obtained by interfacial reaction between 3.3 mM NB/water system is 3.1 nm. Other polar and nonpolar organic
AgNO3 aqueous solution and 1 mM Fc in NB (after reaction for 24 h): solvents, such as 1,2-dichlorobenzene and silicone oil (data not
(a) in Teflon container, (b) in glass container, (c) stopped half-way shown), were also employed to perform the LLIR with the
owing to the depletion of AgNO3 in glass container, (d) the LLIR in a same concentrations of reactants, and the morphology of the
glass container on an active anti-vibration table. interfacial deposits also follows the same trend, in that polar
organic solvents favour the formation of 1D Ag deposits at
continuous film was observed at the NB/water interface in a L/L interfaces.
Teflon container after 24 h of LLIR between 3.3 mM AgNO3 The effect of varying the concentrations of the reagents was
solution and 1 mM Fc in NB (see Fig. 4(a)), in accordance investigated. As shown in Fig. 7(a) and (b), a lower concentra-
with the results described by Scholz and Hasse.27 In contrast, a tion of AgNO3 solutions was employed to react with 5 mM Fc
radial pattern gradually appeared after a period of time in a in DCE. The 0.33 mM AgNO3 (c+Ag/cFc = 0.066) exhibited a
glass container (see Fig. 4(b)), in possible association with tendency to 1D growth, while the 0.07 mM AgNO3 solution
random vibrations. The pattern was quite stable over time, (c+Ag/cFc = 0.014) basically formed Ag aggregates. If the
and exhibited a ‘‘self-recovery’’ capability from external dis- concentration of Fc was varied, as illustrated in Fig. 7(c) and
ruption of the interface. If the LLIR was forced to stop ‘‘half (d), 1D growth could be seen but was not fully developed
way’’ by the depletion of the silver salt, a ring-like thin film in the case of 3.3 mM AgNO3 solution reacted with 0.5 mM
extending from the surface of the glass tube with some (c+Ag/cFc = 6.6) and with 0.1 mM Fc in DCE (c+Ag/cFc = 33).
irregular deposit in the centre was seen, indicative of the The influence of the organic solvent on the resultant composi-
adhesion of Ag nuclei on the hydrophilic surface of glass (as tion of the aqueous phase was also investigated via the visible
shown in Fig. 4(c)). Fig. 4(d) shows that no pattern appeared if absorbance of the aqueous phase (Fig. 8). The toluene/water
the LLIR was carried out on an active anti-vibration table for system shows the highest transfer of Fc+ to water, whereas the
48 h. Hence, the pattern shown in Fig. 4(b) can be interpreted NB/water displays the weakest spectral response. The transfer is
in terms of: (i) the adsorption of the initial Ag nuclei on the also found to be proportional to the concentration of Fc
surface of glass tube; (ii) growth of the Ag deposit to form a employed in the DCE solutions (data not shown).
ring-like interfacial deposit layer as shown in Fig. 4(c); (iii) this
process continues and consequently the interfacial layer is able
to cover the whole L/L interface; (iv) vibrations cause standing
4. Discussion
waves to form at the L/L interface, and the interfacial layer is Scholz and Hasse27 have proposed an electrochemical mecha-
then easily folded since its outer edge is ‘‘pinned’’ to the nism for the deposition of silver via LLIR, where the reaction
surface of the glass container. However, when the Ag nuclei occurs at the L/L interface (see eqn (1), above). In the
are adjacent to the Teflon surface, no adsorption occurs, and treatment of Scholz et al., the nuclei at the L/L interface were
the Ag layer formed by the LLIR ‘‘floats’’ on the L/L inter- viewed as disc-shaped microelectrodes, where the current (i) to
face, hence no such standing waves are set up. Consequently the equivalent disc-shaped silver/electrolyte interface was
no radial pattern appeared after 48 h of reaction. described by:
The microstructure of the interfacial deposits in water/NB
4Da
and water/toluene was observed under SEM. Fig. 5(a) shows idisc ¼ nFAdisc ca ð3Þ
that the interfacial deposit collected from the NB/water inter- pr
face displays an analogous microstructure to that in Fig. 2(d). where n is the number of electrons transferred, F is the
Long and well-defined nanofibres and other short 1D nano- Faraday constant, Adisc is the surface area of the disc, ca and

Fig. 5 SEM micrographs of the Ag interfacial deposits at different LLIR systems: (a) 3.3 mM AgNO3 aqueous solution with 5 mM Fc in NB,
(b) 3.3 mM AgNO3 aqueous solution with 5 mM Fc in toluene.
Da the bulk concentration and diffusion coefficient of

species a, respectively, and r is the radius of the disc. When
the same crystal is growing in a 1D mode, a cylinder electrode
was used by Scholz and Hasse to approximate the current flow
across the silver/liquid interface:
2Da
icyl ¼ nFAcyl ca ð4Þ
r ln t
where t = Dat/r2, and t is the time. Acyl and r are the surface
area and radius of the cylinder, respectively. Since the oxida-
tive process (oxidation of Fc) should balance the reductive one
(reduction of Ag+) at all times, Scholz and Hasse assumed the
1D Ag structure must protrude into the organic phase for the
above-named fluxes to balance under conditions of excess
silver ion, since equating (3) and (4) leads to:
Fig. 6 X-Ray diffraction patterns of the Ag interfacial deposits by the

LLIR between 3.3 mM AgNO3 aqueous solution and 5 mM Fc in (a) Acyl cAgþ ðwÞ 2DAgþ ln t
¼ ð5Þ
DCE, (b) NB and (c) toluene. Adisc cFcðoÞ DFc p
Fig. 7 SEM micrographs of the Ag interfacial deposits as a function of reagent concentration: (a) 0.33 mM AgNO3 aqueous solution with 5 mM
Fc in DCE, (b) 0.07 mM AgNO3 aqueous solution with 5 mM Fc in DCE, (c) 3.3 mM AgNO3 aqueous solution with 0.5 mM Fc in DCE,
(d) 3.3 mM AgNO3 aqueous solution with 0.1 mM Fc in DCE.
This journal is
mechanism being postulated for the 1D growth mode. Ag
nuclei are initially generated by the spontaneous LLIR, and
form a 2D interfacial layer because of the constraint of the L/L
interface. After that, a transformation from 2D layers to 1D
nanostructures occurs as a higher flux of reactants to
the deposit can be sustained by radial diffusion.30 Con-
sequently, parts of the 2D structures appear to dissolve,
accompanied with the emergence of 1D nanostructures. The
1D growth is observed to occur at active sites with high
surface energy, such as independent nuclei, the edges of 2D
structures or the corner of the small triangular crystals,
which show surprisingly well-defined long nanofibres without
any branches. Nanowires from the Ag triangular crystals
can even connect to form nanowire networks. The evolution
of the 1D process is, however, suppressed in less polar
solvents since it requires the (unfavourable) formation of a
Fig. 8 UV-Vis absorbance spectra of the aqueous solutions recorded
ferrocenium nitrate ion pair in the organic phase, by transfer
after 48 h of LLIR between 3.3 mM AgNO3 aqueous solution and
of the nitrate, or the transfer of the ferrocenium to the aqueous
5 mM Fc in (a) toluene, (b) DCE and (c) NB, respectively (deionised
water as reference). The absorbance maximum of Fc+ appears at
phase. The latter process is more favourable, but the extent of
about 620 nm. transfer depends on the distance from the interface where the
ferrocenium ion is formed. In the case of a 2D Ag deposit,
where DAg+ and DFc are the diffusion coefficients of Ag+ in the ferrocenium ion is formed adjacent to the interface
the aqueous phase and Fc in the organic phase, respectively. and is readily transferred. By contrast, if 1D growth occurs,
Eqn (5) indicates that the higher concentration ratio of Ag+ to the ferrocenium ion may be formed some distance from the
Fc increases the ratio of Acyl to Adisc and favours 1D growth, aqueous phase (a distance determined by the length of
whereas the converse case should lead to 2D films. Note that the structure). We therefore suggest that the driving force
the Ag+ reduction can occur at a site distant from Fc behind the morphological change observed in the deposit is the
oxidation, if the electrical conductivity of the deposit is solvation of the ions formed by the LLIR.
sufficient.
The data presented in Fig. 7 act as experimental tests of 5. Conclusions
eqn (5): from inspection of the deposits, it is clear that the
initial concentration ratio of the LLIR is not the sole factor The liquid/liquid interfacial reaction (LLIR) between silver
controlling deposit morphology (cf. eqn (5)), and the concen- nitrate in aqueous solution and ferrocene in various organic
tration of AgNO3 itself actually exerts a large effect on the solvents has been investigated: long and well-defined silver
final deposit. Combined with the observation (in Fig. 3) that nanofibres and thin nanowire networks were obtained in more
no 1D Ag nanostructures were found in the first 25 min of the polar media. In situ optical microscopy and ex situ scanning
LLIR, which also suggests that a secondary crystallisation step electron microscopy indicate that the 1D growth of the inter-
is involved in the 1D growth, this leads to the conclusion that facial deposits is due to directed recrystallization, where geo-
the actual mechanism is more complicated than the simple metric factors associated with the flux to the growing deposit,
electrochemical process suggests. However, the experiments and energetic factors, associated with the solvation of the ions
on the effect of organic solvents demonstrate that the use of generated, play an important role.
non-polar solvents suppressed the formation of 1D structures.
The morphological evolution seen here suggests that 2D thin Acknowledgements
films are formed initially at the L/L interface, followed with a
transformation from 2D to 1D growth, in the case of more The authors thank the financial support from the UK
polar organic solvents. Engineering & Physical Science Research Council (EPSRC,
The spontaneous LLIR between Fc in the organic phase and grant EP/C509773/1).
Ag+ in the aqueous solution initially generates Ag nuclei. An
associated transfer of Fc+ from the organic phases (i.e. DCE, References
NB or toluene) to water, or of nitrate in the reverse direction,
1 Y. N. Xia and P. D. Yang, Adv. Mater., 2003, 15, 351.
must occur to preserve electroneutrality. The visible absor- 2 Y. N. Xia, P. D. Yang, Y. G. Sun, Y. Y. Wu, B. Mayers, B. Gates,
bance band (see Fig. 8) centred on 620 nm is attributed to Fc+, Y. D. Yin, F. Kim and Y. Q. Yan, Adv. Mater., 2003, 15, 353.
on the basis of a previous report,29 but the extent of transfer is 3 B. Gates, B. Mayers, B. Cattle and Y. N. Xia, Adv. Funct. Mater.,
2002, 12, 219.
a function of the polarity of the solvent: the least polar solvent 4 T. J. Trentler, K. M. Hickman, S. C. Goel, A. M. Viano,
(toluene) is least able to solvate the Fc+ nitrate ion pair, hence P. C. Gibbons and W. E. Buhro, Science, 1995, 270, 1791.
in the toluene case, transfer of Fc+ to the aqueous phase 5 Y. Y. Wu and P. D. Yang, J. Am. Chem. Soc., 2001, 123, 3165.
predominates. 6 K. Luo, C. T. Walker and K. J. Edler, Adv. Mater., 2007, 19, 1506.
7 J. H. Song, Y. Y. Wu, B. Messer, H. Kind and P. D. Yang, J. Am.
This observation, combined with the change to 2D morpho- Chem. Soc., 2001, 123, 10397.
logy on using the less polar solvent, leads to the following 8 M. Lai and D. J. Riley, Chem. Mater., 2006, 18, 2233.

9 R. A. W. Dryfe, E. C. Walter and R. M. Penner, ChemPhysChem, 20 C. N. R. Rao, G. U. Kulkarni, P. J. Thomas, V. V. Agrawal and
2004, 5, 1879. P. Saravanan, J. Phys. Chem. B, 2003, 107, 7391.
10 D. Wyrwa, N. Beyer and G. Schmid, Nano Lett., 2002, 2, 419. 21 C. N. R. Rao and K. P. Kalyanikutty, Acc. Chem. Res., 2008, 41, 489.
11 Y. G. Sun, B. Mayers, T. Herricks and Y. N. Xia, Nano Lett., 22 D. Yogev and S. Efrima, J. Phys. Chem., 1988, 92, 5754.
2003, 3, 955. 23 D. Yogev, M. Deutsch and S. Efrima, J. Phys. Chem., 1989, 93,
12 A. Tao, F. Kim, C. Hess, J. Goldberger, R. R. He, Y. G. Sun, 4174.
Y. N. Xia and P. D. Yang, Nano Lett., 2003, 3, 1229. 24 H. Schwartz, Y. Harel and S. Efrima, Langmuir, 2001, 17, 3884.
13 M. Guainazzi, G. Silvestri and G. Serravalle, J. Chem. Soc., Chem. 25 J. K. Sakata, A. D. Dwoskin, J. L. Vigorita and E. M. Spain,
Commun., 1975, 200. J. Phys. Chem. B, 2005, 109, 138.
14 Y. F. Cheng and D. J. Schiffrin, J. Chem. Soc., Faraday Trans., 26 T. Maddanimath, A. Kumar, J. D’Arcy-Gall, P. G. Ganesan,
1996, 92, 3865. K. Vijayamohanan and G. Ramanath, Chem. Commun., 2005, 1435.
15 A. Trojanek, J. Langmaier and Z. Samec, J. Electroanal. Chem., 27 F. Scholz and U. Hasse, Electrochem. Commun., 2005, 7, 541.
2007, 599, 160. 28 C. Suryanarayana and M. G. Norton, X-Ray Diffraction A Prac-
16 V. J. Cunnane and U. Evans, Chem. Commun., 1998, 2163. tical Approach, Plenum Press, New York and London, 1998, vol. 6.
17 F. Reincke, S. G. Hickey, W. K. Kegel and D. Vanmaekelbergh, 29 H. Hotta, S. Ichikawa, T. Sugihara and T. Osakai, J. Phys. Chem.
Angew. Chem., Int. Ed., 2004, 43, 458. B, 2003, 107, 9717.
18 R. A. W. Dryfe, Phys. Chem. Chem. Phys., 2006, 8, 1869. 30 C. M. A. Brett and A. M. O. Brett, Electrochemistry, Principles,
19 C. Johans, K. Kontturi and D. J. Schiffrin, J. Electroanal. Chem., Methods and Applications, Oxford University Press, Oxford, 1993,
2002, 526, 29. ch. 5.
This journal is
The role of nucleophilic catalysis in chemistry and stereochemistry of

ribonucleoside H-phosphonate condensationw
Michal Sobkowski,*a Jacek Stawinskib and Adam Kraszewskia
Received (in Montpellier, France) 24th July 2008, Accepted 10th September 2008
DOI: 10.1039/b812780h
The efficiency and stereoselectivity of condensation of ribonucleoside 3 0 -H-phosphonates with alcohols were
investigated as a function of amines used for the reaction. It was found that irrespective of the presence or absence
of nucleophilic catalysts, the Dynamic Kinetic Asymmetric Transformation (DYKAT) was the major factor
responsible for the stereoselective formation of the DP(SP) isomers of the H-phosphonate diesters, and a
mechanistic rationalization of this observation was proposed. In addition, studies on the reactions carried out in
the presence of various bases led to the conclusion that certain sterically hindered pyridines, e.g. 2,6-lutidine, may
act as nucleophilic catalysts in the condensation of ribonucleoside 3 0 -H-phosphonates with alcohols.
Introduction Recently, we have proposed a Dynamic Kinetic Asymmetric

Transformation (DYKAT) as a possible mechanism for the
P-Chiral oligonucleotide analogues (e.g. phosphorothioates,2 stereoselectivity observed in these reactions.1 According to this
phosphoramidates,3 methylphosphonates,4 or boranophos- model, diastereomers of nucleoside H-phosphonic–pivalic
phates5) having defined configuration at the phosphorus atom mixed anhydrides 2 exist in a rapid equilibrium, and one of
find diverse applications in investigations of nucleic acid inter- them, namely the LP(SP) diastereomer, is significantly more
actions with other biologically important molecules, for exam- reactive towards nucleosides (or alcohols) than the other one
ple proteins, RNA, and DNA.6 Such P-chiral oligonucleotides (Fig. 1 and Chart 1). To simplify mechanistic considerations,
may also be considered as potential drugs for nucleic acid-based in our earlier studies the role of nucleophilic and base catalysis
therapies,7 that could permit a more precise tuning of oligo- by the amines was consciously neglected. However, since the
nucleotide interactions with the biological targets than is possible participation of nucleophilic catalysis in condensation of
with the currently used pools of P-diastereomers. This should H-phosphonates is a well-established phenomenon,11–15 it
also relieve problems of potential variation of therapeutic and was important to examine and to assess its impact on the
toxic effects resulting from different ratios of P-diastereomers asymmetric induction in the reactions investigated. In this
produced in various batches of oligonucleotide drugs. paper we present studies on the role of nucleophilic catalysis
There are several strategies to stereocontrolled synthesis of in the chemistry and stereochemistry of condensation of
P-chiral oligonucleotides.8 One of them, stereoselective (or more ribonucleoside H-phosphonates with alcohols.
precisely, diastereoselective) condensation of ribonucleoside H-phos-
phonates,9 attracted our attention due to its simplicity and high
efficiency. It makes use of commercially available H-phosphonate Results and discussion
synthons which are condensed with nucleosides under standard
reaction conditions commonly used for the synthesis of H-phos- In routine condensations of nucleoside H-phosphonates
phonate diesters to provide DP diastereomersz as major products. pyridine or quinoline (either neat or diluted with non-basic
solvent) is used as a basic component of the reaction mixture.
Both of these weakly basic heterocyclic amines (pKa 5.2 and
a
Institute of Bioorganic Chemistry, Polish Academy of Sciences, 4.9, respectively) secure fast and quantitative formation
Noskowskiego 12/14, 61-704 Poznan, Poland. of H-phosphonate diesters due to their ability to act as
E-mail: msob@ibch.poznan.pl; Fax: +48 61 8520 532;
Tel: +48 61 852 8503 nucleophilic catalysts.11,12 In contrast to this, in the presence
b
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm of more powerful nucleophilic catalysts, e.g. NMI or DMAP,y
University, S-106 91 Stockholm, Sweden nucleoside H-phosphonates are prone to P-acylation that
w Stereochemistry of internucleotide bond formation by the H-phos-
compromises the diester formation.12 Also strongly basic
phonate method. Part 4.1
z For the compounds presented in this paper the DP descriptor refers tertiary amines (e.g. TEA, pKa 11.0) are usually avoided since
to a structure in which the P–H bond is directed to the right in the these can promote undesired base-catalysed bis-acylation of
Fischer projection, and in the LP one, to the left. The full DP/LP H-phosphonate monoesters,13,15 while in the presence of less
notation is described in ref. 10.
basic tertiary amines (e.g. DMA, pKa 5.1) the condensations
y Abbreviations: DABCO, 1,4-diazabicyclo[2.2.2]octane; DIPEA, di-

isopropylethylamine; DMAP, 4-(N,N-dimethylamino)pyridine; DMA,
N,N-dimethylaniline; DTBP, 2,6-di-tert-butylpyridine; EDIPP,
4-ethyl-2,6-diisopropyl-3,5-dimethylpyridine; HMTA, hexamethylene-
tetramine; Lut, 2,6-lutidine; MPO, 4-methoxypyridine N-oxide; NMI,
N-methylimidazole; PvCl, pivaloyl chloride; Py, pyridine; TEA,
triethylamine.

Fig. 1 Putative routes of the reaction during stereoselective condensation of ribonucleoside H-phosphonate monoester 1 with alcohols and
nucleosides according to the DYKAT mechanism in the absence (curved arrows) and in the presence (central pathways) of a nucleophilic catalyst.
solely as base catalysts or as base and nucleophilic catalysts

during H-phosphonate condensations. To this end, the reac-
tions of H-phosphonate 1 with ethanol were carried out in the
presence of selected tertiary amines, various pyridine deriva-
tives, and strong nucleophilic catalysts. The obtained data
(Table 1) showed that irrespective of significant differences in
the yields and stereoselectivity observed for different amines,
Chart 1 the same DP(SP) diastereomer of diester 4 was always formed
as the main product. In the light of our earlier studies,1,18 these
results might suggest that in the absence of nucleophilic
are effective but sluggish (at least 10 times slower than those catalysts, the previously described DYKAT mechanism oper-
for pyridine), presumably due to lack of nucleophilic cata- ated at the level of the mixed anhydride 2 (Fig. 2, Path B),
lysis.12 Thus, it was somewhat surprising that 2,6-lutidine while in the nucleophile-catalyzed reactions, an analogous
(pKa 6.7), which is usually considered as poorly nucleophilic DYKAT took place at the level of adducts of type 3 (Fig. 2,
base,16,17 promoted condensations of ribonucleoside H-phos- Path A2).z
phonates with similar efficiency as pyridine or quinoline.1 Additionally, these experiments confirmed the earlier find-
Moreover, the stereochemistry of the reactions performed in ings11–15 that neither powerful nucleophilic catalysts nor
the presence of 2,6-lutidine was the same as that with pyridine. strongly basic tertiary amines could promote quantitative
The above called into question the commonly accepted condensations of H-phosphonates with alcohols. However,
non-nucleophilic character of 2,6-lutidine and prompted us in contrast to the literature data,11–15 there was no (or very
to consider the involvement of nucleophilic catalysis as an little) side product formation, and the 31P NMR spectra of the
additional process in the DYKAT mechanism (Fig. 1). reaction mixtures revealed only presence of the expected
Since the involvement of P–N+ adducts of type 3 (Fig. 1) in diester 4 and unreacted monoester 1 (Fig. 3). This lack of
ribonucleoside H-phosphonate diester formation has to be by-product formation was tentatively attributed to low
crucial for the rate of condensation as well as for stereo-
chemical outcome of the reaction (Fig. 2), we undertook z Involving a rapid 3-DP " 3-LP equilibrium in which the more
investigations to pinpoint the cases in which amines acted reactive diastereomer 3-DP was esterified preferentially.
This journal is
Fig. 2 Possible stereochemistry of esterification of the more reactive LP(SP) diastereomer of ribonucleoside H-phosphonic—pivalic mixed
anhydride 2 in the presence (Path A) and absence (Path B) of nucleophilic catalysts.
Table 1 Diastereomeric excess (de) of the DP(SP) diastereomer of the H-phosphonate diester 4b (Fig. 1, B = Ura) formed in the presence of
various amines
Entry Amine pKa (H2O)a pKa (DMSO) pKa (ACN) pKHBb dec,d (DP) Yield of diester (%)d
Strong nucleophilic catalysts
1 MPO 2.119 3.520 12.421 62% 27
2 HMTAe 5.2 1.922 57% 66
23
3 NMI 7.0 14.3 2.724 60% 84
4 DABCOe 8.7 8.925 18.326 2.622 53% 42
5 DMAP 9.7 7.927 17.728 2.829 53% 85
Heteroaromatic amines
6 Pyrazine 0.7 1.229 39% 55
7 Pyrimidine 1.2 1.429 39% 70
8 Tetramethylpyrazine 3.6 59% 100
9 Quinoline 4.9 12.028 1.929 63% 100
10 1,10-Phenanthrolinee 4.9 66% 100
11 2,6-Di-tert-butyl-pyridine 5.030 1.031 47% 70
12 Pyridine 5.2 3.227 12.528 1.929 62% 100
13 2-Picoline 5.9 4.027 13.932 2.029 69% 100
14 4-Picoline 6.0 3.827 14.532 2.129 68% 100
15 Neocuproinee 6.2 64% 100
16 2,5-Lutidine 6.4 68% 100
17 3,4-Lutidine 6.5 4.327 14.732 2.229 63% 100
18 2,6-Lutidine 6.7 4.427 14.432 2.129 70% 100
19 2,4-Lutidine 6.7 4.527 15.032 70% 100
20 2,4,6-Collidine 7.5 15.028 2.329 68% 100
21 EDIPP (7.6)f 52% 92
22 ()-Nicotine 8.0 65% 100
23 ()-Nicotine 8.0 64% 100
Tertiary amines
24 DMA 5.1 2.533 11.428 0.534 56% 100
25 N-Methylmorpholine 7.4 15.635 1.722 70% 91
26 TEA 11.0 9.036 18.828 2.022 75% 74
27 DIPEA 11.4 1.122 71% 89
a
Aqueous pKa data, unless otherwise indicated, are taken from ref. 37. b Hydrogen bonding basicity. pKHB = logK(formation of HB complex); larger
values correspond to greater basicity.38 c One should note that the difference between de values, for instance de 52% and de 75%, corresponds to
over two-fold increase of the stereoselectivity measured as a ratio of diastereomers (i.e. B3 : 1 vs. B7 : 1, respectively). d Determined via
integration of the corresponding 31P NMR signals. e For structure, see Chart 1. f Estimated, assuming an additive and similar methyl and ethyl
groups effect on the pKa39 and a linear correlation between a,a 0 -steric hindrance and pKa40 of substituted pyridines.
concentration of the amines in the reaction mixtures (0.3 M or sumed in the acylation of 5 0 -OH or N3-H functions of
ca. 2.5%). uridine.41 These side reactions could compete with the forma-
In order to find sources for the incomplete condensations tion of the mixed anhydride 2 and, at least partly, could
that have been carried out in the presence of the amines be responsible for incomplete condensations. However,
examined herein, the reactivity of pivaloyl chloride towards H-phosphonate condensations were also not quantitative in
nucleosides was investigated in separate experiments. It was the presence of tertiary aliphatic amines alone (Table 1, entries
found that TEA and pyridine derivatives when used alone did 25–27), i.e. under the conditions in which the acylation of
not promote significant acylation of nucleosides, however, in nucleoside components was negligible.41 This issue was
the presence of strong nucleophilic amines (e.g. DMAP) or addressed in additional experiments, which indicated that
TEA–pyridine mixtures, pivaloyl chloride was rapidly con- the mixed anhydride 2 might undergo deacylation by pivalic

Fig. 4 A possible participation of general acid catalysis in deacyla-
tion of the mixed anhydride 2 by pivalic acid.
unhindered endocyclic nitrogen atoms (i.e. having at least one

Fig. 3 31P NMR spectra of the reaction of H-phosphonate 1 with a position unsubstituted), the question might arise, whether
ethanol (3 equiv.) promoted by PvCl (1.5 equiv.) in DCM containing
this could hold also for a,a 0 -dimethylpyridines?
3 equiv. of 2,6-lutidine or TEA. The minor signal (ca. 1.5%) at 3.2 ppm
Although 2,6-lutidine and its derivatives are usually con-
in the upper spectrum is in the region of P-acylated compounds.
sidered as poor nucleophiles,16,17 they can act as nucleophiles
under mild conditions undergoing, for instance, N-alkylation
acid with regeneration of the starting H-phosphonate mono- with alkyl halides,44 alkyl iodonium triflate45 or radical
ester 1 and formation of pivalic anhydride (a poor activator of cations,46 or N-sulfonation with triflic anhydride.47 Notably,
H-phosphonates42). The rate of deacylation was found to in phosphorus chemistry the lack of nucleophilic properties of
correlate well with the ability of an amine conjugated acid to 2,6-lutidine was observed for P(V) compounds, e.g. for phos-
form hydrogen bonds (quantified as a pKHB value8) rather phoroiodidates,16 while whether nucleophilic catalysis by this
than with the amine basicity expressed by pKa. A plausible base may operate for H-phosphonates, remains to be deter-
rationale, which could account for the obtained results in- mined. Since P(V) and P(III) compounds differ significantly in
volved an increased contribution of general acid catalysis electrophilicity,48 and the steric hindrance around the phos-
during decomposition of the mixed anhydride 2 by amines phorus atom in H-phosphonates is clearly lower than that
having high pKHB (Fig. 4).43 in P(V) compounds, significant differences in their reactivity
Thus, it can be tentatively concluded that pivaloyl chloride towards hindered pyridine derivatives cannot be excluded.
promoted coupling of H-phosphonates with alcohols in the To get a better insight into this problem, condensations of
presence of strongly nucleophilic amines, and/or those of high H-phosphonate 1 were performed in the presence of EDIPP
H-bonding basicity, did not go to completion due to con- (a peralkylated 2,6-diisopropylpyridine derivative, pKa
sumption of the condensing agent (PvCl) in the acylation B7.6)49 and DTBP (2,6-di-tert-butylpyridine, pKa 5.0) for
of nucleosides or due to formation of unreactive pivalic which the nucleophilicity might be safely excluded on steric
anhydride via a partial deacylation of the mixed anhydride 2. grounds. The yields of H-phosphonate diester 4 obtained in
In contrast, pyridine and most of its derivatives investigated these reactions (92 and 70%) were similar to those found for
secured quantitative condensations (with an exception of trialkyl amines, while low stereoselectivity (de ca. 50%) was
pyridine derivatives bearing branched substituents in both similar to that observed for tertiary aniline derivatives
a positions)** despite significant differences in their pKa (e.g. DMA, de 56%). In contrast, all the other pyridine
(3.6–8.0) and considerably high pKHB values (1.9–2.3). derivatives, including a,a 0 -dimethylpyridines, differed only
Although it might be argued that the high pKHB of pyridines slightly in stereoselectivity and invariably gave quantitative
should be associated with high catalytic activity of their condensations of H-phosphonate 1. Thus, it seems reasonable
conjugate acids which should lead to deacylation of the mixed to assume that the main route for H-phosphonate diester
anhydride 2 (Fig. 4), apparently it was not the case in the formation in the presence of 2,6-lutidine derivatives could still
reactions discussed. A plausible explanation of the excellent involve the nucleophilic catalysis (preventing in this way
yields obtained for the most of the pyridines examined could deacylation of the mixed anhydride 2, and in consequence,
be the participation of nucleophilic catalysis, i.e. the involve- the yield deterioration), and that only bulky alkyl substituents
ment of intermediate phosphonopyridinium adducts of type 3 in a,a 0 positions were able to suppress the nucleophilic proper-
(Fig. 2) which, as monofunctional entities, should undergo a ties of pyridine.
nucleophilic attack at the phosphorus centre only. While this is In additional experiments the condensations of uridine
readily understandable in the case of pyridine derivatives with H-phosphonate 1 with ethanol performed in the presence of
mixtures of 2,6-lutidine with more nucleophilic amines
(pyridine, NMI, DMAP, MPO) were investigated (Fig. 5). In
8 The pKHB measures the relative strength of the acceptor in hydro- neither case were any specific effects due to the nucleophilic
gen-bonded complex formation with a reference acid (H-bonding
basicity). pKa and pKHB may be unrelated.38 amine noted, and the yields and stereoselectivity of the con-
** Two heteroaromatic amines, pyrazine and pyrimidine, were appar- densations were proportional to the weighted average of the
ently too weakly basic (pKa 0.7 and 1.2, respectively) to be efficient values obtained for each amine used separately. This lent
promoters of the condensations investigated since a significant detri- support to the aforementioned assumption that the same
tylation was observed during the course of reactions, even in the
presence of 6 equiv. of an amine (c E 5%). These amines were thus mechanism (i.e. nucleophilic catalysis) was operating for 2,6-
excluded from further investigations. lutidine and for other amines of known nucleophilic character.
This journal is
highly basic amines (e.g. TEA, pKa 11.0; entries 7 & 8), the rate
of epimerization was always significantly higher than that of
esterification, even in the presence of large excess of an
alcohol. Interestingly, it seems that the behaviour of a given
amine in a kinetic quenching experiment might be exploited as
a marker of its nucleophilic properties towards H-phospho-
nates, according to the following rule of thumb: the higher the
stereoselectivity of ribonucleoside H-phosphonate conden-
sation in neat methanol, the lower the nucleophilicity of the
amine used for the reaction.
Fig. 5 Diastereomeric excess (solid bars) of the DP(SP) diastereomer

Conclusions
of H-phosphonate diester 4b formed in the presence of mixtures of In the previous paper in this series we reported that stereo-
amines, and the total yield of diester 4b (a sum of diastereomers, open selectivity in condensations of ribonucleoside H-phosphonates
bars). Reaction conditions: 0.05 mmol of 1 (B = Ura) + EtOH
1 with alcohols originated from the Dynamic Kinetic Asym-
(3 equiv.) + amines (the number of molar equivalents specified on the
metric Transformation (DYKAT).1 The data presented in this
x axis) + PvCl (1.5 equiv.) in DCM (0.5 mL).
paper confirmed this conclusion and suggested that the equili-
brium between the diastereomers of nucleoside H-phosphonic—
Kinetic quenching experiments
pivalic mixed anhydride (2-DP " 2-LP) was significant
To probe the involvement of nucleophilic catalysis in the for the stereochemical outcome of the reaction only in the
DYKAT mechanism, kinetic quenching experiments for absence of nucleophilic catalysis. In the presence of nucleo-
various amines were carried out using large excess of methanol. philic amines, however, the DYKAT mechanism was
Under such reaction conditions we expected to observe governed most likely by the 3-DP " 3-LP equilibrium between
significant changes in the ratio of diastereomers (with a the putative P–N+ intermediates. In most instances this path
possible reversal of stereoselectivity1) of the produced was also essential for quantitative yield of the condensation.
H-phosphonate diester 4a as a result of substantial increase Pyridine derivatives (excluding those with a large steric
in the rate of esterification of the reactive intermediates (mixed hindrance around the nitrogen atom) secured practically
anhydride 2 and amine adduct 3). Indeed, a remarkable quantitative yields of the condensations along with reasonable
decrease in stereoselectivity was observed for the reactions high stereoselectivity (de 60–70%). Noteworthy, pyridine
involving pyridine or 2,6-lutidine as bases (Table 2). derivatives with methyl groups in the a positions (e.g. 2,6-
Such results can be interpreted as a partial change of the lutidine) also provided fast, clean and highly stereoselective
DYKAT into the Dynamic Thermodynamic Resolution condensations, and thus indicated that the esterification of
(DYTR) mechanism of the asymmetric induction due to H-phosphonate monoesters in the presence of these bases
acceleration of the esterification at high concentration of might proceed with the intermediacy of the P–N+ adducts
MeOH.1 In contrast, in the presence of the poorly nucleophilic of type 3 (i.e. involving nucleophilic catalysis; Fig. 1 and 2). To
amines, the stereoselectivity under the kinetic quenching the best of our knowledge this would be the first documented
conditions decreased only slightly. example of manifestation of nucleophilic properties of
Thus, it seems that the nucleophilic catalysis (Table 2, 2,6-dimethylpyridines in SN2(P) reactions.
entries 1 & 2) speeded up the esterification of intermediates 3 For practical purposes, among investigated bases, 2,6-luti-
more efficiently than their epimerization, while for the base dine was found to be the amine of choice (quantitative yield of
catalysed reactions (entries 3–6 & 9) or in the presence of condensations, high stereoselectivity, and easy availability)
Table 2 Comparison of the yield and the ratio of diastereomers of the methyl uridine H-phosphonate diester 4a (Fig. 1) formed under standard
and kinetic quenching conditions
‘‘Standard’’ 3 equiv. of MeOH 3 equiv. ‘‘Kinetic quenching’’ 2500 equiv. of MeOH,

of amine [1] = 100 mM 30 equiv. of amine [1] = 10 mM
Entry Amine de (DP)a Yield of diester (%)a de (DP)a Yield of diester (%)a
1 Pyridine 63 100 10b 100
2 2,6-Lutidine 68 100 12 100
3 EDIPP 47 100 66 100
4 DMA 56 96 42 100
5 TEA 69 73 51 93
6 Proton sponge 49 95 45 95
7 Pyridine + TEA 1:1c 62 89 60 88
8 2,6-Lutidine + TEA 1:1c 68 80 61 91
9 DMA + TEA 1:1c 60 84 58 94
a 31 b
Determined via integration of the corresponding P NMR signals. Advantage of the LP diastereomer. c 3 + 3 equiv. or 15 + 15 equiv.

and is advised to be used in stereoselective ribonucleoside 30 s toluene (15 mL) was added and the mixture was evapo-
3 0 -H-phosphonate diesters formation. rated almost to dryness under vacuum at temperature o40 1C
(such procedure was obligatory for strongly basic tertiary
amines in order to avoid transesterification52 of the product).
Experimental section The oily residue was dissolved in DCM (0.5 mL) and analyzed
Methods and materials by 31P NMR spectroscopy.
31
P NMR spectra were recorded at 121 MHz on a Varian
Unity BB VT spectrometer. 31P NMR experiments were Acknowledgements
carried out in 5 mm tubes using 0.5 mL of the reaction
The financial support from the Polish Ministry of Science and
mixture and the spectra were referenced to 2% H3PO4 in
Higher Education is gratefully acknowledged.
D2O (external standard). The quantities of phosphorus-
containing compounds were determined via integration of
the corresponding 31P NMR signals. Diastereomeric excess References
was calculated with accuracy of 1.5 percentage points
1 M. Sobkowski, A. Kraszewski and J. Stawinski, Tetrahedron:
(an average of 3 measurements). Asymmetry, 2007, 18, 2336–2348.
Commercial (Sigma-Aldrich, Alfa Aesar, Merck, POCh- 2 W. J. Stec and G. Zon, Tetrahedron Lett., 1984, 25, 5275–5278;
Poland) reagents and were used as purchased unless otherwise W. B. Cruse, S. A. Salisbury, T. Brown, R. Cosstick, F. Eckstein
noted. Ethanol was distilled over magnesium. Dichloro- and O. Kennard, J. Mol. Biol., 1986, 192, 891–905.
3 J. Nilsson and J. Stawinski, Chem. Commun., 2004, 2566–2567.
methane and pyridine were refluxed over P2O5, distilled, and 4 L. A. Wozniak, M. Janicka and M. Bukowiecka-Matusiak, Eur. J.
stored over 4 Å molecular sieves until they contained below Org. Chem., 2005, 5189–5197.
20 ppm of water (Karl Fischer coulometric titration, Metrohm 5 J. Tomasz, B. R. Shaw, K. Porter, B. F. Spielvogel and A. Sood,
Angew. Chem., Int. Ed., 1992, 31, 1373–1375; Y. Jin and G. Just,
684 KF coulometer). Anhydrous triethylamine (TEA) was
Tetrahedron Lett., 1998, 39, 6433–6436.
distilled and kept over CaH2. Commercial p-methoxypyridine 6 P. Guga, Curr. Top. Med. Chem., 2007, 7, 695–713.
N-oxide (MPO) hydrate was rendered anhydrous by co- 7 J. B. Opalinska and A. M. Gewirtz, Nat. Rev. Drug Discovery,
evaporation with dry acetonitrile (1) and dry toluene (2). 2002, 1, 503–514.
8 Y. X. Lu, Mini-Rev. Med. Chem., 2006, 6, 319–330.
Other liquid amines were refluxed for 1 hour with 2,4,6- 9 H. Almer, J. Stawinski and R. Stromberg, Nucleic Acids Res., 1996,
triisopropylbenzenesulfonyl chloride (TPS-Cl) and distilled 24, 3811–3820.
under reduced pressure. 4-Ethyl-2,6-diisopropyl-3,5-dimethyl- 10 M. Sobkowski, J. Stawinski and A. Kraszewski, Nucleosides,
Nucleotides Nucleic Acids, 2005, 24, 1301–1307; M. Sobkowski,
pyridine (EDIPP)49 was a gift from Prof. A. T. Balaban,
J. Stawinski and A. Kraszewski, Nucleosides, Nucleotides Nucleic
Texas A&M University. Uridine H-phosphonate 150 was Acids, 2006, 25, 1363–1375; M. Sobkowski, J. Stawinski and
obtained according to the published method. Racemization A. Kraszewski, Nucleosides, Nucleotides Nucleic Acids, 2006, 25,
of S-()-nicotine was done according to ref. 51. Immediately 1377–1389; M. Sobkowski, J. Stawinski and A. Kraszewski,
‘A Convenient Stereochemical Notation for P-Chiral Nucleotide
prior to all reactions, H-phosphonate 1 was rendered anhy- Analogs’, in Current Protocols in Nucleic Acid Chemistry, ed.
drous by dissolving in toluene (3 mL/0.05 mmol) and evapora- S. L. Beaucage, D. E. Bergstrom, G. D. Glick and R. A. Jones,
tion of this solvent under reduced pressure. After drying under John Wiley & Sons, New York, 2007, A.1E.1–A.1E.16.
vacuum (15 min, 0.5 Torr), the flask was filled with air, dried 11 V. A. Efimov and I. Y. Dubey, Bioorg. Khim., 1990, 16, 211–218;
P. J. Garegg, J. Stawinski and R. Stromberg, J. Chem. Soc., Perkin
up by passing through Sicapent (Merck). Trans. 2, 1987, 1209–1214.
12 I. Y. Dubey, V. A. Efimov, T. V. Lyapina and D. M. Fedoryak,
General procedure for condensation of H-phosphonates of type 1 Bioorg. Khim., 1992, 18, 911–919; V. A. Efimov, I. Y. Dubey and
with alcohols O. G. Chakhmakhcheva, Nucleosides Nucleotides, 1990, 9,
473–477.
Nucleoside H-phosphonate 1 (0.05 mmol) was dissolved in 13 S. Sigurdsson and R. Stromberg, J. Chem. Soc., Perkin Trans. 2,
0.5 mL of DCM and amine (3 equiv.) and EtOH or MeOH 2002, 1682–1688; S. Sigurdsson and R. Stromberg, Nucleosides,
Nucleotides Nucleic Acids, 2003, 22, 1–12.
(3 equiv.) were added, followed by PvCl (1.5 equiv.). The 14 A. Kraszewski and J. Stawinski, ‘Aryl Nucleoside H-Phospho-
reaction mixture was transferred to an NMR tube and the 31P nates. Versatile Intermediates in the Synthesis of Nucleotides and
NMR spectra were recorded within 1 hour. Their Analogues’, in Trends in Organic Chemistry, Research
Trends, Trivandrum India, 2003, vol. 10, pp. 1–19.
Kinetic quenching experiments 15 P. J. Garegg, T. Regberg, J. Stawinski and R. Stromberg, Nucleo-
sides Nucleotides, 1987, 6, 655–662.
Nucleoside H-phosphonate 1 (0.05 mmol) was dissolved in 16 J. Stawinski, R. Stromberg and R. Zain, Tetrahedron Lett., 1992,
33, 3185–3188.
DCM (0.3–0.5 mL), and TEA (0.2 equiv.) and PvCl
17 C. W. Downey and M. W. Johnson, Tetrahedron Lett., 2007, 48,
(1.2 equiv.) were added successively. The formation of the 3559–3562.
mixed anhydride 2 was confirmed by 31P NMR spectroscopy 18 M. Sobkowski, J. Jankowska, J. Stawinski and A. Kraszewski, Nucleo-
(dP 1.47 & 1.56) and the reaction mixture was utilized within sides, Nucleotides Nucleic Acids, 2005, 24, 1469–1484; M. Sobkowski,
J. Jankowska, J. Stawinski and A. Kraszewski, in Collection Sympo-
one hour (no degradation products were found within that siumSeries, ed. M. Hocek, Institute of Organic Chemistry and Bio-
period). chemistry, Academy of Sciences of the Czech Republic, Prague, 2005,
The solution (0.3 mL) of the intermediate 2 (0.5 mmol; vol. 7, pp. 183–187.
generated as described above) was added dropwise by a 19 V. I. Rybachenko, K. Yu Chotii, V. V. Kovalenko and G. Shreder,
Russ. J. Phys. Chem. (Engl. Transl.), 2003, 77, 1695–1698.
syringe to a septum-sealed flask containing vigorously stirred 20 L. Chmurzynski and Z. Warnke, Aust. J. Chem., 1993, 46,
methanol (5 mL) and an amine (2.4% v/v or w/v). After ca. 185–194.
This journal is
21 L. Chmurzynski, G. Wawrzyniak, Z. Warnke and Z. Pawlak, 38 R. W. Taft, D. Gurka, L. Joris, P. von Schleyer and J. W. Rakshys,
J. Heterocycl. Chem., 1997, 34, 215–220. J. Am. Chem. Soc., 1969, 91, 4801–4808.
22 J. Graton, F. Besseau, M. Berthelot, E. Raczynska and 39 A. S. Chia and R. F. Trimble, J. Phys. Chem., 1961, 65, 863–866;
C. Laurence, Can. J. Chem., 2002, 80, 1375–1385. J. Epsztajn and R. M. K. Marcinkowski, Polish J. Chem., 1979, 53,
23 Z. Pawlak, J. Mol. Struct., 1986, 143, 369–374. 601–609; A. Gero and J. J. Markham, J. Org. Chem., 1951, 16,
24 L. Cecchi, F. De Sarlo and F. Machetti, Eur. J. Org. Chem., 2006, 1835–1838.
4852–4860. 40 H. C. Brown and B. Kanner, J. Am. Chem. Soc., 1966, 88, 986–992;
25 R. L. Benoit, D. Lefebvre and M. Frechette, Can. J. Chem., 1987, B. Kanner, Heterocycles, 1982, 18, 411–419.
65, 996–1001. 41 M. Sobkowski, in Collection Symposium Series, ed. M. Hocek,
26 J. F. Coetzee and G. R. Padmanabhan, J. Am. Chem. Soc., 1965, Institute of Organic Chemistry and Biochemistry Academy of
87, 5005–5010. Sciences of the Czech Republic, Prague, 2008, vol. 10, pp. 277–281.
27 D. Augustin-Nowacka, M. Makowski and L. Chmurzynski, 42 R. Stromberg and J. Stawinski, Nucleic Acids Res. Symp. Ser.,
J. Chem. Thermodyn., 2002, 34, 391–400. 1987, 18, 185–188.
28 I. Kaljurand, A. Kutt, L. Soovali, T. Rodima, V. Maemets, I. Leito 43 M. Sobkowski, J. Stawinski and A. Kraszewski, Part 5 of this
and I. A. Koppel, J. Org. Chem., 2005, 70, 1019–1028. series, New J. Chem., submitted.
29 M. Berthelot, C. Laurence, M. Safar and F. Besseau, J. Chem. 44 F. Yang, X. L. Xu, Y. H. Gong, W. W. Qiu, Z. R. Sun, J. W. Zhou,
Soc., Perkin Trans. 2, 1998, 283–290. P. Audebert and J. Tang, Tetrahedron, 2007, 63, 9188–9194;
30 H. P. Hopkins, D. V. Jahagirdar, P. S. Moulik, D. H. Aue, M. Szafran, Z. Dega-Szafran, B. Nowak-Wydra and
H. M. Webb, W. R. Davidson and M. D. Pedley, J. Am. Chem. M. Pietrzak, J. Mol. Struct., 2001, 563–564, 555–564.
Soc., 1984, 106, 4341–4348. 45 T. Umemoto and Y. Gotoh, Bull. Chem. Soc. Jpn., 1991, 64,
31 R. L. Benoit, M. Frechette and D. Lefebvre, Can. J. Chem., 1988, 2008–2010.
66, 1159–1162. 46 V. D. Parker, E. T. Chao and G. Zheng, J. Am. Chem. Soc., 1997,
32 D. Augustin-Nowacka and L. Chmurzynski, Anal. Chim. Acta, 119, 11390–11394.
1999, 381, 215–220. 47 R. W. Binkley and M. G. Ambrose, J. Org. Chem., 1983, 48,
33 R. L. Benoit, M. J. MacKinnon and L. Bergeron, Can. J. Chem., 1776–1777.
1981, 59, 1501–1504. 48 J. Stawinski and A. Kraszewski, Acc. Chem. Res., 2002, 35,
34 E. Marquis, J. Graton, M. Berthelot, A. Planchat and C. Laurence, 952–960.
Can. J. Chem., 2004, 82, 1413–1422. 49 A. T. Balaban, I. Ghiviriga, E. W. Czerwinski, P. De and R. Faust,
35 P. Beltrame, G. Gelli and A. Loi, Gazz. Chim. Ital., 1980, 110, J. Org. Chem., 2004, 69, 536–542.
491–494. 50 J. Jankowska, M. Sobkowski, J. Stawinski and A. Kraszewski,
36 I. M. Kolthoff, M. K. Chantoon and S. Bhowmik, J. Am. Chem. Tetrahedron Lett., 1994, 35, 3355–3358.
Soc., 1968, 90, 23–28. 51 Y. Tsujino, S. Shibata, A. Katsuyama, T. Kisaki and H. Kaneko,
37 D. D. Perrin, Dissociation Constants of Organic Bases in Aqueous Heterocycles, 1982, 19, 2151–2154.
Solution, Butterworth, London, 1965; CRC Handbook of Chemis- 52 M. Sobkowski, J. Stawinski, A. Sobkowska and A. Kraszewski,
try and Physics, CRC Press LLC, Boca Raton, 87th edn, 2007. J. Chem. Soc., Perkin Trans. 2, 1994, 1803–1808.

Two polyaminophenolic fluorescent chemosensors for H+ and Zn(II).

Spectroscopic behaviour of free ligands and of their dinuclear Zn(II)
complexesw
Gianluca Ambrosi,a Cristina Battelli,a Mauro Formica,a Vieri Fusi,*a Luca Giorgi,a
Eleonora Macedi,a Mauro Micheloni,*a Roberto Pontellinia and Luca Prodib
Received (in Durham, UK) 17th June 2008, Accepted 18th September 2008
DOI: 10.1039/b810228g
The UV-Vis and fluorescence optical properties of the two polyamino-phenolic ligands
3,3 0 -bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2 0 -dihydroxybiphenyl (L1) and 2,6-bis{[bis-
(2-aminoethyl)amino]methyl}phenol (L2) were investigated in aqueous solution at different pH
values as well as in the presence of Zn(II) metal ion. Both ligands show two diethylenetriamine
units separated by the 1,1 0 -bis(2-phenol) (BPH) or the phenol (PH) for L1 and L2, respectively.
Both ligands are fluorescence-emitting systems in all fields of pH examined, with L1 showing a
higher fluorescence emission than L2. In particular, the emission of fluorescence mainly depends
on the protonation state of the phenolic functions and thus on pH. The highest emitting species
is H3L3+ for both systems, where the BPH is monodeprotonated (in L1) and the PH is in the
phenolate form (in L2). On the contrary, when BPH and PH are in their neutral form both
ligands show the lowest fluorescence, since H-bonds occurring between the phenol and the closest
tertiary amine functions decrease fluorescence. The Zn(II)-dinuclear species are also fluorescent
in the pH range where they exist; the highest emitting species being [Zn2(H2L1)]2+ and
[Zn2(H1L2)]3+ which are present in a wide range of pH including the physiological one.
Fluorescence experiments carried out at physiological pH highlighted that, in the case of L1, the
presence of Zn(II) ion in solution produces a simultaneous change in lem with a drop in
fluorescence due to the formation of the [Zn2(H2L1)]2+ species, while, in the case of L2, it gives
rise to a strong CHEF effect (a twenty-fold enhancement was observed) due to the formation of
the [Zn2(H1L2)]3+ species. These results, supported by potentiometric, 1H and 13C NMR
experiments, are of value for the design of new efficient fluorescent chemosensors for both H+
and Zn(II) ions.
Introduction offering submicrometer spatial resolution and submillisecond

temporal resolution.11–19 The versatility of fluorescence-based
The development of chemosensors is in continuous expansion sensors originates also from the wide number of parameters
due to their usefulness in many fields; they have a wide range that can be tuned in order to optimize the convenient signal. In
of applications, such as environmental monitoring, process most cases, changes in luminescence intensity represent the
control, food and beverage analysis, medical diagnosis and most directly detectable response to target recognition; more
others.1–8 Due to their use in many disciplines, they are very recently, however, other properties such as excited-state life-
attractive for chemists, biologists, physicists and material time and fluorescence anisotropy have also been preferred as
scientists. For example, in biochemistry, clinical and medical diagnostic parameters, since they are less affected by environ-
sciences, and cell biology, freely mobile sensor molecules are mental and experimental conditions.
employed extensively in microscopy, offering the possibility of Phenol and poly-phenols show well known optical proper-
performing real-space measurements.9,10 ties which mainly depend on their protonation degree;20,21 in
Among the different chemosensors, the fluorescence-based our lab, several polyamino-phenolic ligands of different topol-
ones present many advantages: fluorescence measurements are ogies have been synthesized. In this study, we wanted to
usually very sensitive, low-cost, easily performed and versatile, extend our knowledge to the spectroscopic properties of two
of them to identify their possible applications as chemosensors
a for suitable guests. In this case, we focused our attention on
Institute of Chemical Sciences, University of Urbino,
P.za Rinascimento 6, I-61029 Urbino, Italy the two previously synthesized amino-phenolic ligands L1 and
b
Department of Chemistry, University of Bologna, Via Selmi 2, L2 (Chart 1). They were chosen for several reasons: they have
Bologna, Italy. E-mail: vieri@uniurb.it similar topology; they both show two diethylenetriamine
w Electronic supplementary information (ESI) available: Fig. S1:
Location of acidic hydrogen atoms in the protonated species of L2. (dien) units separated by a phenolic aromatic spacer, the
See DOI: 10.1039/b810228g 1,1 0 -bis(2-phenol) group (BPH) and the phenol for L1 and
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using the fully automatic equipment that has already been
described; the EMF data were acquired with the PASAT
computer program.26 The combined glass electrode was cali-
brated as a hydrogen concentration probe by titrating known
amounts of HCl with CO2-free NaOH solutions and determin-
ing the equivalent point by Gran’s method,27 which gives the
standard potential E1 and the ionic product of water (pKw =
Chart 1 Ligands together with labels for the NMR resonances. 13.73(1) at 298.1 K in 0.15 M NaCl, Kw = [H+][OH]). At
least three potentiometric titrations were performed for each
system in the pH range 2–11, using different molar ratios of
Zn(II)/L2 ranging from 1:1 to 2:1. All titrations were treated
either as single sets or as separate entities, for each system; no
significant variations were found in the values of the deter-
mined constants. The HYPERQUAD computer program was
used to process the potentiometric data.28
Spectroscopic experiments
1
H and 13C NMR spectra were recorded on a Bruker Avance
200 instrument, operating at 200.13 and 50.33 MHz, respec-
tively, and equipped with a variable temperature controller.
Scheme 1 Coordination scheme for Zn(II) in the [Zn2(H2L1)]2+ and The temperature of the NMR probe was calibrated using
[Zn2(H1L2)]3+ complexes.
1,2-ethanediol as calibration sample. For the spectra recorded
in D2O, the peak positions are reported with respect to HOD
L2, respectively; in addition, they easily form dinuclear species (4.75 ppm) for 1H NMR spectra, while dioxane was used as
with transition metal ions. The molecular skeleton of both reference standard in 13C NMR spectra (d = 67.4 ppm).
ligands affords the formation of preorganized dinuclear Fluorescence spectra were recorded at 298 K with a Varian
Zn(II) species where the two Zn(II) ions can cooperate in Cary Eclipse spectrofluorimeter. UV absorption spectra were
binding guests; in particular, it has been demonstrated that recorded at 298 K with a Varian Cary-100 spectrophotometer
in some dinuclear species such as the [Zn2(H2L1)]2+ and equipped with a temperature control unit.
[Zn2(H1L2)]3+ ones, the two zinc ions show, in both systems, The fluorescence quantum yields (Ff) of the highest fluores-
an equal coordination environment, are displaced at fixed cent species were calculated as reported in ref. 29 using
different distances and are able to add guests to saturate the 2-aminopyridine as standard reference.
coordination requirement of the two zinc ions (see Scheme 1).
Although zinc is an essential metal ion in human life and
plays a fundamental role in many biological functions, for
example in the alkaline phosphatase or carbonic anhydrase Solution studies
enzymes,22 excess zinc can be very harmful, as it can lead to
many health problems.23 For this reason, easy recognition of Ligands L1 and L2 as well as the Zn(II)/L systems were studied
the zinc ion is key mainly and as a result many fluorescent by fluorescence spectroscopy in aqueous solution at different
pH values to investigate the fluorescence properties of both
molecular sensors have been developed in recent years, also to
ligands and how these are affected by protonation and the
allow its in vivo mapping.24
presence of Zn(II) ion. 1H and 13C NMR experiments on the
In this work, we have studied the NMR, UV-Vis and
fluorescence properties of the free ligands as well as of their free L1 as well as those reported for the Zn(II)/L1 system25a
zinc complexes in aqueous solution. The aim has been to aided in understanding the role played by both protonation
detect if the optical properties of these systems are affected and Zn(II). The fluorescence quantum yields (Ff) of the highest
by pH as well as by the presence of Zn(II) in solution. fluorescent species are reported in Table 1.
Similar 1H NMR studies carried out on L2 and Zn(II)/L2
system are reported in refs. 30 and 31, respectively. Moreover,
Experimental further studies on the UV-Vis absorption properties of both
L and Zn(II)/L systems were performed in aqueous solution
Synthesis in addition to those already reported.25,30,31
Ligand 3,3 0 -bis[N,N-bis(2-aminoethyl)aminomethyl]-2,2 0 -di-
hydroxybiphenyl (L1) and 2,6-bis{[bis-(2-aminoethyl)amino]- Table 1 Fluorescence quantum yield (Ff) of the main fluorescent
methyl}phenol (L2) were prepared as previously described.25 species in 0.15 mol dm3 NaCl at 298.1 K
Ff
EMF measurements
3+
H3L1 0.34
Equilibrium constants for protonation and complexation H3L23+ 0.01
reactions with L2 were determined by pH-metric measure- [Zn2H2L1]2+ 0.24
[Zn2H1L2]3+ 0.08
ments (pH = log[H+]) in 0.15 M NaCl at 298.1 0.1 K,

L1 and L2 in aqueous solution at different pH values The fluorescence spectra of L1 (lexc = 287 nm) recorded in
3 aqueous solution in the pH range 2–12 are reported in Fig. 1;
Basicity. The basicity of L1 in 0.15 mol dm NaCl aqueous
the trend of the fluorescence emission intensity (E) vs. pH
solution at 298.1 K was potentiometrically studied and the
(lexc = 287 nm) is reported in Fig. 2(a) together with the
results obtained reported in ref. 25a; the protonation constants
maximum absorption ( ) and the emission (---) wavelength
of ligand L2 were determined under these ionic conditions and
trend. Fig. 2(b) reports the trend of the absorption titration at
the stepwise basicity constants of L2 are reported in Table 2.
l = 308 nm (K) together with the distribution curves for the
The basicity of L2 is similar to that previously reported using
species of L1 (—) as a function of pH.
NMe4Cl as ionic medium thus the discussion can be outlined
Excitation of L1 acid solution at pH 2 (lexc = 287 nm) gives
in the same way.30
rise to a fluorescence emission band of very low intensity
Fluorescence of L1 at different pH values. Emission spectra (lem = 403 nm) attributed to the BPH fluorophore. The
performed at different pH values gave information on the intensity of the fluorescence emission of the compound is
interaction between the dien and the 2,2 0 -biphenol (BPH) units highly dependent on the protonation state of the ligand
and on the behavior of the ligand in its excited states. (see Fig. 1 and 2(a)); however the shape and the lem of the
As reported in the literature, BPH shows emission of spectra are substantially pH-independent. In this pH range,
fluorescence depending on the degree to which it is deproto- the free BPH group shows a similar fluorescent behavior
nated;20 in particular, it shows the most intense fluorescence in produced by the monoanionic excited state of BPH.20,32
its monodeprotonated form and the least intense in its neutral Taking into account that the fluorescence of L1 is due to the
one (more than six times lower), while the dianionic form, BPH fluorophore, this suggests that also in L1 the changes in
although fluorescent, is obtainable only at very high pH values fluorescence emission reflect only the ground states acid–base
(pH 4 15).20,32 equilibrium.33 For this reason, no indication of the excited
state proton transfer reaction was found and, as reported for
free BPH, the fluorescence is due to the monoanionic excited
Table 2 Basicity and equilibrium constants for the complexation state of BPH in L1.
reactions of L2 with Zn(II) ion determined in 0.15 mol dm3 NaCl at
298.1 K
In the fluorescence spectra, the emission remains substan-
tially very low and constant (Fig. 2(a)) at acidic pH values
Reaction log K (2 r pH r 5) while it starts increasing at pH 5 in concomi-
+
L + H = HL +
10.04(1)a tance with the appearance of the H3L13+ species in solution,
HL+ + H+ = H2L2+ 9.87(1) reaching a maximum intensity at pH 7.4–8.4 with the complete
H2L2+ + H+ = H3L3+ 9.12(1) formation of the H3L13+ species. A small decrease can be
H3L3+ + H+ = H4L4+ 7.59(1)
H4L4+ + H+ = H5L5+ 2.50(3)
Zn2+ + L + 2H+ = ZnH2L4+ 28.42(1)
Zn2+ + L + H+ = ZnHL3+ 23.82(2)
Zn2+ + L = ZnL2+ 14.67(2)
Zn2+ + L = Zn(H1L)+ + H+ 5.05(2)
2Zn2+ + L = Zn2(H1L)3+ + H+ 17.17(1)
2Zn2+ + L + H2O = Zn2(H1L)OH2+ + 2H+ 8.34(3)
2Zn2+ + L + 2H2O = Zn2(H1L)(OH)2+ + 3H+ 1.63(3)
Zn2(H1L)3+ + OH = Zn2(H1L)OH2+ 4.90
Zn2(H1L)OH2+ + OH = Zn2(H1L)(OH)2+ 3.76
a
Values in parentheses are the standard deviations on the last
significant figure.
Fig. 2 Fluorescent emission titration (lexc = 287 nm, lem = 403 nm)
(E), absorption wavelength trend ( ), and emission wavelength trend
(---) (a); absorption titration at l = 308 nm (K) and distribution
curves of the species (—) (b) as function of pH in aqueous solution:
Fig. 1 Fluorescence spectra of L1 at different pH values. [L1] = 5.0 105 M, I = 0.15 M NaCl, T = 298.1 K.
This journal is
observed in the alkaline range up to pH 10.5 at which the less hydrogen atom of BPH once again leads to a decrease in
protonated species appear in solution; on the contrary, when fluorescence.20b In our case, it is presumable that similar
the pH is increased to 11 emission rises again, reaching H-bonding between the BPH oxygen and the closer nitrogen
maximum intensity at pH 12 with the presence in solution of atoms of the dien units is formed, thus decreasing fluorescence;
the monoanionic H1L1 species. however, the formation of this type of H-bond cannot be the
Bearing in mind the previous studies on BPH,20,32 the trend favourite situation since only a slight drop in fluorescence was
of the emission intensity in the range of pH 2–8 can be easily observed. Moreover, two different H-bonds could be sug-
explained by the deprotonation of the neutral BPH unit to gested in the case of L1: via OH N as well as via O HN+;
form its monoanionic species that occurs with the formation of in other words, in the H2L12+, HL1+ and L1 species, a partial
the H3L13+ species. In other words, in the protonated species stabilization of the acidic hydrogen atom of the monoanionic
H5L15+ and H4L14+, BPH is present in its neutral form while BPH unit could also take place with the closer N atom
in the H3L13+ species it has lost one of the acidic protons (c in Scheme 2), but also a partial ammonium character of
forming the highest emitting species (F = 0.34, Table 1). the closer N atom could give rise to the same quenching
These results are in agreement with those already obtained by H-bond effect with the BPH unit (b in Scheme 2). In any case,
UV-Vis absorption studies which revealed that the deproto- the form (a) shown in Scheme 2 is the favoured form and it is
nation of one of the hydroxyl functions of BPH occurred in the only one present in the H3L13+ as well as in the H1L1
the pH range involving the passage from H4L14+ to H3L13+ species where the highest fluorescence is reached. In addition,
species.25a This was highlighted, as reported in Fig. 2(b), by the absence of fluorescence changes even at highly alkaline pH
the change in absorption at 308 nm which increases when the values once again demonstrates that the full deprotonation of
monoanionic form of BPH is present in solution and is further BPH in L1 is not reachable under our experimental conditions.
underlined by the variation in the trend of the maximum of the
absorption wavelength (Fig. 2(a)) as a function of pH; both L1 1H and 13C NMR studies at different pH values. In order
figures highlight that the changes take place in the field of pH to obtain further structural information about the distribution
where the H3L13+ species forms. Although the absorption and of acidic protons in the protonated species of L1, 1H and 13C
emission wavelength maxima as well as the absorption at NMR spectra were recorded over the pH range of the
308 nm remain constant, increasing the pH to form lesser
protonated species than H3L13+, there is a small decrease
(about 25% at pH 10) in fluorescence intensity occurring with
the formation of the H2L12+, HL1+ and neutral L1 species
(Fig. 2(a)). This trend could be explained by the formation of a
H-bond network involving BPH and the closer nitrogen
atoms. In fact, as reported for free BPH,20,32 the formation
of an intramolecular H-bond interaction occurring between
the two oxygen atoms of BPH in stabilizing the hydrogen
atom in the monoanionic species gives the greatest fluores-
cence intensity, while, on the contrary, the formation of
intermolecular H-bonds with H-accepting molecules, such as
water, gives rise to a very fast nonradiating process through-
out the H-bond, thus leading to a decrease in the fluorescence
(this occurs for example in the neutral form of excited BPH).
In addition, it has been demonstrated that in the presence of
strong proton-accepting molecules such as triethylamine
(TEA), the formation of H-bonding between TEA and a
Fig. 3 Experimental NMR chemical shifts in aqueous solution of L1

Scheme 2 Possible H-bond interactions for the neutral L1 species. as a function of pH: 1H NMR (a); 13C NMR (b).

potentiometric, UV-Vis and fluorescence measurements. density on both the tertiary amine groups and BPH unit
1
H–1H and 1H–13C NMR 2D correlation experiments were occurring in this pH range that can be correlated with the
performed to assign all the signals. The trends for the chemical formation of H-bonding involving the BPH oxygen and the
shift of the 1H and 13C NMR resonances are reported in closer nitrogen atoms in the L1, HL1+ and H2L12+ species, in
Fig. 3(a) and (b). The 1H NMR spectrum recorded at pH 12, agreement with the fluorescence experiments reported above.
where the H1L1 species is prevalent in solution, exhibits two In the pH range 4–6 the H4L4+ species is prevalent and, as
triplets at 2.67 and 2.85 ppm corresponding to the resonance demonstrated both by UV and fluorescence experiments, the
of the hydrogen atoms H2 and H1, respectively, one singlet at fifth protonation step occurs at the BPH group. This was also
3.76 ppm due to the hydrogen atoms H3, one triplet at confirmed in the NMR experiments by the downfield shift of
6.91 ppm for the resonances of H6 and two doublets at 7.31 and the H6 signal in the para position to the phenolic oxygens and
7.42 ppm for H5 and H7, respectively. This spectral feature by the upfield shift of the H7 protons in the 1H NMR spectra,
indicates a C2v symmetry mediated on the NMR time-scale as well as by the accompanying upfield shift of C4, C8 and C9
which is preserved throughout the pH range investigated. In and downfield shift of C6 in the 13C NMR spectra. The strong
agreement with this symmetry, the 13C NMR spectrum upfield shift exhibited by the signal of H7 could be related not
recorded at the same pH value shows only nine signals at d only to a protonation process of the BPH unit but also to a
37.7 (C1), 53.0 (C3), 55.0 (C2), 117.8 (C6), 126.6 (C4), 129.7 change in the angle between the two aromatic rings that
(C8), 130.5 (C5), 130.6 (C7) and 158.0 (C9). At lower pH, probably is affected by the protonation degree of L1 leading
where the species L1, HL1+, H2L12+ and H3L13+ are form- the formation of a new H-bond network involving the neutral
ing (pH = 11–7), the main shift is exhibited by the protons H1 BPH and the unprotonated tertiary amine functions, as
which show a marked downfield shift, suggesting that the four depicted in Fig. 4 for the H4L14+ species; this almost entirely
protonation steps take place mainly on the primary amine quenches the fluorescence (see above). The protonation step
functions. This hypothesis is confirmed by the trend of the 13C giving the H5L5+ species, occurring below pH 4, basically
NMR resonances which mainly shows an upfield shift in the causes a downfield shift of protons H2 and H3 together with
signal of the carbon atom C2, in agreement with the b-effect of an upfield shift in the signals of the carbon atoms C1 and C4,
the protonation of the polyamines.34 However, in this pH suggesting that it takes place on the tertiary amine groups.
range, slight shifts in other 1H NMR resonances could be seen: Once again the H7 and H5 resonances, both of which shift
for example, the resonance of H7 first moves downfield up to downfield, are perturbed by this protonation step, highlighting
pH 9 then decreases with the formation of the H3L13+ species, the formation of a H-bond network with the closer amine
while H3 moves upfield; this suggests little changes in charge functions on the BPH unit different from the previous one; this
Fig. 5 Fluorescence emission titration (lex = 280 nm) (E), absorp-

tion wavelength trend ( ), and emission wavelength trend (---) (a);
absorption titration at l = 290 nm (K) and distribution curves of the
Fig. 4 Location of acidic hydrogen atoms in the protonated species species (—) (b); of L2 as function of pH in aqueous solution: [L2] =
of L1. 5.0 105 M, I = 0.15 M NaCl, T = 298.1 K.
This journal is
affects the chemical shift, modifying the electron density of the towards lower and higher energies, respectively), while an
neutral BPH unit as well as the angle between the two opposite trend was observed at higher pH values (lmax and
aromatic rings. lem shift towards higher and lower energies, respectively) with
A protonation scheme arising from NMR experiments is the formation of the neutral zwitterionic L2 species in which a
summarized in Fig. 4. strong H-bond between the closest tertiary ammonium and
phenolate groups was suggested. Taking into account the
Fluorescence of L2 at different pH values. The same fluores- trend and shift in both lmax and lem, it can be suggested that
cence experiments were carried out on the ligand L2 the fluorescence is yielded by light emission decay from the
and compared to the previous UV-Vis and NMR studies phenolate excited state of all L2 species to different ground
performed in aqueous solution at different pH values.30 The states, characterized by the formation of strong intramolecular
trend in fluorescence emission intensity (E) versus pH (lexc = H-bonds.
280 nm) is reported in Fig. 5(a) together with the maximum In conclusion, although L1 is a much more efficient fluores-
absorption ( ) and emission (---) wavelength trends. Fig. 5(b) cent system than L2 (Table 1), both ligands show fluorescence
reports the trend for the absorption titration at l = 290 nm emission depending on the protonation state of the aromatic
(K) together with the distribution curves of the species of L2 functions. In particular, the highest emitting species are due to
(—) as a function of pH obtained by potentiometry. the monodeprotonated form of BPH of L1 as well as to the
The acidic solutions of L2 up to pH 6 are barely fluorescent, phenolate species of PH of L2, both of which are achieved in
as also reported for the free neutral phenol (PH), while the H3L3+ species; on the contrary, the neutral BPH and PH
fluorescence increases with the formation of the H3L23+ species are very low fluorescence emitters. The presence of the
species, reaching maximum emission at pH 8 together with closer tertiary amine function affects the emission quantum
the maximum presence in solution of the H3L23+ species; at yield in some species by forming intramolecular H-bonding
higher pH values, the emission drops, reaching a plateau at pH with the close phenol oxygen atom of both systems. The
higher than 11 with the formation of the neutral L2 species. H-bonding induces a nonradiative relaxation process of
The fluorescence of ligand L2, which is lower compared to that the excited species, yielding a decrease in the fluorescence in
of L1 (see Table 1), is highly dependent on the protonation both ligands. This H-bonding is weaker in L1 via OH N as
state of the ligand as seen before for L1. The acidic proton well as O HN+, and for this reason only a relatively low
distribution in the several protonated species of L2 obtained efficiency of fluorescence quenching could be observed, while it
by UV-Vis, potentiometry and NMR studies was previously takes place strongly via O HN+ in L2 giving an almost
reported and the scheme is reported in Fig. S1 of the ESI;w the total quenching of the fluorescence of L2. Taking into account
most fluorescent H3L23+ species is the one in which the phenol these results, both ligands behave as chemosensors of H+ in
is deprotonated (i.e. phenolate) and the four acidic protons are that they are able to change their optical absorption and
located on the primary amine functions; this is the same fluorescence properties as a function of pH.
situation found for the H3L13+ species where there are no
H-bond interactions with the closest amine functions, thus
Coordination of Zn(II)
affording the highest emission quantum yield also in the
H3L23+ species. It should be noted that in the free PH, the The coordination behaviour of both systems towards Zn(II)
anion presents a much lower fluorescence intensity than the was potentiometrically studied and the results obtained are
neutral species.21 In this case the opposite behaviour was reported in ref. 25 and 31; as for basicity, the Zn(II)/L2 system
observed; this could be explained (see also below) by a had been studied in NMe4Cl ionic medium,31 thus we per-
decrease in the solvation via H-bond network of the phenolate formed new potentiometric measurements to obtain the stabi-
oxygen atom by the water molecules in the H3L23+ species in lity constants for the Zn(II)/L2 system under the same
comparison with the free PH anion.21a In other words, the experimental conditions as the Zn(II)/L1 system (0.15 mol dm3
presence of the two protonated dien units linked to the PH NaCl aqueous solution at 298.1 K). The potentiometrically
group modifies the accessibility of the solvent molecules to the determined stability constants for the equilibrium reactions of
phenolate oxygen atom decreasing its quenching effect and L2 with Zn(II) are reported in Table 2. The species formed as
thus increasing the emissive relaxation decay of the PH anion. well as the values of the stability constants evaluated are
As reported, an acidic proton redistribution was observed in similar to those previously reported and thus the discussion
the less protonated species involving at least a tertiary amine can be outlined in the same way. The main difference found
function that becomes protonated. This ammonium group, was the formation of the [Zn2(H1L2)(OH)2]+ species in this
found mainly in the neutral L2 species, is stabilized via H-bond ionic medium which was not previously detected. The addition
with the close phenolate oxygen atom (see Fig. S1, ESIw). For of the second OH anion to [Zn2(H1L2)OH]2+ is quite high
this reason, as for ligand L1, the formation of H-bonding with (log K = 3.76) suggesting that it is probably bound in a bridge
the amine function leads to a decrease in its fluorescence. disposition between the Zn(II) ions. The distribution diagrams
This H-bond interaction, which is also monitorable through for the Zn(II)-complexed species for both 2Zn(II)/L systems are
the UV-Vis spectra (see Fig. 5(b)), is also highlighted by the reported in Fig. 6 for L1 and in Fig. 8 for L2 as a function of
change in the maximum of the absorption and emission pH. However, the results previously discussed can be summar-
wavelengths (Fig. 5(a)) as a function of pH. lmax and lem ized in this way: (i) the dinuclear species are prevalent in
shifted in different directions, increasing the Stokes shift when solution and the only species existing at pH higher than 7 is a
the phenol becomes phenolate (pH Z 5, lmax and lem shift L/Zn(II) with a 1:2 molar ratio; (ii) the most prevalent species

mately pH 6, gives rise to a change in the lmax which shifts
from 305 nm in the presence of the mononuclear [Zn(HL1)]3+
species to 298 nm with the complete formation of the more
stable [Zn2(H2L1)]2+ species at pH = 7.4. This lmax is
preserved also at higher pH values where only dinuclear
Zn(II)-complexed species are present in solution. The shift in
lmax observed from the mono- to the di-nuclear species can be
ascribed to the full deprotonation of BPH which loses both
acidic hydrogen atoms in the Zn(II)-dinuclear species, afford-
ing the bi-negative form of BPH; this result is in agreement
with the studies previously reported for the Zn(II)-dinuclear
species of L1. The changes in absorption from the mono-
negative BPH to the bi-negative species are also visible in
Fig. 6(b), where a change in absorptivity can also be observed
when the dinuclear species appear in solution. These changes
are in agreement with a change in the protonation degree of
BPH and thus to its full deprotonation and simultaneous
coordination of each Zn(II) ion by one phenolate oxygen
atom of the BPH unit as already reported. The fluorescence
experiments gave rise to analogous results, with fluorescence
increasing at values starting from acidic pH and reaching
maximum intensity in the field of pH 7.4–8.4 with the maxi-
Fig. 6 Fluorescence emission titration (lex = 283 nm) (E), absorp- mum presence in solution of the [Zn2(H2L1)]2+ species, then
tion wavelength trend ( ), and emission wavelength trend (---) (a); decreasing at higher pH values and reaching a plateau at pH
absorption titration at l = 295 nm (K) and distribution curves of the 4 11 with the presence in solution of the di-hydroxylated
species (–) (b); as a function of pH in aqueous solution: [L1] = 5.0 [Zn2(H2L1)(OH)2] species (Fig. 6). It is interesting to note
105 M, [Zn(II)] = 104 M, I = 0.15 M NaCl, T = 298.1 K. that, unlike the free L1, the lem changes (lexc = 283 nm) by
changing the pH, and as in the absorption experiments
the change occurs at the pH values where there is the forma-
are [Zn2(H2L1)]2+ and [Zn2(H1L2)]3+ for L1 and L2, tion of the Zn(II)-dinuclear species. Specifically, lem shifts from
respectively; (iii) these dinuclear species have similar molecular 403 nm (free ligand) to 379 nm with the formation of the
skeletons indicating a preorganized dinuclear Zn(II) species in [Zn2(H2L1)]2+ species, while remaining constant in the other
which the two Zn(II), similarly coordinated, can cooperate in dinuclear species. Once again, this trend can be related to the
binding suitable guests (see Scheme 1). full deprotonation of BPH, as retrieved in the crystal structure
of the [Zn2(H2L1)(H2O)2]2+ previously reported, which
Fluorescence and UV-Vis of the 2Zn(II)/L1 system at differ- produces changes in the ground as well as in the excited state
ent pH values. Emission and absorption spectra were per- of BPH. Moreover, the formation of the hydroxylated
formed at different pH values using Zn(II)/L1 at a 2 to 1 [Zn2(H2L1)OH]+ and [Zn2(H2L1)(OH)2] species produces
molar ratio. The trend in fluorescence emission intensity (E) a drop in fluorescence emission without changing the lem
versus pH (lexc = 283 nm) is reported in Fig. 6(a) together (Fig. 6(a)); this is due to an increase in electron density
with the maximum absorption ( ) and emission (---) wave-
length trends. Fig. 6(b) reports the trend for the absorption
titration at l = 295 nm (K) together with the distribution
curves for the species of the 2Zn(II)/L1 system (—) as a
function of pH. Moreover, fluorescence titration was carried
out by adding increasing amounts of Zn(II) to a HEPES buffer
(pH = 7.4) solution of L1 and the spectra are reported in
Fig. 7. The fluorescence quantum yield of the highly emitting
species is reported in Table 1.
The UV-Vis absorption spectra of solutions containing
2Zn(II)/L1 recorded at different pH values were discussed
previously;25a they showed spectral profiles indicating the
deprotonation of BPH and simultaneous coordination of the
Zn(II) ions; in these new experiments, some further aspects can
be discussed. The absorption lmax shifts toward lower energy
when monitored from acidic (free ligand) to basic pH values Fig. 7 Fluorescence spectra of the Zn(II)/L1 system in aqueous buffer
(Zn(II)-complexes); up to the presence in solution of the Zn(II)- (HEPES, 5 102 M) solution at pH = 7.4, obtained by adding
mononuclear species it moves from 280 to 305 nm, while the several amounts of Zn(II) up to 2 equivalents with respect to [L1] =
appearance in solution of the dinuclear species, at approxi- 5.0 105 M.
This journal is
the [Zn2(H1L2)]3+ species is prevalent in solution, a slight
increase in absorption with respect to the free ligand can
be observed, while a marked increase is visible at higher
pH values with the formation of the hydroxylated
[Zn2(H1L2)OH]2+ species (see Fig. 8). This finding could
be explained by a different disposition of L2 in forming the
Zn–O–Zn cluster system (O is the phenolate oxygen atom) in
the [Zn2(H1L2)]3+ and [Zn2(H1L2)OH]2+ species. In fact,
while it was demonstrated that the hydroxylated
[Zn2(H1L2)OH]2+ species shows the OH displaced in a
bridged disposition between the two Zn(II) ions,30 on the
contrary, a coordination environment without secondary brid-
ging ligands could be hypothesized in the [Zn2(H1L2)]3+
species. In the latter, the fifth coordination site of each Zn(II)
ion could be saturated by a water molecule or by a chloride
anion of the ionic medium. This may be the reason for the
increase in absorption of the [Zn2(H1L2)OH]2+ with respect
to the [Zn2(H1L2)]3+ species.
Analysis of the fluorescence experiments gives additional
information; examining the maximum of lem (lexc = 275 nm)
from acidic to alkaline field of pH, a shift of the lem is
observable (see Fig. 8) at pH 4 5; lem moves from 354 nm,
typical of the free ligand, reaching a constant value (308 nm) at
Fig. 8 Fluorescence emission titration (lex = 279 nm) (E), absorp-
tion wavelength trend ( ), and emission wavelength trend (---) (a); pH 6, with the full formation of the [Zn2(H1L2)]3+ species.
absorption titration at l = 287 nm (K) and distribution curves of the This change in lem is coupled with an increase in fluorescence,
species (—) (b); as a function of pH in aqueous solution: [L2] = 5.0 which shows its highest emission in the range of the
105 M, [Zn(II)] = 1.0 104 M, I = 0.15 M NaCl, T = 298.1 K. [Zn2(H1L2)]3+ species. These changes are in agreement with
the simultaneous deprotonation of the phenolic oxygen atom
due to the Zn(II) complex formation and its bridging coordi-
of the BPH unit by coordinating the OH species which, nation between the two Zn(II) ions, as phenolate. At pH 4 9, a
as reported in similar cases, increases a thermal relaxation further change in the lem can be highlighted, since it shifts
negatively affecting emission decay mechanisms.20b The from 308 to 325 nm in concomitance with the appearance of
change in lem occurring with the formation of the dinuclear the [Zn2(H1L2)OH]2+ species in solution; this occurs without
[Zn2(H2L1)]2+ is well highlighted by titrating a buffer observing any significant change in fluorescence intensity. This
(pH = 7.4) solution of L1, adding increasing amounts of result may be related, as above, to a different disposition of
Zn(II) up to 2 equivalents (Fig. 7); as shown in the figure, the the secondary ligands in the two complexed [Zn2(H1L2)]3+
lem shifts toward higher energy by adding Zn(II) but, and [Zn2(H1L2)OH]2+ species that could be responsible
at the same time, the fluorescence of the new species of the different lem in the dinuclear [Zn2(H1L2)]3+ and
formed decreases by about 30% and thus none chelation- [Zn2(H1L2)OH]2+ species. As previously discussed for
enhanced fluorescence (CHEF) effects were observed for the [Zn2(H2L1)(OH)2] species, the increase in the total
this system. electron density of the complex in the dihydroxylated
[Zn2(H1L2)(OH)2]+ species affects fluorescence at higher
Fluorescence and UV-Vis of the 2Zn(II)/L2 system at different pH values.
pH values. Analogous fluorescence and absorption experi- The Zn(II)-L2 dinuclear complexes showed very interesting
ments were performed at different pH values using Zn(II)/L2 fluorescent properties; in fact, although free L2 exhibits emit-
at a 2 to 1 molar ratio; the results are reported in Fig. 8. ting species in the same range of pH of the Zn(II)-dinuclear
UV-Vis absorption spectra of solutions containing 2Zn(II)/ one, the fluorescence intensity of the latter is higher, giving a
L2 at different pH values show, as previously reported, strong CHEF effect. This effect, occurring to L2 in the
spectral profiles due to the deprotonated form of PH. How- presence of Zn(II), is highlighted in Fig. 9, which reports the
ever, also in this case, some further aspects can be discussed. fluorescence spectra of L2 obtained by adding several amounts
Observing the lmax of the spectra from acidic to alkaline pH of Zn(II) in aqueous buffer pH = 7.4 solution. At this pH
values (Fig. 8(a)), a shift in the lmax from 273 (free ligand) to value, the species formed in the presence of Zn(II) is the
286 nm (complexed ligand) occurs at pH 4 5 with the [Zn2(H1L2)]3+ species. As can be observed in Fig. 9, the free
appearance in solution of the [Zn2(H1L2)]3+ species, in ligand shows low fluorescence emission with a lem centered
agreement with the deprotonation of PH as previously demon- at 347 nm; by adding Zn(II), the emission increases and lem
strated. The value of lmax 286 nm is enough preserved also at shifts toward higher energy. The spectra preserve the same
higher pH values where only a little decrease is shown with the profile when adding up to 2 equivalents of Zn(II), reaching a
appearance in solution of the dihydroxylated species (lmax = constant emission and lem of 308 nm, in concomitance
282 at pH = 12). On the contrary, in the 6–8 pH range, where with the complete formation of the [Zn2(H1L2)]3+ species.

physiological one. In the [Zn2H2L1]2+, the presence of the
dianionic form of BPH produces a blue shift of lem in the
fluorescence experiments, in comparison with the free ligand.
The interaction with guests such as OH perturbs the emission
but not the absorption of the dinuclear species.
In the [Zn2(H1L2)]3+ species a slight blue shift in lem can
also be observed, as well as, a decrease in fluorescence brought
about by the addition of an anionic guest such as OH.
The main result retrieved is that both L1 and L2 sense the
Zn(II) in aqueous solution at physiological pH 7.4 by fluores-
cence; at this pH the [Zn2(H2L1)]2+ and [Zn2(H1L2)]3+
species are prevalent in solution. The [Zn2(H2L1)]2+ species
shows a simultaneous change in the lem with a drop in
fluorescence, but real and efficient sensing was obtained by
using ligand L2 which, in the presence of two equivalents of
Fig. 9 Fluorescence spectra of the Zn(II)/L2 system in aqueous buffer Zn(II), gives rise to a strong CHEF effect (a twenty-fold
(HEPES, 5 102 M) solution at pH = 7.4, obtained by adding increase) with the formation of the [Zn2(H1L2)]3+ species;
several amounts of Zn(II) up to 2 equivalents with respect to [L2] = in this case, a similar CHEF effect was also found in other
5.0 105 M. fields of pH such as 8 and 10, highlighting the sensing role of
L2 towards Zn(II) in aqueous solution in a biologically im-
(see Fig. 8(b)). At this pH the emission quantum yield is more portant range of pH.
than twenty-fold higher for the [Zn2(H1L2)]3+ species than Concluding, both systems behave as chemosensors for both
for the free ligand; furthermore, a similar CHEF effect was H+ and Zn(II) and their investigation has given much useful
also found in other fields of pH such as 8 and 10, at which the information for the design of more efficient systems. More-
dinuclear species are formed, thus highlighting the sensing role over, taking into account that both [Zn2(H2L1)]2+ and
of L2 towards Zn(II) in aqueous solution in a biologically [Zn2(H1L2)]3+ dinuclear species show the highest fluores-
important range of pH. For this reason, L2 can be considered cence intensity and that they are the most suitable hosting
a potential chemosensor for Zn(II). species for guests, they are a very interesting platform for the
sensing of guest species.
Conclusions
Acknowledgements
The studies highlighted that the intensity of the fluorescence of
both ligands depends on the protonation state of the phenolic The authors thank the Italian Ministero dell’Istruzione
functions, and in the case of L2, the lem is also affected by dell’Università e della Ricerca (MIUR), PRIN2007 for finan-
protonation while this does not occur for L1. For this beha- cial support.
vior, both ligands are suitable chemosensors of H+ in that
they are able to change their optical absorption and fluores- References
cence properties as function of pH.
1 (a) Fluorescent Chemosensors of Ion and Molecule Recognition, eds.
For both systems the most fluorescent species is the same:
J.-P. Desvergne and A. W. Czarnik, NATO-ASI Series, Kluwer
H3L3+ in which the BPH unit of L1 is in its mono-deproto- Academic Publishers, 1996; (b) U. E. Spichiger-Keller, Chemical
nated form, while PH is present as phenolate form in L2; on Sensors and Biosensors for Medical and Biological Applications,
the contrary, when BPH and PH are in their neutral form both Wiley-VCH, 1998; (c) Fluorescent Chemosensors for Ion and
Molecule Recognition, ed. A. W. Czarnik, ACS, Washington,
ligands show the lowest fluorescence. While these results are in DC, 1992.
agreement with those found for free BPH (the more fluores- 2 (a) Chem. Rev., 2000, 100, 2477–2738, special issue on Chemical
cent species is the monoanionic species of BPH), this finding is Sensors, eds. A. B. Ellis and D. R. Walt; (b) Coord. Chem. Rev.,
opposite to that for free PH where the neutral species is the 2000, 205, 1–232, special issue on luminescent sensors, ed.
L. Fabbrizzi; (c) special issue on synthetic receptors as
most fluorescent. This can be explained by a lower solvation of sensors, ed. A. V. Aslin, Tetrahedron, 2004, 60, 11055–11316.
the phenolate oxygen atom in the H3L23+ species which limits 3 (a) Special issue on luminescent sensors, eds. A. P. deSilva and P.
the quenching effect occurring via H-bond with the water Tecilla, J. Mater. Chem., 2005, 15, 2617–2976; (b) A. P. de Silva,
G. D. McClean, T. S. Moody and S. M. Weir, in Handbook of
molecules. The presence of the tertiary amine function close
Photochemistry and Photobiology, ed. H. S. Nalwa, American
to the phenol oxygen affects the emission quantum yield of Institute of Physics, 2003, vol. 3, p. 217.
those species in which the formation of intramolecular 4 L. Fabbrizzi, M. Licchelli and A. Taglietti, Dalton Trans., 2003,
H-bonds is possible, highlighting that the formation of 3471.
5 K. Rurack, Spectrochim. Acta, Part A, 2001, 57, 2161.
H-bonds has a quenching effect to the fluorescence in these 6 R. Martinez-Manez and F. Sancenon, Chem. Rev., 2003, 103, 4419.
systems. 7 (a) K. J. Albert, N. S. Lewis, C. L. Schauer, G. A. Sotzing,
The Zn(II)-dinuclear species are fluorescent in the field of S. E. Stitzel, T. M. Vaid and D. R. Walt, Chem. Rev., 2000, 100,
pH where they exist; the highest emitting species are the 2595; (b) W. Göpel, Sens. Actuators B, 1998, 52, 125;
(c) J. J. Lavigne and E. V. Anslyn, Angew. Chem., Int. Ed., 2001,
[Zn2(H2L1)]2+ and the [Zn2(H1L2)]3+ species, respectively; 40, 3118; (d) A. D’Amico, C. Di Natale and R. Paolesse, Sens.
they are prevalent in a wide range of pH including the Actuators B, 2000, 68, 324.
This journal is
8 (a) L. Prodi, F. Bolletta, M. Montalti and N. Zaccheroni, Coord. Enzymes, Birkauser, Boston, MA, 1986, ch. 25, pp. 341–356;
Chem. Rev., 2000, 205, 59; (b) C. Bargossi, M. C. Fiorini, (f) R. G. Khalifah, J. I. Rogers and J. Mukherjee, in Zinc Enzymes,
M. Montalti, L. Prodi and N. Zaccheroni, Coord. Chem. Rev., Birkauser, Boston, MA, 1986, ch. 26, pp. 357–370.
2000, 208, 17–32; (c) L. Prodi, New J. Chem., 2005, 29, 20. 23 J. M. Berg and Y. Shi, Science, 1996, 271, 1081.
9 (a) ‘‘Advanced Concepts in Fluorescent sensing, Part A: Small 24 (a) P. Jiang and Z. Guo, Coord. Chem. Rev., 2004, 248, 205;
Molecule Sensing’’, in Topics in Fluorescence Spectroscopy, vol. 9; (b) S. C. Burdette, G. K. Walkup, B. Spingler, R. Y. Tsien and
(b) ‘‘Advanced Concepts in Fluorescent sensing, Part B: Macromo- S. J. Lippard, J. Am. Chem. Soc., 2001, 123, 7831; (c) E. M. Nolan
lecular Sensing’’, eds. C. D. Geddes and J. R. Lakowicz, Springer, and S. J. Lippard, Inorg. Chem., 2004, 43, 8310; (d) L. Rodriquez,
2005, vol. 10. J. C. Lima, J. Parola, R. Meitz, R. Aucejo, E. Garcia-España,
10 J. R. Lakowicz, Principles of Fluorescence Spectroscopy, Kluwer J. M. Linares, C. Soriano and J. Alarcón, Inorg. Chem., 2008, 47,
Academic/Plenum Publishers, 1999. 6173.
11 R. Y. Tsien, Annu. Rev. Neurosci., 1989, 12, 227. 25 (a) G. Ambrosi, M. Formica, V. Fusi, L. Giorgi, A. Guerri,
12 A. P. de Silva, H. Q. N. Gunaratne, T. Gunnlaugsson, A. J. M. M. Micheloni, P. Paoli, R. Pontellini and P. Rossi, Inorg. Chem.,
Huxley, C. P. McCoy, J. T. Rademacher and T. E. Rice, Chem. 2007, 46, 309; (b) P. Dapporto, M. Formica, V. Fusi,
Rev., 1997, 97, 1515. M. Micheloni, P. Paoli, R. Pontellini and P. Rossi, Inorg. Chem.,
13 Special Issue on Chemical sensors, guest editors A. B. Ellis and D. 2000, 39, 4663.
R. Walt, Chem. Rev., 2000, 100, 2477–2738. 26 M. Fontanelli and M. Micheloni, I Spanish–Italian Congress
14 K. Rurack, Spectrochim. Acta, Part A, 2001, 57, 2161. Thermodynamics of Metal Complexes, Univ. of Valencia, Spain,
15 L. Fabbrizzi, M. Licchelli and A. Taglietti, Dalton Trans., 2003, 3471. Peñiscola, June 3–6, 1990, p. 41.
16 W. T. Bell and N. M. Hext, Chem. Soc. Rev., 2004, 33, 589. 27 (a) G. Gran, Analyst, 1952, 77, 661; (b) F. J. Rossotti and
17 (a) L. Prodi, New J. Chem., 2005, 29, 20; (b) G. Farrugia, S. Iotti, H. Rossotti, J. Chem. Educ., 1965, 42, 375.
L. Prodi, M. Montalti, N. Zaccheroni, P. B. Savage, V. Trapani, 28 P. Gans, A. Sabatini and A. Vacca, Talanta, 1996, 43, 1739.
P. Sale and F. I. Wolf, J. Am. Chem. Soc., 2006, 128, 344–350; 29 (a) J. N. Demas and G. A. Crosby, J. Phys. Chem., 1971, 75, 991;
(c) G. Farrugia, S. Iotti, L. Prodi, N. Zaccheroni, M. Montalti, (b) M. T. Gandolfi, A. Credi, M. Montalti and L. Prodi, Handbook
P. Savage, G. Andreani, V. Trapani and F. I. Wolf, J. Fluorescence, of Photochemistry, 3rd edn, CRC Press, Boca Raton, FL.
DOI: 10.1007/s10895-008-0374-6; (d) M. Montalti, L. Prodi and 30 N. Ceccanti, M. Formica, V. Fusi, L. Giorgi, M. Micheloni,
N. Zaccheroni, J. Mater. Chem., 2005, 15, 2810–2814. R. Pardini, R. Pontellini and M. R. Tiné, Inorg. Chim. Acta,
18 Theme Issue: Fluorescent Sensors, J. Mater. Chem., 2005, 15, 2001, 321, 153.
2617–2976. 31 P. Dapporto, M. Formica, V. Fusi, L. Giorgi, M. Micheloni,
19 L. Basade-Desmonts, D. N. Reinhoudt and M. Crego-Calama, P. Paoli, R. Pontellini and P. Rossi, Inorg. Chem., 2001, 40, 6186.
Chem. Soc. Rev., 2007, 36, 993. 32 (a) H. Pal and T. N. Das, J. Phys. Chem., 2003, 107, 5876;
20 (a) J. W. Bridges, P. J. Creaven and R. T. Wiliams, Biochem. J., (b) M. Jonsson, J. Lind and G. Merényi, J. Phys. Chem., 2002,
1965, 96, 872; (b) J. Mohanty, H. Pal and A. V. Sapre, Bull. Chem. 106, 4758; (c) M. Jonsson, J. Lind and G. Merényi, J. Phys. Chem.,
Soc. Jpn., 1999, 72, 2193. 2003, 107, 5878.
21 (a) J. Feitelson, J. Phys. Chem., 1964, 68, 691; (b) M. Krauss, 33 (a) A. Testa, J. Photochem. Photobiol. A: Chem., 1992, 64, 73;
J. O. Jensen and H. F. Hameka, J. Phys. Chem., 1994, 9955. (b) G. Wenska, B. Skalski, Z. Gdaniec, R. W. Adamiak,
22 (a) J. E. Coleman, in Zinc Enzymes, Birkauser, Boston, MA, 1986, J. Matulic-Adamic and L. Beigelman, J. Photochem. Photobiol.
ch. 4, pp. 49–58; (b) Lindskog, in Zinc Enzymes, Birkauser, Boston, A: Chem., 2000, 133, 169–176.
MA, 1986, ch. 22, pp. 307–316; (c) E. Erksson, T. A. Jones and 34 (a) J. C. Batchelor, J. H. Prestegard, R. J. Cushley and S. R. Lipsy,
A. Liljas, in Zinc Enzymes, Birkauser, Boston, MA, 1986, ch. 23, J. Am. Chem. Soc., 1973, 95, 6558; (b) A. R. Quirt, J. R. Lyerla,
pp. 317–328; (d) A. C. Sen, C. K. Tu, H. Thomas, G. C. Wynns and I. R. Peat, J. S. Cohen, W. R. Reynold and M. F. Freedman,
Silvermann, in Zinc Enzymes, Birkauser, Boston, MA, 1986, ch. J. Am. Chem. Soc., 1974, 96, 570; (c) J. C. Batchelor, J. Am. Chem.
24, pp. 329–340; (e) Y. Pocker, N. Janjic and C. H. Miao, in Zinc Soc., 1975, 97, 3410.

Dynamic covalent self-assembled macrocycles prepared from 2-formyl-

aryl-boronic acids and 1,2-amino alcoholsw
Ewan Galbraith, Andrew M. Kelly, John S. Fossey, Gabriele Kociok-Köhn,
Matthew G. Davidson, Steven D. Bull* and Tony D. James*
Received (in Durham, UK) 2nd September 2008, Accepted 18th September 2008
DOI: 10.1039/b815138e
Reaction of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results in dynamic covalent self
assembly to quantitatively afford tetracyclic macrocyclic Schiff base boracycles containing
bridging boron–oxygen–boron functionality.
Introduction Results and discussion

The development of boronic acid based saccharide sensors We have recently reported the development of versatile three-
that rely on the dynamic covalent interaction of boronic acids component derivatization protocols for determining the
with diols has been widely investigated.1–9 Boronic ester enantiomeric excess of chiral primary amines, diols or
formation with diols has also been used for the construction diamines.29–35 For the case of amines, this approach involves
of discrete macrocycles and cages.10 The reversible nature derivatization of a chiral amine 1 with 2-formyl-phenyl-
of boronic acid complexation with diols makes this type of boronic acid 2 and enantiopure BINOL (S)-3 in CDCl3 to
interaction highly suitable for the reversible self-assembly of quantitatively afford a mixture of diastereoisomeric imino-
multicomponent systems. With these types of reversible boronate esters (S,S)-4 and (S,R)-5. The diastereoisomeric
systems any errors that occur during the assembly process may ratio of (S,S)-4:(S,R)-5 is then determined by 1H NMR
be corrected because equilibration of the reactive species spectroscopic analysis, and since no kinetic resolution occurs
results in formation of a thermodynamically favoured this value is an accurate reflection of the enantiomeric excess
product. A number of boracycles have been prepared of the parent amine (Scheme 1).
that employ a combination of facile imine formation and We reasoned that this type of three-component derivatiza-
boronic acid esterification to afford multicomponent macro- tion protocol might also be useful for analyzing the enantio-
cycles.11–24 For example, Severin has prepared a series purity of chiral 1,2-amino alcohols. Therefore, (S)-leucinol 6b
of self assembled macrocycles/cages by combining 3- or 4-for- was treated with 2-formyl-phenyl-boronic acid 2 and (S)-
myl-phenyl-boronic acids with bis or tris primary amines BINOL 3 in CDCl3 and its 1H NMR spectrum acquired after
and pentaerythritol (tetraol).25,26 Nitschke has also prepared ten minutes. The resultant 1H NMR spectra revealed the
a macrocycle derived from pentaerythritol, 2-formyl-phenyl- presence of a complicated mixture of interconverting products
boronic acid and para-diaminobenzene, as well as a cage
compound arising from self assembly of cyclotricatechylene,
meta-xylylenediamine and 2-formyl-phenyl-boronic acid.27
Farfan has prepared boracycles from boric acid, 4-diethyla-
mino salicylaldehyde and (R)-phenylglycinol 6d. This
complex was formed in two steps involving reaction of
4-diethylamino salicylaldehyde and (R)-6d to produce an
imine, followed by reflux with boric acid in toluene under
Dean–Stark conditions for 18 h to produce the observed
complex.28
We now report herein that simple room temperature mixing
of 2-formyl-aryl-boronic acids with 1,2-amino alcohols results
in dynamic covalent self assembly to afford stable tetracyclic
macrocyclic Schiff base complexes that contain a rigid brid-
ging boron–oxygen–boron functionality.
Department of Chemistry, University of Bath, Bath, UK BA2 7AY.

E-mail: S.D.Bull@bath.ac.uk. E-mail: T.D.James@bath.ac.uk;
Tel: +44 1225 383810
w CCDC reference numbers 694358–694361 [(S,2R,4S)-7, 8a, 8f and
8h]. For crystallographic data in CIF or other electronic format see Scheme 1 Three-component protocol for determining the enantio-
DOI: 10.1039/b815138e meric purity of chiral amines by 1H NMR spectroscopic analysis.
This journal is
Scheme 2 Formation and X-ray crystal structure of boronic ester
(S,2R,4S)-7.
that was clearly unsuited for carrying out ee determination. Scheme 3 Condensation of 2-formyl-phenylboronic acid 2 with chiral
However, on standing overnight, the crude reaction product amino alcohols 6a–f and achiral amino alcohols 6g, h affords four-
fractionally crystallised to afford the expected oxazolidine- component boracycles 8a–h.
boronate ester (S,2R,4S)-7, whose structure was subsequently
confirmed by X-ray crystallographic analysis (Scheme 2).
In order to investigate this complexation reaction further, it
was decided to determine what products would be formed
when 2-formyl-phenyl-boronic acid 2 was individually reacted
with either (S)-BINOL 3 or (R)-valinol 6a. Two-component
mixing of 2-formyl-phenyl-boronic acid 2 with (S)-BINOL 3
in CDCl3 resulted in no reaction occurring. However, reaction
of 2 with (R)-valinol 6a at room temperature in chloroform
resulted in exclusive formation of a new boracycle (R,R)-8a in
quantitative yield (Scheme 3). The structure of symmetrical
boracycle (R,R)-8a was confirmed by X-ray crystallographic
analysis (Fig. 1), which revealed it to be the condensation
product of two equivalents of 2-formyl-phenyl-boronic acid Fig. 1 Crystal structure of macrocycle 8a. (a) Viewed along the
2 with two equivalents of (R)-valinol 6a, with concomitant boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.
elimination of five molecules of water. This complexation
reaction results in formation of the densely packed central Mass spectrometry indicated that this solution now contained
core of boracycle (R,R)-8a which comprises two fused seven a mixture of three macrocycles, (S,S)-8a (M + H 431 m/z),
membered rings formed from two tetrahedral sp3-boron (S,S)-8b (M + H 445 m/z) and a mixed macrocycle derived
atoms, two imino alcohol fragments, and a central oxygen from (S)-6a and (S)-6b (M + H 417 m/z) in a statistical
atom that bridges both boron atoms. This architecture results 1:1:2 ratio.
in its central fused bicyclic ring structure being further Norman and coworkers have previously reported the synth-
appended by two five-membered rings formed from two esis of achiral boracycle 8g derived from condensation of
imino-boronate ester linkages that confer sp3 character on 2-aminophenol with 2-formyl-phenyl-boronic acid 2 in
the boron atoms. The scope and limitation of this four- ethanol at reflux.36 Attempts to repeat this condensation
component condensation reaction was then investigated via reaction using our mild complexation conditions at room
treatment of a series of five chiral amino alcohols 6b–f with temperature resulted in no reaction occurring. However,
2-formyl-phenyl-boronic acid 2, which resulted in clean for- heating 2-aminophenol 6g (or 4-methyl-2-aminophenol 6h)
mation of their respective boracycles 8b–f in 84–96% isolated with 2-formyl-phenyl-boronic acid 2 at reflux in 95:5 ethanol:
yield (Scheme 3). benzene under Dean–Stark conditions did result in quantita-
The reversible nature of macrocycle formation of these tive formation of the boracycles 8g (or 8h). Comparison of the
boracycles 8a–f was confirmed by adding one equivalent of X-ray crystal structures of boracycle (S)-8a with that of
amino alcohol (S)-6a to macrocycle (S,S)-8b in chloroform. boracycle 8h (Fig. 2) revealed that whilst they belong to the

Conclusions
In conclusion, a range of covalent self-assembled macrocycles
8 and 10 containing bridging O–B–O–B–O have been prepared
and fully characterised. Their ease of preparation suggests that
this class of boracycle is well suited for the reversible self-
assembly of multicomponent systems, and we are currently
investigating the recognition properties of this structurally
diverse class of macrocycle.
Fig. 2 Crystal structure of macrocycle 8h. (a) Viewed along the Experimental
boron–boron axis. (b) Viewed perpendicular to the boron–boron axis.
General synthetic methods
same class of bridging boracycle, their three dimensional The solvents and reagents were reagent grade unless otherwise
architectures are very different. In the case of boracycle 8a, stated and were purchased from Acros Organics, Alfa Aesar,
the central bridging oxygen atom lies on the opposite side to Fisher Scientific UK, Frontier Scientific Europe Ltd., TCI
the other two oxygen atoms about the plane bisected by the Europe or Sigma-Aldrich Company Ltd., and were used
two boron atoms. This results in the alkyl side-chains of their without further purification. Infra-red spectra were recorded
amino alcohol fragments adopting a conformation that creates on a Perkin Elmer Spectrum RX spectrometer between 4400 cm 1
the walls of a potential binding cavity centred around its and 450 cm 1. Samples were evaporated from CHCl3 on
bridging oxygen atom, with its aryl rings acting as buttressing to a NaCl disc (film). Nuclear magnetic resonance spectra
elements to contribute structural rigidity. Conversely, for the were run in either chloroform-d. A Bruker AVANCE 300 was
case of macrocycle 8h, the presence of the more rigid amino- used to acquire 1H-NMR spectra and recorded at 300 MHz,
11
phenol fragments results in the three oxygen atoms now being B-NMR spectra at 100 MHz and 13C{1H} NMR spectra at
presented on the same face of the plane bisected by the boron 75 MHz. Chemical shifts (d) are expressed in parts per million
atoms. This, in turn, results in the aryl rings of the boronic and are reported relative to the residual solvent peak or to
acid fragment forming the walls of a cavity centred around the tetramethylsilane as an internal standard in 1H and 13C{1H}
bridging oxygen atom, with its aminophenol derived frag- NMR spectra. Boron trifluoride diethyl etherate was used as
ments now adopting the role of buttressing substituents to an external standard in 11B NMR spectra. Mass spectra were
confer structural rigidity. acquired with a micrOTOFQ electrospray time-of-flight
We have also varied the nature of the boronic acid template (ESI-TOF) mass spectrometer (Bruker Daltonik GmbH).
used for supramolecular assembly, demonstrating that com-
plexation of 2-formyl-furanyl-boronic acid 9 with chiral General procedure for the preparation of boracycles 8a-f and
aminoalcohols 6a–e in chloroform quantitatively affords their 10a–e
corresponding four-component boracycles 10a–e in 85–92% 2-Formyl-phenyl-boronic acid 2 (60 mg, 0.4 mmol) or 3-formyl-
isolated yield (Scheme 4). 11B NMR spectroscopic analysis of furanyl-2-boronic acid 9 (56 mg, 0.4 mmol) was stirred with a
these macrocycles reveals that the boron atoms of the furan chiral 1,2-amino alcohol 6a–f or 6a–e (0.4 mmol) in chloro-
derived boracycles 10a–e (d 4.6–5.4 ppm) have more tetra- form (5 mL) for 10 min. The solvent was then removed
hedral character than their corresponding phenyl derived under reduced pressure to afford boracycles 8a–f or 10a–e in
boracycles 8a–f (d 10.5–11.5 ppm). This increased tetrahedral 84–96% yield.
character may be a consequence of the need to incorporate a
more geometrically constrained five-membered furan ring into (R,R)-8a. Yellow oil (70 mg, 84%); [a]20 D +22.0 (c 1.0,
these complexes. It may also explain why reaction of achiral CH2Cl2); vmax (film) 1628 (CQN); dH (300 MHz; CDCl3)
amino alcohols 6g–h with 2-formyl-furanyl-boronic acid 9 did 8.08 (2H, s, CHQN), 7.51 (2H, d, J 7.4, ArH), 7.35–7.27
not result in clean formation of their corresponding four (4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1, ArH), 4.26 (2H, dd,
component boracycles, which may be precluded by the oppos- J 12.2 and 1.3, CHAHB(O)), 3.98 (2H, dd, J 12.2 and 1.3,
ing steric demands of incorporating tetrahedral sp3 boron CHAHB(O)), 3.13 (2H, m, CH(iPr)–N), 2.96–2.83 (2H, m,
atoms and vicinal sp2 aryl carbon atoms into the central CH(CH3)2), 1.02 (6H, d, J 6.8, C(CH3)(CH3)) and 0.88
boracyclic core of the macrocyclic ring system. (6H, d, J 6.8, C(CH3)(CH3)); dC (75 MHz; CDCl3) 167.3
(CQN), 136.8, 133.6, 129.4, 127.2, 127.0, 126.2, 76.0, 60.9,
27.0, 21.1 and 19.4; dB (100 MHz; CDCl3) 10.7; m/z LRMS
(ESI+) 418 [(M + H)+, 13%], 283.2 (100), 200.1 (2); HRMS
(ESI+) found 417.2531 ([M + H]+ C24H30B2N2O3 requires
417.2515).
(S,S)-8b. Yellow solid (79 mg, 89%); m.p. 206–210 1C (dec);

[a]20
D 26.1 (c 1.0, CH2Cl2); vmax (film) 1628 (CQN);
dH (300 MHz; CDCl3) 8.16 (2H, s, CHQN), 7.51 (2H, d,
Scheme 4 Preparation of boracycles 10a–e. J 7.4, ArH), 7.36–7.27 (4H, m, ArH), 7.11 (2H, dt, J 7.4 and 1.1,
This journal is
ArH), 4.35 (2H, dd, J 11.9 and 1.7, CHAHB(O)), 3.81–3.73 8g. 2-Aminophenol 6g (200 mg, 1.83 mmol) and 2-formyl-
(4H, m, CHAHB(O) and CH–N), 2.16–2.06 (2H, m, phenylboronic acid 2 (275 mg, 1.83 mmol) were dissolved in
CHAHBC(N)), 2.02–1.92 (2H, m, CHAHBC(N)), 1.72–1.63 95:5 ethanol–benzene (25 mL) in a round bottom flask fitted
(2H, m, CH(CH3)2) and 0.90 (12H, app t, J 6.8, C(CH3)2); with a Dean–Stark condenser and stirred at reflux for 4 h. The
dC (75 MHz; CDCl3) 166.9 (CQN), 136.9, 133.5, 133.1, 129.4, reaction mixture was cooled and the solvent removed under
127.2, 126.1, 66.7, 62.5, 40.4, 24.8, 23.0 and 22.9; dB (100 MHz; reduced pressure. Washing with a little cold methanol afforded
CDCl3) 11.5; m/z LRMS (ESI+) 445 [(M + H)+, 14%], 412.4 8g as a yellow powder (709 mg, 90%): m.p. 182–183 1C (dec.)
(100), 292.2 (66), 227.2 (15); HRMS (ESI+) found 445.2873 (Lit. 180 1C (dec.)36); dH (300 MHz, CDCl3) 8.65 (s, 2H), 7.49
([M+H]+ C26H34B2N2O3 requires 445.2828). (2H, d, J = 7.5 Hz), 7.40–7.37 (2H, m, Ar), 7.29–7.12 (8H, m),
6.92 (4H, m); dC (75 MHz, CDCl3) d = 160.9, 155.5, 135.1,
(R,R)-8c. Yellow oil (69 mg, 88%); [a]20 D +14.7 (c 1.0, 134.2, 134.13, 133.1, 132.9, 131.5, 127.9, 118.7, 115.8, 113.7; dB
CH2Cl2); vmax (film) 1628 (CQN); dH (300 MHz; CDCl3) (96.3 MHz, CDCl3) 9.6; m/z HRMS (ESI+) found 429.1571.
8.13 (2H, s, CHQN), 7.50 (2H, t, J 7.4, ArH), 7.3–7.26 ([M + H]+ C26H19B2N2O3 (M + H+) requires 429.1582).
(4H, m, ArH), 7.12–7.07 (2H, m, ArH), 4.33 (2H, dd, J 12.0 and
1.7, CHAHB(O)), 3.78 (2H, dd, J 12.0 and 1.7, CHAHB(O)), 8h. 2-Hydroxy-5-methylaniline 6h (123 mg, 1.0 mmol) and
3.51 (2H, m, CH(Et)–N), 2.20–2.09 (4H, m, CHAHBMe) and 2-formyl-phenyl-boronic acid 1 (150 mg, 1.0 mmol) were
0.93 (6H, t, J 7.6, CH3); dC (75 MHz; CDCl3) 167.3 (CQN), dissolved in 95:5 ethanol–benzene (20 mL) in a round bottom
136.9, 133.5, 133.3, 129.3, 127.2, 126.2, 70.7, 62.4, 24.8 flask fitted with a Dean–Stark condenser and stirred at reflux
and 11.5; dB (100 MHz; CDCl3) 11.2; m/z LRMS (CI+) 389 for 4 h. The reaction mixture was cooled and the solvent
[(M + H)+, 6%], 188.2 (50), 106.0 (46), 72.0 (100); HRMS removed under reduced pressure. Washing with a little cold
(EI+) found 388.2126 (2 11B) (M+ C22H26B2N2O3 requires methanol afforded 8h as a orange powder (374 mg, 82%): m.p.
388.2124). 231–232 1C (dec.); dH (300 MHz, CDCl3) 8.64 (2H, s,
CHQN), 7.42 (2H, m, ArH), 7.36 (2H, s, ArH), 7.29–7.16
(R,R)-8d. Yellow oil (88 mg, 91%); [a]20 D +21.1 (c 1.0, (6H, m, ArH), 7.11 (2H, d, J 8.4 ArH), 6.85 (2H, d, J 8.4), 2.35
CH2Cl2); vmax (film) 1627 (CQN); dH (300 MHz; CDCl3) (6H, s, CH3); dC (75 MHz, CDCl3) 158.24, 154.9, 148.8, 134.9,
7.66–7.63 (4H, m, CHQN and ArH), 7.43–7.30 (12H, m, 134.1, 133.9, 132.9, 131.2, 128.2, 127.8, 115.3, 113.8, 21.5; dB
ArH), 7.20 (2H, br t, J 7.4, ArH), 7.09 (2H, dt, J 7.4 and (100 MHz, CDCl3) 8.9; m/z HRMS (ESI+) found 457.2011.
0.8, ArH), 5.25 (2H, m, CHAHB(O)), 4.65 (2H, dd, J 11.9 and ([M + H]+ C28H23B2N2O3 (M + H+) requires 457.1889).
10.4, CH(Ph)-N), 3.95 (2H, m, CHAHB(O)); dC (75 MHz;
CDCl3) 166.1 (CQN), 137.0, 135.7, 133.9, 133.5, 132.3, 130.0, (S,S)-10a. Dark brown solid (74 mg, 93%); m.p. 131–140 1C
129.9, 129.7, 129.5, 127.2, 126.8, 126.7, 71.4, and 69.1; dB (100 (dec); [a]20
D 36.8 (c 1.0, CH2Cl2); vmax (film) 1649 (CQN);
MHz; CDCl3) 11.3; m/z LRMS (ESI+) 485 [(M + H)+, 9%], dH (300 MHz; CDCl3) 8.13 (2H, d, J 3.0 CHQN), 7.35 (2H, d,
368.2 (10), 312.1 (100), 278.2 (16); HRMS (ESI+) found J 1.9, ArH), 6.33 (2H, d, J 1.9, ArH), 4.39 (2H, dd, J 9.4 and
485.2230 ([M + H]+ C30H26B2N2O3 requires 485.2202). 6.2, CHAHB(O)), 4.15 (2H, dd, J 9.4 and 4.0, CHAHB(O)),
3.90–3.84 (2H, m, CHQN), 2.28–2.17 (2H, m, CH(CH3)2) and
(R,R)-8e. Yellow solid (140 mg, 95%); m.p. 125–129 1C 1.06 (12H, app dd, J 6.8 and 7.2, C(CH3)2); dC (75 MHz;
(dec); [a]20
D +19.4 (c 1.0, CH2Cl2); vmax (film) 1635 (CQN); dH CDCl3) 157.2, 144.5, 132.6, 123.3, 110.2, 69.3, 63.5, 32.6, 20.0
(300 MHz; CDCl3) 8.25 (2H, s, CHQN), 7.64 (2H, d, J 7.0, and 17.4; dB (100 MHz; CDCl3) 4.7; m/z LRMS (ESI+) 397
ArH), 7.48–7.14 (16H, m, ArH), 5.46 (2H, br d, J 9.8, [(M + H)+, 9%], 345.2 (100), 283.2 (36); HRMS (ESI+)
CHAHB(N)), 4.50–4.42 (2H, m, CH(Ph)(O)) and 4.03 (2H, found 397.2122 ([M + H]+C20H26B2N2O5 requires 397.2100).
br d, J 9.8, CHAHB(N)); dC (75 MHz; CDCl3) 166.0, 137.0,
135.6, 133.9, 133.5, 132.3, 130.0, 129.9, 129.7, 129.4, 128.0, (S,S)-10b. Red oil (76 mg, 90%); [a]20 D 34.0 (c 1.0, CH2Cl2);
127.3, 126.8, 71.3 and 65.8; dB (100 MHz; CDCl3) 10.5; m/z vmax (film) 1649 (CQN); dH (300 MHz; CDCl3) 8.13 (2H, d, J
LRMS (ESI+) 485 [(M + H)+, 100%], 312.1 (99); HRMS 3.0, CHQN), 7.36 (2H, d, J 1.9, ArH), 6.32 (2H, d, J 1.9,
(ESI+) found 485.2219 ([M + H]+C30H26B2N2O3 requires ArH), 4.39 (2H, dd, J 8.9 and 6.0, CHAHB(O)), 4.24–4.15
485.2202). (2H, m, CH–N), 3.99 (2H, dd, J 8.9 and 7.4, CHAHB(O)),
1.77–1.65 (6H, m, CHAHBCH(CH3)2) and 1.00 (12H, app t, J
(rac)-8f. Yellow solid (85 mg, 96%); m.p. 142–144 1C (dec); 5.5, C(CH3)2); dC (75 MHz; CDCl3) 157.2, 144.7, 132.7, 122.8,
vmax (film) 1625 (CQN); dH (300 MHz; CDCl3) 8.20 (2H, d, J 110.0, 71.9, 52.2, 32.6, 20.5, 8.9 and 8.1; dB (100 MHz; CDCl3)
3.0, CHQN), 7.47 (2H, d, J 6.8, ArH), 7.35 (2H, d, J 7.4, 4.6; m/z LRMS (ESI+) 425 [(M + H)+, 32%], 412.4 (27),
ArH), 7.28 (2H, app dt, J 7.5 and 1.1, ArH), 7.10 (2H, app dt, 389.3 (35), 375.2 (100); HRMS (ESI+) found 425.2452
J 7.5 and 1.1, ArH), 3.96–3.88 (2H, m, CH(N)), 3.79–3.70 (2H, ([M + H]+ C22H30B2N2O5 requires 425.2419).
m, CH(O)), 2.26 (2H, br d, J 12.0, CHAHBC–O), 1.88–1.81
(4H, m, CHAHBC–O and CHAHBC–N), 1.71–1.66 (2H, m, (R,R)-10c. Red oil (134 mg, 91%); [a]20 D +33.0 (c 1.0,
CHAHBC–N) and 1.50–1.12 (8H, m, 2(CH2)2); dC (75 MHz; CH2Cl2); vmax (film) 1656 (CQN); dH (300 MHz; CDCl3)
CDCl3) 164.0 (CQN), 137.2, 133.2, 129.9, 129.1, 126.9, 126.3, 8.13 (2H, s, CHQN), 7.34 (2H, d, J 1.9, ArH), 6.31 (2H, d,
65.6, 36.3, 29.8, 27.3, 24.9 and 24.8; dB (100 MHz; CDCl3) J 1.9, ArH), 4.42–4.39 (2H, m, CHAHB(O)), 4.09–3.99 (4H, m,
10.8; m/z LRMS (ESI+) 440 [(M + H)+, 100%], 290.2 (15); CHAHB(O) and CH–N), 2.05–1.90 (4H, m, CH2Me) and 1.07
HRMS (ESI+) found 441.2549 ([M + H]+ C26H30B2N2O3 (6H, t, J 7.0, CH3); dC (75 MHz; CDCl3) 156.3, 144.5, 132.6,
requires 441.2515). 123.3 110.2, 67.7, 65.7, 26.4 and 10.4; dB (100 MHz; CDCl3)

4.8; m/z LRMS (ESI+) 369 [(M+H)+, 65%], 288.2 (100), 9 L. I. Bosch, T. M. Fyles and T. D. James, Tetrahedron, 2004, 60,
201.1 (34); HRMS (ESI+) found 369.1791 ([M+H]+ 11175–11190.
10 N. Fujita, S. Shinkai and T. D. James, Chem.–Asian J., 2008, 3,
C18H22B2N2O5 requires 369.1785). 1076–1091.
11 H. Hopfl, Struct. Bonding, 2002, 103, 1–56.
(R,R)-10d. Red solid (79 mg, 85%); m.p. 115–118 1C (dec); 12 N. Farfan, H. Hopfl, V. Barba, M. E. Ochoa, R. Santillan,
[a]20
D +39.6 (c 1.0, CH2Cl2); vmax (film) 1657 (CQN); dH E. Gomez and A. Gutierrez, J. Organomet. Chem., 1999, 581,
(300 MHz; CDCl3) 7.83 (2H, d, J 3.0, CHQN), 7.53–7.44 70–81.
(10H, m, ArH), 7.42 (2H, d, J 1.9, ArH), 6.24 (2H, d, J 1.9, 13 V. Barba, E. Gallegos, R. Santillan and N. Farfan, J. Organomet.
Chem., 2001, 622, 259–264.
ArH), 5.35–5.28 (2H, m, CH(Ph)–N) and 4.57–4.45 (4H, m, 14 M. Sanchez, H. Hopfl, M. E. Ochoa, N. Farfan, R. Santillan and
CHAHB(O)); dC (75 MHz; CDCl3) 158.3, 144.9, 136.6, 131.4, S. Rojas-Lima, Chem.–Eur. J., 2002, 8, 612–621.
129.8, 129.60, 129.59, 129.55, 129.50, 124.6, 110.3, 71.3 15 V. Barba, H. Hopfl, N. Farfan, R. Santillan, H. I. Beltran and
L. S. Zamudio-Rivera, Chem. Commun., 2004, 2834–2835.
and 70.4; dB (100 MHz; CDCl3) 5.4; m/z LRMS (ESI+) 465
16 V. Barba, R. Villamil, R. Luna, C. Godoy-Alcantar, H. Hopfl,
[(M + H)+, 100%], 415.2 (33), 335.2 (36), 292.1 (32), 215.1 (10); H. I. Beltran, L. S. Zamudio-Rivera, R. Santillan and N. Farfan,
HRMS (ESI+) found 465.1833 ([M + H]+C26H22B2N2O5 Inorg. Chem., 2006, 45, 2553–2561.
requires 465.1787). 17 V. Barba and I. Betanzos, J. Organomet. Chem., 2007, 692,
4903–4908.
(R,R)-10e. Dark brown solid (85 mg, 92%); m.p. 124–126 1C 18 H. Hopfl, M. Sanchez, V. Barba, N. Farfan, S. Rojas and
R. Santillan, Inorg. Chem., 1998, 37, 1679–1692.
(dec); [a]20
D +18.5 (c 1.0, CH2Cl2); vmax (film) 1662 (CQN); dH 19 H. Hopfl and N. Farfan, J. Organomet. Chem., 1997, 547, 71–77.
(300 MHz; CDCl3) 8.26 (2H, br s, CHQN), 7.56 (4H, br d, 20 A. Mitra, L. J. Depue, J. E. Struss, B. P. Patel, S. Parkin and
ArH), 7.45 (2H, d, J 1.9, ArH), 7.39–7.26 (6H, m, ArH), 6.34 D. A. Atwood, Inorg. Chem., 2006, 45, 9213–9224.
(2H, d, J 1.9, ArH), 5.56–5.51 (2H, m, CHAHB(N)) and 21 G. Vargas, I. Hernandez, H. Hopfl, M. E. Ochoa, D. Castillo,
N. Farfan, R. Santillan and E. Gomez, Inorg. Chem., 2004, 43,
4.11–4.08 (4H, m, CHAHB(N)) and CH(Ph)(O)); dC 8490–8500.
(75 MHz; CDCl3) 157.7, 145.1, 142.1, 129.7, 128.8, 128.6, 22 M. Sanchez, H. Hopfl, M. E. Ochoa, N. Farfan, R. Santillan and
128.1, 126.7, 124.5, 110.4, 76.2 and 63.7; dB (100 MHz; CDCl3) S. Rojas, Inorg. Chem., 2001, 40, 6405–6412.
23 M. Sanchez, T. S. Keizer, S. Parkin, H. Hopfl and D. A. Atwood,
5.0; m/z LRMS (ESI+) 465 [(M + H)+, 65%], 415.2 (100), J. Organomet. Chem., 2002, 654, 36–43.
323.2 (83); HRMS (ESI+) found 465.1841 ([M + H]+ 24 N. Yalcin, A. Kenar, C. Arici, O. Atakol and M. Tastekin, Main
C26H22B2N2O5 requires 465.1787). Group Met. Chem., 2001, 24, 247–248.
25 N. Christinat, R. Scopelliti and K. Severin, J. Org. Chem., 2007,
72, 2192–2200.
Acknowledgements 26 N. Christinat, R. Scopelliti and K. Severin, Angew. Chem., Int. Ed.,
2008, 47, 1848–1852.
We would like to acknowledge the EPSRC, Royal Society, the 27 M. Hutin, G. Bernardinelli and J. R. Nitschke, Chem.–Eur. J.,
Leverhulme Trust, Beckman-Coulter and University of Bath 2008, 14, 4585–4593.
28 H. Reyes, J. M. Rivera, N. Farfan, R. Santillan, P. G. Lacroix,
for funding. C. Lepetit and K. Nakatani, J. Organomet. Chem., 2005, 690,
3737–3745.
References 29 Y. Perez-Fuertes, A. M. Kelly, J. S. Fossey, M. E. Powell,
S. D. Bull and T. D. James, Nat. Protocols, 2008, 3, 210–214.
1 T. D. James, in Boronic Acids in Organic Synthesis and Chemical 30 Y. Perez-Fuertes, A. M. Kelly, A. L. Johnson, S. Arimori,
Biology, ed. D. G. Hall, Wiley-VCH, Weinheim, 2005, pp. 441–480. S. D. Bull and T. D. James, Org. Lett., 2006, 8, 609–612.
2 T. D. James, Top. Curr. Chem., 2007, 277, 107–152. 31 A. M. Kelly, Y. Perez-Fuertes, S. Arimori, S. D. Bull and
3 Boronic Acids in Saccharide Recognition, ed. T. D. James, T. D. James, Org. Lett., 2006, 8, 1971–1974.
M. D. Phillips, S. Shinkai, 2006. 32 A. M. Kelly, Y. Perez-Fuertes, J. S. Fossey, S. L. Yeste, S. D. Bull
4 J. S. Fossey and T. D. James, in Reviews in Fluorescence, ed. and T. D. James, Nat. Protocols, 2008, 3, 215–219.
C. D. Geddes and J. R. Lakowicz, Springer, 2008, p. in press. 33 A. M. Kelly, S. D. Bull and T. D. James, Tetrahedron: Asymmetry,
5 T. D. James, K. Sandanayake and S. Shinkai, Angew. Chem., Int. 2008, 19, 489–494.
Ed. Engl., 1996, 35, 1911–1922. 34 P. Axe, S. D. Bull, M. G. Davidson, C. J. Gilfillan, M. D. Jones,
6 T. D. James, P. Linnane and S. Shinkai, Chem. Commun., 1996, D. Robinson, L. E. Turner and W. L. Mitchell, Org. Lett., 2007, 9,
281–288. 223–226.
7 T. D. James and S. Shinkai, Top. Curr. Chem., 2002, 218, 159–200. 35 P. J. M. Taylor and S. D. Bull, Tetrahedron: Asymmetry, 2006, 17,
8 A. P. Davis and T. D. James, in Functional Synthetic Receptors, ed. 1170–1178.
T. Schrader and A. D. Hamilton, Wiley-VCH, Weinheim, 2005, 36 D. W. Norman, J. P. Edwards, C. M. Vogels, A. Decken and
pp. 45–110. S. A. Westcott, Can. J. Chem., 2002, 80, 31–40.
This journal is
N-Inversion in 2-azabicyclopentane derivatives: model simulations

for a laser controlled molecular switch
Bastian Klaumünzer* and Dominik Kröner
Received (in Montpellier, France) 17th July 2008, Accepted 18th September 2008
DOI: 10.1039/b812319e
We report model quantum simulations for the nitrogen inversion in 2-azabicyclo[1.1.1]pentane

derivates controlled by laser pulses proposing to use this class of molecules as molecular switches.
The derivatives trans-5-fluoro-2-methyl-2-azabicyclo[1.1.1]pentane and cis-5-fluoro-2-methyl-2-
azabicyclo[1.1.1]pentane are investigated by means of density functional theory and quantum
wave packet dynamics. The molecules have two stable, i.e. energetically well-separated,
conformers along the N-inversion coordinate. In 1D model simulations the transformation from
one conformer to the other is accomplished in the electronic ground state by using two
overlapping chirped linearly polarized IR laser pulses for the trans- and cis-isomer or alternatively
via an electronic excited state employing a pump-dump sequence of ultrashort UV laser pulses.
1. Introduction ammonia in a trigonal pyramid geometry (tertiary amine)

undergoes rapid nitrogen inversion. This interconversion is
Currently molecular switches are of interest in the field of very fast at room temperature because the energy barrier
nanotechnology, e.g. for application in molecular electronics.1,2 (24.2 kJ mol1) is relatively small.15 However, if the nitrogen
In addition, they are also important in biology since has sterically demanding substituents or is part of a rigid ring
many biological functions are based on them, for instance, system, it cannot easily invert around the lone electron pair
allosteric regulation and vision. In general, theoretical and making the two conformers separable at room temperature.
experimental research on photo-switchable compounds has Here we report quantum dynamical simulations of laser
mainly focused on cis-trans isomerization or photocyclic controlled N-inversion of two 2-azabicycles. This class of
reactions.3–5 Examples are chiroptical switches based on steri- azabicyclic molecules has a particularly high inversion barrier
cally overcrowded alkenes,6 azobenzenes used as surface due the bicyclic effect, which has been of great experimental
mounted molecular switches7,8 or the laser controlled rever- and theoretical interest.13,16,17 We propose that derivatives of
sible ring-opening of cyclohexadiene.9 5-X/Y-2-azabicyclo[1.1.1]pentane could serve as laser pulse
Conformational transformations in molecules without controlled molecular switches, which change according to
affecting the bond order have been, however, of rather less their conformation the size and direction of their dipole
interest for the design of molecular switches. The reason is moment mainly originating from an electronegative substitu-
obvious since the barrier separating conformers is often in the ent X/Y, see Fig. 1. For a defined setup of the molecular switch
order of 1–10 kJ mol1 making differentiation and, hence, this system could be immobilized by chemi- or physisorption
detection of the switchable molecular property, at room on a surface via an adequate linking group R, see Fig. 1.
temperature difficult if not impossible. Nevertheless, energy In this paper we investigate cis-5-fluoro-2-methyl-2-azabi-
barriers between conformers can be increased by sterically cyclo[1.1.1]pentane (X = F, Y = H and R = CH3 in Fig. 1)
demanding substituents making those molecules more attrac- and trans-5-fluoro-2-methyl-2-azabicyclo[1.1.1]pentane (X =
tive for controlled conformational switching. For instance, H, Y = F and R = CH3 in Fig. 1). These molecules possess
Umeda et al. presented quantum simulations for the optical two conformers of different dipole moments separated by a
isomerization of helical difluorobenzo[c]phenanthrene10 and high N-inversion barrier. In the following we will demonstrate
Hoki et al. performed quantum simulations for the change of how these molecular systems can be switched via vibrational or
axial chiral 1,1 0 -binaphthyl from its P- to M-form by laser
induced torsion around a single bond.11 Recently, we reported
a laser controlled axial chiral molecular switch, which allows
for the selective transformation between the achiral and either
the left- or right-handed form of an F-substituted styrene
derivative by torsion around a C–C single bond.12
A particular type of conformational change is the nitrogen
inversion (N-inversion).13,14 A nitrogen compound like
Fig. 1 Model for a laser controlled molecular switch: N-inversion of

Universität Potsdam, Institut für Chemie, Karl-Liebknecht-Str. 24-25, 5-X/Y-2-R-2-azabicyclo[1.1.1]pentane with X/Y being an electro-
D-14476 Potsdam, Germany. negative substituent (here: cis X = F/Y = H and trans X = H/Y
E-mail: bastian.klaumuenzer@uni-potsdam.de = F) and R being e.g. a linker for a surface (here R = methyl).

vibronic states. For these purposes control mechanisms coordinate, see Fig. 2. (In practice, first, the hydrogen atoms of
employing ultrafast laser pulses have been developed. the methyl group are rotated clockwise around z-axis by b and
The remainder of the paper is organized as follows: The afterwards the whole methyl group is rotated around the
model and the applied theoretical methods are explained in y-axis by a.)
section 2, the results of the quantum chemical and quantum For the laser control via the ground state N-inversion states,
dynamical calculations including the laser control are pre- see section 3.3, the unrelaxed potential energy surface (PES) of
sented in section 3. Section 4 provides a summary. the electronic ground state along a is calculated by B3LYP/
ANO-L-DZ while keeping the rest of the geometrical para-
meters frozen to the minimum energy geometry trans-Min1 or
2. Model and methods cis-Min1. For the trans-switch the calculations are also per-
2.1 Quantum chemistry formed along b obtaining a two-dimensional PES. Accord-
ingly, the permanent dipole moment along a is obtained on the
The geometries of the two N-inversion conformers of both same level of theory as the PES.
isomers, namely the trans- and cis-isomer, were optimized with For the control scenario using UV laser pulses for the
density functional theory (DFT) employing the B3LYP18,19 cis-isomer, see section 3.4, the first ten singlet electronic excited
functional and the ANO-L-DZ20 basis set as implemented in states along a are calculated by time-dependent DFT
the Molcas 6.4 program package.21 The obtained geometries (TDDFT) with B3LYP and 6-31G(d,p) as implemented in
are denoted trans-Min1 and trans-Min2 for the trans-molecule the GAUSSIAN0322 package. Transition dipole moments
or cis-Min1 and cis-Min2 for the cis-molecule, see section between ground and any of the electronic excited states are
3.1 and Fig. 2 and 4. The transition states, called trans-TS obtained on the same level of theory. As previously cis-Min1 is
and cis-TS, were also calculated at the same level of theory. used as reference geometry.
To simulate the change of conformation the molecules are
assumed to be oriented with their N–C1-bond along the space 2.2 Model Hamiltonian
fixed z-axis, as shown in Fig. 2. Then, the N-inversion is
approximated by a partial rotation of the methyl group As the moment of inertia of the methyl group with respect to
around the y-axis while keeping the rest of the molecule fixed the space fixed y-axis is about 100-times smaller than that of
in space. The angle a between the N–C1-bond and the x-axis is the rest of the molecule, we assume the F-azabicyclo group
used as reaction coordinate. In addition, for the trans-isomer being fixed in space with only the methyl group moving,23 see
the free rotation of the methyl group around the N–C1-bond is Fig. 2. To obtain the N-inversion eigenenergies eiv and eigen-
simulated by a rotation of the hydrogen atoms of the methyl functions fiv of the ith electronic state the time-independent
group around the N–C1-bond. Here the dihedral b, measured Schrödinger equation
between the H1–C1-bond and the x-axis, is used as reaction Ĥimol(a)fiv(a) = eivfiv(a) (1)
is solved numerically. The molecular Hamiltonian Ĥimol(a) is

given as
2 d2
^ i ðaÞ ¼ h
H mol þ V i ðaÞ: ð2Þ
2Iy da2
Vi(a) is the potential energy curve of the ith electronic state

with i = 0 for the electronic ground states and i 4 0 for
electronic excited states, cf. Fig. 5. Iy is the moment of inertia
for the rotation of the methyl group around the y-axis: Iy =
P 2
AmArA. The distances rA of the atoms A with mass mA,
namely C1 and the hydrogens attached to it, are obtained from
the minimum energy geometry trans-Min1 or cis-Min1, see e.g.
Fig. 2. We obtain Iy = 247390.32 mea20 for the trans- and
Iy = 246484.74 mea20 for the cis-isomer. Note that, the N-in-
version is here modelled as a partial rotation of the methyl
group around the space-fixed y-axis while keeping the rest of
the molecule fixed in space, as described in section 2.1. Eqn (1)
is, then, solved by the Fourier Grid Hamiltonian method24
using N = 256 grid points in the IR-pulse case and N = 1024
Fig. 2 Optimized geometries of trans-5-fluoro-2-methyl-2-azabicyclo- points in the UV-pulse case, i.e. the coordinate a is
[1.1.1]pentane obtained from B3LYP/ANO-L-DZ: trans-Min1 is expressed as
the global minimum with angle a set to 90.01 in the space fixed
coordinate system. trans-Min2 is the optimized geometry of the second ai = a0 + iDa, i = 0, . . ., N 1, (3)
N-inversion conformer at a E1891. trans-TS is the transition state
geometry at a E1651. trans-Min3 is the unrelaxed minimum along a where a0 = 601 and Da = 0.70591 in the IR case (section 3.3)
with a E1931 using trans-Min1 as reference. and Da = 0.15641 (section 3.4) in the UV case.
This journal is
2.3 Quantum dynamics 3. Results and discussion
To describe the laser-driven quantum dynamics the time- 3.1 Geometries and PESs
dependent Schrödinger equation is solved numerically:
The geometry optimization of the trans-5-fluoro-2-methyl-2-
@ azabicyclo[1.1.1]pentane with B3LYP/ANO-L-DZ resulted in
ih Cða; tÞ ¼ Hða; tÞCða; tÞ: ð4Þ
@t two stable minima trans-Min1 and trans-Min2, shown in
Fig. 2, where trans-Min1 is the global minimum. In terms of
for the angle a the two minima are at 901 (trans-Min1) and at
0 1 189.41 (trans-Min2) according to the space fixed coordinate
C0 ða; tÞ
B .. C system. Thus, the transformation between them is achieved by
Cða; tÞ ¼ @ . A; ð5Þ
a rotation of the methyl group around the y-axis by about
Ci ða; tÞ 1001. At the transition state trans-TS of the nitrogen inversion
the angle a E140.21. The molecule has CS-symmetry with
with C0(a,t) being the wave function of the electronic ground respect to the xz-plane in all conformations. The energy
state and Ci(a,t) the wave function of the ith excited state. The difference between the transition state trans-TS and the abso-
Hamilton operator H(a,t) is given by: lute minimum trans-Min1 is 6397.9 cm1 corresponding to
0 00 1 76.5 kJ mol1 which is more than three times higher than the
H^ ... H ^ 0i
B .. C inversion barrier of ammonia (24.2 kJ mol1).15 As one can see
Hða; tÞ ¼ @ ... ..
. . A; ð6Þ
from Fig. 2 the methyl group is rotated around the C1–N bond
H^ i0 . . . H
^ ii by about 1801 while going from trans-Min1 to trans-Min2.
Therefore a two-dimensional PES (Fig. 3) along a and b was
within the semiclassical dipole approximation: calculated.
îi ! The PES shows three minima belonging to three different
^ ii ¼ H
^ i !
H mol m ðaÞ E ðtÞ; ð7Þ molecular structures. We find minima at a = 901/b = 01
(trans-Min1), at a = 1901/b = 01 (trans-Min3) and at a =
îj
^ ij ¼ !
! 1901/b = 1801 (trans-Min4), while the latter corresponds to
H m ðaÞ E ðtÞ; ð8Þ
the unrelaxed geometry of trans-Min2. Additionally there
^
! are three distinct maxima: trans-Max1 at a = 901/b = 1801,
where mii ðaÞ are the permanent dipole moments of the ith
îj
!
trans-Max2 at a = 1501/b = 01, which belongs to the
electronic state and m ðaÞ are the electronic transition dipole unrelaxed geometry of trans-TS, and trans-Max3 at a =
moments. For the dynamical simulations we set the permanent 1501/b = 1801. The energy differences between trans-Min1
dipole moments of the ith excited state equal to that of the and trans-Max1 and the barrier height between trans-Min4
^
! ^
!
electronic ground state ðmii ðaÞ ¼ m00 ðaÞÞ , the transition dipole and trans-Min3 are approximately of the same size, namely
^
! ^
! 1000 cm1 (12 kJ mol1). This barrier, resulting from the free
moments are set m0i ðaÞ ¼ mi0 ðaÞ and the transition dipole
rotation of the methyl group around the C1–N bond, is, as
moments between all other electronic excited states are set
^
!
expected, of the same height as the rotational barrier of ethane
zero ðjmij j ¼ 0Þ . (12 kJ mol1).27 The PES shows that the N-inversion should
The electric field E(t) ~ of the laser pulses used here is
not significantly be affected by the free rotation of the methyl
given by: group, see Fig. 3. Yet, the methyl group used here represents
merely a placeholder for an arbitrary substituent R, for
! ! pðt tc Þ p
E ðtÞ ¼ e j E 0 cosðo ðt tc Þ þ ZÞsin2 þ ; ð9Þ instance, a linker to a surface. The free rotation of the methyl
2fwhm 2
for |t tc| r fwhm. Z is the time-independent phase and fwhm

the full width at half maximum (2fwhm equals the pulse
duration). The polarization vector ~ ej = ~ excos(j) + ~ ezsin(j)
with polarization angle j, where ~ ex/z is the unit vector along
the x/z-axis. Hence, the laser is chosen to propagate in
y-direction. E0 is the electric field amplitude and tc the pulse
center, i.e. the time when the sin2 shape-function reaches its
maximum. The laser pulse frequency o can be linearly chirped
by o_ ¼ do=dt :
oðtÞ ¼ o0 þ o_ ðt tc Þ; ð10Þ
where o0 is the central frequency at t = tc. All quantum

dynamical propagations were performed with the wavepacket Fig. 3 Unrelaxed potential energy surface along a and b for trans-5-
program package25 using the second order splitting26 in grid fluoro-2-methyl-2-azabicyclo[1.1.1]pentane (B3LYP/ANO-L-DZ).
representation with a time step of 0.25 fs for the IR case trans-Min1 denotes the minimum energy geometry which was used
(section 3.3) and 0.025 fs for the UV case (section 3.4). as reference geometry.

group around the C1–N bond is neglected in the following, i.e.
the unrelaxed PES only along a with trans-Min1 as reference
geometry is used for all dynamical simulations.
It should be noted, as an aside, that a normal mode analysis
of the relaxed minimum geometry trans-Min1 employing
B3LYP/6-31G(d,p) reveals three modes that should be con-
sidered important for the dynamical simulations: (i) The
rotation of the methyl group around the C1–N bond (b) at
245 cm1, (ii) the bending of the C1–N-bicylo-angle describing
the rotation of the methyl group around the y-axis at 251 cm1
(a), and (iii) the torsion of the C1–N-bicylo-dihedral describ-
ing the rotation of the methyl group around the x-axis at
286 cm1 (all frequencies scaled according to ref. 29). Hence, a
coupling of mode (ii), which characterizes our model reaction
coordinate a, to modes (i) and (iii) cannot completely be ruled
out for higher excited states, because their energies lie within
the range of the inversion excitation energies, see section 3.2.
Due to the unrelaxed geometry the inversion barrier is
approx. 1600 cm1 higher compared to the relaxed one. To
Fig. 4 Optimized geometries of cis-5-fluoro-2-methyl-2-azabicyclo-
get an idea whether the barrier can be crossed thermally
[1.1.1]pentane obtained from B3LYP/ANO-L-DZ: cis-Min1 is the
we calculated N-inversion rates according to the theory of
global minimum with angle a set to 90.01 in the space fixed coordinate
Eyring.28 The necessary thermodynamic quantities were ob- system. cis-Min2 is the optimized geometry of the second N-inversion
tained with the GAUSSIAN03 program package employing conformer at a E1791. cis-TS is the transition state geometry
B3LYP/6-31G(d,p). At 298 K we obtain an inversion rate at a E1651. cis-Min3 is the unrelaxed minimum along a with a
from trans-Min1 to trans-Min2 of 2.20 s1. So at room E1911 using cis-Min1 as reference.
temperature we find a rather small rate for spontaneous
N-inversion compared to ammonia (about 109 s1 without Fig. 5. The inversion barrier height is 8000 cm1 and due to
tunneling). As the backward reaction rate is also fairly small at the unrelaxed geometry approx. 1600 cm1 higher than in the
room temperature (3.54 s1) the here investigated conformers relaxed case (cis-TS). As noted previously, due to the frozen
are considered thermally sufficiently stable to monitor the geometry the inversion angles at the top of the inversion
change of the dipole moment, see discussion below. For a barrier (cis-Max2) and for cis-Min3 differ from those of the
more detailed discussion the reader is referred to ref. 23. optimized geometries, i.e. a(cis-Max2) E1481 and a(cis-Min3)
The geometry optimization of the cis-5-fluoro-2-methyl-2- E1911. Here we can denote that the 1D cut of the potential
azabicyclo[1.1.1]pentane with B3LYP/ANO-L-DZ resulted in energy surface of the trans- and cis-isomer, Fig. 5, are quanti-
two stable minima, denoted cis-Min1 and cis-Min2. The tatively similar, so that the curves overlap in the figure.
corresponding structures are shown in Fig. 4. Cis-Min1 is
the global minimum, however, the energy difference between
the two minima is only 7 cm1. In terms of the inversion angle
a the two minima are found at 901 (cis-Min1) by definition and
at 179.81 (cis-Min2), i.e. the transformation between them is
achieved by flipping the methyl group by about 901. As the
steric interactions of the X-substituent (X = F) with
the methyl group (R) is stronger than for the trans-isomer
(X = H), the change in a going from one conformer to the
other (E901) is smaller than for the trans-isomer (E1001).
At the transition state cis-TS of the nitrogen inversion
the angle a E164.71. The molecule has a mirror plane in the
xz-plane in all conformations. The energetic difference
between the transition state cis-TS and the absolute minimum
cis-Min1 is now 6358.6 cm1 corresponding to 76.1 kJ mol1.
Hence, the barrier height is similar to the one of the trans-
isomer (76.5 kJ mol1).
For the cis-isomer we also observe that the methyl group is
Fig. 5 Potential energy surface of 5-fluoro-2-methyl-2-azabicyclo-
rotated around the C1–N bond by about 1801 while going
[1.1.1]pentane along a for the electronic ground state S0 (B3LYP/
from cis-Min1 to cis-Min2. As the coupling of the N-inversion ANO-L-DZ) (fitted from 33 single point calculations with a cubic
to the rotation of the methyl group is, as discussed above, spline) and first three electronic excited states, S1 to S3 (TD-B3LYP/
rather weak, only the one-dimensional PES along a starting 6-31G(d,p)). Min1 denotes cis- and trans-Min1, Min3 cis- and trans-
from cis-Min1 is considered. The unrelaxed electronic ground Min1 and Max2 denotes cis- and trans-Max2, since the potentials for
state potential along a (B3LYP/ANO-L-DZ) is shown in the cis- and trans-isomers overlap on the scale of the picture.
This journal is
^
!
For the UV laser pulse control of the cis-isomer electronic The components of the permanent dipole moment m00 along
excited states were calculated as explained in section 2.1. The a are shown in Fig. 6(a) for the trans-isomer. Because of the
first three excited states S1, S2 and S3 (TD-B3LYP/6-31G(d,p)) Cs-symmetry in the xz-plane the permanent dipole moment
of the cis-isomer are depicted in Fig. 5. The shape of the along y is zero at all a. The laser will, therefore, be chosen to
excited state potentials are similar to those of other aliphatic propagate in y-direction, see eqn (9). The major change in
tertiary amines calculated by Solling et al. with TD-B3LYP/ m00 00
x occurs in range of 150–2101, while mz has its major change
6-31++G(2df).30 We observe a vertical excitation energy in the range of 70–1501.
from S0 to S1 at a = 901 of approx. 7.2 eV (58071.9 cm1). For the cis-isomer the components of the permanent dipole
Compared to the amines in ref. 30 the here computed excita- ^
!
moment, m00 ðaÞ , and of the transition dipole moments from S0
tion energies are similar, so that we consider the level of theory ^01
!
used for the calculation of the electronic excited states to be to S1, m ðaÞ , are plotted in Fig. 6(b) and (c). For reasons of
sufficient for our needs, although Rydberg states might not be symmetry again m00 y = 0 for all a. In contrast to the trans-
described precisely due to the restrictions of the basis set used isomer the major change in m00 x is in range of 70–1201, while for
here, i.e. the lack of diffuse functions. An orbital analysis m00

z the major change occurs in the range of 120–2101 now. For
shows that the transitions are predominantly of n - p and an efficient pump–dump mechanism31,32 for both the trans- and
n - s character in accordance to the amines in ref. 30. the cis-isomer the laser pulses will be polarized in accordance
The topology of the excited states differ from the ground to the regions of largest change in the dipole components, see
state. Instead of two minima along a there is only one single section 3.3. For the electronic transition to the S1 state of the
minimum. The topology of the S1 potential is suited well for cis-isomer, UV laser pulses will be xz-polarized as well, as
switching the molecule via this excited state since no barrier transitions in y polarization are forbidden by symmetry.
has to be crossed on V1 by switching from one conformer to
the other, see section 3.4. 3.2 Inversion eigenstates
The inversion eigenstates of the ground state were calculated
as described in section 2.2. There are 36 eigenstates (trans-
isomer)/35 eigenstates (cis-isomer) below the barrier whose
eigenfunctions f0v are localized in the left and 21 eigenstates
(both isomers) whose eigenfunctions f0v are localized in the
P
right potential well. All eigenfunctions f0v which satisfy K1 i=1
0 2
|fv (ai)| Da Z 0.999 are called ‘‘left localized’’ eigenfunctions.
Correspondingly, an eigenfunction is called ‘‘right localized’’ if
PN 0 2
K+1|fv (ai)| Da Z 0.999 is fulfilled, where aK is the grid
point defined by the maximum of the inversion barrier V0(aK)
(trans-Max2/cis-Max2). All states in the left quantum well are
termed ‘‘L’’ and those in the right quantum well are termed
‘‘R’’. The associated wave functions f0v are denoted fuL with
f0L to f35L/f34L (trans/cis) for the left well and fuR with f0R to
f20R for the right well. (The superscript 0 is omitted for the
‘‘localized’’ eigenfunctions since the concept applies only for the
ground state.) In addition, there are two more eigenstates below
the barrier (both isomers) which are considered ‘‘delocalized’’
in these terms. Table 1 lists the two lowest N-inversion
eigenenergies e0v in each ground state minimum, their energy
difference De = e0v0 e0v and the corresponding dipole matrix
elements hf0v0|m00 0
x/z|fv i = hmx/zi for trans- and cis-isomer.
3.3 Switching via ladder climbing

For the quantum dynamical simulations the system is
initially assumed to be in the inversion ground state 0L, i.e.
Table 1 Selection of eigen-energies e0v in cm1 of the electronic

ground state for the trans- and cis-isomer, energy differences De and
transition dipole matrix elements hmx/zi in Debye
trans cis
Isomer f0L f1L f0R f1R f0L f1L f0R f1R

Fig. 6 x-, y- and z-component along a for the permanent dipole e0v 126.2 379.0 3397.2 3649.3 124.5 389.7 3383.9 3642.0
moment ~m 00 (B3LYP/ANO-L-DZ) of (a) trans- and (b) cis-5-fluoro-2- De 252.8 252.1 265.2 258.1
methyl-2-azabicyclo[1.1.1]pentane, and (c) the transition dipole hmxi 0.0095 0.029 0.078 0.019
^
! hmzi 0.044 0.0082 0.013 0.051
moments m01 to S1 (TD-B3LYP/6-31G(d,p)) for the cis-isomer.

C(t = 0) = f0L. The goal of the laser control is, to transfer the 3.3.1 Switching the trans-isomer. The electric field consists
population to the R states. This is achieved, first, by climbing of an overlapping pump–dump sequence, see Fig. 7(a), with
up the vibrational ladder until the wave packet is above the optimal parameters as given in Table 2. All pulse parameters
barrier. Then, a dump laser pulse will be used to induce a were tuned manually to obtain the best possible result. In
downward ladder climbing in the right potential well to trap general, the laser parameters are chosen in accordance with the
the wave packet there. To achieve a most efficient ladder molecular properties, i.e., transition dipole moment elements
climbing the laser pulses will be linearly chirped33–35 according and energy differences. This approach allows for a deeper
to eqn (10) to compensate for the anharmonicity of the understanding and more flexible control of the underlying
potential at higher energies. switching mechanism. As initial guess we set the frequency
Fig. 7(a)/(d) show the time evolution of the electric field of o0 of the pump/dump pulse to the transition frequency of
the laser pulse sequences for switching the trans- (a) or cis- 0L - 1L (252.8 cm1)/1R - 0R (252.1 cm1). Further fine
isomer (d). The resulting time evolution of the expectation tuning then lead to a frequency close to a transition frequency
value of the angle a and the population of the L (PL) and R between higher R states (202.00 cm1). Initially the polariza-
hmz i 36
(PR) states are shown in Fig. 7(b)/(e) and (c)/(f) for trans (b, c) tion angles j were estimated by tanj ¼ hm for the transition
xi
or cis (e, f), respectively. The populations in the L and R states between 0L and 1L (77.801) and 1R and 0R (15.801). Further
and the population in all other states (PD) are calculated as optimization of the pulse parameter resulted in almost the
follows: same values for the pump (77.801) and dump pulse (15.951),
35=34
X see Table 2. A non-overlapping sequence of pump and dump
PL ðtÞ ¼ jhCðtÞjfuL ij2 ; ð11Þ pulse sequence was found less efficient. At first, the overall
u¼1
pulse is more z-polarized and has a negative chirp; after
450–500 fs it changes its polarization towards x-direction
X
20
PR ðtÞ ¼ jhCðtÞjfuR ij2 ; ð12Þ and the chirp becomes positive. One can see the change in
u¼1 polarization direction as well as the frequency chirp more
clearly in the Husimi probability distributions in Fig. 8. The
PD(t) = 1 PL(t) PR(t). (13) Husimi distribution37 is obtained from:
Z Z 0 2 0 2
1 0 ðtt Þ kðee Þ
PH ðt; eÞ ¼ dt0 de e k e h
PW ðt0 ; e0 Þ ð14Þ
h

with PW being the Wigner probability distribution:38
Z1
1 2it0 e
PW ðt; eÞ ¼ dt0 E ? ðt t0 ÞEðt þ t0 Þe h :
ð15Þ
p
1
where E is the x- or z-component of the electric field, and

k = 2s2 the parameter of the gaussian distribution with
s ¼ 4000 h=Eh , e the energy, and t the time.
From Fig. 7(b) one can see that once the propagation is
started the wave packet begins to oscillate in the left quantum
well until it crosses the barrier after 500 fs and is dumped into
the right quantum well (a = 1851). The final population is
spread over several R states such that the expectation value of
a still oscillates around 1851 as the mainly R-localized wave
packet evolves in time. Nevertheless, the switching of the
molecule was successful as at final time 92.5% of the popula-
tion has been transferred from the left potential well (a = 901)
to the right potential well (a = 1911). States 0R to 6R are the
most populated eigenstates after the laser pulse sequence. The
missing 7.5% of population remains in the D-states, i.e. mainly
above the barrier.
It should be noted that the mean peak intensity
(I¯ = 0.5e0c|E0|2) of the IR pulse is rather high: I¯ =
16.5 TW cm2 due to the high N-inversion barrier and the
comparatively small change of the dipole moment components
along a. The high laser amplitudes could be decreased by using
Fig. 7 Laser pulse sequence for the N-inversion via IR ladder
climbing from trans-Min1 to trans-Min3 (a)–(c) and cis-Min1 to longer pulses. But longer pulses could cause a decrease of
cis-Min3 (d)–(f); for the laser pulse parameters see Table 2. Time efficiency in transferring population from L to R for effects as
evolution of (a)/(d) the x- and z- component of the electric field, (b)/(e) wave packet broadening. For very long times even intramole-
the expectation value of the inversion angle hai, and (c)/(f) the cular vibrational redistribution (IVR) cannot be neglected any
population of the L, R and D-states according to eqns (11)–(13). more. Therefore, we considered the cis-isomer in the next
This journal is
Table 2 Laser pulse parameters for the IR laser pulse sequences, depicted in Fig. 7(a) and (d), for the trans- and cis-isomer
1
Isomer Pulse type j (1) fwhm/fs tc/fs E 0/GV m1 o0/cm1 _
o/cm fs1 Z/rad
trans Pump 77.80 640 640 16.5 243.25 0.365 3.25
Dump 15.95 955 1060 16.5 202.00 0.178 0.125
cis Pump 10.00 400 400 8.0 252.25 0.036 0.25
Dump 75.00 550 650 11.5 220.25 0.180 0.75
concerning the expectation value of a and the population

dynamics, see Fig. 7(d–f). The pulse sequence is found with
90% PR at final time almost as efficient as what we achieved
for the trans-isomer. The population is mostly transferred to
the states 3R–9R. As expected the intensity of the laser pulse
(I¯ = 11.5 TW cm2) was lowered by 5 TW cm2, however, it is
still high. For that reason a switching mechanism via the
electronic excited states will be investigated in the following
section.
3.4 Switching the cis-isomer via S1

For the transformation of the cis-isomer of the azabicycle via
the excited state S1 the initial state is the inversion ground state
0L as in the previous case. Now the wave packet is to be
excited to S1 employing a UV pump laser pulse, and after some
short time the wave packet is dumped into the right potential
well of the electronic ground state. The criterion for a success-
ful propagation is again that a large part of population is
transferred to the twenty R states below the central barrier of
the ground state potential. Higher states are omitted at this
point, see discussion below.
Fig. 9 shows (a) the electric field of the UV pump dump
pulse sequence, (b) the expectation value of angle a, (c) and the
population (P) of S0 (P(S0)), S1 (P(S1)) and of the R states (PR).
Fig. 8 Husimi probability distributions of the (a) z- and (b) x-com- We obtain a sequence of pulses where the pump and dump
ponent of the electric field of the IR switching pulse sequence for the pulse do not overlap at all. The UV pulse sequence is polarized
trans-isomer. in the xz-direction. The pulse parameters for the initial guess
were obtained in analogy to the procedure discussed above:
section which has greater transition dipole matrix elements, cf. We set the frequency o0 to the energy difference V1–V0 at a =
Table 1, between the eigenstates and such should lead to a 901 for the pump pulse and at a = 1901 for the dump pulse.
decrease of the laser pulse intensities. ^
!
From the transition dipole moments hf00L jm01 jf170 i and
^
!
3.3.2 Switching the cis-isomer. For switching the cis-isomer hf170 jm01 jf00R i we computed the initial polarization angles
the electric field consists as in the previous case of an over- j of the pump pulse (83.11) and of the dump pulse (7.41),
lapping pump–dump sequence with optimal parameters as see 3.2. For the pump pulse we obtained j = 83.21 and for
given in Table 2. Again a non-overlapping sequence of pump the dump pulse j = 10.51 after further manual optimization.
and dump pulse sequence was found less efficient. However, During the control sequence the pump pulse transfers 99%
now the pump pulse is more x-polarized while the dump pulse of the population from S0 to S1 (t = 360 fs), see Fig. 9(c). The
is more z-polarized, according to the regions where major center of the wave packet then travels on S1 back and forth
changes in the dipole moment components occur, cf. Fig. 6 until the dump pulse transfers 91.5% of the population back
and discussion in section 3.1. Here the polarization angles to the ground state (t = 600 fs) where the wave packet is then
were initially determined as above for the 0L–1L transition as mostly trapped in the right potential well of the ground state
j = 9.51 and for the 1R–0R transition as j = 69.61. (89.5%), see Fig. 9(c). All the population transferred from S1
Hence, the optimized polarization angle for the pump pulse to the R-states of S0 is found in the inversion states 14R to
(10.01) is in a good agreement with the calculated one, for 17R; so the wave packet is still highly vibrationally excited and
the dump pulse the optimized angle (751) differs slightly. it is therefore oscillating between a = 1631 and a = 1881, see
For getting the wave packet above the barrier a pump pulse Fig. 9(b). The missing 2% of the ground state population
with a slight positive chirp was found beneficial. The second remains above the barrier (Max2). 8.5% of the electronically
pulse, then, has a notable positive chirp and dumps the wave excited population remains in S1.
packet into the right potential well. The wave packet propaga- The goal of reducing the laser pulse intensity is reached. The
tion shows almost the same behaviour as for the trans-isomer intensity was brought down to 0.83 TW cm2 for the pump

ferred back to S0 is excited to S2 by the dump pulse such that at
the end of the propagation only 50% of the population is
transferred to the R states of S0 (not shown). Hence, we have a
loss of efficiency, when S2 is included. When including more
states up to S10 there is only additional population transfer to
S6 by 2%. There will be, however, no population transfer to
S3, S4, S7 and S8 as the transitions from S0 are symmetry
forbidden in x and z direction. For energetic reasons there is
also no population transfer to S9 or S10. Furthermore, due to
the different sign of the transition dipole moment of S5 in the z
direction the coupling to the x–z polarized dump pulse is
rather weak due to the improper polarization. Therefore, no
significant population transfer to S5 takes place. Here we also
note, that a more precise description of the electronic excited
state potentials might be necessary in order to correctly
account for avoided crossings in the regions of a = 1651 to
2151 which might lead to nonadiabatic transitions. In sum-
mary, while the laser induced switching via electronic excited
states is faster and allows for more realistic laser parameters—
at least within the framework of our model—the efficiency is
reduced due to undesired electronic excitations mainly to S2.
4. Summary and conclusions

Quantum simulations for a laser driven model system were
Fig. 9 Laser pulse sequence for the transformation of the cis-isomer presented based on the approximate description of the nitro-
via the excited state S1 from cis-Min1 to cis-Min3; for the laser pulse gen inversion in two azabicycles. Each of the two proposed
parameters see Table 3. Time evolution of (a) the x- and z-component molecules, cis- and trans-5-X-2-R-2-azabicyclo[1.1.1]pentane,
of the envelope function of the electric field, (b) the expectation value possesses two stable conformers due to the sterically hindered
of the inversion angle hai, and (c) the population in S0, S1 and R-states. N-inversion. The molecules change the size and direction of
their dipole moment upon N-inversion where the electronega-
tive substituent X/Y mainly determines this property. The
Table 3 Laser pulse parameters for the UV laser pulse sequence substituent R can be used to immobilize the system, for
depicted in Fig. 9(a) instance, by mounting it via a linker group R on a surface.
Pulse fwhm/ E0/GV o0 / _
o/cm 1 To investigate the possibilities of laser control we chose here
type j (1) fs tc/fs m1 cm1 fs1 Z/rad for a toy model X/Y = F and R = CH3. For trans-5-fluoro-2-
methyl-2-azabicyclo[1.1.1]pentane a two-dimensional poten-
Pump 83.20 180 180 2.5 58170.0 0.0 0.0
Dump 10.50 155 535 4.5 51387.0 0.86 0.0 tial along a and b was calculated, where a models the
N-inversion and b describes the free rotation of the methyl
group around its single bond to N. For the cis-isomer the
pulse and 2.3 TW cm2 for the dump pulse. As the population potential energy curve only along the nitrogen inversion
is transferred to high N-inversion states of S1, namely eigen- coordinate (a) was computed. In addition, the potential energy
states 67–72, whereas 70 is the most populated, the wave curve was evaluated along a for several electronic excited
packet is not in a compact form any more on the excited state states. The designed laser pulse sequences allow to transfer
and hence it turned out to be very difficult to dump the the molecules from their energetically more stable conformer
population effectively to the ground state. The transition (Min1) to the less stable conformer (Min3) along the model
frequency of the pump pulse o0 = 58170 cm1 is close to reaction coordinate (N-inversion). Linearly polarized laser
the energy difference of the eigenenergies of the eigenstates f170 pulses were used to switch the molecule by either IR induced
and f0L (58169.65 cm1). Neither shortening or prolonging ladder climbing or alternatively using the electronic excited
the laser pulse durations nor lowering or increasing their state (S1) as intermediate state in case of the cis-isomer.
intensity increased the population of the R states. In the case of vibrational ladder climbing two overlapping
Comparing the ladder climbing mechanism to the excited laser pulses with chirped frequencies in the IR range were used
state mechanism one can say that almost the same amount of to switch the molecules. Thereby excitation and de-excitation
the population is transferred to the twenty R states below the were mainly controlled by changing the chirp and the polari-
barrier. But in the ladder climbing case lower vibrational R zation of the laser pulse. But the obtained laser intensities are
states have been populated, which leads to smaller oscillations rather high.
in a. In the UV case the laser pulse durations are much shorter Hence, we applied a control mechanism for the cis-isomer via
(690 fs) than in the IR case (1200 fs). However, upon including the first electronic excited S1. In this case the molecule is initially
the excited state S2 in the calculations the population trans- excited by a UV pump laser pulse to a highly vibrational state
This journal is
of S1. Afterwards a second UV laser pulse brings it down to the 2 A. H. Flood, J. F. Stoddart, D. W. Steuerman and J. R. Heath,
electronic ground state in the right potential well. Science, 2004, 306, 2055.
3 M. Irie, Chem. Rev., 2000, 100, 1685.
In all cases the molecule was switched effectively as at least 4 C. Ciminelli, G. Granucci and M. Persico, Chem. Phys., 2008, 349,
90% of population was found in the target potential well. 325.
However, if the second excited state S2 is considered as well 5 N. Tamai and H. Miyasaka, Chem. Rev., 2000, 100, 1875.
there is only population transfer of 50% to the R states in case 6 R. A. van Delden, M. K. J. ter Wiel and B. L. Feringa, Chem.
Commun., 2005, 200.
of UV pulses. 7 G. Füchsel, T. Klamroth, J. Dokic and P. Saalfrank, J. Phys.
The efficiency of the population transfer could be dimin- Chem. B, 2006, 110, 16337.
ished due to dissipative effects as intramolecular vibrational 8 S. Hagen, F. Leyßner, D. Nandi, M. Wolf and P. Tegeder, Chem.
Phys. Lett., 2007, 444, 850.
redistribution (IVR). However, due to the overlapped pump-
9 D. Geppert, L. Seyfarth and R. de Vivie-Riedle, Appl. Phys. B:
dump control scheme the system will most probably return to Lasers Opt., 2004, 79, 987.
its thermal equilibrium geometry from where it can be 10 H. Umeda, M. Takagi, S. Yamada, S. Koseki and Y. Fujimura,
switched again, cf. ref. 14. The inversion mode may also J. Am. Chem. Soc., 2002, 124, 9265.
11 K. Hoki, S. Koseki, T. Matsushita, R. Sahnoun and Y. Fujimura,
couple to other bending modes of the methyl group making J. Photochem. Photobiol., A, 2006, 178, 258.
the proposed control strategy more complicated. Here, simu- 12 D. Kröner and B. Klaumünzer, Phys. Chem. Chem. Phys., 2007, 9,
lations including more degrees of freedom could help to 5009.
quantify the effect. In this sense the mechanism via electronic 13 J. M. Lehn, Fortschr. Chem. Forsch., 1970, 311.
14 G. K. Paramonov and P. Saalfrank, Chem. Phys. Lett., 1999, 301,
excited states could be more efficient as the switching process is 509.
faster than in the case of vibrational ladder climbing. The 15 J. D. Swalen and J. A. Ibers, J. Chem. Phys., 1962, 36, 1914.
switching process via electronic excited states contains, how- 16 S. F. Nelsen, J. T. Ippoliti, T. B. Frigo and P. A. Petillo, J. Am.
Chem. Soc., 1989, 111, 1776.
ever, the possible risk of undesired photochemical pathways 17 A. M. Belostotskii, H. G. Gottlieb and M. Shakhen, J. Org. Chem.,
which could lead to a diminution of the desired control. 2002, 67, 9257.
The degree of orientation of the molecule with respect to the 18 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B: Condens. Matter
polarization vector of the laser field determines the efficiency Mater. Phys., 1988, 37, 785.
19 A. D. Becke, J. Chem. Phys., 1993, 98, 5648.
of the control mechanism. There are, however, theoretical and 20 P. O. Widmark, P. Å. Malmqvist and B. O. Ross, Theor. Chim.
experimental methods for orienting or aligning molecules, e.g. Acta, 1990, 77, 291.
in strong electric fields,39,40 using elliptically polarized lasers41 21 G. Karlström, R. Lindh, P. Å. Malmqvist, B. O. Roos, U. Ryde,
V. Veryazov, P. O. Widmark, M. Cossi, B. Schimmelpfennig,
or applying optimal control theory.42
P. Neogrady and L. Seijo, Comput. Mater. Sci., 2003, 28, 222.
For the molecular system to be used in electronic devices, it 22 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
should be immobilized e.g. by adsorption to a surface. For this M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr.,
one has to find a suitable linking group. By immobilizing the T. Vreven, K. N. Kudin, J. C. Burant, J. M. Millam,
S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi,
molecule on a surface the switching mechanism will be different G. Scalmani, N. Rega, G. A. Petersson, H. Nakatsuji, M. Hada,
from those presented here since the azabicycle will flip instead M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida,
of the R-group. Investigations along this thread are on the way. T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li,
Still, different fixed molecular orientations (with potentially J. E. Knox, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo,
J. Jaramillo, R. Gomperts, R. E. Stratmann, O. Yazyev,
restricted rotations with respect to the surface normal) are A. J. Austin, R. Cammi, C. Pomelli, J. Ochterski, P. Y. Ayala,
possible upon chemisorption depending on the symmetry of K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg,
the surface and the linker group. For surface mounted mole- V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain,
O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari,
cules with different orientation along the surface normal sto- J. B. Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford,
chastically optimized elliptically polarized laser pulses were J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz,
found efficient for control of molecular isomerization.43 Note I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
that the coupling of the vibrational and electronic degrees of C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill,
B. G. Johnson, W. Chen, M. W. Wong, C. Gonzalez and
freedom of the molecule to the surface degrees of freedom J. A. Pople, GAUSSIAN 03 (Revision C.02), Gaussian, Inc.,
(phonons, electron-hole pairs) may intensify energy dissipation Wallingford, CT, 2004.
depending on the nature of the solid and the linking groups. 23 B. Klaumünzer, Diplomarbeit, Universität Potsdam, 2008, URL:
http://opus.kobv.de/ubp/volltexte/2008/1748/ (URN: urn:nbn:de:
Nevertheless, the model molecules presented here could be a
kobv:517-opus-17482).
good supplement to the model molecular switches which are 24 C. C. Marston and G. G. Balint-Kurti, J. Chem. Phys., 1989, 91,
based on cis–trans isomerization or photocyclization reaction. 3571.
25 B. Schmidt, Wavepacket: A program package for quantum-
mechanic wave packet propagation, 1999.
Acknowledgements 26 M. D. Feit and J. A. Fleck, Jr, J. Chem. Phys., 1983, 78, 301.
27 J. D. Kemp and K. S. Pitzer, J. Chem. Phys., 1936, 4, 749.
28 H. Eyring, J. Chem. Phys., 1935, 3, 107.
We thank P. Saalfrank for stimulating discussions. Financial
29 K. Irikura, R. Johnson and R. Kacker, J. Phys. Chem. A, 2005,
support by the Deutsche Forschungsgemeinschaft, project KR 109, 8430.
2942/1 is gratefully acknowledged. 30 T. I. Solling, C. Kotting and A. H. Zewail, J. Phys. Chem. A, 2003,
107, 10872.
31 D. J. Tannor and S. A. Rice, J. Chem. Phys., 1985, 83, 5013.
References 32 D. J. Tannor, R. Kosloff and S. A. Rice, J. Chem. Phys., 1986, 85,
5805.
1 B. L. Feringa, R. A. van Delden and M. K. J. ter Wiel, Pure Appl. 33 S. Chelkowski, A. D. Bandrauk and P. B. Corkum, Phys. Rev.
Chem., 2003, 75, 563. Lett., 1990, 65, 2355.

34 D. J. Maas, D. I. Duncan, R. B. Vrijen, W. J. van der Zande and 39 H. J. Loesch and A. Remscheid, J. Chem. Phys., 1990, 93, 4779.
L. D. Noordam, Chem. Phys. Lett., 1998, 290, 75. 40 B. Friedrich and D. R. Herschbach, Nature, 1991, 353, 412.
35 T. Witte, T. Hornung, L. Windhorn, D. Proch, R. de Vivie-Riedle, 41 J. J. Larsen, K. Hald, N. Bjerre, H. Stapelfeldt and T. Seideman,
M. Motzkus and K. L. Kompa, J. Chem. Phys., 2003, 118, 2021. Phys. Rev. Lett., 2000, 85, 2470.
36 D. Kröner and B. Klaumünzer, Chem. Phys., 2007, 338, 268. 42 K. Hoki and Y. Fujimura, Chem. Phys., 2001, 267, 187.
37 K. Husimi, Proc. Phys.-Math. Soc. Jpn., 1940, 4, 264. 43 D. Kröner, B. Klaumünzer and T. Klamroth, J. Phys. Chem. A,
38 E. Wigner, Phys. Rev., 1932, 40, 749. 2008, 112, 9924.
This journal is
How does non-covalent Se SeQO interaction stabilize selenoxides at

naphthalene 1,8-positions: structural and theoretical investigationsw
Satoko Hayashi,a Waro Nakanishi,*a Atsushi Furuta,a Jozef Drabowicz,b
Takahiro Sasamoric and Norihiro Tokitohc
Received (in Montpellier, France) 9th June 2008, Accepted 25th September 2008
DOI: 10.1039/b809763a
Bis-selenides (LL), such as 8-[MeSe(X)]-1-[MeSe(Z)]C10H6 (1 (LL)), 8-[EtSe(X)]-1-[EtSe(Z)]C10H6

(2 (LL)), 8-[p-YC6H4Se(X)]-1-[MeSe(Z)]C10H6 (3 (LL)) and 8-[p-YC6H4Se(X)]-1-[p-YC6H4Se(Z)]C10H6
(4 (LL)) were oxidized with ozone at 0 1C, where (X, Z) = (lone pair, lone pair) for LL.
Bis-selenoxides, 1 (OO), 3 (OO) and 4 (OO) where (X, Z) = (oxygen, oxygen), were obtained in
the oxidation of 1 (LL), 3 (LL) and 4 (LL), respectively, via corresponding selenide-selenoxides,
1 (LO), 3 (LO) and 4 (LO), respectively. A facile Se–C bond cleavage was observed in 2 (LL).
The structures of 1 (LO) and 1 (OO) were determined by the X-ray analysis. Three Se SeQO
atoms in 1 (LO) and four OQSe SeQO atoms in 1 (OO) align linearly. While the non-covalent
Se SeQO 3c–4e interaction operates to stabilize 1 (LO), the non-covalent OQSe SeQO 4c–4e
interaction would not stabilize 1 (OO). The 3c–4e interaction must play an important role to
control the stereochemistry of selenoxides. The 8-G-1-[MeSe(OH)2]C10H6 (n (OHOH)) are the key
intermediates in the racemization of 8-G-1-[MeSe(O)]C10H6 (n (O)) in solutions, where G = SeMe
(1), H (5), F (6), Cl (7) and Br (8). Energies of n (OHOH), relative to n (O), are evaluated based
on the theoretical calculations. G of SeMe is demonstrated to operate most effectively to protect
from racemization of selenoxides among n = 1 and 5–8, since the relative energies
for G of cis- and trans-SeMe are largest.
Introduction der Waals radii minus 1 Å.8,9 Various types of non-covalent

interactions are detected in naphthalene 1,8-positions.8–11 The
Selonoxides1–4 [RSe(O)R 0 ] afford optically active enantiomers, s-type three center-four electron interactions (s(3c–4e)),12–14
as well as sulfoxides,5,6 if R and R 0 are not the same, since Se s(2c–4e),12 p(2c–4e),12 distorted p(2c–4e),12 and Z4 4c–6e13
in each selenoxide is three-coordinated containing a lone pair. are typical examples. Such non-covalent interactions are
However, it is usually difficult to utilize optical active selen- demonstrated to control the fine structures of molecules.15
oxides to introduce the optical activity in a target mole- Recently, we investigated fine structures of 8-G-1-(arylseleninyl)-
cule,1,2,4,7 since the racemization of optical active selenoxides naphthalene with G = H, F, Cl and Br, together with
is usually very fast. Nevertheless, some efforts have been made the factors to control the structures, as the first step to
to stabilize the stereochemistry of selenoxides, by taking control the stereochemistry of selenoxides.16 The factors are
advantage of non-covalent coordination by the neighboring called G, O and Y dependences, which originate from the
groups (G) of the G SeQO type.2,4,7 np(G) s*(Se–O), np(O) p(Nap) and np(O) p(Ar) interac-
Naphthalene 1,8-positions supply a good system to investi- tions, respectively.16
gate such interactions, since the non-bonded distances between We paid much attention to G = MeSe and ArSe in 8-G-1-
heteroatoms at the positions are close to the sum of the van (arylseleninyl)naphthalenes, since many conformers are plau-
sible around the two Se–CNap bonds, relative to the case of
a
Department of Material Science and Chemistry, Faculty of Systems G = H and halogens. Scheme 1 shows the orbitals taking part
Engineering, Wakayama University, 930 Sakaedani, Wakayama in the non-covalent Se SeQO interaction. A bis-selenide
640-8510, Japan. E-mail: nakanisi@sys.wakayama-u.ac.jp;
Fax: +81 73 457 8253; Tel: +81 73 457 8253
b
Center of Molecular and Macromolecular Studies, Polish Academy
of Science, Sienkiewicza, 112, 90-363 Lodz, Poland
c
Institute for Chemical Research, Kyoto University, Gokasho, Uji,
Kyoto 611-0011, Japan
w Electronic supplementary information (ESI) available: Energies and
relative energies for 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5), F
(6), Cl (7) and Br (8) with X = lone pair (L), O (O), OH+ (OH+) and
O2H2 (OHOH)], the packing structures of 1 (OO), counter map for
1 (OO), Cartesian coordinates for optimized structures of 1 and 5–8
with X = lone pair (L), O (O), OH+ (OH+) and O2H2 (OHOH)].
CCDC reference numbers 688690 (1 (LO)) and 688691 (1 (OO)). For
ESI and crystallographic data in CIF or other electronic format see Scheme 1 Orbitals taking part in the non-bonded Se SeQO inter-
DOI: 10.1039/b809763a actions in naphthalene 1,8-positions.

performed on 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5),
F (6), Cl (7) and Br (8) with X = lone pair (L), O (O), OH+
(OH+) and O2H2 (OHOH)], where OHOH must be the key
intermediate in the racemization of 1 and 5–8, in the presence
of a trace of water. The relative energy [DE = E(n (OHOH))
(E(n (O)) + E(H2O)) (n = 1 and 5–8)] is evaluated: that for
G = MeSe is largest among them. The larger value must
correspond to a selenoxide with the stronger resistance for
racemization, although n (OHOH) is not the transition state.
The G SeQO interactions containing the Se SeQO
and OQSe SeQO interactions are also analyzed with the
natural orbital (NBO)19,20 and atoms-in-molecules (AIM)21,22
analyses.
Oxidation of 1,8-bis(selanyl)naphthalenes (LL) with ozone
is well controlled and monitored, which gives 1,8-bis(seleninyl)-
naphthalenes (OO) via 8-selanyl-1-seleninylnaphthalenes (LO).
Chart 1 Bis(selanyl)naphthalenes, 1–4, together with 5–8. Factors to control the fine structures of 1 (LO) and 1 (OO) are
clarified based on QC calculations, after determination of the
contains double ns(Se), np(Se), s(Se–C) and s*(Se–C) orbitals. structures. The Se SeQO interaction is demonstrated to
However, ns(O), np(O), np 0 (O), s(Se–O) and s*(Se–O) appear control the fine structure of 1 (LO), whereas the role of the
newly with the quit of an np(Se), when a selenide-selenoxide is OQSe SeQO interaction in 1 (OO) is critically discussed.
formed from the bis-selenide. The role of G in 1 and 5–8 in the racemization process is also
The oxidation and formation of 8-[2RSe(X)]-1- evaluated.
[ RSe(Z)]C10H6 (1 (1R = 2R = Me), 2 (1R = 2R = Et), 3
1
(1R = Me, 2R = p-YC6H4: Y = H (a), MeO (b) and NO2 (d))

and 4 (1R = 2R = p-YC6H4: Y = H (a) and tBu (c)) are
investigated for LL where (X, Z) = (lone pair, lone pair), LO Survey of oxidation
(lone pair, oxygen) and OO (oxygen, oxygen) (Chart 1). The
Bis-selenides (n (LL): n = 1–4) were oxidized with ozone in the
reactions are easily controlled and each process is followed by
methylene dichloride solution of each bis-selenide at 0 1C. The
the spectroscopic method. Non-bonded OQSe SeQO
bis-selenides (n (LL)) gave corresponding bis-selenoxides
interactions are also the subject of interest.
(n (O)) via corresponding selenide-selenoxides (n (LO)), except
The structures around the naphthyl group (Nap) in 8-G-1-
for 2 (LL). While 1 (LL) gave 1 (LO), followed by the quanti-
RSeC10H6 are well explained by three types, type A (A), B and
tative formation of 1 (OO), a facile Se–C bond cleavage
C.8c,d,f–h,17,18 The combined notation are used to specify the
occurred on the oxidation of 2 (LL), resulting in the formation
structures of 1–4 with G = RSe, where the notation, such as
AA, BA or CA, shows the conformers around the two CNap–Se of naphtho-1,8-[c,d]-1,2-diselenole (9).23 b-Elimination of the
selenoxide may be responsible for the facile Se–C bond
bonds. Scheme 2 draws the notations employed in this work,
cleavage. In the case of 3 (LL), the methylselanyl Se atoms
exemplified by 1 (LO).
were attacked exclusively. 3 (LO) were consumed to produce
The structures of 1 (LO) and 1 (OO) are determined by
the corresponding 3 (OO) with more ozone. 4 (LO) were also
X-ray crystallographic analysis. Quantum chemical (QC) cal-
produced from the corresponding 4 (LL) with ozone, followed
culations are performed on 1 (LO) and 1 (OO), to elucidate the
by the formation of the corresponding 4 (OO), respectively.
role of the Se SeQO interaction in 1 (LO) and the
The results are summarized in Chart 1. The reactions are well
OQSe SeQO interaction in 1 (OO) as the factor to control
followed by NMR.
the fine structures. Orbitals of two Se atoms in 1 (LO) and
1 (OO) must overlap directly with each other, which would Structures of 1 (LO) and 1 (OO)
stabilize the fine structures. QC calculations are also
Single crystals of 1 (LO) and 1 (OO) were obtained via slow
evaporation of methylene dichloride-hexane solutions and one
of suitable crystals was subjected to X-ray crystallographic
analysis for each compound.24 Only one type of structure
corresponds to each of 1 (LO) and 1 (OO) in the crystals.
Table 1 shows the crystallographic data of 1 (LO) and
1 (OO). Fig. 1 shows the structures of 1 (LO) and 1 (OO).25
The packing structure of 1 (OO) is shown in Fig. S1 of the
Electronic Supplementary Information (ESIw). Selected inter-
atomic distances, angles and torsional angles of the com-
pounds 1 (LO) and 1 (OO) are collected in Table 2, together
Scheme 2 Structures around naphthyl group in 8-G-1-[RSe(X)]C10H6, with those of 1 (LL), which contains two types, 1 (LL)A
exemplified by 1 (LO). and 1 (LL)B.26
This journal is
Table 1 Crystallographic data for 1 (LO) and 1 (OO) interaction operates effectively to keep the Se–O bond on the
naphthyl plane in 1 (LO) (G dependence).16 These results show
1 (LO) 1 (OO)
that the structure of 1 (LO) is well stabilized by the O and G
Empirical formula C12H12OSe2 C12H12O2Se22.5H2O dependences observed in 1-naphthyl selenoxides.16
Formula weight 330.14 391.18 On the other hand, there is no np(Se) in 1 (OO). Therefore,
Temperature/K 298(2) 103(2)
Crystal system Monoclinic Monoclinic the G dependence of the np(Se) s*(Se–O) type cannot
Space group P21/n (#14) C2/c (#15) operate in 1 (OO). Consequently, the driving force for the
a/Å 5.8460(19) 25.549(9) structure must come from the O dependence for both Se–O
b/Å 14.473(3) 5.8653(18)
c/Å 14.1490(16) 20.850(8) bonds. Namely, the non-covalent O–Se Se–O s(4c–4e) in-
b/1 97.660(17) 117.329(4) teraction must be carefully examined as a factor to stabilize the
3
V/Å 1186.5(5) 2775.6(16) fine structure of 1 (OO), although the non-bonded Se Se
Z 4 8 distances are less than the sum of van der Waals radii by
Dc/g cm3 1.848 1.872
F(000) 640 1544 ca. 0.65 Å.27 The s(4c–4e) interaction seems not so important.
Reflections observed [I 4 2s(I)] 2200 2435 How does G of MeSe control the fine structure and the
Parameters 136 190 behavior? QC calculations are performed on 1 and 5–8.
R1 [I 4 2s(I)] 0.032 0.021
R1 [all data] 0.082 0.022
oR2 [I 4 2s(I)] 0.065 0.053 QC calculations
oR2 [all data] 0.077 0.054
Goodness-of-fit on F2 1.029 1.109 QC calculations were performed on 1 (LO) with the B3LYP/
6-311+G(d) method of the Gaussian 98 program.28–30 QC
calculations revealed energy profiles of the compounds.31
Table 3 collects the results of the QC calculations. The NBO
analysis19,20 were performed on 1 (LO) and 1 (OO) with the
B3LYP/6-311+G(d) method. The results are shown in
Table 4. The AIM parameters21,22 are calculated for 1 (LO)
and 1 (OO) with the Gaussian 03 program32 employing the
6-311+G(3df) basis sets for Se with the 6-311+G(3d,2p) basis
sets for C and H at the B3LYP level. They are analyzed
employing the AIM 2000 program.33 Table 5 collects the
results of AIM calculations.
Indeed, the results of QC calculations essentially correspond
to those in the gas phase, but the factors to control and/or
stabilize the structures in gas phase must also operate in solid
states and in solutions. Therefore, it must be instructive to
consider those predicted by QC calculations, although we
must be careful for the crystal packing effect in crystals and
the solvent effect in solutions, since such effects often larger
than the predicted factors.
The effect of G to stabilize 8-G-1-[MeSe(X)]C10H6 [G =
MeSe (1), H (5), F (6), Cl (7) and Br (8) with X = lone pair
(L), O (O), OH+ (OH+) and O2H2 (OHOH)] will be dis-
cussed in detail, here. The results clarified the factors for the
racemization of selenoxides. n (OHOH) (n = 1 and 5–8) must
be the key intermediates in the racemization of n (O), in the
presence of (a trace of) water in solutions.
Fig. 1 Structures of 1 (LO) (a) and 1 (OO) (b) with atomic numbering Effect of G in 1 and 5–8
scheme for selected atoms (thermal ellipsoids are shown at the 50%
probability level). Racemization of an optically active selenoxide is believed to
proceed via a selenide dihydroxide (n (OHOH)).4a–d Scheme 3
shows a hypothetical racemization process of optically active
The structures of 1 (LO) and 1 (OO) are all AA for two n (O*) via n (OHOH).
methyl groups (Fig. 1 and Table 2).15 The planarity of the Protonation of n (O*) occurs at O of an optically active
naphthyl (Nap) planes is very good. All Se–O bonds are placed isomer of n (O*: R) to give n (O*H+: R) at the initial stage of
in the naphthyl plane. The superior tendency of the Se–O the reaction. n (OHOH) will form in the reaction of n (O*H+:
bonds to stay on the naphthyl plane (O dependence)16 must be R) with water followed by the deprotonation to yield n (OH
the driving force for the structures of 1 (LO) and 1 (OO). Three OH). Elimination of water from n (OHOH) results in the
Se Se–O atoms align linearly (+SeSeO = 173.31(15)1) and racemization, since of n (OHOH) is not optically active as a
the Se–O bond is almost perpendicular to another CNapSeCMe whole. Similar reactions occur starting from n (O*: S) to yield
plane in 1 (LO). The non-covalent np(Se) s*(Se–O) 3c–4e n (OHOH) via n (O*H+: S), which also leads to racemization.

Table 2 Selected interatomic distances (Å), angles (1) and torsional angles (1) around Se atom in 1 (LO) and 1 (OO), together with those of 1 (LL)
1 (LL)Aa 1 (LL)Ba 1 (LO) 1 (OO)

Interatomic distances
Se1–Se2 3.051(4) 3.064(4) 3.1587(10) 3.1512(8)
Se1–C1 1.929(4) 1.932(3) 1.983(5) 1.959(2)
Se1–C11 1.944(4) 1.953(4) 1.954(5) 1.940(2)
Se1–O1 1.653(4) 1.6771(15)
Se2–C9 1.926(4) 1.932(4) 1.928(5) 1.970(2)
Se2–C12 1.944(4) 1.949(4) 1.938(6) 1.934(2)
Se2–O2 1.680(15)
Angles
Se2–Se1–C11 164.47(3) 146.46(3) 85.93(16) 88.26(7)
Se2–Se1–O1 173.31(15) 167.54(5)
Se1–Se2–C12 150.34(3) 159.73(3) 85.65(18) 89.41(7)
Se1–Se2–O2 167.51(5)
Se1–C1–C10 122.9(3) 123.9(3) 126.9(4) 124.33(16)
C1–Se1–C11 99.29(16) 98.41(16) 96.0(2) 94.73(9)
C1–Se1–O1 101.1(2) 102.69(8)
C11–Se1–O1 100.7(2) 102.85(9)
Se2–C9–C10 123.9(3) 122.9(3) 124.1(4) 124.67(16)
C9–Se2–C12 99.27(16) 98.50(16) 98.1(2) 93.38(9)
C9–Se2–O2 102.21(8)
C12–Se2–O2 102.29(9)
C1–C10–C9 126.4(3) 127.2(3) 127.0(4) 128.1(2)
Torsional angles
Se1–C1–C10–C5 173.5(2) 176.0(2) 177.6(4) 179.19(15)
C10–C1–Se1C11 154.1(3) 136.8(3) 82.8(4) 86.49(19)
C10–C1–Se1–O1 175.0(4) 169.19(17)
Se2–C9–C10–C5 172.2(2) 170.2(2) 178.8(4) 178.90(15)
C10–C9–Se2–C12 138.8(3) 148.0(3) 84.6(4) 87.10(19)
C10–C9–Se2–O2 169.54(18)
O1–Se1–Se2–O2 140.3(3)
a
Ref. 26.
Table 3 Energies and relative energies for 8-G-1-[MeSe(OiHj)]C10H6 Table 4 Second order perturbation energies in the donor (D)–accep-
(i, j = 0, 1 and 2)a tor (A) interactions of the n(G) s*(Se–O) type in 8-G-1-[MeSe(O)]-
C10H6 and 8-G-1-[MeSe+(OH)]C10H6, calculated with the NBO
Form O: A/AAb OH+: A/AAb OHOH: AC methodab
5 (G = H) 2902.0303 2902.4017 2978.4686 D; A np(G); s*(Se–O) np(G): s*(Se+–OH)
Qn(Se) 1.309 1.307 1.324
Qn(O) 0.968 0.837 0.996, 0.993 G = F 1.44 9.15 (0.87)c
Qn(H) 0.497 0.433, 0.433 G = Cl 3.29 13.65 (1.09)c
+Wc 2978.4741 2978.2198 2978.4686 G = Br 3.73 27.95 (1.19)c
Dd,e as 0.0 667.7 (as 0.0) 14.4 (as 0.0) G = cis-SeMe 4.77d 34.99 (1.76)c
6 (G = F) 3001.3000 3001.6744 3077.7371 G = trans-SeMe 5.52 41.86 (2.69)c
+Wc 3077.7438 3077.4925 3077.7371 G = trans-SeMee 5.86
Dd,e as 0.0 659.8 (7.9) 17.6 (3.2) G = trans-Se(O)Mee 1.53 (2)f
7 (G = Cl) 3361.6478 3362.0250 3438.0833
+Wc 3438.0916 3437.8431 3438.0833
a
The 6-311+G(d) basis sets being employed. b In kcal mol1. c Corres-
Dd,e as 0.0 652.4 (15.2) 21.8 (7.4) ponding to the ns(G) s*(Se+–OH) interaction. d 0.76 kcal mol1 for
8 (G = Br) 5475.5651 5475.9442 5552.0007 the ns(Se) s*(Se–O) type interaction. e The 6-311+G(3df) basis sets
+Wc 5552.0089 5551.7623 5552.0007 being employed for Se with the 6-311+G(3d,2p) basis sets for C and
Dd,e as 0.0 647.4 (20.2) 21.5 (7.1) H. f Corresponding to the ns(Se) s*(Se–O) interactions.
1 (G = trans-MeSe) 5342.8896 5343.2854 5419.3241
+Wc 5419.3334 5419.1035 5419.3241
Dd,e as 0.0 603.6 (64.1) 24.4 (10.0)
1 (G = cis-MeSe) 5342.8869 5343.2821 5419.3214
+Wc 5419.3307 5419.1002 5419.3214 Table 5 Second order perturbation energies in the donor–acceptor
Dd,e as 0.0f 612.3 (55.4) 31.5 (17.1) interactions of the n(G) s*(Se–O) type at the naphthalene 1,8-
a positions in 1 (LO) and 1 (OO), calculated with the NBO methoda
Calculated with the B3LYP/6-311+G(d) method. b A for 5–8 and
AA for 1. c Evaluated based on the values of E(H2O2) = 151.5891 au, Compound ro(Se, Se)/Å rb(rc)/eao3 Drb(rc)/eao5 Hb(rc)/au
E(H2O) = 76.4438 au and E(OH) = 75.8181 au calculated with
the same method. d Relative to that of the corresponding n (O): A. 1 (LO) 3.2521 0.0195 0.0420 0.0005
e
Relative to the same structure derived from 5 (G = H) being 1 (OO) 3.2851 0.0160 0.0393 0.0002
given in parenthesis. f 7.1 kJ mol1 from the corresponding species of a
The 6-311+G(3df) basis sets being employed for Se and the
1 (G = trans-MeSe; O): AA. 6-311+G(3d,2p) basis sets for C and H.
This journal is
H2O2) E(n (O) + H2O)) (see Table S1 in the ESIw). Simi-
larly, eqn (2) and (3) exhibit DE(n (OH+)) and DE(n (OHOH)),35
respectively, which are defined as [E(n (OH+) + HO)
E(n (O) + H2O)] and [E(n (OHOH)) E(n (O) + H2O)],
respectively.36
DE(n (LO)) = E(n (L) + H2O2) E(n (O) + H2O)

G = H (121.8 kJ mol1) o F (131.3) o cis-MeSe (133.9)
o Cl (136.8) r Br (137.6) o trans-MeSe (141.0) (1)
DE(n (OH+)) = E(n (OH+) + HO) E(n (O) + H2O)

G = H (667.7 kJ mol1) 4 F (659.8) 4 Cl (652.4) 4 Br
(647.4) c cis-MeSe (605.2) 4 trans-MeSe (603.6) (2)
Scheme 3 Mechanism for racemization of n (O*) via n (OHOH) (n = 1
and 5–8).
DE(n (OHOH)) = E(n (OHOH)) E(n (O) + H2O)
G = H (14.4 kJ mol1) o F (17.6) o Cl (21.8) E Br (21.5)
Water may originate from the solvent and the racemization o trans-MeSe (24.4) o cis-MeSe (31.5) (3)
would proceed under the neutral conditions. The stability of
n (OHOH) must affect on the rates of racemization for the The order in eqn (1) corresponds the energy lowering effect
optical active selenoxides. by the G Se–O interactions in the formation selenoxides
The effect of G on the stability of 8-G-1-[MeSe(OiHj)]C10H6 relative to the G Se–C interactions in selenides. However, we
[1 and 5–8: L (i = j = 0), O (i = 1, j = 0), OH+ (i = j = 1) must be careful to examine the values for G = cis-MeSe and
and OHOH (i = j = 2)] are examined based on the QC trans-MeSe, since the structure of the corresponding selenide is
calculations. The results of QC calculations performed with commonly CC (see Table S1 in the ESIw).
the B3LYP/6-311+G(d) method are collected in Table 3. Eqn (2) exhibits that the protonation on the seleninyl O
Table 3 also contains natural charges (Qn) of Se and O atom occurs more easily in the order of G = H o F o Cl o
calculated employing the natural population analysis.20 Br { cis-MeSe o trans-MeSe. The results show that the
Scheme 4 shows optimized structures of the global minimum protonation occurs more easily when G become better donors,
for each of 1 (LL), 1 (LO) and 1 (LOH+), together with the especially for G = MeSe. The evaluated DE(n (OH+)) values
three types, AA 0 , BB and AC, for 1 (LOHOH). The values for are very large in magnitudes, however, they do not mean that
AC of n (LOHOH) are given in Table 3, since AC is most the process is very difficult to occur. The large magnitudes are
stable among the three for each.34 the results of the calculations for the charge separated species
Energy differences of the reactions in Scheme 3 are exam- of the n (OH+) + HO type. Only the relative values are
ined based on the values shown in Table 3. The energy of n (O) + important, since protonation will occur easily in solutions.
H2O (E(n (O) + H2O)) is taken as the standard for each, for Resulting hypervalent np(G) s*(Se–OH+) interactions sta-
convenience of comparison. How are the selenoxides stabilized bilize further the species in the order shown in eqn (2), relative
by G at the 8-position? The effect of G on the stabilization of to the case of the selenoxides.
selenoxides is examined before discussion the energy profile The activation energies for the racemization of optically
shown in Scheme 3. active selenoxides are closely related to the values shown in
Eqn (1) shows the energies of n (L) + H2O2 (E(n (L) + eqn (3), although they are the energies for the intermediates,
H2O2)) relative to E(n (O) + H2O) [DE(n (LO) = E(n (L) + n (OHOH). The activation energies are expected to increase in
this order. The activation energy for G = cis-MeSe is pre-
dicted to be larger than that with trans-MeSe. However, cis-
MeSe and trans-MeSe isomers interconvert with each other.
Therefore, it may be better to evaluate the value by G = trans-
MeSe under the experimental conditions: The activation
energy of 1 (LO) with G = MeSe is estimated to be about
10 kJ mol1 larger than that of 5 (L) with G = H and the
former is also larger than the case of G = Br by ca. 3 kJ mol1.
Fig. 2 summarizes the effect of G given in eqn (2).
G at the 8-position will protect sterically from the racemiza-
tion of an optical active n (O*). G must stabilize the optical
active n (O*) and the protonated n (O*H+) whereas G would
destabilize n (OHOH). The steric congestion at the backside
of the Se+–OH bond in n (O*H+) by G will block the space
Scheme 4 Optimized structures for 1 (G = SeMe) and the deriva- for H2O to attack to produce n (OHOH) (Scheme 4). We must
tives. be careful, since G could also stabilize n (OHOH) in some

Fig. 2 Energies of n (OHOH), relative to n (O) for n = 1 and 5–8.
cases. The calculated values might correspond to the total

effects of the electronic and steric effects. Energy profiles for Fig. 4 Contour map of rb(rc) for 1 (LO) in the SeSeC9 plane, together
the racemization evaluated by above calculations must contain with BCPs ( ), ring critical points ( ) and bond paths. The contours
main factors. The energies for the transition states must be [eao3] are at 2l (l = 8, 7,. . .0) and 0.0047 (heavy line). Two Me
close to those of the intermediates, n (OHOH). groups are located upside and downside of the SeSeC9 plane. The C2,
C3, C6 and C7 atoms with the C–H bonds deviate substantially from
the plane.
NBO analysis for n(G) r*(Se–O) interactions
Table 4 summarizes the second order perturbation energies AIM analysis of 1 (LO) and 1 (OO)
(E(2)) for the charge transfer (CT) interactions of the
The AIM analysis are carried out on 1 (LO) and 1 (OO). The
n(G) s*(Se–O) type in 8-G-1-[MeSe(O)]C10H6 and 8-G-1-
6-311+G(3df) basis sets are employed for Se and the
[MeSe+(OH)]C10H6 evaluated with the NBO method.37 The
6-311+G(3d,2p) basis sets for C and H at the B3LYP level.
B3LYP/6-311+G(d) method is employed for the calculations.
Table 5 collects the AIM parameters of 1 (LO) and 1 (OO) for
The E(2) values becomes larger in an order shown in eqn (4).
the bond critical points (BCPs: rc) on the interaction lines
between non-bonded Se atoms.
E(2): G = F (1.44) o Cl (3.29) o Br (3.73) o cis-MeSe
The low values of electron densities at BCPs (rb(rc)) in
(4.77) o trans-MeSe (5.52) (4)
1 (LO) and 1 (OO) (0.016–0.020 eao3) show that the interac-
tions are ionic in nature. Laplacian values of rb(rc) (Drb(rc))
The E(2) values are also evaluated for 1 (LO) and 1 (OO),
are both positive, whereas the total electron energy densities at
employing the 6-311+G(3df) basis sets for Se and the
BCPs (Hb(rc)) for 1 (LO) is negative but it is positive for
6-311+G(3d,2p) basis sets for C and H at the B3LYP level.38
1 (OO). The results strongly suggest that the np(G) s*(Se–O)
Table 4 also contains the values. The np(G) s*(Se–O) inter-
interaction in 1 (LO) is the CT interaction in nature similarly
action are evaluated to be 5.9 kcal mol1 for 1 (LO)39 and as
to the case of R2Se Br2 (MC) but the ns(G) s*(Se–O)
1.5 ( 2) kcal mol1 for the ns(G) s*(Se–O) interactions in
interactions in 1 (OO) seems weaker than such CT interac-
1 (OO). The larger value for 1 (LO) relative to 1 (OO) implies
tions.40
the more effective interaction of the np(G) s*(Se–O) type in
Fig. 4 shows the counter map of rb(rc) in the SeSeC9 plane
1 (LO). The contribution of the 4c–4e interaction of the
for 1 (LO), together with BCPs ( ), ring critical points ( ),
O–Se Se–O type was not detected by the NBO analysis.
bond paths and the interaction lines. BCP are detected on the
Fig. 3 summarizes the interactions.
Se Se and O 2H interaction lines. The BCP on the Se Se
The nature of the np(G) s*(Se–O) interaction in 1 (LO)
interaction line well visualize the np(Se) s*(Se–O) interac-
and the ns(G) s*(Se–O) interactions in 1 (OO) are evaluated
tion in 1 (LO). While BCP is also detected on the O 2H
based on the AIM analysis, next.
interaction line, the interaction is very small. A similar counter
map is also drawn for 1 (OO), which is shown in Fig. S2 of the
ESI.w
Conclusion
X-Ray crystallographic analysis of 8-methylselanyl-1-(methyl-
seleninyl)naphthalene (1 (LO)) and 1,8-bis(methylseleninyl)-
naphthalene 1 (OO) revealed that the three Se SeQO
atoms in 1 (LO) and the four OQSe SeQO atoms in
1 (OO) align linearly. All Se–O bonds are placed in the
Fig. 3 The np(G) s*(Se–O) interaction in 1 (LO) and the naphthyl plane. The superior tendency for the Se–O bonds
ns(G) s*(Se–O) interactions in 1 (OO) evaluated by the NBO method. to stay on the naphthyl plane (O dependence) must be the
This journal is
driving force for the fine structures of 1 (LO) and 1 (OO). The TMS): 13.3, 125.7, 128.3, 131.9, 132.3, 135.3, 135.6; 77Se NMR
noncovalent np(Se) s(Se–O) 3c–4e interactions (G depen- (76 MHz, CDCl3, d, ppm, Me2Se): 231.4. Anal. Calc. for
dence) operate effectively to stabilize the structure of 1 (LO). 1 (LL) (C12H12Se2): C, 45.88; H, 3.85%. Found: C, 45.73;
On the other hand, the driving force for the structure of 1 (OO) H, 3.77%.
must mainly come from the O dependence for each Se–O bond
in 1 (OO), since the G dependence cannot operate without 8-Methylselanyl-1-(methylseleninyl)naphthalene (1 (LO)).
np(Se). 1 (LL) (0.98 mg, 3.12 mmol) was dissolved in 20 mL of CH2Cl2
QC calculations clarify the factors that protect from race- and the solution was bubbling with the ozone for 5 min. TLC
mization of selenoxides. The energies of 8-G-1-[MeSe(OH)2]- was checked for the completion of the reaction (rf = 0.07
C10H6 from (8-G-1-[MeSe(O)]C10H6 + H2O) are shown to be (chloroform)). Then the solution was evaporated and dried
in an order of G = H (14.4 kJ mol1) o F (17.6) o Cl (21.8) in vacuo. The crude product was purified by column chromato-
E Br (21.5) o trans-SeMe (24.4) o cis-SeMe (31.5). The graphy (flash column, Al2O3, CH2Cl2). 1 (LO) gave 85% yield
activation energies for the racemization should increase in this as colorless powder, mp 129.8–130.1 1C; 1H NMR
order, since 8-G-1-[MeSe(OH)2]C10H6 must be the key inter- (400 MHz, CDCl3, d, ppm, TMS): 2.29 (s, 3H), 2.78 (s, 3H),
mediates. The activation energy of 1 (LO: G = MeSe) is 7.48 (t, J 7.6 Hz, 2H), 7.76 (t, J 7.7 Hz, 2H), 7.98–8.05 (m, 2H),
evaluated to be larger than that of 5 (L: G = H) and 8 8.10 (dd, J 1.1 and 7.2 Hz, 1H), 8.88 (dd, J 1.2 and 7.4 Hz,
(L: G = Br) by 10 and 3 kJ mol1, respectively. The results 1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS): 13.87, 41.12,
will help to design the optically stable selenoxides. The NBO 125.73, 126.28, 126.35, 126.57, 131.01, 132.44, 133.06, 136.13,
and AIM analyses support the discussion and visualize the 138.93, 141.34; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se):
interactions. 210.8, 833.0. Anal. Calc. for 1 (LO) (C12H12OSe2): C, 43.66; H,
Investigations on the chiral 3a (LO), prepared in the oxida- 3.66%. Found: C, 43.61; H, 3.60%.
tion of 3a (LL) with chiral reagents, are in progress. Details
1,8-Bis(methylseleninyl)naphthalene (1 (OO)). 1 (LL) (0.58 g,
will be reported elsewhere.
0.30 mmol) was dissolved in 20 mL of CH2Cl2 and the solution
was bubbling with the ozone for 15 min. TLC was checked for
Experimental the completion of the reaction (rf = 0.00 (chloroform)). Then
the solution was evaporated and dried in vacuo. The crude
General considerations product was purified by column chromatography (flash
Manipulations were performed under an argon atmosphere column, Al2O3, CH2Cl2). 1 (OO) gave 59% yield as colorless
with standard vacuum-line techniques. Glassware was dried at powder, mp 154.8–155.2 1C; 1H NMR (400 MHz, CDCl3, d,
130 1C overnight. Solvents and reagents were purified by ppm, TMS): 2.71 (s, 6H), 7.84 (t, J 7.7 Hz, 2H), 8.18 (dd, J 1.2
standard procedures if necessary. Melting points were deter- and 6.9 Hz, 2H), 8.71 (dd, J 1.4 and 6.9 Hz, 2H); 77Se NMR
mined on a Yanaco MP-S3 melting point apparatus and (76 MHz, CDCl3, d, ppm, Me2Se): 821.3. Anal. Calc. for
uncorrected. NMR spectra were recorded at room tempera- 1 (OO) (C12H12O2Se2): C, 41.64; H, 3.49%. Found: C, 41.55;
ture on a JEOL AL-300 spectrometer (1H, 300 MHz; 13C, H, 3.45%. Anal. Calc. for 1 (OO)2.5H2O (C24H24O4Se4
75 MHz) and on a JEOL Lambda-400 spectrometer (1H, 400 5H2O): C, 36.84; H, 4.38%. Found: C, 36.87; H, 4.41%.
MHz; 77Se, 76 MHz). The 1H, 13C and 77Se NMR spectra were
1,8-Bis(ethylselanyl)naphthalene (2 (LL)). Following the
recorded in CDCl3. Chemical shifts are given in ppm relative
similar method to that used for 1 (LL), 2 (LL) gave 80% yield
to Me4Si for the 1H and 13C NMR spectra and relative to
as colorless powder, mp 52.3–52.8 1C; 1H NMR (400 MHz,
reference compound MeSeMe for the 77Se NMR spectra.
CDCl3, d, ppm, TMS): 1.35 (t, J 7.4 Hz, 6H), 2.89 (q, J 7.5 Hz,
Column chromatography was performed by using silica gel
4H), 7.32 (t, J 7.6 Hz, 2H), 7.70 (dd, J 1.2 and 8.1 Hz, 2H),
(Fujishilysia PSQ-100B) and basic alumina (E. Merck) and
7.76 (dd, J 1.1 and 7.2 Hz, 2H); 77Se NMR (76 MHz, CDCl3,
analytical thin layer chromatography was performed on pre-
d, ppm, Me2Se): 341.7. Anal. Calc. for 2 (LL) (C14H16Se2): C,
coated silica gel plates (60F-254) with the systems (v/v)
49.14; H, 4.71%. Found: C, 49.23; H, 4.72%.
indicated.
8-Phenylselanyl-1-(methylseleninyl)naphthalene (3a (LO)).
Syntheses
Following the similar method to that used for 1 (LO),
Bis(methylselanyl 1,8-bis(methylselanyl)naphthalene (1 (LL)). 3a (LO) gave 80% yield as colorless needles, mp 129.8–130.2
To a solution of the dianion of naphtho[1,8-c,d]-1,2-diselenole, 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.72 (s, 3H),
which was prepared by reduction of the diselenole 923 (1.03 g, 6.98–7.02 (m, 2H), 7.11–7.16 (m, 3H), 7.56 (t, J 7.6 Hz, 1H),
3.64 mmol) with NaBH4 in an aqueous THF solution, was 7.76 (t, J 7.7 Hz, 1H), 8.05 (dd, J 1.2 and 8.0 Hz, 1H), 8.10
added methyl iodide (1.29 g, 9.06 mmol) at room temperature. (dd, J 1.3 and 8.1 Hz, 1H), 8.15 (dd, J 1.3 and 7.2 Hz, 1H),
After a usual workup, the crude was purified by column 8.82 (dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d,
chromatography (flash column, SiO2, hexane). Recrystalli- ppm, TMS) 40.56, 123.19, 126.51, 126.57, 126.75, 126.88,
zation of the chromatographed product from hexane gave 128.42 (2J(Se,C) 5.9 Hz), 129.63, 131.95, 132.42, 133.03,
1 (LL) as colorless prisms in 98% yield, mp 85.0–85.5 1C, 1H 133.50, 136.29, 140.89, 141.37; 77Se NMR (76 MHz, CDCl3,
NMR (300 MHz, CDCl3, d, ppm, TMS): 2.33 (s, 6H), 7.32 (t, 2H, d, ppm, Me2Se): 398.2, 831.4. Anal. Calc. for 3a (LO)
J = 7.7 Hz), 7.70 (dd, 2H, J = 1.2 and 8.2 Hz), 7.73 (dd, 2H, (C17H14OSe2): C, 52.06; H, 3.60%. Found: C, 52.11;
J = 1.2 and 7.5 Hz); 13C NMR (75 MHz, CDCl3, d, ppm, H, 3.66%.

8-Phenylseleninyl-1-(methylseleninyl)naphthalene (3a (OO)). dissolved in 100 mL of dry THF and the solution was added to
Following the similar method to that used for 1 (OO), nBuLi (15.0 mL, 23.94 mmol, 1.6 N) at 78 1C. After 20 min,
3a (OO) gave 63% yield as colorless needles, mp 148.0–148.8 1C; a THF solution of phenylselenobromide (22.80 mmol) was
1
H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.74 (s, 3H), added to the above solution at 78 1C. Then the reaction
7.33–7.50 (m, 3H), 7.51–7.58 (m, 2H), 7.78 (t, J 7.7 Hz, 1H), mixture was stirring for 2 h and warmed up room temperature.
7.81 (t, J 7.7 Hz, 1H), 8.13 (dd, J 1.1 and 8.1 Hz, 1H), 8.14 (dd, Then, 20 mL of 5% acetone hydrochloric acid and 100 mL of
J 1.1 and 8.1 Hz, 1H), 8.63 (dd, J 1.4 and 7.4 Hz, 1H), 8.72 benzene were added. The organic layer was separated, washed
(dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d, with brine, 10% aqueous solution of sodium hydroxide,
ppm, TMS): 38.25, 126.72, 126.80, 126.85, 127.01, 127.64, saturated aqueous solution of sodium bicarbonate and brine.
127.92, 130.02, 131.70, 133.33, 133.71, 135.55, 138.88, Then the solution was dried over sodium sulfate, evaporated
139.22, 141.66; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): and dried in vacuo. The crude product was purified by column
820.0, 832.5. Anal. Calc. for 3a (OO) (C17H14O2Se2): C, 50.02; chromatography (flash column, SiO2, hexane). 4a (LL) gave
H, 3.46%. Found: C, 50.07; H, 3.57%. 89% yield as yellow prisms, mp 64.0–64.8 1C; 1H NMR
(300 MHz, CDCl3, d, ppm, TMS): 7.22–7.28 (m, 8H),
8-p-Anisylselanyl-1-(methylseleninyl)naphthalene (3b (LO)).
7.39–7.45 (m, 4H), 7.64 (dd, J 1.1 and 7.3 Hz, 2H), 7.74
Following the similar method to that used for 1 (LO),
(dd, J 1.1 and 8.3 Hz, 2H); 13C NMR (75 MHz, CDCl3,
3b (LO) gave 88% yield as colorless needles, mp 129.6–130.4 1C;
1 d, ppm, TMS): 126.0, 127.4, 129.2, 129.4, 131.4, 133.4, 135.18,
H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.70 (s, 3H),
135.19, 135.5, 135.9; 77Se NMR (76 MHz, CDCl3, d, ppm,
3.82 (s, 3H), 6.70 (d, J 8.8 Hz, 2H), 7.01 (d, J 8.8 Hz, 2H), 7.51
Me2Se): 435.4. Anal. Calc. for 4a (LL) (C22H16Se2): C, 60.29;
(t, J 7.2 Hz, 1H), 7.74 (t, J 7.2 Hz, 1H), 7.88 (dd, J 1.1 and
H, 3.68%. Found: C, 60.21; H, 3.75%.
6.8 Hz, 1H), 8.01 (dd, J 1.1 and 6.8 Hz, 1H), 8.03 (dd, J 1.1
and 6.8 Hz, 1H), 8.10 (dd, J 1.1 and 6.8 Hz, 1H); 77Se NMR 8-Phenylselanyl-1-(phenylseleninyl)naphthalene (4a (LO)).
(76 MHz, CDCl3, d, ppm, Me2Se): 385.9, 833.9. Anal. Calc. Following the similar method to that used for 1 (LO),
for 3b (LO) (C18H16O2Se2): C, 51.20; H, 3.82%. Found: C, 4a (LO) gave 65% yield as colorless prisms, mp 155.5–156.3 1C;
50.98; H, 3.83%. 1
H NMR (400 MHz, CDCl3, d, ppm, TMS): 6.90–6.95
(m, 4H), 7.10–7.13 (m, 6H), 7.22–7.26 (m, 6H), 7.48–7.53
8-p-Anisylseleninyl-1-(methylseleninyl)naphthalene
(m, 4H), 7.52 (t, J 8.2 Hz, 1H), 7.83 (d, J 7.7 Hz, 1H), 8.07
(3b (OO)). Following the similar method to that used for
(dd, J 1.3 and 7.2 Hz, 1H), 8.08 (dd, J 1.3 and 8.2 Hz, 1H), 9.02
1 (OO), 3b (OO) gave 43% yield as colorless powder, mp
(dd, J 1.3 and 7.3 Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm,
144.5–145.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS):
TMS): 123.90, 126.45, 126.51, 126.79, 127.86, 127.91, 128.70,
2.75 (s, 3H), 3.76 (s, 3H), 6.87 (d, J 8.9 Hz, 2H), 7.45 (d, J 8.9
129.17, 129.49, 130.11, 131.73, 132.76, 133.27, 133.78, 136.31,
Hz, 2H), 7.83 (t, J 7.7 Hz, 2H), 8.15 (dd, J 1.0, 8.2 Hz, 1H),
140.17, 140.71, 146.21; 77Se NMR (76 MHz, CDCl3, d, ppm,
8.17 (dd, J 1.0, 8.2 Hz, 1H), 8.69 (dd, J 1.3, 9.1 Hz, 1H), 8.71
Me2Se): 400.1, 863.7. Anal. Calc. for 4a (LO) (C22H16OSe2):
(dd, J 1.2, 9.1 Hz, 1H); 77Se NMR (76 MHz, CDCl3, d, ppm,
C, 58.17; H, 3.55%. Found: C, 58.11; H, 3.65%.
Me2Se): 821.6, 846.4. Anal. Calc. for 3b (OO) (C18H16O3Se2):
C, 49.33; H, 3.68%. Found: C, 49.30; H, 3.73%. 1,8-Bis(phenylseleninyl)naphthalene (4a (OO)). Following
8-p-Nitrophenylselanyl-1-(methylseleninyl)naphthalene the similar method to that used for 1 (OO), 4a (OO) gave
(3d (LO)). Following the similar method to that used for 78% yield as colorless prisms, mp. 187.5–188.3 1C; 1H NMR
1 (LO), 3d (LO) gave 61% yield as colorless powder, mp (400 MHz, CDCl3, d, ppm, TMS): 7.21–7.30 (m, 8H), 7.37 (tt,
141.5–142.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): J 1.5 and 6.8 Hz, 2H), 7.76 (t, J 7.7 Hz, 2H), 8.15 (dd, J 0.9 and
2.67 (s, 3H), 7.07 (dt, J 2.1 and 9.0 Hz, 2H), 7.64 (t, J 7.5 Hz, 7.5 Hz, 2H), 8.47 (dd, J 1.1 and 6.2 Hz, 2H); 77Se NMR
1H), 7.83 (t, J 7.5 Hz, 1H), 7.99 (dt, J 2.4 and 9.0 Hz, 2H), 8.11 (76 MHz, CDCl3, d, ppm, Me2Se): 877.1. Anal. Calc. for
(dd, J 1.2 and 6.9 Hz, 2H), 8.18 (dd, J 1.2 and 4.2 Hz, 1H), 4a (OO) (C22H16O2Se2): C, 56.19; H, 3.43%. Found: C, 56.22;
8.21 (dd, J 1.5 and 4.8 Hz, 1H), 8.84 (dd, J 1.2 and 6.0 Hz, H, 3.53%.
1H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 426.4,
1,8-Bis[(p-tert-butylphenyl)selanyl]naphthalene (4c (LL)).
835.6. Anal. Calc. for 3d (LO) (C17H13NO3Se2): C, 46.70; H,
Following the similar method to that used for 4a (LL),
3.00; N, 3.20%. Found: C, 46.75; H, 3.03; N, 3.22%.
4c (LL) gave 87% yield as yellow prisms, mp 97.8–98.3 1C;
1
8-p-Nitrophenylseleninyl-1-(methylseleninyl)naphthalene H NMR (400 MHz, CDCl3, d, ppm, TMS): 1.30 (s 18H), 7.24
(3d (OO)). Following the similar method to that used for (t, J 7.7 Hz, 2H), 7.27 (d, J 8.6 Hz, 4H), 7.38 (d, J 8.6 Hz, 4H),
1 (OO), 3d (OO) gave 82% yield as colorless powder, mp 7.65 (dd, J 1.3 and 6.1 Hz, 2H), 7.73 (dd, J 1.3 and 7.0 Hz,
151.2–152.0 1C; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 424.6.
2.83 (s, 3H), 7.72–7.92 (m, 4H), 8.12–8.27 (m, 4H), 8.57 (dd, Anal. Calc. for 4c (LL) (C30H32Se2): C, 65.45; H, 5.86%.
J 1.1 and 6.2 Hz, 1H), 8.74 (dd, J 1.3 and 6.1 Hz, 1H); 77Se Found: C, 65.41; H, 5.88%.
NMR (76 MHz, CDCl3, d, ppm, Me2Se): 821.4, 849.0. Anal.
8-[(p-tert-Butylphenyl)selanyl]-1-[(p-tert-butylphenyl)seleninyl]-
Calc. for 3d (OO) (C17H13NO4Se2): C, 45.05; H, 2.89; N,
naphthalene (4c (LO)). Following the similar method to that
3.09%. Found: C, 45.12; H, 2.83; N, 3.12%.
used for 1 (LO), 4c (LO) gave 86% yield as colorless powder,
1,8-Bis(phenylselanyl)naphthalene (4a (LL)). Under an argon mp 179.5–180.2 1C; 1H NMR (400 MHz, CDCl3, d,
atmosphere, 1,8-diiodonaphthalene (4.33 g, 11.40 mmol) was ppm, TMS): 1.22 (s, 9H), 1.27 (s 9H), 6.91 (d, J 8.3 Hz, 2H),
This journal is
7.15 (d, J 8.1 Hz, 2H), 7.28 (d, J 8.8 Hz, 2H), 7.43 (d, J 8.6 Hz, program.27 Calculations are performed at the density func-
2H), 7.51 (t, J 7.9 Hz, 1H), 7.82 (t, J 7.7 Hz, 1H), 8.07 (d, J 8.3 tional theory (DFT) level of the Becke three parameter hybrid
Hz, 3H), 9.01 (dd, J 1.3 and 7.5 Hz, 1H); 77Se NMR (76 MHz, functionals combined with the Lee-Yang-Parr correlation
CDCl3, d, ppm, Me2Se): 393.2, 861.2. Anal. Calc. for 4c (LO) functional (B3LYP).28,29 QC calculations are also performed
(C30H32OSe2): C, 63.61; H, 5.69%. Found: C, 63.55; on 8-G-1-[MeSe(X)]C10H6 [G = MeSe (1), H (5), F (6), Cl (7)
H, 5.58%. and Br (8) with X = lone pair (L), O (O), OH+ (OH+) and
O2H2 (OHOH)], employing the B3LYP/6-311+G(d) method.
1,8-Bis[(p-tert-butylphenyl)seleninyl]naphthalene (4c (OO)). The NBO19,20 analysis were performed with the B3LYP/
Following the similar method to that used for 1 (OO), 6-311+G(d) method. The AIM21,22 analysis are performed on
4c (OO) gave 87% yield as colorless powder, mp 172.5–173.2 1C; 1 (LO) and 1 (OO) with the Gaussian 03 program employing the
1
H NMR (400 MHz, CDCl3, d, ppm, TMS): 1.63 (s, 18H), 6-311+G(3df) basis sets for Se with the 6-311+G(3d,2p) basis
7.39 (d, J 8.6 Hz, 4H), 7.47 (d, J 8.3 Hz, 4H), 7.83 (d, J 7.6 Hz, sets for C and H at the B3LYP level. They are analyzed
2H), 8.16 (dd, J 0.8 and 7.3 Hz, 2H), 8.73 (dd, J 1.0 and 6.2 employing the AIM 2000 program.21,22 NBO analysis are also
Hz, 2H); 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): 843.7. performed on 1 (LO) and 1 (OO) with the same method for the
Anal. Calc. for 4c (OO) (C30H32O2Se2): C, 61.86; H, 5.54%. AIM analysis. Optimized structures and the molecular orbitals
Found: C, 61.93; H, 5.58%. are drawn using MolStudio R3.2 (Rev 1.0).43
1-(Methylselanyl)naphthalene (5 (L)). Following the similar
method to that used for 1 (LL), 5 (L) gave 99% yield as pale Acknowledgements
yellow oil; 1H NMR (400 MHz, CDCl3, d, ppm, TMS): 2.37
(s, 2JSe,H 11.7 Hz, 3H), 7.35 (dd, J 7.3 and 8.1 Hz, 1H), 7.47 This work was partially supported by a Grant-in-Aid for
(ddd, J 1.6, 6.9 and 8.2 Hz, 1H), 7.53 (ddd, J 1.6, 6.9 and 8.3 Scientific Research (Nos. 16550038, 19550041 and 20550042)
Hz, 1H), 7.66 (dd, J 1.1 and 7.3 Hz, 1H), 7.71 (d, J 8.2 Hz, from the Ministry of Education, Culture, Sports, Science and
1H), 7.80 (dd, J 1.7 and 7.9 Hz, 1H), 8.24 (ddd, J 0.7, 1.6 and Technology, Japan.
8.1 Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS):
36.54, 122.08 (J 14.9 Hz), 124.03 (J 6.2 Hz), 126.11, 126.79, References
127.56, 129.35, 130.27, 131.40, 133.88, 138.68; 77Se NMR
1 (a) The Chemistry of Organic Selenium and Tellurium Compounds,
(76 MHz, CDCl3, d, ppm, Me2Se): 158.6. Anal. Calc. for 5 (L) eds. S. Patai and Z. Rappoport, John-Wiley and Sons, New York,
(C11H10Se): C, 59.74; H, 4.56%. Found: C, 59.90; H, 4.49%. 1986, vol. 1; (b) The Chemistry of Organic Selenium and Tellurium
Compounds, ed. S. Patai, John-Wiley and Sons, New York, 1986,
1-(Methylseleninyl)naphthalene (5 (O)). Following the simi- vol. 2; (c) Organoselenium Chemistry, A Practical Approach, ed.
lar method to that used for 1 (LO), 5 (O) gave 67% yield as T. G. Back, Oxford University Press, Oxford, 1999. See also refs
cited therein.
colorless needles, mp 97.2–97.8 1C; 1H NMR (400 MHz, 2 T. Shimizu and N. Kamigata, Synthesis and Stereochemistry of Optically
CDCl3, d, ppm, TMS): 2.71 (s, 2JSe,H 12.3 Hz, 3H), Active Chalcogen Compounds, in Handbook of Chalcogen Chemistry
7.56–7.65 (m, 2H), 7.70 (dd, J 7.4 and 8.2 Hz, 1H), New Perspectives in Sulfur Selenium and Tellurium, ed. F. A.
Devillanova, Royal Society of Chemistry, Cambridge, 2006, ch. 10.1.
7.81–7.87 (m, 1H), 7.95–8.02 (m, 2H), 8.29 (dd, J 1.1 and 7.3 3 (a) P. Nagy, A. Csampai, D. Szabo, J. Varga, V. Harmat, F. Ruff
Hz, 1H); 13C NMR (75 MHz, CDCl3, d, ppm, TMS): 7.52, and A. Kucsman, J. Chem. Soc., Perkin Trans. 2, 2001, 339–349;
125.83, 126.14, 126.39, 126.63, 127.16, 128.58, 128.67, 131.10, (b) C. Reichardt, H.-P. Erfurt, K. Harms and G. Schafer, Eur. J.
133.29, 133.77; 77Se NMR (76 MHz, CDCl3, d, ppm, Me2Se): Org. Chem., 2002, 439–452.
4 (a) T. Shimizu, M. Enomoto, H. Taka and N. Kamigata, J. Org.
809.3. Anal. Calc. for 5 (O) (C11H10OSe): C, 55.71; H, 4.25%. Chem., 1999, 64, 8242–8247; (b) H. Taka, A. Matsumoto,
Found: C, 55.88; H, 4.18%. T. Shimizu and N. Kamigata, Chem. Lett., 2000, 726–727;
(c) H. Taka, Y. Yamazaki, T. Shimizu and N. Kamigata, J. Org.
X-Ray crystal structure determination. The colorless crystals Chem., 2000, 65, 2127–2133; (d) H. Taka, A. Matsumoto,
of 1 (LO) and 1 (OO) were grown by slow evaporation of T. Shimizu and N. Kamigata, Heteroat. Chem., 2001, 12,
227–237; (e) T. Soma, T. Shimizu, K. Hirabayashi and
methylene dichloride-hexane solutions at room temperature. N. Kamigata, Heteroat. Chem., 2007, 18, 301–311; (f) T. Soma,
A crystal of 1 (LO) was measured on a Rigaku AFC5R N. Kamigata, K. Hirabayashi and T. Shimizu, Bull. Chem. Soc.
diffractometer with graphite monochromated Mo-Ka radia- Jpn., 2007, 80, 2389–2394. For the N Si interactions at naphtha-
lene 1,8-positions, see: P. M. Dominiak, G. P. Schiemenz and
tion source (l = 0.71069 Å) and a rotating anode generator at K. Woz’niak, Pol. J. Chem., 2007, 81, 663–681.
298(2) K. That of 1 (OO) was measured on a Rigaku/MSC 5 Organic Sulfur Chemistry: Theoretical and Experimental Advances,
Mercury CCD diffractometer equipped with a graphite-mono- eds. F. Bernardi, I. G. Csizmadia and A. Mangini, Elsevier,
chromated Mo-Ka radiation source (l = 0.71070 Å) at 103(2) K. Amsterdam, 1985.
6 (a) S. Nakamura, H. Yasuda and T. Toru, Tetrahedron: Asymme-
The structures of 1 (LO) and 1 (OO) were solved by direct try, 2002, 13, 1509–1518; (b) S. Nakamura, H. Yasuda,
method (SHELXS-97)41 and refined by full-matrix least- Y. Watanabe and T. Toru, J. Org. Chem., 2000, 65, 8640–8650;
square method on F2 for all reflections (SHELXL-97).42 All (c) S. Nakamura, H. Yasuda, Y. Watanabe and T. Toru, Tetra-
hedron Lett., 2000, 41, 4157–4160.
the non-hydrogen atoms were refined anisotropically.
7 (a) J. Drabowicz, Hypervalent Sulfuranes as Transient and Isolable
Structures: Occurrence, Synthesis, and Reactivity in Chemistry of
QC calculations Hypervalent Compounds, ed. K.-y. Akiba, Wiley-VCH, New York,
QC calculations are performed on 1 (LO) and 1 (OO), as the 1999, ch. 7; (b) J. Drabowicz, Heteroat. Chem., 2002, 5, 437–442.
8 (a) W. Nakanishi, Chem. Lett., 1993, 2121–2122; (b) W. Nakanishi,
models of n (LO) and n (OO) (n = 1, 3 and 4), respectively, S. Hayashi and S. Toyota, Chem. Commun., 1996, 371–372;
employing the 6-311+G(d) basis sets of the Gaussian 98 (c) W. Nakanishi, S. Hayashi and H. Yamaguchi, Chem. Lett.,

1996, 947–948; (d) W. Nakanishi, S. Hayashi, A. Sakaue, G. Ono Chem. Res., 1985, 18, 9–15; (f) T. H. Tang, R. F. W. Bader and
and Y. Kawada, J. Am. Chem. Soc., 1998, 120, 3635–3640; P. MacDougall, Inorg. Chem., 1985, 24, 2047–2053; (g) F. Biegler-
(e) W. Nakanishi, S. Hayashi and S. Toyota, J. Org. Chem., König, J. Schönbohm and D. Bayles, J. Comput. Chem., 2001, 22,
1998, 63, 8790–8800; (f) S. Hayashi and W. Nakanishi, J. Org. 545–559; (h) F. Biegler-König and J. Schönbohm, J. Comput.
Chem., 1999, 64, 6688–6696; (g) W. Nakanishi, S. Hayashi and Chem., 2002, 23, 1489–1494. See also: W. Nakanishi,
T. Uehara, J.Phys. Chem. A, 1999, 103, 9906–9912; T. Nakamoto, S. Hayashi, T. Sasamori and N. Tokitoh, Chem.
(h) W. Nakanishi and S. Hayashi, J. Org. Chem., 2002, 67, 38–48. Eur. J., 2007, 13, 255–268.
9 (a) G. Gafner and F. H. Herbstein, Acta. Crystallogr., 1962, 15, 23 J. Meinwald, D. Dauplaise and J. Clardy, J. Am. Chem. Soc., 1977,
1081–1092; (b) M. A. Davydova and Yu. T. Struchkov, Zh. Strukt. 99, 7743–7744.
Khim., 1962, 3, 184; (c) M. A. Davydova and Yu. T. Struchkov, 24 The structures of 3b (LO) and 3a (OO) are also determined by the
Zh. Strukt. Khim., 1968, 9, 1968; (d) H. Bock, M. Sievert and X-ray crystallographic analysis. The results are essentially the same
Z. Havlas, Chem. Eur. J., 1998, 4, 677–685; (e) R. D. Jackson, as those of 1 (LO) and 1 (OO), respectively, which will be reported
S. James, A. G. Orpen and P. G. Pringle, J. Organomet. Chem., elsewhere.
1993, 458, C3–C4; G. Mugesh and H. B. Singh, Acc. Chem. Rev., 25 Water molecules in 1 (OO) are omitted for clarity.
2002, 35, 226–236. 26 S. Hayashi and W. Nakanishi, Bull. Chem. Soc. Jpn., 2008, 12, in
10 (a) R. S. Glass, S. W. Andruski, J. L. Broeker, H. Firouzabadi, press (CCDC 640537 for 1 (LL)).
L. K. Steffen and G. S. Wilson, J. Am. Chem. Soc., 1989, 111, 27 A. Bondi, J. Phys. Chem., 1964, 68, 441–451.
4036–4045; (b) R. S. Glass, L. Adamowicz and J. L. Broeker, 28 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
J. Am. Chem. Soc., 1991, 113, 1065–1072; (c) F. B. Mallory, M. A. Robb, J. R. Cheeseman, V. G. Zakrzewski, J. A.
C. W. Mallory, K. B. Butler, M. B. Lewis, A. Q. Xia, Montgomery, Jr., R. E. Stratmann, J. C. Burant, S. Dapprich,
E. D. Luzik, Jr, L. E. Fredenburgh, M. M. Ramanjulu, J. M. Millam, A. D. Daniels, K. N. Kudin, M. C. Strain,
Q. N. Van, M. M. Francl, D. A. Freed, C. C. Wray, C. Hann, O. Farkas, J. Tomasi, V. Barone, M. Cossi, R. Cammi,
M. Nerz-Stormes, P. J. Carroll and L. E. Chirlian, J. Am. Chem. B. Mennucci, C. Pomelli, C. Adamo, S. Clifford, J. Ochterski,
Soc., 2000, 122, 4108–4116. G. A. Petersson, P. Y. Ayala, Q. Cui, K. Morokuma, P. Salvador,
11 (a) A. Singh and B. Ganguly, J. Phys. Chem. A, 2007, 111, J. J. Dannenberg, D. K. Malick, A. D. Rabuck, K. Raghavachari,
6468–6471; (b) N. Chanda and P. R. Sharp, Organometallics, J. B. Foresman, J. Cioslowski, J. V. Ortiz, A. G. Baboul,
2007, 26, 3368–3373; (c) R. Panisch, M. Bolte and T. Muller, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi,
Organometallics, 2007, 26, 3524–3529; (d) A. F. Pozharskii, R. Gomperts, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,
A. V. Degtyarev, O. V. Ryabtsova, V. A. Ozeryanskii, C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill,
M. E. Kletskii, Z. A. Starikova, L. Sobczyk and A. Filarowski, B. G. Johnson, W. Chen, M. W. Wong, J. L. Andres, C. Gonzalez,
J. Org. Chem., 2007, 72, 3006–3019. M. Head-Gordon, E. S. Replogle and J. A. Pople, GAUSSIAN 98
12 (a) G. C. Pimentel, J. Chem. Phys., 1951, 19, 446–448; J. I. Musher, (Revision A.11), Gaussian, Inc., Pittsburgh, PA, 2001.
Angew. Chem., Int. Ed. Engl., 1969, 8, 54–68; R. J. Hatch and 29 C. Lee, W. Yang and R. G. Parr, Phys. Rev. B, 1988, 37, 785–789;
R. E. Rundle, J. Am. Chem. Soc., 1951, 73, 4321–4324; B. Miehlich, A. Savin, H. Stoll and H. Preuss, Chem. Phys. Lett.,
(b) R. E. Rundle, J. Am. Chem. Soc., 1963, 85, 112–113. 1989, 157, 200–2006.
13 (a) R. A. Hayes and J. C. Martin, Sulfurane Chemistry, in Organic 30 A. D. Becke, Phys. Rev. A, 1988, 38, 3098–3100; A. D. Becke,
Sulfur Chemistry: Theoretical and Experimental Advances, eds. J. Chem. Phys., 1993, 98, 5648–5652.
F. Bernardi, I. G. Csizmadia and A. Mangini, Elsevier Scientific, 31 S. Hayashi and W. Nakanishi, J. Mol. Struct. (THEOCHEM),
Amsterdam, 1985, ch. 8; (b) J. Bergman, L. Engman and J. Siden, 2007, 811, 293–301.
Tetra- and Higher-Valent (Hypervalent) Derivatives of Selenium 32 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,
and Tellurium, in The Chemistry of Organic Selenium and Tellurium M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr, T. Vreven,
Compounds, eds. S. Patai and Z. Rappoport, John Wiley & Sons, K. N. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi,
New York, 1986, vol. 1, ch. 14; (c) Chemistry of Hypervalent V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega,
Compounds, ed. K.-y. Akiba, Wiley-VCH, New York, 1999; G. A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota,
(d) W. Nakanishi, Hypervalent Chalcogen Compounds, in Hand- R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda,
book of Chalcogen Chemistry: New Perspectives in Sulfur, Selenium O. Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox,
and Tellurium, ed. F. A. Devillanova, Royal Society of Chemistry, H. P. Hratchian, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo,
London, 2006, ch. 10.3. R. Gomperts, R. E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi,
14 For the 3c–4e treatment of the CT complexes, see: W. Nakanishi, C. Pomelli, J. W. Ochterski, P. Y. Ayala, K. Morokuma,
S. Hayashi and H. Kihara, J. Org. Chem., 1999, 64, 2630–2637. G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski,
15 For the weak interactions, see, (a) Molecular Interactions. From van S. Dapprich, A. D. Daniels, M. C. Strain, O. Farkas, D. K. Malick,
der Waals to Strongly Bound Complexes, ed. S. Scheiner, Wiley, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. Ortiz,
New York, 1997; (b) K. D. Asmus, Acc. Chem. Res., 1979, 12, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov,
436–442; (c) W. K. Musker, Acc. Chem. Res., 1980, 13, 200–206. G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin,
16 S. Hayashi, H. Wada, T. Ueno and W. Nakanishi, J. Org. Chem., D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. Nanayakkara,
2006, 71, 5574–5585. M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen,
17 W. Nakanishi, S. Hayashi and T. Uehara, Eur. J. Org. Chem., M. W. Wong, C. Gonzalez and J. A. Pople, GAUSSIAN 03
2001, 3933–3943. (Revision B.05), Gaussian, Inc., Pittsburgh, PA, 2003.
18 The structure is A if the Se–CAr bond is placed almost perpendi- 33 The AIM2000 program (Version 2.0) is employed to analyze and
cular to the naphthyl plane, it is B when the bond is located on the visualize atoms in molecules: F. J. Biegler-König, Comput. Chem.,
plane and C is the intermediate between A and B. 2000, 21, 1040–1048; see also ref. 22g.
19 A. E. Reed, R. B. Weinstock and F. Weinhold, J. Chem. Phys., 34 Data for A and B, together with LL, are given in the ESIw.
1985, 83, 735–746; J. E. Carpenter and F. Weinhold, J. Mol. 35 The type C of 1 (OHOH) is discussed which is predicted to be most
Struct. (THEOCHEM), 1988, 169, 41–62. stable among the three44.
20 E. D. Glendening, A. E. Reed, J. E. Carpenter and F. Weinhold, 36 Eqn (R1) shows the energies of n (L) + H2O2 (E(n (L) + H2O2))
NBO Ver. 3.1. relative to E(n (O) + H2O) [DE(n (LO)) = E(n (L) + H2O2)
21 Atoms in Molecules. A Quantum Theory, ed. R. F. W. Bader, Oxford E(n (O) + H2O)], although E(n (L)) are not given in Table 3.45
University Press, Oxford, 1990; The Quantum Theory of Atoms in
Molecules: From Solid State to DNA and Drug Design, eds. DE(n (LO)) = E(n (L) + H2O2) E(n (O) + H2O)
C. F. Matta and R. J. Boyd, Wiley-VCH, Weinheim, 2007, ch. 1. G = H (121.8 kJ mol1) o F (131.3) o cis-MeSe (133.9)
22 (a) R. F. W. Bader, T. S. Slee, D. Cremer and E. Kraka, J. Am. o Cl (136.8) r Br (137.6) o trans-MeSe (141.0) (R1)
Chem. Soc., 1983, 105, 5061–5068; (b) R. F. W. Bader, Chem. Rev.,
1991, 91, 893–926; (c) R. F. W. Bader, J. Phys. Chem. A, 1998, 102, 37 NOB analysis were also performed on the AC conformer of 8-G-1-
7314–7323; (d) F. Biegler-König, R. F. W. Bader and T. H. Tang, [MeSe(O2H2)]C10H6. However, the corresponding CT interactions
J. Comput. Chem., 1982, 3, 317–328; (e) R. F. W. Bader, Acc. were not detected.
This journal is
38 The nonbonded Se Se distance in 1 (LO) is predicted to be 44 Three structures (type A, type B and type C) were optimized
shorter than that of 1 (OO) by ca. 0.03 Å, while the observed for each of n (OHOH). The type C is the global minimum,
values are almost equal (see Table 5). The crystal packing effect which is slightly stable than type B and much stable than
might contribute to the results. type A, although the steric repulsion between OH and G seems
39 The value is very close to that evaluated with the B3LYP/ largest.
6-311+G(d) method. 45 Eqn (R1)36 shows that selenoxides are stabilized in this order
40 W. Nakanishi, S. Hayashi and K. Narahara, unpublished results. through the non-bonded n(G) s*(Se–O) 3c–4e interactions,
41 G. M. Sheldrick, SHELXS-97, Program for Crystal Structure together with the O dependence.16 While G = trans-MeSe is
Solution, Universität Göttingen, Germany, 1997. demonstrated to be most effective to stabilize in the selenoxide
42 G. M. Sheldrick, SHELXL-97, Program for Crystal Structure relative to the corresponding bis-selenide, the effect of G = cis-
Refinement, University of Göttingen, Germany, 1997. MeSe places between F and Cl, where the CC form is postulated
43 MolStudio R3.2 (Rev 1.0), NEC Corporation, 1997–2003. for the bis-selenide.

Mechanistic aspects of nitrate ion reduction on silver electrode:

estimation of O–NO2 bond dissociation energy using
cyclic voltammetry
Mohsin Ahmad Bhat,w Pravin Popinand Ingole, Vijay Raman Chaudhari
and Santosh Krishna Haram*
Received (in Montpellier, France) 27th August 2008, Accepted 9th October 2008
DOI: 10.1039/b814895c
Voltammetric investigations of mechanistic aspects and estimation of thermo-chemical parameters

of nitrate ion reduction at silver electrode, in alkaline medium are reported. The activation barrier
determined from cyclic voltammetry fits a quadratic relation rather than the expected Butler-
Volmer kinetics. Intrinsic barrier calculations show that the reduction of nitrate ion on silver
follows a concerted mechanism, involving electron transfer initiated bond cleavage, followed by
chemical reaction. The bond dissociation energy for the O–NO2 bond was estimated to be
48.40 kcal mol1, which matches well with the reported value of 47.5 kcal mol1, determined
from photodissociation experiments.
1. Introduction nitrate ion reduction, and is thus strongly advocated for

their electrochemical sensing.10,17,18 For better understanding
The high water solubility of nitrate ions is responsible for its and development of Ag as a nitrate ion sensor, it is of utmost
virtual presence everywhere. Serious clinical symptoms have importance to have knowledge about the mechanism of this
been reported to be caused by their ingestion,1–3 which neces- reduction—especially with respect to the rate determining
sitates effective monitoring and development of sensing tools step. To our knowledge, these aspects have not been con-
for this ion. For its detection and estimation, a series of sidered so far. Thus, it was of our immense interest to study the
methods have been proposed in refs. 4–8. Among them, the mechanism of this reaction on Ag-electrode, voltammetrically.
electrochemical methods have proved to be advantageous in With this aim, the kinetic investigations of nitrate ion
terms of reproducibility, accuracy, time response and durability.9 reduction in alkaline media were undertaken through cyclic
The voltammetric detection is based on the irreversible two- voltammetry. Our analysis for the first time revealed that the
electron transfer process shown in eqn (1):10 nitrate ion reduction on Ag follows a dissociative electron
transfer mechanism. Besides, the related calculations led
O–NO2 + 2e + H2O - NO2 + 2OH (1)
to the quantification of thermo-chemical parameters, such
Using conventional voltammetry,11,12 in combination with as bond dissociation energy of the O–NO2 bond, which is
electrochemical scanning tunneling microscopy, surface otherwise estimated through thermal- and photo-dissociation
enhanced Raman spectroscopy,13 and differential electro- measurements.19
chemical mass spectrometry,14 it is reported that the nitrate
ion reduction is very sensitive to the solution conditions, pH
and the nature of the electrode material. For example, on 2. Experimental
polycrystalline platinum electrode, it proceeds through a dis- Potassium nitrate and sodium hydroxide were purchased from
sociative adsorption pathway,15 albeit with slow kinetics. Merck. Ag-bulk electrode was prepared by sealing a 2 mm
Similar results have been also reported for palladium electro- diameter Ag (99.9%) wire in a glass tube, with the help of
des,16 while on Cu, the reduction is found to be very facile epoxy adhesive. The electrode surface was exposed by grinding
and proceeds through the formation of NO2 in alkaline it on emery paper. It was polished with commercially available
medium.13 Dima et al.14 have reported varying activity of silver cleaner, followed by 0.2 mm alumina powder. Ag/AgCl,
transition and coinage metals and proposed a probable general KCl (3.0 M), and a Pt rod from Metrohm devices were used as
scheme for the nitrate ion reduction process. In general, nitrate reference and counter electrodes, respectively. Cyclic voltam-
reduction is understood to be a multistep process with the first metric (CV) investigations were performed using Metrohm
electron transfer as the rate determining step.12–14 Among PGSTAT 100 POTENTIOSTAT/GALVANOSTAT in a
all the metals studied, silver shows highest sensitivity for three-electrode setup. All the measurements were performed
under an argon atmosphere. Prior to measurements, the Ag
Department of Chemistry, University of Pune, Ganeshkhind, Pune, electrode was electrochemically activated by cycling the
411007, India. E-mail: haram@chem.unipune.ernet.in; potential twenty times (scan rate 1 V s1) in the potential
Fax: +91 20 2569 3981; Tel: +91 20 2560 1394
w Permanent address: Department of Chemistry, University of Kashmir, range 1.3 to 1.0 V, followed by ten potential steps
Srinagar-190006, India. (of 1 s duration) in increasing order of potential, ranging from
This journal is
0.25 to 0.9 V in 2.0 M NaOH. CVs used for analysis were
background corrected for the charging current. In view of the
reported complications observed during nitrate ion reduction
at Ag-electrode,17 every scan used for the analysis was re-
corded on a freshly polished and electrochemically cleaned
electrode surface. All the measurements were carried out in
thermostatted condition at 298 0.1 K.

A typical CV recorded using the Ag electrode in 10 mM KNO3
and 2 M NaOH (pH = 12) at the scan rate of 10 mV s1 is
shown in Fig. 1. High pH helps to shift hydrogen evolution
towards more negative potential in comparison to the nitrate
ion reduction. A cathodic peak at 0.94 V is assigned to the
reduction of nitrate ions. The linear relationship between ip Fig. 2 Cyclic voltammograms recorded on Ag electrode in 10 mM
KNO3 and 2 M NaOH, at varying scan rates from 10 to 500 mV s1.
and the square root of scan rate (n1/2) (Fig. 1, inset) indicates
Inset shows peak potential vs. scan rate, which indicates that the
that the process is diffusion controlled.20 The scan rate depen-
reduction is irreversible.
dent shift in peak potential (Ep), as shown in Fig. 2, is
attributed to the irreversibility in the electron transfer process.
The magnitude of Ep Ep/2 was in the range 47 to 96 mV,
which is an indication of electron transfer being the rate
determining step.21 Interestingly, ip/n1/2 (Fig. 3) and Ep
Ep/2 (Table 1) were found to be scan rate dependent. Addi-
tionally, peak broadening with increase in scan rate is ob-
served (Fig. 2). Prima facie, both these observations could
be attributed to the uncompensated iR drop and charging
current contributions. However, the electrolyte used was
highly conducting and moreover, we had subtracted back-
ground charging current. Therefore, the contributions of iR
drop and the capacitance are ruled out. Thus, the shift in
the potential and Ep Ep/2 with the scan rate are attributed
to the potential dependent electron transfer coefficient (a)
for the reaction22 and nitrate ion reduction does not follow
a normal Butler–Volmer kinetics. Since the ip vs. n1/2 plot
shows that the process is diffusion controlled, it also suggests Fig. 3 ip/n1/2 vs. scan rate for NO3 reduction on Ag electrode in
that the potential dependent free energy of activation for the alkaline medium, indicating a deviation from Butler-Volmer kinetics.
Table 1 Analysis of cyclic voltammetric (CV) data obtained for

nitrate ion reduction (10 mM) at an Ag electrode in 2 M NaOH at
298 K
DGoz/
Scan rate/V s1 104Ip/A Ep/V (Ep Ep/2)/V kcal mol1
0.01 0.891 0.944 0.060 19.97
0.02 1.40 0.920 0.065 19.56
0.04 2.01 0.926 0.072 19.66
0.08 2.70 0.932 0.078 19.77
0.1 2.80 0.934 0.083 19.80
0.2 3.74 0.944 0.085 19.97
0.3 4.27 0.948 0.087 20.04
0.4 4.77 0.958 0.089 20.22
0.5 5.03 0.962 0.094 20.28
reaction is a quadratic function of electrode potential, as per

eqn (2):23
Fig. 1 Typical cyclic voltammogram recorded on Ag electrode in
10 mM KNO3 and 2 M NaOH, at a scan rate of 10 mV s1. Inset
DGo 2
shows a linear fit of the peak current (ip) vs. square root of scan rate DGz ¼ DGoz 1 þ ð2Þ
(n1/2), which indicates diffusion controlled reaction. 4DGoz

where, mercury, such information is not available for other metal
o o0 electrodes. We used another simple approach for calculation
DG = F(E E ) (3)
of the barrier using cyclic voltammetry, without any convolu-
in which Eo 0 is the formal potential for overall reaction and tion analysis, which is as follows.
has a value of 0.01 V24 and DGoz, is the intrinsic energy barrier The free energy of activation at peak potentials obtained in
for the reduction reaction. cyclic voltammograms is given by eqn (12):31
The potential dependent rate constant (k(E)) is given by " rffiffiffiffiffiffiffiffiffiffiffiffi! #
eqn (4): z RT RT
DGP ¼ ln Z 0:78 ð12Þ
F FanD
DGz
kðEÞ ¼ Z: exp ð4Þ
RT Knowing the value of a calculated from Ep Ep/2, where Ep
is the peak potential and Ep/2 is the potential where the current
1/2
where, Z (= (RT/2pM) , M is the molecular mass of = NO3)
is at half the peak value (Table 1), through eqn (13):20
2521.79 cm s1.

Such dissociative redox reactions initiated with electron 1:86RT
a¼ ð13Þ
transfer can occur through two plausible mechanisms, namely FjEp Ep=2 j
stepwise (eqn (5) and (6)) and concerted (eqn (7)):
and D (1.9 105 cm2 s1), DGPz values for the various scan
A–B + e - A–B (5) rates were calculated. These values were substituted in eqn (2)
A–B - A –B (6) and the resulting quadratic equation was solved for DGoz with
the help of the FORTRAN program, written specifically for
A–B + e - A + B
(7) this purpose. Among the two roots obtained, the negative root
was not considered as the value emerged out to be less than
Products formed through both these mechanisms can un-
that obtained from eqn (8), which is the bare minimum value
dergo further electron transfer or chemical reactions, which
expected for the overall reaction. The positive root, gives a
affect the thermodynamic and kinetic aspects of the overall
value of DGoz much greater than that expected for a stepwise
process. Theory as well as experimental predictions associated
mechanism (eqn (5) and (6)) and hence negating the possibility
with these mechanisms for alkyl halides,25 peroxides22,26 and
that the reduction follows a stepwise mechanism. Therefore,
other analytes27,28 have been well documented in the literature.
the reaction occurring through the concerted mechanism as
The two mechanisms can be differentiated on the basis of
shown in eqn (7) is inferred. Preference of a concerted
difference in the value of intrinsic energy barrier, as given
mechanism over a stepwise one is also realized by considering
below (eqn (8) and (9)):
the resonance structure of nitrate ion and the nitrite ion as
l0 þ li against the open shell structure of NO3 2—an intermediate
DGoz ðstepwiseÞ ¼ ð8Þ
4 which would be formed in a stepwise mechanism.
The bond dissociation energy was calculated by substituting
l0 þ li þ BDFE the value of DGoz (from the above procedure) and lo
DGoz ðconcertedÞ ¼ ð9Þ
4 (from eqn (10)) in eqn (9) and found to be ca. 48.4 kcal mol1,
which matches well with the value of 47.5 kcal mol1, reported
where, BDFE is the bond dissociation free energy, and l0, the
from photodissociation measurements.19 The small difference
solvent reorganization energy, which is calculated through the
is attributed to the neglecting the value of li in the calculations
Marcus equation (10):
as a first approximation.
e 1 1 Based on our experimental findings and earlier re-
l0 ¼ ð10Þ
8peo ao eo es ports,13,14,32,33 we conclude that, electron transfer to the
nitrate ion is the rate determining step, similar to the process
Here, eo and es are the optical and static dielectric constants of
reported for Cu, and following the overall reaction scheme
the solvent, respectively and ao, the effective radius of the
given by eqn (14) and (15):
analyte, which is calculated using eqn (11):
NO3 + e - NO2 + O (rate determining step) (14)
2aAB aB
ao ¼ aB ð11Þ
aAB O + e + H2O - 2OH (15)
where aAB = aNO3 = 2.64 Å and aB = aO = 1.76 Å are as Results published recently by Broder et al.34 also suggest the
reported previously.29 li is regarded as the internal reorgani- formation of O as an intermediate in reduction of nitrate ion
zation energy and can be neglected due to its comparatively at Pt electrode in room-temperature ionic liquids.
small magnitude. l0 was calculated using reported values for
optical and static dielectric constants for water.30 Use of
4. Conclusion
convolutive analysis of CVs has been reported for the calcula-
tion of intrinsic barriers and other mechanistic details of such For the first time, we have used a simple procedure for
electron transfer reactions. Though, the method has many analyzing the cyclic voltammetric data for nitrate ion reduc-
advantages, its use is limited due to the requirement of tion at a silver electrode. Data fits very well in the dissociative
information regarding the double layer structure. Except for electron transfer concerted mechanism. Besides, the value of
This journal is
the bond dissociation energy, ca. 48.4 kcal mol1, calculated 11 K. Bouzek, M. Paidar, A. Sadilkova and H. Bergmann, J. Appl.
from these investigations, matches with 47.5 kcal mol1 the Electrochem., 2001, 31, 1185.
12 J. Davis, M. J. Moorcroft, S. J. Wilkins, R. G. Compton and
value obtained from photodissociation measurements. This M. F. Cardosi, Analyst, 2000, 125, 737.
knowledge of mechanistic and thermo-chemical parameters is 13 S.-E. Bae, K. L. Stewart and A. A. Gewirth, J. Am. Chem. Soc.,
believed to be useful in designing Ag electrodes as nitrate ion 2007, 129, 10171.
sensors. 14 G. E. Dima, A. C. A. de Vooys and M. T. M. Koper,
J. Electroanal. Chem., 2003, 554, 15.
15 M. C. P. M. da cunha, M. Weber and F. C. Nart, J. Electroanal.
Chem., 1996, 414, 163.
Acknowledgements 16 M. Wasberg and G. Horanyi, Electrochim. Acta, 1995, 40, 615.
17 D. Kim, I. B. Goldberg and J. W. Judy, Analyst, 2007, 132, 350.
M. A. B. would like to thank the University authorities,
18 M. Fedurco, P. Kedzierzawski and J. Augustynski, J. Electrochem.
especially Vice Chancellor, University of Kashmir, and Head, Soc., 1999, 146, 2569.
Department of Chemistry, University of Kashmir, for sanction 19 B. Kim, PhD Thesis, University of California, USA, 1991.
of study leave. P. P. I. thanks CSIR—India, for a fellowship. 20 A. J. Bard and L. R. Faulkner, Electrochemical Methods: Funda-
mentals and Applications, Wiley, New York, 2nd edn, 2001.
V. R. C. thanks the BARC–Pune University collaborative PhD 21 C. P. Andrieux and J. M. Saveant, in Investigations of Rates and
program for financial support. The authors would like to thank Mechanisms of Reactions, ed. C. F. Bernasconi, Wiley, New York,
CNQS, University of Pune, for financial support. 1986, part 2, vol. VI/4E.
22 S. Antonello, M. Musumeci, D. D. M. Wayney and F. Maran,
J. Am. Chem. Soc., 1997, 119, 9541.
References 23 J. M. Saveant, in Advances in Electrontransfer Reactions, ed.
P. S. Mariano, JAI Press, Greenwich, 1994, vol. 4, p. 53.
1 G. Ellis, I. Adatia, M. Yazdanpanah and S. K. Makela, Clin. 24 Handbook of Electrochemistry, ed. C. G. Zoski, Elsevier, Amsterdam,
Biochem., 1998, 31, 195. 1st edn, 2007.
2 C. S. Bruning-Fann and J. B. Kaneene, Vet. Hum. Toxicol., 1993, 25 J. M. Saveant, J. Am. Chem. Soc., 1987, 109, 6788.
35, 237. 26 S. Antonello and F. Maran, J. Am. Chem. Soc., 1999, 121, 9668.
3 National Research Council, Ground Water Vulnerability Assess- 27 A. Cardinale, A. A. Isse, A. Gennaro, M. Robert and
ment, Predicting relative contamination potential under conditions of J. M. Saveant, J. Am. Chem. Soc., 2002, 124, 13533.
uncertainty, National Academy Press, Washington DC, 1993, 28 R. L. Donkers and M. S. Workentin, J. Phys. Chem. B, 1998, 102,
p. 14. 4061.
4 M. A. Ferree and R. D. Shannon, Water Res., 2001, 35, 327. 29 Handbook of Chemistry and Physics, CRC Press, New York, 80th
5 S. Kage, K. Kudo and N. Ikeda, J. Chromatogr. B: Biomed. Appl., edn, 1999–2000.
2000, 742, 363. 30 J. A. Riddick and W. B. Bunger, in Organic Solvents: Physical
6 J. A. Morales, L. S. de Graterol and J. Mesa, J. Chromatogr. A, Properties and Methods of Purification, John Wiley and Sons, New
2000, 884, 185. York, 3rd edn, 1970, vol. II.
7 V. Jedlickova, Z. Paluch and S. Alusik, J. Chromatogr. B: Anal. 31 L. Pause, M. Robert and J. M. Saveant, J. Am. Chem. Soc., 2000,
Technol. Biomed. Life Sci., 2002, 780, 193. 122, 9829.
8 T. Miyado, Y. Tanaka, H. Nagai, S. Takeda, K. Saito, K. Fukushi, 32 O. M. Magnussen, Chem. Rev., 2002, 102, 679.
Y. Yoshida, S. Wakida and E. Niki, J. Chromatogr. A, 2004, 1051, 33 M. Kleinert, A. Cuesta, L. A. Kibler and D. M. Kolb, Surf. Sci.,
185. 1999, 430, L521.
9 M. J. Moorcroft, J. Davis and R. G. Compton, Talanta, 2001, 54, 785. 34 T. L. Broder, D. S. Silvester, L. Aldous, C. Hardacre, A. Crossley
10 J. Krista, M. Kopanica and L. Novotny, Electroanalysis, 2000, 12, 199. and R. G. Compton, New J. Chem., 2007, 31, 966.

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