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Insights on Selenium and Tellurium Diaryldichalcogenides:

A Benchmark DFT Study
Francesco Zaccaria,[a] Lando P. Wolters,[b] Celia Fonseca Guerra,*[a] and Laura Orian*[b]
Selenium based diaryl dichalcogenides are compounds that
are receiving attention in organic synthesis as eco-friendly oxidation agents as well as in pharmaceutical chemistry, where,
together with tellurium-based derivatives, are appealing drugs
mainly for their antioxidant properties. A benchmark study to
establish optimal density functional theory (DFT) methods for
the description of their molecular and electronic structure as
well as for their energetics is presented here. Structural fea-

tures, such as the orientation of the phenyl rings, as well as

energetic aspects, i.e., the chalcogen-chalcogen bond strength,
are discussed, with the aim of applying the novel insights to
quantum mechanics-based investigations of their reactivity
C 2016 Wiley Periodicals, Inc.
and to facilitate drug design. V

Introduction

diphenyl diselenides with an amine in ortho position to selenium: according to their hypothesis, the diselenide bond is
cleaved in presence of one equivalent of thiol and a zwitterionic form of selenol forms, which can reduce H2O2 in a threestep mechanism analogous to the enzymatic one.[10]
The step of H2O2 reduction catalyzed by N,N-dimethylbenzylamine diselenide was investigated in silico by Coulson and
Boyd,[11] who employed DFT methods to assess that the zwitterion form of selenol is energetically favored. In contrast, the
path involving the direct oxidation of the diselenide by H2O2
to form the selenoxide was discarded. The same authors
reported a higher activation energy for H2O2 reduction when
ebselen diselenide is used instead of ebselen and ebselen selenol.[12] Mugesh et al.[13] carried out experimental studies on
the GPx activity of several diaryl diselenides with intramolecular coordinating amino groups which, besides being able to
generate the zwitterion form of selenol, facilitate the catalysis,
preventing further oxidation of the selenenic intermediate and
priming the nucleophilic attack of thiol at selenium. Mugesh[14]
reported also interesting results on the combined effect of a
methoxy and amine group in ortho position to selenium in
diaryl diselenides and on the possibility of tuning their GPx
activity by using sec-amino substituted diselenides rather than
the analogous tert-amine-based compounds. Numerous experimental contributions about GPx-like activity of diphenyl diselenides are due to the group of Rocha.[15]

The catalytic properties of diphenyl diselenides are exploited

in organic chemistry since 1978,[1] especially for their selectivity in numerous oxidative transformations. For example, as
recently reported, diphenyl diselenides can selectively oxidize
activated alcohols with stable hydroperoxides.[2] More in general, they are efficient catalysts for the oxidation of several
organic functionalities such as olefins, alkynes, carbonyl compounds, and amines.[3] Interestingly, dichalcogenides are
unique examples of molecules with inherently chiral chromophores because their two helical enantiomeric conformations,
arising from their peculiar skewed arrangement, are differently
stabilized in a chiral environment and this gives rise to Cotton
effect in CD spectra.[4] Besides their important application in
organic synthesis, the use of organoselenium compounds in
chemistry and pharmacology is mainly related to their antioxidant gluthathione peroxidase (GPx)-like activity.[5] In fact,
they can reduce harmful organic hydroperoxides or H2O2 to
their corresponding alcohols or water, respectively. The catalytic process occurs in presence of a thiolate able to act as the
glutathione cofactor, which, in the enzymatic system, reduces
the selenenic intermediate of GPx to the initial selenol form
(Scheme 1).[6]
The anti-oxidant activity of diphenyl diselenides was first
reported by Spectors group in 1989,[7] only five years after the
discovery of ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one),
which is the best known anti-oxidant GPx mimic and belongs
to the class of cyclic selenenylamides.[8] Two compounds were
prepared, i.e. N,N-dimethyl- and pyrrol-benzylamine diselenide,
displaying peroxidase activity one order of magnitude higher
than that of ebselen. Diaryldiselenides offer promising advantages: their synthesis is easier than that of selenenyl amides; in
addition their activity can be modulated by inserting suitable
ring substituents. In particular, it was found that a strong basic
group near selenium primes the reaction.[9] Iwaoka and
Tomoda proposed a mechanism for the peroxidase activity of
1672

Journal of Computational Chemistry 2016, 37, 16721680

DOI: 10.1002/jcc.24383

[a] F. Zaccaria, C. F. Guerra

Department of Theoretical Chemistry and Amsterdam Center for
Multiscale Modeling, Vrije Universiteit Amsterdam, De Boelelaan 1083,
Amsterdam, 1081 HV, the Netherlands
E-mail: c.fonsecaguerra@vu.nl
[b] L. P. Wolters, L. Orian
Dipartimento Di Scienze Chimiche, Universit
a Studi Di Padova, via
Marzolo 1, Padova, 35129, Italy
E-mail: laura.orian@unipd.it
Contract grant sponsor: Universita degli Studi di Padova; Contract grant
number: CPDA127392/12
C 2016 Wiley Periodicals, Inc.
V

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metries and homolytic dissociation energies of diphenyl

diselenides and diphenyl ditellurides, and discuss the essential
features of their molecular and electronic structure; in some
cases, results for disulfides will also be included for completeness. Scalar relativistic effects, which are mandatory in particular for tellurium derivatives, are included in all our calculations.

Computational Details

Scheme 1. Enzymatic mechanism of H2O2 reduction mediated by GPx.

Diphenyl ditellurides also proved to be particularly efficient

peroxidase mimics as well as anticancer drugs, and surprisingly
they are not significantly more toxic than organoselenium analogs.[5a,16] Engman[17] first reported on diaryl ditellurides and
very recently several contributions were presented by Rocha
and co-workers.[18] In addition, tellurium compounds have
been investigated also as chemopreventive agents, and
diphenyl ditelluride appears to have a very high capacity of
inducing apoptotic cell death.[19]
Despite the claimed importance of these molecules, no systematic elementary studies on the structural and electronic
properties of diphenyl dichalcogenides are known, which
might be used for advanced mechanistic studies and rational
drug design. To this last purpose, some of us have very
recently parametrized a general Amber force field for a series
of diaryl diselenides and diaryl ditellurides, paving the route to
their bioincorporation in suitable protein scaffolds or simply to
testing their activity in a realistic biological environment.[20]
From the investigation of the PES of diphenyl diselenides and
diphenyl ditellurides with different substituents in para position of the rings (amino, methoxy, methyl, chlorine, and nitro
groups), carried out at B3LYP/cc-PVTZ, it emerged that some
structural features of this class of compounds, i.e., the mutual
orientation of the phenyl rings, easily change with a modest
energy cost. In this case, the choice of the quantum chemistry
methodology was driven by the analogy with methods traditionally used in GAFF (General Amber Force Field) parametrization[21a] and for example the popular B3LYP[22] functional was
preferred to the B3PW91[22a,23,21b] benchmarked by Boyd and
Coulson for organic monoselenides.[24] One of the major outcomes of this study is in agreement with the expectation that
an energetically easier stretching of the interchalcogen bond
as well as of the chalcogencarbon bond, as well as an easier
torsion of the dihedrals about the chalcogenchalcogen and
chalcogencarbon bonds, should be found, when moving
downwards in the chalcogens group. Thus, how can the accuracy of the structure and energy values, needed for rigorous
reactivity studies, be conciliated with the intrinsic softness of
these molecular systems?
In this work, we show the results of evaluating the performance of density functional theory methods in predicting geo-

All density functional theory (DFT) calculations have been

done with the Amsterdam Density Functional (ADF) program.[25] Scalar relativistic effects are accounted for through
the zeroth-order regular approximation (ZORA).[26] In the first
set of calculations carried out on Ph2Se2 and Ph2Te2 twentythree density functionals have been used in combination with
the TZ2P basis set for all elements (Supporting Information
Table S1). The TZ2P basis set is a large uncontracted set of
Slater-type orbitals (STOs), of triple-f quality and augmented
with two sets of polarization functions on each atom: 2p and
3d in the case of H, 3d and 4f in the case of C, 4d and 4f in
the case of Se and 5d and 4f in the case of Te. An auxiliary set
of s, p, d, f, and g STOs was used to fit the molecular density
and to represent the Coulomb and exchange potentials accurately in each SCF cycle. All-electron (ae) computations have
been performed to allow a rigorous comparison among the
chosen functionals (for some of them small frozen-core (sc)
approximation is not implemented). In combination with
selected functionals, i.e. OPBE[27] and BLYP-D3(BJ)[28], the basis
sets TZP and QZ4P have also been tested. All the geometries
discussed in the paper were fully optimized (i.e., without any
symmetry restriction) using analytical gradient techniques. All
fully optimized minima were verified by frequency analysis: all
normal modes have real frequencies except for three structures showing very small imaginary frequencies. These three
imaginary frequencies have been verified to be the rotation of
phenyl rings along the X-C axis or rotation of methyl groups,
which are energetically negligible contributions (see SI).
Enthalpies (DH) at 298.15 K and 1 atm were calculated from
electronic bond energies (DE) and our frequency computations
using standard statistical-mechanics relationships for an ideal
gas. Results in toluene have been obtained using COSMO
model for solvation,[29] as implemented in the ADF program.[30] We have used a solvent-excluding surface with an
effective radius for toluene of 2.53 A, derived from the macroscopic density, molecular mass, and a relative dielectric constant of 0.866 g/mL, 92.14 g/mol, and 2.379. The empirical
parameter in the scaling function in the COSMO equation was
chosen as 0.0. The radii of the atoms were taken to be MM3
for H, 1.700 A
for C,
radii,[31] divided by 1.2, giving 1.350 A

1.908 A for Se, and 2.033 A for Te.

Results and Discussion

Structural investigation
Our investigation started from searching in the Cambridge
Structural Database (CSD)[32] compounds containing the Ph2X2
(X 5 Se,Te; Ph 5 C6H5) moiety; we found 181 diselenides and
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Figure 1. Schematic molecular structures of Ph2Se2 and Ph2Te2, in their

closed and open geometry, respectively, including the atom numbering as
used for the definitions of the dihedrals W, U1, and U2, and the closed and
open saloon doors these structures resemble.

81 ditellurides. Among all these compounds, tri- and polychalcogenides were excluded; we extracted from the database
only the simplest compounds with molecular formula Ph2X2,
here after defined as parent compounds, and those bearing
substituents on the phenyl rings; the number of molecules
was reduced to 67 and 40, respectively. We have initially identified as common structural features of all these diaryl dichalcogenides: (i) the chalcogen-chalcogen bond length X-X
(X 5 Se,Te), which has an average value of 2.32 A and of 2.71
for the diselenides and ditellurides here considered; (ii) the
A
value of the dihedral angle W (C1-X-X-C1) (Fig. 1), which, for
the parent compounds and diphenyl dichalcogenides with
substituents only in para position, has absolute values in the
range 7581008 (average value 888 6 2 for Se and 898 6 2 for
Te compounds), and (iii) the mutual orientation of the phenyl
rings, which can be quantified defining the dihedrals U1 (C2C1-X-X) and U2 (X-X-C10 -C20 ) (Fig. 1). Referring to these last
dihedrals, which for molecular symmetry can be simply

denoted U, two extreme different orientations of the phenyl

rings can be distinguished: lying in approximately parallel planes,
almost parallel to the plane orthogonal to the chalcogenchalcogen bond, and rotated by W, or lying in planes each containing the chalcogen-chalcogen bond, and also in this case
rotated by W. These conformations are assigned by measuring
the dihedrals U1 and U2: open compounds are characterized by
U1 and U2 both close to 908, while in closed compounds the
values of these dihedrals tend both to 08. Open and closed refer
to the analogy of the Ph2X2 moiety, oriented as in Figure 1, with
a saloon door. All compounds extracted from CSD show a broad
distribution of the values of these U dihedrals, suggesting that
the rotation of the phenyls about their axis indeed requires low
energy and that their mutual orientation in crystalline state is
certainly affected by the lattice forces as well as by temperature
and anharmonic effects.
In Table 1, the relevant geometric parameters of selected
diselenides and ditellurides measured on the crystallographic
structures are shown; all species with substituents in para position have been considered to get rid of steric effects which
might also influence the mutual orientation of the rings.
We first performed a benchmark analysis to choose the optimal DFT level of theory for the geometrical description of
these species. Twenty-three popular functionals have been
tested on the parent compounds, which show closed (Ph2Se2)
and open (Ph2Te2) conformations in solid state, despite they
crystallize in the same spatial group and unitary cell. The
results of these calculations are included in the Supporting
Information, in Table S1, and are summarized in Figure 2 (A to
H), where the deviations from the crystallographic values of
chalcogen-chalcogen (A,E) and carbon-chalcogen (B,F) bond
lengths, carbon-chalcogen-chalcogen (C,G) angle and carbonchalcogen-chalcogen-carbon (D,H) dihedral are shown.
Deviations from the reference crystallographic values are
generally larger for Ph2Te2 than for Ph2Se2. All the reported
deviations for the first three parameters are rather small and
fall within the typical accuracy of DFT methods; in contrast,
the W dihedral varies significantly with changing the functional, but the deviations are in almost all cases within the
range of the values spanned by W in the structures taken

Table 1. Relevant interatomic distances (A) and angles (8) of selected crystallographic structures taken from CSD.

1674

Substituent

X-X

C-X-X (h)

C-X-X-C (W)

X-C

X-X-C-C (U1, U2)

Conformer

2.027

84

p-Cl

2.332

Ph2Se2

YUXPIR

2.307

p-CH3-Ph2Se2

QQQGBV01

p-CH3

2.328

p-Cl-Ph2Te2

CLPHTE01

p-Cl

2.680

Ph2Te2

DPHDTE01

2.707

p-CH3-Ph2Te2

DPTOTE

p-CH3

2.696

1.789
1.790
1.929
1.911
1.946
1.934
1.923
1.910
2.144
2.160
2.131
2.115
2.125
2.131

20
1
61
74
23
0
90
73
13
10
84
90
37
37

Closed

CLPHSE

104.9
106.2
98.6
98.9
102.4
103.5
102.0
101.2
99.6
101.6
100.7
97.7
101.5
100.0

Compound

CSD identifier

Ph2S2

YUXPEN01

p-Cl-Ph2Se2

Journal of Computational Chemistry 2016, 37, 16721680

74
85
100
89
90
86

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Open
Closed
Open
Closed
Open
Closed

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Figure 2. Deviation from the crystallographic values of relevant interatomic distances and angles for Ph2Se2 (left) and Ph2Te2 (right) with different functionals and TZ2P-ae basis set; scalar ZORA approximation is used. The functionals are grouped using the different colours from left to right as LDA (red), GGA
(BLYP, BP86, OLYP, PBE, OPBE, RPBE, revPBE, HTBS, PW91, mPBE, mPW) (blue), metaGGA (TPSS, M06-L) (green), HYBRID (B3LYP, PBE0, OPBE0, mPW1PW) (yellow), metaHYBRID (M06, TPSSH) (orange), and dispersion corrected functionals (BLYP-D3(BJ), BP86-D3(BJ), PBE-D3(BJ)) (white). [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]

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), deviation D (%) from the X-ray structure, and changes in Ph2S2, Ph2Se2 and Ph2Te2 total molecular
Table 2. Chalcogenchalcogen bond length (A
energy (kcal mol21) between a fully optimized geometry and a constrained geometry with interchalcogen distance set equal to the crystallographic
value.[a]
Functional

S-S

X-ray
BLYP
OLYP
HTBS
OPBE
BLYP-D3(BJ)
BP86-D3(BJ)

2.03
2.06
2.03
2.03
2.01
2.06
2.04

D
1.48%
0.00%
0.00%
0.99%
1.48%
0.99%

DE

Se-Se

10.2
0.0
0.0
10.2
10.2
0.0

2.31
2.36
2.34
2.31
2.30
2.36
2.32

D
2.16%
1.30%
0.00%
0.43%
2.12%
0.43%

DE

Te-Te

DE

10.3
0.0
0.0
10.2
10.2
0.0

2.71
2.78
2.73
2.71
2.69
2.77
2.74

2.58%
0.74%
0.00%
0.74%
2.21%
1.11%

10.4
0.0
0.0
0.0
10.4
10.1

[a] All computations were performed with the QZ4P-ae basis set.

from CSD. Since all the optimizations have been started from
the crystallographic structures, the most evident observation is
that in all cases the open/closed conformation is retained. This
prompted us to look for the existence of both conformers at
least in several cases and found that the energy difference is
indeed very small (Supporting Information Table S5). OPBE[27],
HTBS[33] and the meta-hybrids M06 and M06-L[34] predict a relative stability of the conformers of the diselenide which is in
agreement with the closed conformation of the crystallographic structure; in contrast, OPBE, OLYP,[35] BLYP-D3(BJ),[28]
BLYP,[36] HTBS,[33] but not the meta-hybrids M06 and M06-L,
predict a relative stability of the conformers of the ditelluride
which is in agreement with the open conformation of the crystallographic structure. The main issues we want to address,
which will lead to the choice of the preferred method, is how
accurate the prediction of the inter-chalcogen bond length
must be and the importance of the phenyl rings orientation, if
any, to have meanignful structural and energetic results in silico for this class of compounds.

also performing very well, but due to the limited application

of this functional presented so far, further testing is recommended. BP86-D3(BJ) and BLYP-D3(BJ) also perform well and
have the advantage of including the dispersion correction
which might become fundamental to weigh those conformations in which the phenyl rings are stacked close to each
other.
In order to verify the optimal basis set as compromise
between quality and time consumption, we have tested several basis sets combined with two out of the six selected functionals on the parent compounds, i.e. OPBE and BLYP-D3(BJ).
The results are included in Supporting Information Tables S3
and S4. We have found that TZ2P-sc can be safely used in
combination with either OPBE or BLYP-D3(BJ) to obtain reliable
interchalcogen distances for diphenyldichalcogenides. The
inclusion of spin-orbit effects has been investigated for Ph2Te2
at SO-ZORA/OPBE with TZ2P-ae and QZ4P-ae (Supporting
Information Table S4); the interchalcogen distance becomes
even closer to the experimental value, but a larger deviation is
found for the dihedral W (see next paragraph).

Chalcogenchalcogen bond length

We have thus chosen a subset of performing functionals and,
focussing on the chalcogen-chalcogen bond, whose strength
is an important parameter for the reactivity of these compounds, we have set up a computational protocol to determine how errors on this bond length might affect the total
molecular energy. The following functionals were tested:
BLYP,[36] BLYP-D3(BJ),[28] OLYP,[35] OPBE,[27] BP86-D3(BJ)[28], and
HTBS,[33] all combined with the accurate all-electron QZ4P
basis set. With each of these functionals, the energy difference
between the fully optimized geometry and the one with the
interchalcogen distance frozen to the crystallographic value
was calculated. The results are shown in Table 2. The straightforward conclusion is that the energy of the system is not
importantly affected by X-X bond shortening (lengthening in
the case of OPBE). The same observation holds for selected
substituted compounds (Supporting Information Table S6).
This leads to the important insight that the interchalcogen distance is not a critical parameter for the choice of the functional, since its variations imply only negligible structural and
energetic changes. On the basis of the obtained results, and
its performance for analogous compounds,[37] we consider
OPBE a good functional for geometry optimizations. HTBS is
1676

Journal of Computational Chemistry 2016, 37, 16721680

Dihedral angles
In order to gain insight into the overall molecular geometry of
diaryl dichalcogenides, we have performed accurate relaxed
scans of the main dihedral angles of the parent compounds,
identified as W and U, at ZORA/TZ2P-ae level, using these
functionals: OPBE,[27] BLYP,[35] BLYP-D3(BJ)[28] and OLYP.[35]
Starting from the minimum energy structures of Ph2Se2 and
Ph2Te2, two conformational analysis have been carried out
varying (i) W and (ii) one of the dihedrals U. The resulting
energy profiles are shown in Figures 3 and 4, respectively.
At all levels of theory, the lowest-energy structure has a
dihedral angle W close to 90 (or the equivalent 290 ). This is,
as has been explained in detail for diaryl and dialkyl disulfide
compounds[38] because the binding of the phenyl substituents
to the Se-Se/Te-Te moiety results from overlap of the singly
occupied molecular orbital (SOMO) on the phenyl fragment
with the different p* orbitals of the Se-Se/Te-Te moiety; one
phenyl SOMO overlaps with the px*, while the SOMO of the
other phenyl overlaps with the py* orbital, which is perpendicular to the px*.
We furthermore find that for the dispersion-corrected BLYPD3(BJ) functional the attractive dispersion interactions
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Figure 3. Energy profiles for the variation of W for Ph2Se2 and Ph2Te2; level of theory: ZORA/TZ2P-ae.

between the phenyl substituents lead to the stabilization of

conformations with a dihedral angle W in the range between
290 and 90 , that is, when the two substituents are relatively
close to each other. This implies also a lower relative energy
for the eclipsed conformation (W 5 0 ), which for BLYP-D3(BJ)
is destabilized by 34 kcal mol21 relative to the global minimum, whereas with the other functionals the same difference
raises to 79 kcal mol21. The barrier for rotation into the other
direction (via the maximum at 180 ) is obviously less affected
by the dispersion correction and remains at 5 to 6 kcal mol21
for both Ph2Se2 and Ph2Te2. Also, we note that for the BLYPD3(BJ) energy profiles there is a slight asymmetry with respect

to 08. This is caused by the fact that at W 5 0 the compounds

do not assume a full C2v-symmetric geometry, but are only C2symmetric, with both phenyl fragments rotated slightly out of
the plane perpendicular to the chalcogenchalcogen bond,
and facing each other. The energy changes related to such
rotations of the phenyl rings are, however, rather insignificant.
This follows from the energy profiles for variation of the dihedral U, which are shown in Figure 4. In the two graphs on the
top, we show the energy profile at the same scale used in Figure 4, up to 10 kcal mol21, to accentuate the different energy
ranges corresponding to variation of the dihedrals W and U:
the energy profile for the latter is rather flat.

Figure 4. Energy profiles on different energy scales for the variation of U1 for Ph2Se2 and Ph2Te2; level of theory: ZORA/TZ2P-ae.

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Table 3. Homolytic dissociation energies DE (DH) of H2X2 and (CH3)2X2; TZ2P-ae basis set was used and all values are in kcal mol21.
H2S2[a]
BLYP
BLYP-D3(BJ)
OLYP
OPBE
B3LYP

H2Se2[b]

64.2
66.9
67.4
74.6

55.4
58.6
56.6
63.2
52.8

(58.1)
(61.3)
(59.6)
(66.3)
(55.9)

H2Te2

(CH3)2S2[c]

47.6
51.6
47.6
54.0
46.4 (49.0)

58.3
63.3
60.0
64.9

(CH3)2Se2[d]

(CH3)2Te2

53.5
58.7
51.2
55.0
52.1

48.2
54.0
44.6
48.3
46.9

(57.5)
(62.8)
(55.5)
(53.2)
(56.0)

(52.0)
(58.1)
(48.5)
(50.1)
(50.4)

[a] Experimental value is DH 5 66 6 2 kcal mol21 [Ref. 42]. [b] Values computed at B3LYP/PVDZ and GMP2 are DH 5 51.1 and DH 5 55.1 kcal mol21,
respectively. [Ref. 40]. [c] Experimental value DH 5 62 6 2 kcal mol21 [reported in Ref. 43]. [d] Values computed at B3PW91/6-311 1 G(2df,p)//B3PW91/631G(d,p) and B3PW91/6-311 1 G(2df,p)//B3PW91/6-311 1 G(2df,p) are DE 5 51.7 and DE 5 51.8 kcal mol21, respectively. [Ref. 41].

In the two graphs at the bottom in Figure 4 we show the

energy profiles for variation of the U dihedral on a more
appropriate scale. It should be noted, however, that this scale
covers only 1 kcal mol21, and some energy profiles are entirely
within 0.5 kcal mol21. As such, we approach here the limits of
the accuracy of the method. This also leads to the numerical
noise becoming clearly manifested for these energy profiles.
Interestingly, the energy minima corresponding to the closed
conformation (U 5 08) of Ph2Te2 do not appear in the energy
profile obtained with BLYP and OLYP, even though this conformation has been located using the exact same methodology.
This is a consequence of the two U dihedral angles being
decoupled in the conformational analyses for which the results
are depicted in Figure 4. These energy profiles result from
optimizations with only one U dihedral being constrained to a
certain value, whereas the other is free to rotate. Small rotational barriers may prevent the other phenyl to rotate to its
optimal position, leading to a small energy barrier instead of a
shallow local minimum. The conclusions that can be drawn
from these energy profiles are: (i) OPBE and BLYP-D3(BJ) seem
to be slightly better suited to locate both the open and closed
conformations of these compounds, and (ii) rotation of the
phenyls is for both Ph2Se2 and Ph2Te2 feasible in presumably
all practical situations, and not too much importance must be
given to their mutual orientation. This is in line with the analyses of the crystallographic data discussed before, in which a
variety of different conformations can be found. It is also
worth noting that the intramolecular motion of diphenyldichalcogenides was addressed in a pioneering study approximately 40 years ago with measures of spin-lattice relaxation
times (T1) of 13C.[39] Assuming a rigid anisotropic model corre-

Table 4. SeSe and TeTe homolytic bond dissociation energies DE (DH)

in vacuo; level of theory: ZORA, TZ2P-ae and all values are in kcal mol21.
Ph2Se2
Closed
BLYP
BLYP-D3(BJ)
BP86
BP86-D3(BJ)
OLYP
OPBE
HTBS
B3LYP

1678

39.7
48.4
45.0
53.2
38.3
43.8
47.5
52.1

(40.1)
(50.3)
(46.3)
(55.8)
(39.7)
(45.2)
(50.1)
(54.8)

sponding to the skew conformation of the dichalcogenides

(W 5 90 ), the authors investigate the tumbling of the phenyl
rings and draw the conclusion that the rotation is increasingly
less hindered when going from S to Se and Te. The results of
this study of the dynamics in solution of diphenyldichalcogenides is thus in exact agreement with our findings on the
energetics of these compounds.

Chalcogenchalcogen bond strength

The chalcogenchalcogen bond strength was investigated by
computing the energy cost associated to the generation of
two radical monochalcogenides (homolytic dissociation) in the
parent compounds Ph2X2. A fair estimate of this value is
important since the reactivity of dichalcogenides implies the
breaking of this bond. For comparison with data already
reported in literature,[4043] we included two alkyldichalcogenides, i.e. H2X2 and (CH3)2X2; dissociation energies for these
compounds were calculated first and are shown in Table 3,
where, for completeness, data for disulfides are also
presented.[44]
The BDE values are all very close, show a slight decrease for
Te compounds, as expected. For diphenyldiselenides and
diphenylditellurides, the BDEs have been measured combining
calorimetric and stopped-flow kinetics analysis and are 41 and
33 kcal mol21, respectively with an estimated error of 63
kcal mol21.[45] Thus, BLYP and OLYP seem to be the best
choice (Table 4). The calculations have been repeated in toluene using BLYP, BLYP-D3(BJ), B3LYP and OLYP and the results
are shown in Table 5. It is confirmed that the inclusion of dispersion leads to overestimation of the BDE, but, more important, among the chosen functionals, only OLYP and B3LYP
predict the lower BDE for the ditelluride. In particular, we recommend OLYP to study the energy landscape and the mechanistic aspects of this class of compounds.

Ph2Te2
Open

40.2
48.6
44.5
53.0
39.1
43.7
47.2
53.1

(41.7)
(50.1)
(46.0)
(54.6)
(40.6)
(45.2)
(50.0)
(55.3)

Closed
39.3
48.4
43.8
53.0
36.4
41.3
46.5
47.7

(40.5)
(49.6)
(45.0)
(54.1)
(37.5)
(42.6)
(48.8)
(59.9)

Journal of Computational Chemistry 2016, 37, 16721680

Open
40.0
48.5
43.8
52.9
37.4
41.6
46.6
48.6

(41.4)
(49.9)
(45.2)
(54.2)
(38.7)
(43.0)
(49.2)
(50.1)

Table 5. SeSe and TeTe homolytic bond dissociation energies

DE (DH) in toluene; level of theory: ZORA, TZ2P-ae and all values are in
kcal mol21.
Ph2Se2
BLYP
BLYP-D3(BJ)
OLYP
B3LYP

39.4
48.2
52.8
38.8

(41.8)
(50.2)
(54.4)
(40.7)

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Ph2Te2
39.8
48.3
47.1
37.0

(42.3)
(50.9)
(49.7)
(38.4)

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Conclusions
We have analyzed in detail the molecular structure and energy
features of diphenyldiselenides and diphenylditellurides. Starting from the crystallographic data, 23 functionals have been
benchmarked for the parent diselenide and ditelluride, including ZORA scalar relativistic effects and using a TZ2P-ae basis
set. Six functionals were chosen for their good performance
and tested on the parent compounds and on p-Cl- and p-CH3diphenyldiselenides/ditellurides to analyze the effect of interchalcogen bond deformation. We concluded that variation of
, which are the accuracy of these methods, of
hundredths of A
the chalcogen-chalcogen bond does not affect significantly
the total energy. Thus we suggest for geometry optimization
the popular OPBE or a dispersion corrected functional, i.e.
BP86-D3(BJ) and BLYP-D3(BJ) combined with TZ2P-sc basis set,
since higher quality basis sets do not affect significantly the
results.
Another important feature of these molecules is the value
of the C-X-X-C dihedral, which is close to 908 and is fairly
reproduced by almost all the benchmarked functionals. In contrast, we demonstrate that the mutual orientation of the phenyl rings, which is related to the values of the two dihedrals CC-X-X, is not relevant, despite its effect on the overall molecular aspect. In fact, the energy involved in the rotation of the
phenyl rings about their axes is negligible and this is in agreement with the structures extracted from the CSD in which
these dihedrals assume many randomly different values and
with the dynamics probed with measurements of 13C spin lattice relaxation times. From accurate scanning along the C-X-XC dihedral we have concluded that as expected for dichalcogenides the global minima are 290 and 190 , but when including the dispersion interaction, we observe a stabilization of
the conformer with U 5 0 (rings facing each other), which is
otherwise the energetically less favoured situation.
Finally, we have evaluated the homolytic dissociation energy
of the Se-Se and Te-Te bonds with different functionals and
drawn out that for energetics OLYP functional is recommended
because it adequately predicts a lower BDE for the ditelluride
than for the diselenide in solvent. Alternatively, the popular
B3LYP also performs well.
In conclusion, in computational mechanistic studies involving diphenyldichalcogenides, which are compounds of paramount importance in organic catalysed oxidation processes as
well as promising drug-like molecules with anti-oxidant activity, we suggest as optimal levels of theory ZORA-OPBE/TZ2P-sc
for geometry optimization and ZORA-OLYP/TZ2P-sc for the
energy landscape and the mechanistic investigations. This
information is valuable for mechanistic investigation of the catalyzed H2O2 reduction process, which so far has never been
studied in detail for this class of catalysts/drugs, despite their
intense usage in the lab.

Acknowledgments
Computational resources in CINECA (http://www.cineca.it, Casalecchio di Reno, Italy) have been available through the ISCRA projects

IDEAS (In silico Design of Enzymatic Anti-oxidant Systems) and

IDEAS2, PI: Laura Orian). F.Z. acknowledges Universita degli Studi di
Padova for a pre-doctoral grant in 2014.
Keywords: diaryldichalcogenides  GPx
tellurium  OPBE  OLYP  ZORA

mimics  selenium 

How to cite this article: F. Zaccaria, L. P. Wolters, C. Fonseca

Guerra, L. Orian. J. Comput. Chem. 2016, 37, 16721680. DOI:
10.1002/jcc.24383

Additional Supporting Information may be found in the

online version of this article.

[1] D. H. R. Barton, A. G. Brewster, A. H. F. Hui, D. J. Lester, S. V. Ley, T. G.

Back, J. Chem. Soc. Chem. Comm 1978, 952.
[2] J. C. van der Toorn, G. Kempermann, R. A. Sheldon, I. W. C. E. Arends,
Eur. J. Org. Chem. 2011, 23, 4345.
[3] J. D. Woollins, R. S. Laitinen, Eds. Selenium and Tellurium Chemistry
From Small Molecules to Biomolecules and Materials, Springer Verlag:
Berlin, Heidelberg, 2011.
[4] T. Kurtan, S. Antus, G. Pescitelli, In N. Berova, P. L. Polavarapu, K. Nakanishi, R. W. Woody, (eds.) Comprehensive Chiroptical Spectroscopy,
Vol. 2, Chap. 3, Wiley: New Jersey, 2011.
[5] (a) C. W. Nogueira, G. Zeni, J. B. T. Rocha, Chem. Rev. 2004, 104, 6255;
(b) G. Mugesh, W.-W. du Mont, H. Sies, Chem. Rev. 2001, 101, 2125; (c)
L. Orian, S. Toppo, Free Rad. Biol. Med. 2014, 66, 65; (d) L. P. Wolters, L.
Orian Curr. Org. Chem. 2016, 20, 189.
[6] L. Orian, P. Mauri, A. Roveri, S. Toppo, L. Benazzi, V. Bosello-Travain, A.
De Palma, M. Maiorino, G. Miotto, M. Zaccarin, A. Polimeno, L. Floh
e, F.
Ursini, Free Rad. Biol. Med. 2015, 87, 1.
[7] S. R. Wilson, P. A. Zucker, R. R. C. Huang, A. Spector, J. Am. Chem. Soc
1989, 111, 5936.
[8] (a) A. Wendel, M. Fausel, H. Safayhi, G. Tiegs, R. Otter, Biochem. Pharmacol. 1984, 33, 3241; (b) A. Muller, E. Cadenas, P. Graf, H. Sies, Biochem. Pharmacol. 1984, 33, 3235.
[9] K. P. Bhabak, G. Mugesh, Acc. Chem. Res. 2010, 43, 1408.
[10] M. Iwaoka, S. Tomoda, J. Am. Chem. Soc. 1994, 116, 2557.
[11] (a) G. S. Heverly-Coulson, R. J. Boyd, J. Phys. Chem. A 2010, 114, 1996.;
(b) J. K. Pearson, R. J. Boyd J. Phys. Chem. A 2007, 111, 3152.
[12] J. K. Pearson, R. J. Boyd, J. Phys. Chem. A 2006, 110, 8979.
[13] (a) G. Mugesh, A. Panda, H. B. Singh, N. S. Punekar, R. J. Butcher J. Am.
Chem. Soc. 2001, 123, 839; (b) K. P. Bhabak, G. Mugesh Chem. Eur. J.
2008, 14, 8640;
[14] K. P. Bhabak, G. Mugesh, Chem. Eur. J 2009, 15, 9846.
[15] (a) I. J. Kade, M. W. Paixao, O. E. D. Rodrigues, N. B. V. Barbosa, A. L.
Braga, D. S. Avila, C. W. Nogueira, J. B. T. Rocha, Neurochem. Res. 2008,
33, 167; (b) M. Ibrahim, N. Muhammad, M. Naeem, A. M. Deobald, J. P.
Kamdem, J. B. T. Rocha, Tox. In Vitro 2015, 29, 947; (c) B. Fiuza, N.
Subelzu, P. Calcerrada, M. R. Straliotto, L. Piacenza, A. Cassina, J. B. T.
Rocha, R. Radi, A. F. de Bem, G. Peluffo Free Rad. Res. 2015, 49, 122;
(d) W. Hassan, C. S. Oliveira, H. Noreen, J. P. Kamdem, C. W. Nogueira,
J. B. T. Rocha Curr. Org. Chem. 2016, 20, 218; (e) V. Nascimento, N. L.
Ferreira, R. F. S. Canto, K. L. Schott, E. P. Waczuk, L. Sancineto, C. Santi,
J. B. T. Rocha, A. L. Braga Eur. J. Med. Chem. 2014, 87, 131; (f ) I. J.
Kade, J. B. T. Rocha, J. Appl. Toxicol. 2010, 30, 688.
[16] E. R. T. Tiekink, Dalton Trans. 2012, 41, 6390.
[17] (a) C.-M. Andersson, A. Hallberg, R. Brattsand, I. A. Cotgreave, L.
Engman, J. Persson, J. Bioorg. Med. Chem. Lett. 1993, 3, 2553; (b) L.
Engman, D. Stern, M. Pelcman, C. M. Andersson J. Org. Chem. 1994,
59, 1973.
[18] (a) M. Ibrahim, W. Hassan, D. F. Meinerz, M. dos Santos, C. V.
Klimaczewski, A. M. Deobald, M. S. Costa, C. W. Nogueira, N. B. V.
Barbosa, J. B. T. Rocha Mol. Cell Biochem. 2012, 371, 97; (b) C. A.
Prauchner, A. D. Prestes, C. W. Nogueira, J. B. T. Rocha Tox. Mech. Meth.
2013, 23, 660; (c) R. L. Puntel, D. H. Roos, R. L. Seeger, J. B. T. Rocha
Tox. In Vitro 2013, 27, 59.

Journal of Computational Chemistry 2016, 37, 16721680

1679

FULL PAPER

WWW.C-CHEM.ORG

[19] (a) W. Hassan, J. B. T. Rocha, Molecules 2012, 17, 12287; (b) D. F.

Meinerz, J. Allebrandt, D. O. C. Mariano, E. P. Waczuk, F. A. Soares, W.
Hassan, J. B. T. Rocha, Peer J; 2014 2:e290.
[20] M. Torsello, C. A. Pimenta, L. P. Wolters, I. S. Moreira, L. Orian, A.
Polimeno, unpublished results.
[21] (a) J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman, D. A.; Case, J.
Comput. Chem. 2004, 25, 1157; (b) P. J. Stephens, F. J. Devlin, C. F.
Chabalowski and M. J. Frisch, J. Phys. Chem. 1994, 98, 11623.
[22] (a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648; (b) C. Lee, W. Yang, R. G.
Parr, Phys. Rev. B 1988, 37, 785; (c) S. H. Vosko, L. Wilk, M. Nusair, Can.
J. Phys. 1980, 58, 1200.
[23] J. P. Perdew, Y. Wang, Phys. Rev. B 1992, 45, 13244.
[24] J. K. Pearson, F. Ban, R. J. Boyd, J. Phys. Chem. A 2005, 109, 10373.
[25] (a) G. te Velde, F. M. Bickelhaupt, E. J. Baerends, C. Fonseca Guerra, S.
J. A. van Gisbergen, J. G. Snijders, T. Ziegler, J. Comput. Chem. 2001,
22, 931. (b) Computer code ADF2014.01: E.J. Baerends, T. Ziegler, J.
Autschbach, D. Bashford, A. B
erces, F.M. Bickelhaupt, C. Bo, P.M.
Boerrigter, L. Cavallo, D.P. Chong, L. Deng, R.M. Dickson, D.E. Ellis, M.
van Faassen, L. Fan, T.H. Fischer, C. Fonseca Guerra, M. Franchini, A.
Ghysels, A. Giammona, S.J.A. van Gisbergen, A.W. G
otz, J.A.
Groeneveld, O.V. Gritsenko, M. Gr
uning, S. Gusarov, F.E. Harris, P. van
den Hoek, C.R. Jacob, H. Jacobsen, L. Jensen, J.W. Kaminski, G. van
Kessel, F. Kootstra, A. Kovalenko, M.V. Krykunov, E. van Lenthe, D.A.
McCormack, A. Michalak, M. Mitoraj, S.M. Morton, J. Neugebauer, V.P.
Nicu, L. Noodleman, V.P. Osinga, S. Patchkovskii, M. Pavanello, P.H.T.
Philipsen, D. Post, C.C. Pye, W. Ravenek, J.I. Rodrguez, P. Ros, P.R.T.
Schipper, H. van Schoot, G. Schreckenbach, J.S. Seldenthuis, M. Seth,
J.G. Snijders, M. Sola, M. Swart, D. Swerhone, G. te Velde, P. Vernooijs,
L. Versluis, L. Visscher, O. Visser, F. Wang, T.A. Wesolowski, E.M. van
Wezenbeek, G. Wiesenekker, S.K. Wolff, T.K. Woo, A.L. Yakovlev.
(ADF2014, SCM, Theoretical Chemistry, Vrije Universiteit, Amsterdam,
The Netherlands, http://www.scm.com).
[26] E. van Lenthe, E. J. Baerends, J. G. Snijders, J. Chem. Phys. 1994, 101,
9783.
[27] M. Swart, A. W. Ehlers, K. Lammertsma, Mol. Phys. 2004, 102, 2467.
[28] S. Grimme, S. Ehrlich, L. Goerigk, J. Comp. Chem. 2011, 32, 1456.
[29] (a) A. Klamt, G. J. Schuurmann, Chem. Soc., Perkin Trans. 1993 2, 799;
(b) A. Klamt, J. Phys. Chem. 1995, 99, 2224.

1680

Journal of Computational Chemistry 2016, 37, 16721680

[30] C. C. Pye, T. Ziegler, Theor. Chem. Acc; 1999, 101, 396.

[31] N. L. Allinger, X. Zhou, J. Bergsma, J. Mol. Struct. (THEOCHEM) 1994,
312, 69.
[32] F. H. Allen, Acta. Cryst. 2002, B58, 380.
[33] P. Haas, F. Tran, P. Blaha, K. H. Schwartz, Phys. Rev. B 2011, B83,
205117.
[34] (a) Y. Zhao, D. G. Truhlar, J. Chem. Phys., 2006, 125, 194101; (b) Y.
Zhao, D. G. Truhlar, Th. Chem. Acc. 2008, 120, 215.
[35] N. C. Handy, A. J. Cohen, Mol. Phys. 2001, 99, 403.
[36] (a) A. D. Becke Phys. Rev. A 1988, 38, 3098; (b) C. Lee, W. Yang, R. G.
Parr, Phys. Rev. B 1988, 37, 785; (c) B. G. Johnson, P. M. W. Gill, J. A.
Pople, J. Chem. Phys. 1993, 98, 5612; (d) T. V. Russo, R. L. Martin, P. J.
Hay, J. Chem. Phys. 1994, 101, 7729.
[37] A. T. P. Carvalho, M. Swart, J. N. P. van Stralen, P. A. Fernandes, M. J.
Ramos, F. M. Bickelhaupt, J. Phys. Chem. B 2008, 112, 2511.
[38] F. M. Bickelhaupt, M. Sola, P. V. R. Schleyer, J. Comput. Chem. 1995, 16,
465.
[39] M. Baldo, A. Forchioni, K. J. Irgolic, G. C. Pappalardo, J. Am. Chem. Soc.
1978, 100, 97.
[40] D. Kaur, P. Sharma, P. V. Bharatam, J. Mol. Struct. TEOCHEM 2007, 810,
31.
[41] G. S. Heverly-Coulson, R. J. Boyd, J. Phys. Chem. A 2011, 115, 4827.
[42] D. F. McMillen, D. M. Golden, Annu. Rev. Phys. Chem. 1982, 33, 493.
[43] B. S. Jursic, Int. J. Quantum. Chem. 1997, 62, 291.
[44] The basis set superposition error (BSSE) has not been accounted for.
In fact, as recently discussed in L. M. Mentel, E. J. Baerends. In addition
J. Chem. Th. Comp 2013, 10, 252. Counterpoise correction further
reduces the basis set error of the monomer (already smaller than the
error of the dimer), leading to larger deviations in the corrected energies than in the uncorrected ones.
[45] J. E. McDonough, J. J. Weir, M. J. Carlson, C. D. Hoff, Inorg. Chem.
2005, 44, 3127.

Received: 27 January 2016

Revised: 17 March 2016
Accepted: 17 March 2016
Published online on 19 April 2016

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