Supramolecular catalysis

and nanoreactors

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Supramolecular catalysis
stability
selectivity
Catalyst Catalyst-substrate
active site (Receptor) Substrate Complex
BINDING

REACTION
TURNOVER (Cleavage)

+ +
RELEASE
Products

Catalysis by supramolecular systems and nanoreactors can influence (i) the yield of
the reaction, (ii) the pathway (i.e. products regiochemistry and stereochemistry), (iii)
the size and morphology of the products (in the case of crystals)

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 ATCase: a self-regulating enxyme

Active a b
site

CTP

Schematics of the operation of the enzyme aspartate

carbamoyltransferase (ATCase). The catalytic and regulatory subunits are
shown as white and shaded cartoons, respectively. (a) The active site is
available; (b) cytidine triphosphate (CTP), one of the final products of the
enzyme chain, binds to a regulatory domain, shutting the active site off.

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Catalysis of aryl ester hydrolysis by β-cyclodextrin

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna
 Supramolecular catalysis

stability
selectivity
Catalyst Catalyst-substrate
active site Substrates
(Receptor) Complex
BINDING
+ +

TURNOVER REACTION
(Bond formation)

+
RELEASE
Product

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Supra-
molecular
catalysis

The enthalpic gain

associated to the
complexation of the
reactants and their
preorganization in the
complex cause the
acceleration of the
reaction.

The product is more

tightly bound to the
catalyst compared to
the reactants. Hence,
the latter is inhibited,
unless the product is
removed from the
reaction environment.

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Catalysis of a Diels-Alder reaction within a nanocapsule

The hydrogen-bond
assembled “softball”
composed of two
identical subunits 20

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Control of the
stereochemistry
of a reaction within
a macrocyclic host

The acceleration of the reaction

occurs simply by virtue of the
binding of the reactants. Its
exo favorable enthalpic gain
compensates for the highly
unfavorable entropy of activation.
large cavity
The direction of the Diels-Alder
reaction is controlled by means of
the geometrical constraints of
cyclic porphyrin hosts.
endo
small cavity Product inhibition of the catalyst
is observed.

Chem. Rev.
2005, 105, 1445

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Control of cross-photodimerization within a nanocapsule

Managing the selectivity between the cross- and homo-coupling reactions is a difficult challenge because it
requires the selective encapsulation of two different olefins within the cage. This pairwise selectivity could be
nicely controlled by a careful choice of the steric restrictions of the substrates within the capsule: only when a
5-ethoxysubstituent was present on the naphthoquinone was the syn cross-dimer formed exclusively and in
high yield. In case of a 5-methoxy, or in the absence of a substituent, also homodimers were formed.

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Catalytic processes inside dendrimers

Three different types of catalytically active dendrimers:

(a) dendrimer with a catalytically active core;
(b) free-energy driven dendrimer nanoreactor;
(c) catalytically active metal nanoparticle stabilized inside a dendrimer

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Self-replication processes

+ E F
E

E F F
E

E F E F

E F E F
+

A. Robertson, A.J. Sinclair, D. Philp, “Minimal Self-replicating Systems”, Chem. Soc. Rev., 2000, 29, 141

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Self-replication processes

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Self-replicating systems

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Evolution in artificial chemical systems:
Mutation and self-replication

hν
350 nm

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Evolution in artificial chemical systems:
Hybridization

Self-replicating System E-F Self-replicating System G-H

Hybrid E-H Hybrid G-F

“Fertile” “Sterile”

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Micellar catalysis

Micelles can accelerate chemical reactions by virtue of their ability to

solubilize both polar and nonpolar reactants from the aqueous phase

The enhancement of the reaction rate results

from the following phenomena:

1. increased local concentration of the reactants

at the surface or in the interior of the micelle;

2. stabilization of the transition state

of the reaction

3. medium effect (polarity, microviscosity

and charge effects inside the micelle)

Unfortunately, aqueous micelles are kinetically very labile, with average lifetimes
(millisecond range) comparable or faster than most chemical reactions

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Catalysis in closed bilayer structures
Bilayer structures are better organized and considerably more stable than micelles. Therefore,
one can expect an improved catalytic activity for vesicles or liposomes compared to micelles

In closed bilayer structures catalysis can occur

(i) within the (liquid) bilayer membrane

(ii) in the inner aqueous compartment

For the case (ii) the requirements for a liposome to function as a micro- or nano-reactor are:
1. efficient entrapment of the catalyst in the vesicle inner compartment;
2. (selective) diffusion of the reactants and products across the membrane
3. insensitiveness to external influences (pH, temperature, ionic strength, …)
Moreover, if the reactor has to be used in living systems, it should be innocuous.

Spontaneous transport across the bilayer membrane can occur in two ways:
1. molecules with some hydrophobic character will partly dissolve
in the bilayer and diffuse across it
2. ionic solutes take advantage of defects in the bilayer to cross the permeability barrier

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Membrane-supported catalytic systems

Incorporation of the hydrophobic vitamin B12

within the bilayer membrane does not affect
the stability and morphology of the vesicle

Chem. Rev.
1996, 96, 721

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna

 Membrane-
supported
catalytic systems
Reaction mechanism:
1) binding of pyruvate oxidase
to the vesicles;
2) oxidative decarboxylation
of pyruvic acid with the
concomitant reduction of
enzyme-bound FAD to FADH2
3) electron transfer from
FADH2 to AmFl
4) reduction of Mn(III) to Mn(II)
by the reduced AmFl
5) binding and reductive activation
of molecular oxygen to produce
a high-valent manganese
oxo species responsible for
hydrocarbon oxidation.

DPPC = dipalmitoylphosphatidylcholine
Chem. Rev.
1996, 96, 721

A. Credi Nanotecnologia Molecolare LS-FCM Università di Bologna