A supramolecular approach to an allosteric catalyst

Article abstract of DOI:10.1021/ja035621h

The design and synthesis of a novel, supramolecular allosteric catalyst system, assembled via the weak-link approach, is presented. The catalyst contains two structural Rh(I) centers in thioether- and phosphine-rich hemilabile pockets, and two functional Cr(III) centers bound within salen-based moieties. The catalytic properties of the supramolecular catalyst are compared to those of a Cr(III)-salen monomeric analogue in the context of the asymmetric ring opening of cyclohexene oxide by TMSN₃. Allosteric control is afforded via reactions that occur at distal sites which open the macrocyclic cavity and facilitate the catalytic reaction. Kinetic data show a significant rate increase upon opening of the catalyst's flexible macrocyclic cavity and enhanced selectivity and reactivity with respect to the monomeric Cr(III)-salen analogue. The work presented represents a new approach to the construction of abiotic allosteric catalysts. Copyright

Full text of DOI:10.1021/ja035621h

Published on Web 08/08/2003
A Supramolecular Approach to an Allosteric Catalyst
Nathan C. Gianneschi,† Paul A. Bertin,† SonBinh T. Nguyen,† Chad A. Mirkin,*,†
Lev N. Zakharov,‡ and Arnold L. Rheingold‡
Department of Chemistry and the Institute for Nanotechnology, Northwestern UniVersity, 2145 Sheridan Road,
EVanston, Illinois, 60201-3113, and Department of Chemistry and Biochemistry, UniVersity of Delaware,
Newark, Delaware 19716
Received April 14, 2003; E-mail: camirkin@chem.northwestern.edu
Scheme 1. The Supramolecular Allosteric Catalysta
Allosteric regulation is a well-known form of control for
biological molecules but is a rarity for synthetic catalysts.1 However,
with the advent of supramolecular approaches to building multi-
metallic architectures,2 researchers now have a great deal of control
over the spatial arrangement of ligand and metal building blocks
so that the concept of designer catalysts, which offer more complex
function by virtue of such synthetic control, may become a reality.
Indeed, important recent advances have been made in the use of
supramolecular compounds as catalysts.3
We hypothesized that it might be possible to build an allosteric
supramolecular catalyst with an active site that could be opened
and closed by effecting chemistry at one or more distal sites within
the structure. This, in turn, could modulate the catalytic activity of
the complex. Herein, we report the design and synthesis of one
such compound (3 in Scheme 1), a tetrametallic complex prepared
via the weak-link approach to supramolecular chemistry,2d,4 that
behaves as an allosteric catalyst for the ring opening of cyclohexene
oxide.
The weak-link approach is particularly well suited for building
structures with allosteric control because it yields supramolecular
entities whose cavities can be “opened” and “closed” in a reversible
manner. The allosteric effect is achieved through a modification
of catalytic activity via the binding of a CO molecule and a Cl-
ion to each Rh(I) metal at the structure control sites, distal from
the Cr(III) metal centers at functional sites within the same
macrocyclic assembly. In addition, the enhanced selectivity and
activity of the supramolecular catalyst in the asymmetric ring
opening of cyclohexene oxide, as compared to a Cr(III)-salen
Counterions are BF4-. Reagents and solvents: (i) Rh(norbornadiene)2BF4,
a
monomeric analogue, is presented.
The ring opening of epoxides using Cr(III)- and Co(III)-based
salen catalysts is a well-established method for the preparation of
CH2Cl2; (ii) PPNCl/CO, benzonitrile; 3 and 4 may be synthesized from 5
and 6, respectively, by the removal of CO in vacuo or by N2 purge.
a range of ring-opened products from a variety of epoxides and
complexes. Hence, the Rh(I) centers could act as switches for
for the kinetic resolution of epoxides.5 Jacobsen et al. have estab-
catalysis, the switches being addressable via simple ligand substitu-
lished through kinetic studies that the rate-determining step of the
tion chemistry with CO and Cl-. Given that salen-type catalysts
reaction between HN3 and cyclohexene oxide, catalyzed by a mono-
have been shown to catalyze several reactions in a bimetallic fashion
meric Cr(III)-salen catalyst, involves a bimetallic intermediate.6 In
and the vast array of catalytic transformations that are possible with
addition, macrocyclic and linear oligomeric versions of the catalyst
metal salen complexes,5 it was determined that a Cr(III)-salen-based
have been synthesized and show activities significantly greater than
active site would be an attractive candidate for incorporation in
those of their monomeric analogues.7 In the work described here,
the allosteric macrocycle.
The novel, enantiomerically pure hemilabile ligands 1 and 2 were
our goal is to demonstrate the utility of directed supramolecular
assembly in the creation of related catalysts that employ biologically
synthesized in six steps (see Supporting Information) and incor-
inspired allosteric control over activity and selectivity.
porate binding sites for Rh(I) metal centers (Scheme 1). Compounds
In designing compound 3, we determined that the reversible
binding of Cl- and CO at the structural Rh(I) metal centers would
result in changes in the activity of the functional Cr(III) metal
centers. We reasoned that such an effect would be related to the
3 and 4 were synthesized in almost quantitative yield by reacting
1 and 2, respectively, with Rh-(norbornadiene)2BF4 in CH2Cl2.
Compound 3 has been characterized by elemental analysis, 31P
NMR spectroscopy, and electrospray mass spectrometry, and all
data are consistent with its proposed structure. In addition, 4 has
been fully characterized in solution and in the solid state8 (Figure
dramatic difference in shape between the closed (3) and open (5)
† Northwestern University.
‡ University of Delaware.
1). Compounds 3 and 4 can be converted to 5 and 6, respectively,
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C O M M U N I C A T I O N S
3 and 5 in solvents that have been shown to support higher ee’s
for 7.5 Subsequent versions of 3 will focus on the addition of
solubilizing phosphine groups to create systems that provide a
controlled basis for comparison to monomeric analogues such as 7
under optimized conditions.
This work represents the first demonstration of an allosteric
catalyst made possible through supramolecular coordination chem-
istry. In addition, 3 exhibits a significant increase in the rate and
selectivity of the ring opening of cyclohexene oxide as compared
to the monomeric analogue under these reaction conditions. Taken
together, these results show how one can use the weak-link approach
to design and build supramolecular systems with unique function.
Efforts are underway to determine the mechanistic details and
differences between 3 and 5.
Figure 1. Thermal ellipsoid drawing of 4-(pyridine)2‚CH2Cl2 showing the
labeling scheme for selected atoms and elipsoids at 30% probability.
Hydrogen atoms are omitted for clarity. Zn-Zn distance: 5.24 Å. Rh-Rh
distance: 24.66 Å.
Acknowledgment. C.A.M. acknowledges NSF and the AFOSR
for support of this research.
Supporting Information Available: Experimental procedures,
spectral data for all new compounds (PDF), and X-ray crystallographic
data for 4-(pyridine)2‚CH2Cl2 in CIF format. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
Figure 2. Graph A: Initial rate kinetics for the ring opening of cyclohexene
oxide by TMSN3 catalyzed by 3 (2) (2.6 mM) and a monomeric Cr(III)-
salen complex 7 (b) (5.2 mM) in benzonitrile at room temperature. The
catalyst concentrations are the same with respect to Cr(III). Graph B: Initial
rate kinetics for the ring opening of cyclohexene oxide by TMSN3, as
catalyzed by 3 (2) and 5 (9) each at 2.6 mM, in benzonitrile/pyridine at
room temperature.
(1) Allosteric regulation of catalysts is the control of activity by the reversible
binding of small molecules to structural sites that are remote from, but
induce, conformational changes at the active site. (a) Fritsky, I. O.; Ott,
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by reaction with 2 equiv of PPNCl and CO (1 atm) in benzonitrile
at room temperature. Compounds 5 and 6, which exhibit diagnostic
ν
CO bands at 1978 and 1976 cm-1, respectively,4 are only stable in
(3) (a) Merlau, M. L.; del Pilar Mejia, M.; Nguyen, S. T.; Hupp, J. T. Angew.
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solution. Vacuum removal of solvent results in their quantitative
conversion to 3 and 4 as determined by 31P NMR spectroscopy.
The 31P{1H} NMR spectroscopy of 5 and 6 also confirms the
proposed structures with each exhibiting a single resonance at δ
25. The chemical shifts and coupling constants are diagnostic of
square planar trans-phosphine trans-Cl/CO complexes of Rh(I).4e
The catalytic properties of 3 were compared to those of a
Cr(III)-salen monomeric analogue 7 in the context of the ring
opening of cyclohexene oxide by TMSN3 to yield 1-azido-2-
(trimethylsiloxy)cyclohexane (Figure 2).
These reactions result in product formation with 68% ee for 3,
while the Cr(III)-salen monomeric analogue 7 gives 12% ee. This
increased ee for our macrocyclic system is coupled with a significant
20-fold increase in rate as compared to that observed for the
monomeric system under these conditions (Figure 2: Graph A).
These data are consistent with supramolecular cooperativity also
observed by Jacobsen and co-workers for a topologically similar
oligomeric Co(III)-based catalyst.7c
As an initial demonstration of the ability of 3 to act as an
allosteric catalyst, the ring opening of cyclohexene oxide by TMSN3
was studied. The rate of formation of 1-azido-2-(trimethylsiloxy)-
cyclohexane, in the presence and absence of the allosteric activators
Cl- and CO, was determined by GC analysis (Figure 2: Graph
B). Consistent with our hypothesis regarding the allosteric properties
of this system, a doubling of reaction rate is observed upon addition
of PPNCl and CO to complex 3 to generate 5 in situ. Because of
the lack of solubility of this initial system, we are unable to study
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L.; Stern, C. L. Organometallics 1999, 18, 4856-4868. (d) Holliday, B.
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(8) Crystal data for 4-(pyridine)2‚CH2Cl2: The asymmetric unit contains two
molecules of CH2Cl2 that were highly disordered and treated as diffuse
contributions using the program SQUEEZE (A. Spek; Platon Library).
Additionally, the counterions were refined with a common B-F distance.
The relatively large thermal parameters of the atoms in the pyridine
molecule coordinated to the Zn atom appear to be related to a disorder in
the alignment of the molecular plane. The atoms of the pyridine molecule
were refined with isotropic thermal parameters and restrictions on the
C-N and C-C distances. For additional crystallographic data, see the
Supporting Information.
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