Chapter 8: Selective Stoichiometric and Catalytic Reactivity in the Confines of a Chiral Supramolecular Assembly

Published in: Michael D. Pluth, Robert G. Bergman, Kenneth. N. Raymond, “Selective Stoichiometric and Catalytic Reactivity in the Confines of a Chiral Supramolecular Assembly,” chapter in Supramolecular Catalysis; Ed. Piet W. N. M. van Leeuwen, Wiley-VCH, 2008; pp. 165-191. http://www.interscience.wiley.com/ Chapter 8 Selective Stoichiometric and Catalytic Reactivity in the Confines of a Chiral Supramolecular Assembly Michael D. Pluth, Robert G. Bergman, Kenneth. N. Raymond Department of Chemistry, University of California, Berkeley, CA 94720-1460 and Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 8.1 Introduction Nature uses enzymes to activate otherwise unreactive compounds in remarkable ways. For example, DNases are capable of hydrolyzing phosphate diester bonds in DNA within seconds,[1-3] – a reaction with an estimated half-life of 200 million years without an enzyme.[4] The fundamental features of enzyme catalysis have been much discussed over the last sixty years in an effort to explain the dramatic rate increases and high selectivities of enzymes. As early as 1946, Linus Pauling suggested that enzymes must preferentially recognize and stabilize the transition state over the ground state of a substrate.[5] Despite the intense study of enzymatic selectivity and ability to catalyze chemical reactions, the entire nature of enzyme-based catalysis is still poorly understood. For example, Houk and co-workers recently reported a survey of binding affinities in a wide variety of enzyme-ligand, enzyme-transition-state, and synthetic host-guest complexes and found that the average binding affinities were insufficient to generate many of the rate accelerations observed in biological systems.[6] Therefore, transition-state stabilization cannot be the sole contributor to the high reactivity and selectivity of enzymes, but rather, other forces must contribute to the activation of substrate molecules. Inspired by the efficiency and selectivity of Nature, synthetic chemists have admired the ability of enzymes to activate otherwise unreactive molecules in the confines of an active site. Although much less complex than the evolved active sites of enzymes, synthetic host molecules have been developed that can carry out complex reactions with their cavities. While progress has been made toward highly efficient and selective reactivity inside of synthetic hosts, the lofty goal of duplicating enzymes’ specificity remains.[7-9] Pioneered by Lehn, Cram, Pedersen, and Breslow, supramolecular chemistry has evolved well beyond the crown ethers and cryptands originally studied.[10-12] Despite the increased complexity of synthetic host molecules, most assembly conditions utilize self-assembly to form complex highly-symmetric structures from relatively simple subunits. For supramolecular assemblies able to encapsulate guest molecules, the chemical environment in each assembly – defined by the size, shape, charge, and functional group availability – greatly influences the guest-binding characteristics.[6, 13-17] Over the last decade, the Raymond group has made efforts toward understanding how encapsulation of molecules within a synthetic host affects the reactivity of the guest. A number of host molecules of the stoichiometry M 4 L 6 (M = Ga III (1), Al III , In III , Fe III , Ti IV , or Ge IV , L =