Biomimetic chemistry

Several cases are described in which the chelate effect contributes to binding and catalysis. In the first examples, dimers made up of linked cyclodextrins show very strong selective substrate binding, and with catalytic groups in the linkers they are effective catalysts of reactions of bound substrates. In later examples, chelate binding of transition states by a base and an acid produce effective catalysts whose geometric preferences reflect the detailed mechanisms of the catalyzed processes. In the final examples, chelate binding to biological receptors of some molecules with two polar end groups produces a class of particularly effective cytodifferentiating agents, of potential use in cancer chemotherapy. Enzymes differ from simple catalysts in several respects. For one, they bind their substrates in well-defined geometries. For another, they generally use simultaneous bifunctional or even polyfunctional catalyses. The results of these stylistic advantages are well known-improved rates and high selectivities. To learn how to apply these enzymatic principles in simpler chemical systems, we started work over 40 years ago in a field that we named (1) "biomimetic chemistry." Although this has now become a very large area of research, we will describe only our own recent work in this field, together with some earlier references. BINDING BY CYCLODEXTRIN DIMERS Many forces can contribute to the binding of a substrate to an enzyme, but a principal one is hydrophobicity. Although one need not imitate Nature by using water as a solvent, much of our work has focussed on catalyst-substrate complexes formed in water using hydrophobic binding. For this purpose, the highly available cyclodextrins have been particularly attractive. In water, a well-fitting hydrocarbon such as an adamantyl group or a t-butylphenyl group can bind into P-cyclodextrin (cycloheptaamylose) with an association constant of the order of 104 M-1. While this is enough to permit the use of simple cyclodextrin derivatives as mimics of many enzymes, stronger and more welldefined binding would be better. For this reason, some years ago we set out to construct and study a new class of enzyme mimics-cyclodextrin dimers in which a catalytic group was located in the linker. Our early studies (2) on binding by cyclodextrin dimers such as 1. showed that with appropriate double ended substrates (e.g. 2 we could achieve Ka's as high as 109 M-1 in