Bifunctional Binding and Catalysis in Host‐Guest Chemistry

AbstractSome dimers of cyclodextrin have been prepared that can bind appropriate substrates in water with binding constants as strong as those of strong antigen/antibody complexes. Doubly linking two cyclodextrins with connections at neighboring glucose units produces a hinged molecule that resembles a clamshell. Another isomer is also produced, in the so‐called loveseat configuration, in which the two cyclodextrin units cannot cooperate in binding a single substrate. When the two links are of different length, the clamshell dimer preferentially binds a non‐linear substrate with an affinity exceeding 1011 M−1, at least 103 better than the binding of a linear substrate isomer. Binding of substrates occurs by induced fit, in which the host closes around and engulfs the substrate. Mechanistic studies on models for the enzyme ribonuclease have led to a proposed mechanism different from that normally suggested for the enzyme. This mechanism has guided the synthesis of a new enzyme mimic with improved properties. Isotope studies show that this enzyme mimic uses a simultaneous bifunctional mechanism, as does the enzyme. The double binding of the transition state by the two imidazole units