HostGuest Chemistry: Combinatorial Receptors

At the heart of host—guest chemistry is the design and construction of artificial receptors. While great progress has been achieved in the specific recognition of a multitude of substrates, rational design has still failed to equal the degree of association strength and substrate specificity observed in nature. Evolutionary selection has allowed biopolymers to take advantage of their large size to position varied functionality in the rigid context of tertiary structure, but the limitations of chemical synthesis dictate that artificial receptors will be smaller, less structurally defined, and, as a result, less effective. Combinatorial chemistry offers a new approach to the task of receptor design by quickly creating a library of combinatorial receptors containing a variety of binding or catalytic groups, and subsequently determining the most active component of that library (1 –5 }). Combinatorial receptors also provide the possibility for using substrate binding to selectively create a receptor from a dynamic library (6 –8 ). To be effective, however, library synthesis should require minimal synthetic expenditure and the entire library must be screened efficiently.