Ultrastable Host-Guest Complexes and Their Applications

Abstract

This review describes monovalent synthetic receptor-ligand (or host-guest) pairs with extremely high binding affinity, comparable to that of the biotin-avidin pair, and their applications. Cucurbit[7]uril (CB[7]), a member of the host family cucurbit[n]uril (CB[n], n=5-8,10), forms ultra-stable host-guest complexes with ferrocene-, adamantaneor bicyclo[2.2.2]octane-based molecules having ammonium groups properly positioned to interact with the carbonyl oxygens at the portals of CB[7]. The extremely high affinity is achieved by a large enthalpic gain arising from the near perfect size/shape complementarity between the rigid CB cavity and the rigid core of the guest molecules, with the critical assistance of the positive entropy change due to the extensive dehydration of the host and guest. The high stability of the complexes allowed us and others to explore several biological applications such as immobilization of biomolecules on a solid surface, protein isolation, triggering intracellular events, and regulating enzymatic activities. These complexes with their exceptional affinity, chemical robustness, simple preparation, biocompatibility, and easy handling may replace the biotin-(strept) avidin system in diverse areas of research, including affinity chromatography, high throughput biochemical assays, imaging, and sensor technologies.