Toward Reversible Control of Cucurbit[n]uril Complexes

Conspectus The cucurbit­[n]­uril (CBn) host family consists of a group of rigid macrocyclic hosts with barrel-like shapes and limited solubility in aqueous media. These hosts are capable of reaching high binding affinities with positively charged hydrophobic guests. In optimum cases, equilibrium association constant (K) values as high as 1017 M–1 have been reported, exceeding the binding affinity of the avidin–biotin host–guest pair. The synthetic CBn receptors have shattered the notion that highly stable noncovalent complexes can form only when one of the partners is a molecule of biological origin. The work described in this Account is concerned with the development of methods geared toward the reversible modulation of the binding affinity of CBn inclusion complexes under mild conditions. A good fraction of the research work has dealt with redox active guests, such as 4,4′-bipyridinium (viologen), ferrocene, and cobaltocenium derivatives. Our experimental results show that the thermodynamics and kinetics of the electron transfer reactions of these compounds can be substantially altered by complexation with CBn hosts, and therefore, electron transfer reactions can be used to exert a measure of control on the overall binding affinity of the CBn complexes. We have also developed systems in which proton transfer reactions have a strong effect on the binding affinity. With more structurally elaborate guests containing more than one adjacent binding sites, proton transfer reactions may affect the average location of the CBn host within the complexes. A series of guest compounds containing paramagnetic 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) residues also exhibit interesting binding properties with CB7 and CB8. The latter host forms a very stable host–guest pair with TEMPO subunits, in which the nitroxide group resides inside the host cavity. Finally, with suitable ditopic guests, we have detected distinct microscopic complexes using experimental techniques with relatively slow time scales, such as NMR spectroscopy. These unusual findings are the result of the considerable thermodynamic and kinetic stability of CBn inclusion complexes.