Two Mechanisms of Slow Host-Guest Complexation between Cucurbit[6]uril and Cyclohexylmethylamine: pH-Responsive Supramolecular Kinetics

Abstract

20 times more rapid is the complexation of the organic ammonium ion receptor cucurbit[6]uril (CB6) with cyclohexylmethylamine than with the cyclohexylmethylammonium species (see scheme). Within the narrow pH region around the pKa value of the amine, the complexation kinetics are accelerated but the binding constant remains essentially unaffected. In this region, the ammonium complex is formed through binding of the amine form followed by fast protonation and not through direct complexation of the ammonium form. Molecular dynamics calculations suggest that the amine form undergoes a direct inclusion into CB6 while the ingression of the ammonium form is retarded by the formation of an association complex, which reacts through a different, higher lying transition state to the inclusion complex.