Correlating Kinetics and Thermodynamics of Conformational Changes in Ammonium Complexes of a Flexible Naphthocage

Although conformational changes are fundamental processes in many natural and synthetic supramolecular systems, understanding of the relationship between conformational kinetics and thermodynamics of host-guest binding is very limited because low-energy structural changes are usually fast and difficult to monitor. Described in this work is a kinetic study of the conformational conversion of the inclusion complexes consists of a flexible naphthocage host and quaternary ammonium guests featuring a relatively slow “guest dissociation-host conformational change-guest re-association” con-formational exchange mechanism. For guests of comparable structural features, the overall rate of the conformational change is found to be inversely correlated to the thermodynamic stability of the host-guest complexes, which in turn is related to both the overall structure and local steric properties of the guests. Results from this work that bridge the kinet-ics and thermodynamics of molecular recognition to conformational changes are valuable for an in-depth understanding of the kinetic contributions in guest binding and selectivity.