Host-rotaxanes model proteins that promote ligand association through a favorable change in configurational entropy

Abstract

Proteins can reduce the entropic penalty for ligand association through a favorable change in configurational entropy. To investigate this process, the ΔG^o, ΔH^o, and ΔS^o of complexes formed between host-rotaxanes and guests were determined and compared to discover the relationship between rotaxane-structure and the energies involved in guest-association in water and DMSO. Fluorescence quenching assays provided the association constants. Van't Hoff analysis of variable temperature assays gave the enthalpies of binding. The driving force for the association of a guest and a host-rotaxane can switch from being enthalpically to entropically driven with a change in the solvent or guest. This study shows that a dramatic increase in the entropy of binding can be obtained through the addition of a rotaxane-wheel to a synthetic host. An increased motion of the wheel appears to be the source of the positive binding entropy, which would be an example of favorable configurational entropy promoting complex formation.