Lipid bilayer environments control exchange kinetics of deep cavitand hosts and enhance disfavored guest conformations

Abstract

The effects on the molecular recognition properties of water-soluble deep cavitand hosts upon embedding them in phosphocholine lipid bilayer environments have been studied by 2D NMR experiments. By employing suitable guests containing ¹⁹F or ¹³C nuclei that can be encapsulated inside the host, 2D EXSY NMR experiments can be used to analyze and compare the in/out guest exchange rates in aqueous solution, isotropically tumbling micelles, or magnetically ordered bicelles. These analyses show that embedding the deep cavitands in lipid bilayers slows the guest exchange rate, due to the lipids acting as a “compression sleeve” around the host, restricting guest egress. This effect also enhances guest conformations in the host that are not observed in free solution, such as axial cyclohexane conformers and ketone hydrates.