Water and the Cation-π Interaction.

Yujie Zhu,Minmin Tang,Christopher A Hunter,Julius Rebek,Pablo Ballester,Yang Yu,Huibin Zhang,Faiz-Ur Rahman

doi:10.1021/jacs.1c06510

Abstract

The cation-π interaction and the hydrophobic effect are important intermolecular forces in chemistry and play major roles in controlling recognition in biological systems. We compared their relative contributions to the binding of molecular "dumbbell" guests in synthetic container hosts in water. The guests offered direct, intramolecular competition between trimethylammonium groups, -N+(CH3)3, and tert-butyl groups, -C(CH3)3, for the internal surfaces (aromatic panels) of the containers. In contrast with previous studies, the container molecules consistently preferred binding to the uncharged tert-butyl groups, regardless of the presence of anionic, cationic, or zwitterionic groups on the container peripheries. This preference is determined by solvation of the polar trimethylammonium group in water, which outcompetes the attraction between the positive charge and the π-surfaces in the container. The synthetic container complexes provide a direct measure of the relative strengths of cation-π interactions and desolvation in water. Interactions with the uncharged tert-butyl group are more than 12 kJ mol-1 more favorable than the cation-π interactions with the trimethylammonium group in these cavitand complexes.

Highlights

The cation−π interaction and the desolvation of hydrophobic groups are recognized as important forces for complex formation in water and often control the recognition properties of biological systems
The upfield shifts correlate with the depth in the cavity.[26−29] Earlier studies in related cavitands showed that both t-butyl and trimethylammonium groups are accommodated in the cavity and occupy the same position, at the bottom of the binding pocket.[30]
These ionic groups are remote from the binding pocket, on the outside side of the aromatic walls, and provide an opportunity to study the effects of long-range electrostatic interactions on guest binding

Summary

Introduction

The cation−π interaction and the desolvation of hydrophobic groups are recognized as important forces for complex formation in water and often control the recognition properties of biological systems. The less polarized CH bonds of the t-butyl predict that CH−π interactions will be weaker than the cation−π interaction, and this is borne out in nonpolar media.[14−21] the formation of an intermolecular complex in solution is a competition that involves the solvent−solute and solvent−solvent interactions. We describe experiments designed to distinguish between the effects of the positive charge and desolvation for cation−π interactions in water

Results

Discussion

Conclusion