Exploiting the Catenane Mechanical Bond Effect for Selective Halide Anion Transmembrane Transport

Abstract

AbstractThe first examples of [2]catenanes capable of selective anion transport across a lipid bilayer are reported. The neutral halogen bonding (XB) [2]catenanes were prepared via a chloride template‐directed strategy in an unprecedented demonstration of using XB⋅⋅⋅anion interactions to direct catenane assembly from all‐neutral components. Anion binding experiments in aqueous‐organic solvent media revealed strong halide over oxoanion selectivity, and a marked enhancement in the chloride and bromide affinities of the catenanes relative to their constituent macrocycles. The catenanes additionally displayed an anti‐Hofmeister binding preference for bromide over the larger iodide anion, illustrating the efficacy of employing sigma‐hole interactions in conjunction with the mechanical bond effect to tune receptor selectivity. Transmembrane anion transport studies conducted in POPC LUVs revealed that the catenanes were more effective anion transporters than the constituent macrocycles, with high chloride over hydroxide selectivity, which is critical to potential therapeutic applications of anionophores. Remarkably these outperform existing acyclic halogen bonding anionophores with regards to this selectivity. Record chloride over nitrate anion transport selectivity was also observed. This represents a rare example of the direct translation of intrinsic anion binding affinities to anion transport behaviour, and demonstrates the key role of the catenane mechanical bond effect for enhanced anion transport selectivity.