Chloride-Selective Transmembrane Channel Formation by Meta-Positioned Halogen Bond Donors

Abstract

A major hurdle in current research on supramolecular anion channels is achieving the specificity and selectivity necessary for biological and pharmaceutical applications. To address this limitation, the present study reports a series of 3,5-dihalobenzamide derivatives designed to achieve selective anion transport via halogen-bonding interactions. Ion transport assays reveal that the diiodo derivative (3) exhibits superior activity compared with its dibromo (2) and dichloro (1) analogues. Fluorescence and electrophysiological experiments confirm that 3 functions as a selective chloride channel via an antiport mechanism. Furthermore, theoretical calculations confirm that intermolecular hydrogen bonding drives the self-assembly of 3 into supramolecular barrel-rosette structures that span the lipid bilayer. The study also highlights the pivotal role of halogen bonding in the recognition and transmembrane transport of the chloride ions.