Chloride-Selective Transmembrane Channel Formation by <i>Meta</i> -Positioned Halogen Bond Donors

High Resolution Image Download MS PowerPoint Slide 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.