The influence of varied amide bond positions on hydraphile ion channel activity

Abstract

Hydraphile compounds have been prepared in which certain amine nitrogens have been replaced by amide residues. The amide bonds are present either in the side chain, the spacer chain, or the central relay. Sodium cation transport through phospholipid vesicles mediated by each hydraphile was assessed. All of the amide-containing hydraphiles showed increased levels of Na⁺ transport compared to the parent compound, but the most dramatic rate increase was observed for sidearm amine to amide replacement. We attribute this enhancement to stabilization of the sidearm in the bilayer to achieve a better conformation for ion conduction. Biological studies of the amide hydraphiles with Escherichia coli and Bacillus subtilis showed significant toxicity only with the latter. Further, the consistency between the efficacies of ion transport and toxicity previously observed for non-amidic hydraphiles was not in evidence.