Selective anion transport mediated by strap-extended calixpyrroles

Abstract

Synthetic anion receptors that facilitate transmembrane chloride transport are of interest as potential therapeutic agents for cancer and cystic fibrosis. Transporters selective for chloride over protons are desired for therapeutic applications to avoid autophagy inhibition and cytotoxicity. Examples of such compounds are rare because the majority of anion transporters can interact with the carboxylate head groups of fatty acids leading to proton leakage. In this paper, we report the synthesis, anion binding and transmembrane anion transport properties of two novel bis-triazole-functionalized calixpyrroles with extended straps, and compare them to previously reported shorter-strap analogues known to exhibit high Cl- > H+ selectivity. We demonstrate improved chloride transport activitities of the strap-extended compounds that likely benefits from increased lipophilicity, and reduced Cl- > H+ selectivity due to the larger anion binding cavities facilitating interaction with fatty acids. The results are instructive for future design of ideal anion transporters with potent activity and high selectivity against proton leakage.