Synthetic anion transporters show much promise as potential anti‐cancer agents and therapeutics for diseases associated with mis‐regulation of protein anion channels. In such applications high activity and anion selectivity are crucial to overcome competing proton or hydroxide transport which dissipates cellular pH gradients. Here, highly active bidentate halogen bonding and chalcogen bonding anion carriers based on electron deficient iodo‐ and telluromethyl−triazole derivatives are reported. Anion transport experiments in lipid bilayer vesicles reveal record nanomolar chloride transport activity for the bidentate halogen bonding anion carrier, and remarkably high chloride over proton/hydroxide selectivity for the chalcogen bonding anionophore. Computational studies provide further insight into the role of sigma‐hole mediated anion recognition and desolvation at the membrane interface. Comparison with hydrogen bonding analogues demonstrates the importance of employing sigma‐hole donor motifs in synthetic anionophores for achieving both high transport activity and selectivity.

Transmembrane ion transport by synthetic anionophores is typically achieved using polar hydrogen bonding anion receptors. Here we show that readily accessible halogen and hydrogen bonding 1,2,3triazole derivatives can efficiently mediate anion transport across lipid bilayer membranes with unusual anti-Hofmeister selectivity. Importantly, the results demonstrate that the iodo-triazole systems exhibit the highest reported activity to date for halogen bonding anionophores, and enhanced transport efficiency relative to the hydrogen bonding analogues. In contrast, the analogous fluoro-triazole systems, which are unable to form intermolecular interactions with anions, are inactive. The halogen bonding anionophores also exhibit a remarkable intrinsic chloride over hydroxide selectivity, which is usually observed only in more complex anionophore designs, in contrast to the readily accessible acyclic systems reported here. This highlights the potential of iodo-triazoles as synthetically accessible and versatile motifs for developing more efficient anion transport systems. Computational studies provide further insight into the nature of the anion-triazole intermolecular interactions, examining the origins of the observed transport activity and selectivity of the systems, and revealing the role of enhanced charge delocalisation in the halogen bonding anion complexes.a Effective concentration to reach 50% of maximal activity in the HPTS assay, determined from Hill analysis of the relative uorescence intensity at t ¼ 288 s, immediately prior to vesicle lysis. Experiments conducted in LUVs of POPC (mean diameter 200 nm) loaded with 1 mM HPTS, NaCl (100 mM) and buffered at pH 7.0 with 10 mM HEPES. For compounds of low activity, estimated lower bounds for the EC 50 value are given. b Hill coefficient. c Calculated log P. d Insufficient activity for Hill analysis.

Lipid bilayer membranes form compartments requisite for life. Interfacing supramolecular systems, including receptors, catalysts, signal transducers and ion transporters, enables the function of the membrane to be controlled in artificial...

Stimuli-responsive transmembrane ion carriers allow for targeted and controllable transport activity, with potential applications as therapeutics for channelopathies and cancer, and in fundamental studies into ion transport phenomena. These applications...