An Artificial Single Molecular Channel Showing High Chloride Transport Selectivity and pH‐Responsive Conductance

作者：Wenlong Huang, Xudong Wang, Yu‐Fei Ao, Qi‐Qiang Wang, De‐Xian Wang · 发表于：Angewandte Chemie International Edition · 年份：2023 · DOI：10.1002/anie.202302198 · 被引用次数：63 · 研究领域：Ion channel regulation and function、Lipid Membrane Structure and Behavior、Molecular Sensors and Ion Detection

Abstract Inspired by the unique structure and function of the natural chloride channel (ClC) selectivity filter, we present herein the design of a ClC‐type single channel molecule. This channel displays high ion transport activity with half‐maximal effective concentration, EC50, of 0.10 μM, or 0.075 mol % (channel molecule to lipid ratio), as determined by fluorescent analysis using lucigenin‐encapsulated vesicles. Planar bilayer lipid membrane conductance measurements indicated an excellent Cl−/K+ selectivity with a permeability ratio P /P up to 12.31, which is comparable with the chloride selectivity of natural ClC proteins. Moreover, high anion/anion selectivity (P /P =66.21) and pH‐dependent conductance and ion selectivity of the channel molecule were revealed. The ClC‐like transport behavior is contributed by the cooperation of hydrogen bonding and anion–π interactions in the central macrocyclic skeleton, and by the existence of pH‐responsive terminal phenylalanine residues.