Flexible Crown‐Ether Polyimides Break the K <sup>+</sup> /Na <sup>+</sup> Selectivity Barrier in Artificial K <sup>+</sup> Channels
Fei Gou, Yilin Yao, Qiuting Wang, Qing‐Yan Liu, Fuzhen Zheng, Wenju Chang, Jie Shen, Huaqiang Zeng
Abstract
Abstract Natural potassium channels such as KcsA exhibit extraordinary K + /Na + selectivity (>1000), whereas the best biomimetic counterparts have reached only 41.3. To close this performance gap, we developed a modular design comprising three tunable components: a flexible aliphatic polyimide ( PI ) backbone, variable alkyl linkers (C n H 2n+1 , n = 4–16), and ion‐binding 18‐crown‐6 units. This architecture promotes robust membrane integration via the PI scaffold and precise control of crown ether conformation and spatial arrangement through linker optimization, enabling exceptionally selective and efficient K + transport. Of four synthesized polymer channels, three display high K + conductance (36.8–47.0 pS) —up to twice that of gramicidin A (23.2 pS) —together with K + /Na + selectivity exceeding 100. Notably, channel 4 , incorporating the longest C 16 H 33 linker, achieves an unprecedented selectivity of 153.2 ± 5.3. This synergistic combination of ultrahigh selectivity and superior conductance establishes a new benchmark for artificial potassium channels and provides a versatile platform for biomimetic membrane technologies, channel‐targeted therapeutics, and biosensing applications.