Highly Efficient Artificial Potassium Ion Channels Constructed via Supramolecular Cooperativity

Artificial ion channels, as synthetic analogues of biological ion channels, hold great promise in biomedical applications, particularly in the treatment of ion channel-related diseases. Building on our previous discovery of artificial potassium ion channel, we developed a series of biomimetic K+ channels by incorporating directional supramolecular interactions (π stacking, hydrogen bonding) so as to enhance molecular assembly inside the lipid membrane. Surprisingly, these aromatic helix-based channels with a pore size of 2.7 Å exhibit remarkable K+ selectivity. Notably, one of these channels exhibits high ion selectivity among synthetic models, achieving a K+/Na+ selectivity ratio of 37.8, which reaches 48% of that of the canonical KcsA potassium channel under identical experimental conditions. Furthermore, these helix-based channels can efficiently transport potassium ions, with the highest transport activity (EC50) reaching as low as 6.4 nM, which represents the best performance among artificial K+ channels and is comparable to that of natural gramicidin A as well. Studies on the structure–property relationships reveal that nanopore preorganization and supramolecular cooperativity are critical for efficient ion transport. Importantly, the supramolecular cooperativity mediated by hydrogen bonding achieves a 5-fold enhancement in transport activity. These findings present a fundamental supramolecular strategy for the design of highly efficient artificial ion channels, which will facilitate their applications in the treatment of ion channelopathies.