Functionalization‐Level‐Dependent Transport Activity and Cancer Cell‐Activated Characteristic via Polyether‐Based Artificial Proton Transport System

ABSTRACT The construction of artificial ion transport systems exhibiting tunable functionality is essential for enhancing our understanding of the complex mechanisms underlying natural channel proteins (NCPs). This study presents a biomimetic transmembrane proton transport system, synthesized by a one‐pot light‐induced iron‐catalyzed alkylation of C─H bonds in polyethers. Controlling the reaction time to modulate the functionalization level of polyethers, and thereby the amphiphilicity, results in a system that demonstrates adjustable transport activity. Additionally, it emulates natural proton channels, efficiently promoting proton transport by forming multiple hydrogen‐bonding chains while efficiently excluding other ions and water molecules. Patch‐clamp measurements revealed a high proton transport rate ( = 97 ± 3 pS, ≈ 50% of natural gramicidin A's 213 ± 4 pS) and significant proton selectivity ( P H+ / P K+ = 106.7, P H+ / P Na+ = 168.2, P H+ / P Cl‐ = 10.6) for this system. The markedly greater proton gradient across the plasma membrane of cancer cells compared to normal cells means that this proton transport system can be selectively activated by cancer cells and induce their apoptosis. This work is expected to enhance understanding of the underlying mechanisms of NCPs and contribute to the treatment of cancer and other diseases.