Photo-modulation of Proton / Water Transmembrane Transport through bis(imidazole-amide)-tetrafluoro-azobenzene switch

Abstract

Water and proton transport across biological membranes are essential for cellular function. The development of stimuli-responsive artificial transport systems to replace malfunctioning protein channels is crucial for potential therapeutic applications. Here, we report a photoswitchable azobenzene based channel that envelops a coherent water wire and efficiently regulates water and proton transport across lipid bilayers using light as an external trigger. The molecule undergoes reversible E↔Z photoisomerization, where the Z-isomer adopts a compact, folded, π-stacked conformation encapsulating and stabilizing a water wire that can assemble into a well-defined, directional channel. In contrast, the E-isomer forms an extended, less ordered conformation that disrupts coherent water alignment. The synthesised proton/water transporter demonstrates robust photoswitching behavior, maintaining function over multiple irradiation cycles. Ion transport assays reveal complete rejection of alkali metal cations for both isomers, with no detectable ion transport even in the presence of the protonophore FCCP. Proton transport assays in the presence of valinomycin show that the Z-isomer exhibits a 100% increase in electrogenic proton transport rate compared to the E-isomer at higher concentrations. Water permeability measurements mirror this trend, with the Z-isomer showing 20–35% higher net water transport relative to the E-form. These results highlight how photo-controlled conformational changes in foldamer architecture can be leveraged to create efficient, light-regulated water and proton channels.