Photoresponsive supramolecular chloride channels formed through anion-induced self-assembly of azo-urea molecular...

Light-regulated synthetic chloride channels have attracted significant attention in the recent past due to their controllable activation, high specificity, and promising therapeutic applications. Herein, we developed a series of azobenzene-based molecular photoswitches (DAB·X; X = 2CF₃, CF₃, Br, H, and OMe), in which the urea residues are installed proximal to the azobenzene unit to alter anion binding and transport through photoswitching. The photoswitching behaviour of these compounds was initially investigated using ¹H NMR and UV-Vis spectroscopy, in which all the molecules exhibited rapid trans → cis photoisomerization upon 450 nm blue light irradiation and gradual thermal back relaxation. Anion binding studies demonstrated that DAB·2CF₃ displayed the strongest anion binding across the series. The strongest anion binding, along with the increased lipophilicity of DAB·2CF₃, enabled superior ion transport activity (EC₅₀ = 26.84 nM) across synthetic lipid vesicles. Single-crystal X-ray diffraction studies on DAB·2CF₃ revealed a planar geometry in the solid state; however, in the presence of Cl^- anions, the molecule adopted a bent conformation and self-assembled to form supramolecular channel-like architectures. This chloride-induced channel-like assembly formation was further evident from electrophysiological measurements and the morphological transition from nanofiber-to-nanosheet in DAB·2CF₃ upon chloride addition. Upon photoswitching, the cis-form exhibited a slightly reduced transport activity compared to the trans-form, due to partial disruption of the self-assembled chloride channel. Importantly, the transport activity could be restored upon thermal relaxation, demonstrating reversible photoresponsive ion transport behaviour. This study highlights the design of photoresponsive chloride channels, demonstrating how structural tuning of azo-urea photoswitches alters their anion binding and transporting abilities upon light irradiation, with potential implications in membrane biophysics and photopharmacology.