Triply Responsive Control of Anion/Cation Transport with an Artificial Ion Channel Responsive to Multiple Stimuli

10.26434/chemrxiv-2025-sbp1x

⊕
azo-p5 ion channels. We present a synthetic ion channel whose activity can be controlled by three orthogonal stimuli (light, pH, guest/ligand). The channel is formed from a pillar[5]arene functionalized with photoswitchable tetrafluoroazobenzene moieties. We demonstrate excellent control over E:Z switching across ten incorporated photoswitches (E to Z 87%, Z to E quant.). We show that the most active isomer – the Z-isomer – forms dimeric ion channels in membranes, with selectivity for M+/Cl− symport. Single molecule planar bilayer conductance studies show distinct high and low conductance states dependent on irradiation wavelength. Finally, we demonstrate that this activity can be modulated over 170-fold by controlling pH, irradiation, and guest addition, creating a powerful addition to the canon of synthetic ion channels.