Stimuli-responsive anion transport utilising caged hydrazone-based anionophores

Ion transport across biological membranes, facilitated by naturally occurring ion channels and pumps, plays a crucial role in biological processes. Gating is an important aspect of these systems, whereby transport is regulated by a range of external stimuli such as light, ligands and membrane potential. While synthetic ion transport systems, especially those with gating mechanisms, are rare, they have garnered significant attention due to their potential applications in targeted therapeutics as anticancer agents or to treat channelopathies. In this work, we report stimuli-responsive anion transporters based on dynamic hydrogen bonding interactions of hydroxyl-functionalised hydrazone anionophores. Caging of the hydroxyl groups with moities that are responsive to light and H₂S locks the hydrazone protons through intramolecular hydrogen bonding, rendering them unavailable for anion binding and transport. Upon decaging with light or H₂S, the hydrogen bonding pattern is reversed, rendering the hydrazone protons available for anion binding, and leading to efficient switch-on of ion transport across the lipid bilayer membrane.