Transmembrane Delivery of an Aryl Azopyrazole Photo‐switchable Ion Transporter Relay

Stimuli-responsive synthetic ionophores allow for spatial and temporal control over ion transport, with promise for applications in targeted therapy. Relay transporters have emerged as a new class of ion transporters - these are anchored carriers that sit in both leaflets of the bilayer and mediate transport across the membrane by passing ions between them. The relays are themselves membrane impermeable, and so must be incorporated into the membrane during vesicle preparation. Here we show that relay transporters can be delivered to both sides of the membrane of vesicles using a synthetic flippase. By incorporating an aryl azopyrazole photo-switch into the movable arm of the relay transporters the ion transport activity can be very efficiently and reversibly switched between off and on states. This control is achieved by extension and contraction of their movable arms via photo-isomerization of the central aryl azopyrazole moiety, hence modulating the ability of the relays to pass ions across the membrane.