Responsive anion transport with a Hamilton receptor-based anionophore controlled by photo-activation and host-guest competitive inhibition

Abstract

Ion transport across biological membranes, facilitated by naturally occurring ion channels and pumps, is crucial for many biological functions. Many of these transport systems are gated, such that ion transport is regulated by a range of external stimuli, including light, small molecule ligand binding, and membrane potential. Synthetic ion transport systems, including those with similar gating mechanisms, 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 Hamilton-receptor-based anionophores. Caging of the hydroxyl groups with a light-responsive ortho-nitrobenzyl (ONB) moiety locks the amide protons through intramolecular hydrogen bonding, making them unavailable for anion binding and transport. Decaging with light reverses the hydrogen bonding pattern, rendering the amide protons available for anion binding and transport. Addition of a barbiturate ligand switches OFF the ion transport activity by blocking the anion binding cavity through competitive inhibition. OFF-ON-OFF reversible control over anion transport is therefore achieved using a combination of light and competitive small molecular ligand binding.