Photomodulation of Transmembrane Transport and Potential by Stiff-Stilbene Based Bis(thio)ureas

Membrane transport proteins fulfill important regulatory functions in biology with a common trait being their ability to respond to stimuli in the environment. Various small-molecule receptors, capable of mediating transmembrane transport, have been successfully developed. However, to confer stimuli-responsiveness on them poses a fundamental challenge. Here we demonstrate photocontrol of transmembrane transport and electric potential using bis(thio)ureas derived from stiff-stilbene. UV-vis and H-1 NMR spectroscopy are used to monitor E-Z photoisomerization of these bis(thio)ureas and H-1 NMR titrations reveal stronger binding of chloride to the (Z)-form than to the (E)-form. Additional insight into the binding properties is provided by single crystal X-ray crystallographic analysis and DFT geometry optimization. Importantly, the (Z)-isomers are much more active in transmembrane transport than the respective (E)-isomers as shown through various assays. As a result, both membrane transport and depolarization can be modulated upon irradiation, opening up new prospects toward light-based therapeutics as well as physiological and optopharmacological tools for studying anion transport-associated diseases and to stimulate neuronal activity, respectively.

Automated summary

Membrane transport proteins have important regulatory functions in biology and can respond to environmental stimuli. Using bis(thio)ureas derived from stiff-stilbene, photocontrol of transmembrane transport and electric potential has been demonstrated through UV-vis and H-1 NMR spectroscopy. The (Z)-isomers show stronger binding properties and are more active in transmembrane transport compared to the (E)-isomers.