A Water-Soluble Diarylethene Base for Light-Controlled pH Modulation in Biological Systems

Molecular photoswitches capable of controlled pH changes are often limited in a critical application, biological systems, by poor aqueous solubility, which hinders their ability to generate large and sustained pH shifts. Herein, we report the synthesis and photophysical characterization of a highly water-soluble, photoswitchable diarylethene base that modulates pH through light-controlled changes in the p K a of an N -heterocyclic imine (NHI) moiety. Using experimentally determined p K a values, we developed and validated a model showing that this NHI-diarylethene exhibits photoacidic behavior over a wide range of pH 6–11 and photobasic behavior over the range pH 3–6, making it the first photoswitch reported to demonstrate dual functionality and to operate in the basic pH regime. By alternating UV and visible light irradiation, this NHI-diarylethene switch achieved a change of >1.7 pH units and was reversibly cycled in both buffered and unbuffered aqueous solutions. We applied this photoswitch to reversibly control the assembly of the pH-responsive, cationic reflectin protein, which shows promise for biophotonic applications. This photoswitch is a powerful tool for bioinspired systems that operate in aqueous environments, where precise, sustained, and reversible pH control is essential for mimicking dynamic biological functions such as assembly, signaling, and responsiveness.