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 pK_a of an N-heterocyclic imine (NHI) moiety. Using experimentally determined pK_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.