Highly Water-Soluble Visible-Light-Responsive Azo Photoswitch

Azo derivatives constitute one of the most widely explored classes of molecular photoswitches. However, low aqueous solubility and UV-induced E → Z isomerization have limited their widespread applications, particularly in biological systems. Herein, guided by computation-aided heteroaryl azo design, we report a novel class of imidazoleazopyrazole (IAP) photoswitches with high water solubility (up to 115.0 mM) and visible-light-responsive isomerization. The IAPs exhibit excellent reversible photoswitching (E → Z up to 90%, Z → E >99%), high quantum yields (ΦE→Z: 0.38–0.41, ΦZ→E: 0.54–0.67), and tunable half-lives from hours to days in water. Notably, a representative IAP demonstrates robust performance across a wide pH range, over a range of concentrations, and under reductive conditions. Moreover, IAPs show broad application potential, as exemplified by TRPM5 modulation and reversible information storage in photoresponsive hydrogels. This work establishes heteroaryl incorporation as a rational design principle for highly water-soluble visible-light-responsive azo photoswitches, providing a versatile platform for applications in aqueous and biological environments.