Excited-State Branching in Optovin: Resolving the Photophysics of a Gene-Free Optopharmacological Tool

Abstract Optovin is a small, light-activated molecule that enables optical control of TRPA1 ion channels without genetic modification, making it a landmark tool in optopharmacology. However, the excited-state pathways initiated by photoexcitation, and how these may relate to optovin function, have remained unresolved. Here, we show that optovin’s photophysics in solution are governed by competition between rapid photoisomerization and intersystem crossing. Violet-light excitation prepares the bright S2(ππ*) state, which rapidly relaxes over picoseconds to the dark S1(nπ*) state. Most excited molecules subsequently decay through torsional Z-E photoisomerization over tens of picoseconds, providing a reversible nonradiative pathway. In parallel, a minor fraction (10–30% depending on solvent) of the excited-state population undergoes intersystem crossing to form a short-lived triplet state that persists for up to a nanosecond. Direct near-infrared detection of singlet oxygen confirms triplet-mediated oxygen sensitization, although with a low apparent quantum yield of a fraction of a percent, with no dependence on the initial isomeric composition of optovin. These results identify competition between torsional internal conversion and intersystem crossing as the central branching process in optovin photophysics. These intrinsic excited-state dynamics provide experimentally defined constraints on models of TRPA1 activation and establish photophysical design principles for next-generation, gene-free optopharmacological agents.