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

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Brouwer, Jonathan Q., Cook, Alex J., Ashworth, Eleanor K., Fatima, Anam ORCID: https://orcid.org/0000-0003-2388-4390, Siddiqui, Khalid M., Chambrier, Isabelle, Cammidge, Andrew N. ORCID: https://orcid.org/0000-0001-7912-4310, Chakraborty, Pratip ORCID: https://orcid.org/0000-0002-0248-6193, Browne, Wesley R., Meech, Stephen R. ORCID: https://orcid.org/0000-0001-5561-2782 and Bull, James N. ORCID: https://orcid.org/0000-0003-0953-1716 (2026) Excited-State Branching in Optovin: Resolving the Photophysics of a Gene-Free Optopharmacological Tool. Journal of the American Chemical Society. ISSN 0002-7863

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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.

Item Type: Article
Uncontrolled Keywords: das to be completed,2026 ,/dt/atira/pure/keyword/DAStatement/das_to_be_completed
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
UEA Research Groups: Faculty of Science > Research Groups > Synthetic and Medicinal Chemistry
Faculty of Science > Research Groups > Physical Chemistry and Pharmaceutics
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Depositing User: LivePure Connector
Date Deposited: 03 Nov 2026 10:10
Last Modified: 04 Nov 2026 00:07
URI: https://ueaeprints.uea.ac.uk/id/eprint/104963
DOI: 10.1021/jacs.6c13271

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