Incorporation of the trimethoxyphenyl group at position 7 of flavin can drastically change the photophysical properties of flavin. We show unique fast singlet 1(π,π*) excited state deactivation pathway through nonadiabatic transition to the 1(n,π*) excited- state, and subsequent deactivation to the ground electronic state (S0), closing the photocycle. This mechanism explains the exceptionally weak fluorescence and the short excited-state lifetime for the flavin trimethoxyphenyl derivative and the lack of excited triplet T1 state formation. Full recovery of flavin in its ground state takes place within a 15 ps time window after photoexcitation in a polar solvent such as acetonitrile. According to quantum chemical calculations, the C(2)-O distance elongates by 0.16 Å in the 1(n,π*) state, with respect to the ground state. Intermediate-state structures are predicted by theoretical ab initio calculations and their dynamics are investigated using broadband vis-NIR time-resolved transient absorption and fluorescence up-conversion techniques.

Department of Biomolecular Mechanisms Max Planck Institute for Medical Research Jahnstrasse 29 69120 Heidelberg Germany

Department of Organic Chemistry University of Chemistry and Technology Prague 16628 Prague Czech Republic

Faculty of Chemistry Adam Mickiewicz University Uniwersytetu Poznanskiego 8 61 614 Poznan Poland

Faculty of Physics and Astronomy Adam Mickiewicz University Uniwersytetu Poznanskiego 2 61 614 Poznan Poland

Institute of Physics Polish Academy of Sciences Aleja Lotników 32 46 02 668 Warsaw Poland

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Massey, V. The chemical and biological versatility of Riboflavin. Biochem. Sos Trans. 28, 283–296. 10.1042/bst0280283 (2000). PubMed

Cibulka, R. & Fraaije, M. W. Flavin-Based Catalysis: Principles and Applications (Viley-VCH, 2021).

Silva, E. & Edwards, A. M. Flavins: Photochemistry and Photobiology (Royal Society of Chemistry, 2006).

Sideri, I. K., Voutyritsa, E. & Kokotos, C. G. Photoorganocatalysis, small organic molecules and light in the service of organic synthesis: the awakening of a sleeping giant. Org. Biomol. Chem. 16, 4596–4614. 10.1039/c8ob00725j (2018). PubMed

Romero, N. A. & Nicewicz, D. A. Organic photoredox catalysis. Chem. Rev. 116, 10075–10166. 10.1021/acs.chemrev.6b00057 (2016). PubMed

Srivastava, V., Singh, P. K. & Singh, P. P. Recent advances of visible-light photocatalysis in the functionalization of organic compounds. J. Photochem. Photobiol. C Photochem. Rev. 50, 100488. 10.1016/j.jphotochemrev.2022.100488 (2022).

Rehpenn, A., Walter, A. & Storch, G. Molecular editing of flavins for catalysis. Synthesis 53, 2583–2593. 10.1055/a-1458-2419 (2021).

Iida, H., Imada, Y. & Murahashi, S. I. Biomimetic flavin-catalysed reactions for organic synthesis. Org. Biomol. Chem. 13, 7599–7613. 10.1039/c5ob00854a (2015). PubMed

Sikorska, E., Sikorski, M., Steer, R. P., Wilkinson, F. & Worrall, D. R. Efficiency of singlet oxygen generation by alloxazines and isoalloxazines. J. Chem. Soc. Faraday Trans. 94, 2347–2353. 10.1039/A802340I (1998).

Sikorska, E., Khmelinskii, I. V., Koput, J. & Sikorski, M. Electronic structure of lumiflavin and its analoguesin their ground and excited states. J. Mol. Struct. (Theochem.) 676, 155–160. 10.1016/j.theochem.2004.02.007 (2004).

Sikorska, E. et al. Spectroscopy and photophysics of lumiflavins and lumichromes. J. Phys. Chem. A 108, 1501–1508. 10.1021/jp037048u (2004).

Heelis, P. F. The photophysical and photochemical properties of flavins (isoalloxazines). Chem. Soc. Rev. 11, 15–39. 10.1039/CS9821100015 (1982).

Kowalczyk, M. et al. Spectroscopy and photophysics of flavin-related compounds: Isoalloxazines. J. Mol. Struct. (Theochem.) 756, 47–54. 10.1016/j.theochem.2005.09.005 (2005).

Sikorska, E., Khmelinskii, I. V., Worrall, D. R., Koput, J. & Sikorski, M. Spectroscopy and photophysics of iso- and alloxazines: experimental and theoretical study. J. Fluoresc. 14, 57–64. 10.1023/B:JOFL.0000014660.59105.31 (2004). PubMed

Čubiňák, M. et al. Tuning the photophysical properties of flavins by attaching an aryl moiety via direct C – C bond coupling. J. Org. Chem. 88, 218–229. 10.1021/acs.joc.2c02168 (2023). PubMed

Visser, A. J. W. G. & Müller, F. Absorption and fluorescence studies on neutral and cationic isoalloxazines. Helv. Chim. Acta 62, 593–608. 10.1002/hlca.19790620227 (1979).

Kar, R. K. & Miller, A. F. Understanding flavin electronic structure and spectra. WIREs Comput. Mol. Sci. 12, e1541. 10.1021/acs.jpcb.1c07306 (2022).

Pakiari, A. H., Slarhaji, M., Abdollahi, T. & Safapour, M. The redox potential of flavin derivatives as a mediator in biosensors. J. Mol. Model. 27, 96. 10.1007/s00894-020-04650-8 (2021). PubMed

Kar, R. K., Chansen, S., Mroginski, M. A. & Miller, A. F. Tuning the quantum chemical properties of flavins via modification at C8. J. Phys. Chem. B 125, 12654–12669. 10.1021/acs.jpcb.1c07306 (2021). PubMed

Etz, B. D., DuClos, J. M. & Vyas, S. Investigating the photochemistry of C7 and C8 functionalized N(5)-ethyl-flavinium cation: a computational study. J. Phys. Chem. A 124, 4193–4201. 10.1021/acs.jpca.0c01938 (2020). PubMed

Salzmann, S. & Marian, C. M. The photophysics of alloxazine: a quantum chemical investigation in vacuum and solution. Photochem. Photobiol. Sci. 8, 1655–1666. 10.1039/b9pp00022d (2009). PubMed

Chang, X. P., Xie, X. Y., Lin, S. Y. & Cui, G. QM/MM study on mechanistic photophysics of alloxazine chromophore in aqueous solution. J. Phys. Chem. A 120, 6129–6136. 10.1021/acs.jpca.6b02669 (2016). PubMed

Kabir, M. P., Ghosh, P. & Gozem, S. Electronic structure methods for simulating flavin’s spectroscopy and photophysics: comparison of multi-reference, TD-DFT, and single-reference wave function methods. J. Phys. Chem. B. 128, 7545–7557. 10.1021/acs.jpcb.4c03748 (2024). PubMed PMC

Tolba, A. H., Vávra, F., Chudoba, J. & Cibulka, R. Tuning flavin-based photocatalytic systems for application in the mild chemoselective aerobic oxidation of benzylic substrates. Eur. J. Org. Chem. 10, 1579–1585. 10.1002/ejoc.201901628 (2020).

Pokluda, A. et al. Robust photocatalytic method using ethylene-bridged flavinium salts for the aerobic oxidation of unactivated benzylic substrates. Adv. Synth. Catal. 363, 1–10. 10.1002/adsc.202100024 (2021).

Pavlovska, T. et al. Primary and secondary amines by flavin-photocatalyzed consecutive desulfonylation and dealkylation of sulfonamides. Adv. Synth. Catal. 365, 4662–4671 (2023).

McBride, R. A., Barnard, D. T., Jacoby-Morris, K., Harun-Or-Rashid, M. & Stanley, R. J. Reduced flavin in aqueous solution is nonfluorescent. Biochemistry 62, 759–769. 10.1021/acs.biochem.2c00538 (2023). PubMed

Imada, Y., Iida, H., Ono, S., Masui, Y. & Murahashi, S. I. Flavin-catalyzed oxidation of amines and sulfides with molecular oxygen: biomimetic green oxidation. Chem. Asian J. 1, 136–147. 10.1002/asia.200600080 (2006). PubMed

Golczak, A. et al. Tetramethylalloxazines as efficient singlet oxygen photosensitizers and potential redox–sensitive agents. Sci. Rep. 13, 13426. 10.1038/s41598-023-40536-4 (2023). PubMed PMC

LMFIT. Non-Linear Least-Square Minimization and Curve-Fitting for Python (0.8.0) (Zenodo, 2014).

Wendel, M. et al. Time-resolved spectroscopy of the singlet excited state of betanin in aqueous and alcoholic solutions. Phys. Chem. Chem. Phys. 17, 18152–18158. 10.1039/c5cp00684h (2015). PubMed

Gierczyk, B., Murphree, S. S., Rode, M. F. & Burdzinski, G. Blockade of persistent colored isomer formation in photochromic 3H–naphthopyrans by excited–state intramolecular proton transfer. Sci. Rep. 12, 19159. 10.1038/s41598-022-23759-9 (2022). PubMed PMC

Møller, C. & Plesset, M. S. Note on an aproximation treatment for many-electron systems. Phys. Rev. 46, 618–622. 10.1103/PhysRev.46.618 (1934).

Hättig, C. Advances in Quantum Chemistry (ed Jensen, H. J. Å.), Vol. 50, 37–60 (Academic Press, 2005).

Schirmer, J. Beyond the random-phase approximation: a new approximation scheme for the polarization propagator. Phys. Rev. A 26, 2395–2416. 10.1103/PhysRevA.26.2395 (1982).

Trofimov, A. B. & Schirmer, J. An efficient polarization propagator approach to valence electron excitation spectra. J. Phys. B Mol. Opt. Phys. 28, 2299–2324. 10.1088/0953-4075/28/12/003 (1995).

Tuna, D. et al. Assessment of approximate coupled-cluster and algebraic-diagrammatic-construction methods for ground- and excited-state reaction paths and the conical-intersection seam of a retinal-chromophore model. J. Chem. Theory Comput. 11, 5758–5781. 10.1021/acs.jctc.5b00022 (2015). PubMed

Dunning, T. H. Jr. Gaussian basis sets for use in correlated molecular calculations. I. The atoms boron through neon and hydrogen. J. Chem. Phys. 90, 1007–1023. 10.1063/1.456153 (1989).

Christiansen, O., Koch, H. & Jørgensen, P. The second-order approximate coupled cluster singles and doubles model CC2. Chem. Phys. Lett. 243, 409–418. 10.1016/0009-2614(95)00841-Q (1995).

Hättig, C. & Weigend, F. CC2 excitation energy calculations on large molecules using the resolution of the identity approximation. J. Chem. Phys. 113, 5154–5161. 10.1063/1.1290013 (2000).

TURBOMOLE V7.1 2016, a Development of University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2007, TURBOMOLE GmbH. http://www.turbomole.com (2016).

Mojr, V. et al. Flavin photocatalysts for visible-light [2+ 2] cycloadditions: structure, reactivity and reaction mechanism. CheCatChem 10, 1–11. 10.1002/cctc.201701490 (2018).

Oziminski, W. P. & Dobrowolski, J. C. s- and p-electron contributions to the substituent effect: natural population analysis. J. Phys. Org. Chem. 22, 769–778. 10.1002/poc.1530 (2009).

Dobrowolski, J. C., Lipinski, P. F. J. & Karpinska, G. Substituent effect in the first excited singlet state of monosubstituted benzenes. J. Phys. Chem. A 122, 4609–4621. 10.1021/acs.jpca.8b02209 (2018). PubMed

Rode, M. F. & Sobolewski, A. L. Effect of chemical substituents on energetical landscape of a molecular switch: an ab initio study. J. Phys. Chem. A 114, 11879–11889. 10.1021/jp105710n (2010). PubMed

Perun, S., Sobolewski, A. L. & Domcke, W. Conical intersections in thymine. J. Phys. Chem. A 110, 13238–13244. 10.1021/jp0633897 (2006). PubMed

Kao, Y. T. et al. Ultrafast dynamics of flavins in five redox states. J. Am. Chem. Soc. 130, 7695–7701. 10.1021/ja8045469 (2008). PubMed PMC