Photooxygenation of flavonoids leads to the release of carbon monoxide (CO). Our structure-photoreactivity study, employing several structurally different flavonoids, including their 13C-labeled analogs, revealed that CO can be produced via two completely orthogonal pathways, depending on their hydroxy group substitution pattern and the reaction conditions. While photooxygenation of the enol 3-OH group has previously been established as the CO liberation channel, we show that the catechol-type hydroxy groups of ring B can predominantly participate in photodecarbonylation.

Department of Chemistry Faculty of Science Masaryk University Kamenice 5 625 00 Brno Czech Republic

Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences Flemingovo nám 542 166 00 Prague Czech Republic

Laboratory of Biotransformation Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 142 00 Prague Czech Republic

RECETOX Faculty of Science Masaryk University Kamenice 5 625 00 Brno Czech Republic

Zobrazit více v PubMed

Panche A. N.; Diwan A. D.; Chandra S. R. Flavonoids: an overview. J. Nutr. Sci. 2016, 5, e4710.1017/jns.2016.41. PubMed DOI PMC

Sharif S.; Nabais P.; Melo M. J.; Pina F.; Oliveira M. C. Photoreactivity and stability of flavonoid yellows used in cultural heritage. Dyes Pigm. 2022, 199, 11005110.1016/j.dyepig.2021.110051. DOI

Machlin L. J.; Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1987, 1, 441–445. 10.1096/fasebj.1.6.3315807. PubMed DOI

Sisa M.; Bonnet S. L.; Ferreira D.; Van der Westhuizen J. H. Photochemistry of flavonoids. Molecules 2010, 15, 5196–5245. 10.3390/molecules15085196. PubMed DOI PMC

Westlake D. W. S.; Roxburgh J. M.; Talbot G. Microbial production of carbon monoxide from flavonoids. Nature 1961, 189, 510–511. 10.1038/189510a0. PubMed DOI

Zenkevich I. G.; Eshchenko A. Y.; Makarova S. V.; Vitenberg A. G.; Dobryakov Y. G.; Utsal V. A. Identification of the products of oxidation of quercetin by air oxygen at ambient temperature. Molecules 2007, 12, 654–672. 10.3390/12030654. PubMed DOI PMC

Russo M.; Stacko P.; Nachtigallova D.; Klan P. Mechanisms of orthogonal photodecarbonylation reactions of 3-hydroxyflavone-based acid–base forms. J. Org. Chem. 2020, 85, 3527–3537. 10.1021/acs.joc.9b03248. PubMed DOI

Schwartz B. J.; Peteanu L. A.; Harris C. B. Direct observation of fast proton transfer: femtosecond photophysics of 3-hydroxyflavone. J. Phys. Chem. 1992, 96, 3591–3598. 10.1021/j100188a009. DOI

Studer S. L.; Brewer W. E.; Martinez M. L.; Chou P. T. Time-resolved study of the photooxygenation of 3-hydroxyflavone. J. Am. Chem. Soc. 1989, 111, 7643–7644. 10.1021/ja00201a071. DOI

Matsuura T.; Matsushima H.; Nakashima R. Photoinduced reactions—XXXVI: Photosensitized oxygenation of 3-hydroxyflavones as a nonenzymatic model for quercetinase. Tetrahedron 1970, 26, 435–443. 10.1016/S0040-4020(01)97840-8. DOI

Matsuura T.; Matsushima H.; Sakamoto H. Photosensitized oxygenation of 3-hydroxyflavones. Possible model for biological oxygenation. J. Am. Chem. Soc. 1967, 89, 6370–6371. 10.1021/ja01000a078. PubMed DOI

Kim H. P.; Ryter S. W.; Choi A. M. K. CO as a cellular signaling molecule. Annu. Rev. Pharmacol. 2006, 46, 411–449. 10.1146/annurev.pharmtox.46.120604.141053. PubMed DOI

Fischer K.; Luttge U. Light-dependent net production of carbon monoxide by plants. Nature 1978, 275, 740–741. 10.1038/275740a0. DOI

Wu L.; Wang R. Carbon monoxide: endogenous production, physiological functions, and pharmacological applications. Pharmacol. Rev. 2005, 57, 585–630. 10.1124/pr.57.4.3. PubMed DOI

Slanina T.; Sebej P. Visible-light-activated photoCORMs: rational design of CO-releasing organic molecules absorbing in the tissue-transparent window. Photochem. Photobiol. Sci. 2018, 17, 692–710. 10.1039/c8pp00096d. PubMed DOI

Kumar S.; Pandey A. K. Chemistry and biological activities of flavonoids: An overview. Sci. World J. 2013, 2013, 16275010.1155/2013/162750. PubMed DOI PMC

Anderson S. N.; Richards J. M.; Esquer H. J.; Benninghoff A. D.; Arif A. M.; Berreau L. M. A structurally-tunable 3-hydroxyflavone motif for visible light-induced carbon monoxide-releasing molecules (CORMs). ChemistryOpen 2015, 4, 590–594. 10.1002/open.201500167. PubMed DOI PMC

Dávila Y. A.; Sancho M. I.; Almandoz M. C.; Blanco S. E. Solvent effects on the dissociation constants of hydroxyflavones in organic–water mixtures. determination of the thermodynamic pKa values by UV–visible spectroscopy and DFT calculations. J. Chem. Eng. Data 2013, 58, 1706–1716. 10.1021/je400153r. DOI

Herrero-Martínez J. M.; Sanmartin M.; Rosés M.; Bosch E.; Ràfols C. Determination of dissociation constants of flavonoids by capillary electrophoresis. Electrophoresis 2005, 26, 1886–1895. 10.1002/elps.200410258. PubMed DOI

Han Y.; Jia Y.; Wang X.; Chen Z.; Jin P.; Jia M.; Pan H.; Sun Z.; Chen J. Ultrafast excited state dynamics of two non-emissive flavonoids that undergo excited state intramolecular proton transfer in solution. Chem. Phys. Lett. 2023, 811, 14018910.1016/j.cplett.2022.140189. DOI

Yang Y.; Zhao J.; Li Y. Theoretical study of the ESIPT process for a new natural product quercetin. Sci. Rep. 2016, 6, 32152.10.1038/srep32152. PubMed DOI PMC

Martinez M. L.; Studer S. L.; Chou P. T. Direct evidence of the triplet-state origin of the slow reverse proton transfer reaction of 3-hydroxyflavone. J. Am. Chem. Soc. 1990, 112, 2427–2429. 10.1021/ja00162a058. DOI

Russo M.; Orel V.; Stacko P.; Srankova M.; Muchova L.; Vitek L.; Klan P. Structure–photoreactivity relationship of 3-hydroxyflavone-based CO-releasing molecules. J. Org. Chem. 2022, 87, 4750–4763. 10.1021/acs.joc.2c00032. PubMed DOI

Engler G.; Nispel M.; Marian C.; Kleinermanns K. Transient spectroscopy of UV excited flavone: Triplet–triplet absorption and comparison with theory. Chem. Phys. Lett. 2009, 473, 167–170. 10.1016/j.cplett.2009.03.051. DOI

Nakayama T.; Shimizu T.; Torii Y.; Miki S.; Hamanoue K. A comparison of the photochemistry of flavanone with that of flavone originating from their lowest excited triplet states in ethanol. J. Photochem. Photobiol., A 1997, 111, 35–39. 10.1016/S1010-6030(97)00235-9. DOI

Norikane Y.; Itoh H.; Arai T. Photophysical properties of 5-hydroxyflavone. J. Photochem. Photobiol., A 2004, 161, 163–168. 10.1016/S1010-6030(03)00285-5. DOI

Tournaire C.; Croux S.; Maurette M.-T.; Beck I.; Hocquaux M.; Braun A. M.; Oliveros E. Antioxidant activity of flavonoids: Efficiency of singlet oxygen (1Δg) quenching. J. Photochem. Photobiol., B 1993, 19, 205–215. 10.1016/1011-1344(93)87086-3. PubMed DOI

Zhang W.-J.; Wu J.-F.; Zhou P.-F.; Wang Y.; Hou A.-J. Total syntheses of norartocarpin and artocarpin. Tetrahedron 2013, 69, 5850–5858. 10.1016/j.tet.2013.05.024. DOI

Wang Q.; Zhang J.; Liu M.; Yang J.; Zhang X.-m.; Zhou L.; Cao L.; Liao X.-l. Modified syntheses of the dietary flavonoid luteolin. J. Chem. Res. 2015, 39, 550–552. 10.3184/174751915X14404221529907. DOI

Jiang W.-J.; Ishiuchi K. i.; Furukawa M.; Takamiya T.; Kitanaka S.; Iijima H. Stereospecific inhibition of nitric oxide production in macrophage cells by flavanonols: synthesis and the structure–activity relationship. Bioorg. Med. Chem. 2015, 23, 6922–6929. 10.1016/j.bmc.2015.09.042. PubMed DOI

Trouillas P.; Marsal P.; Svobodová A.; Vostálová J.; Gažák R.; Hrbáč J.; Sedmera P.; Křen V.; Lazzaroni R.; Duroux J.-L.; Walterová D. Mechanism of the antioxidant action of silybin and 2,3-dehydrosilybin flavonolignans: A joint experimental and theoretical study. J. Phys. Chem. A 2008, 112, 1054–1063. 10.1021/jp075814h. PubMed DOI

Jensen F.; Foote C. Chemistry of singlet oxygen—48. Isolation and structure of the primary product of photooxygenation of 3,5-di-t-butyl catechol. Photochem. Photobiol. 1987, 46, 325–330. 10.1111/j.1751-1097.1987.tb04776.x. PubMed DOI

Matsuura T.; Matsushima H.; Kato S.; Saito I. Photoinduced reactions—LVII: Photosensitized oxygenation of catechol and hydroquinone derivatives: Nonenzymic models for the enzymatic cleavage of phenolic rings. Tetrahedron 1972, 28, 5119–5129. 10.1016/S0040-4020(01)88931-6. DOI

Shurygina M. P.; Kurskii Y. A.; Druzhkov N. O.; Chesnokov S. A.; Abakumova L. G.; Fukin G. K.; Abakumov G. A. Photolytic decarbonylation of o-benzoquinones. Tetrahedron 2008, 64, 9784–9788. 10.1016/j.tet.2008.07.008. DOI

Valentine R. L.; Zepp R. G. Formation of carbon monoxide from the photodegradation of terrestrial dissolved organic carbon in natural waters. Environ. Sci. Technol. 1993, 27, 409–412. 10.1021/es00039a023. DOI

Carbon Monoxide-Releasing Activity of Plant Flavonoids

Structure-Photoreactivity Relationship Study of Substituted 3-Hydroxyflavones and 3-Hydroxyflavothiones for Improving Carbon Monoxide Photorelease