Carbon monoxide (CO) is notorious for its toxic effects but is also recognized as a gasotransmitter with considerable therapeutic potential. Due to the inherent challenges in its delivery, the utilization of organic CO photoreleasing molecules (photoCORMs) represents an interesting alternative to CO administration characterized by high spatial and temporal precision of release. This paper focused on the design, synthesis, and photophysical and photochemical studies of 20 3-hydroxyflavone (flavonol) and 3-hydroxyflavothione derivatives as photoCORMs. Newly synthesized compounds bearing various electron-donating and electron-withdrawing groups show bathochromically shifted absorption maxima and considerably enhanced CO release yields compared to the parent unsubstituted flavonol, exceeding 0.8 equiv of released CO in derivatives exhibiting excited states with a charge-transfer character. Until now, such outcomes have been limited to flavonol derivatives possessing a π-extended aromatic system. In addition, thione analogs of flavonols, 3-hydroxyflavothiones, show substantial bathochromic shifts of their absorption maxima and enhanced photosensitivity but provide lower yields of CO formation. Our study elucidates in detail the mechanism of CO photorelease from flavonols and flavothiones, utilizing steady-state and time-resolved spectroscopies and photoproduct analyses, with a particular emphasis on unraveling the structure-photoreactivity relationship and understanding competing side processes.

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

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

Zobrazit více v PubMed

Ryter S. W.; Otterbein L. E. Carbon monoxide in biology and medicine. BioEssays 2004, 26, 270–280. 10.1002/bies.20005. PubMed DOI

Thom S. R. Hyperbaric-oxygen therapy for acute carbon monoxide poisoning. N. Engl. J. Med. 2002, 347, 1105–1106. 10.1056/NEJMe020103. PubMed DOI

Ernst A.; Zibrak J. D. Carbon monoxide poisoning. New England J. Med. 1998, 339, 1603–1608. 10.1056/NEJM199811263392206. PubMed 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

Verma A.; Hirsch D. J.; Glatt C. E.; Ronnett G. V.; Snyder S. H. Carbon monoxide: a putative neural messenger. Science 1993, 259, 381–384. 10.1126/science.7678352. PubMed DOI

Wang R. Resurgence of carbon monoxide: an endogenous gaseous vasorelaxing factor. Can. J. Physiol. Pharmacol. 1998, 76, 1–15. 10.1139/y97-187. PubMed DOI

Scragg J. L.; Dallas M. L.; Wilkinson J. A.; Varadi G.; Peers C. Carbon monoxide inhibits L-type Ca2+ channels via redox modulation of key cysteine residues by mitochondrial reactive oxygen species. J. Biol. Chem. 2008, 283, 24412–24419. 10.1074/jbc.M803037200. PubMed DOI PMC

Oliveira S. R.; Queiroga C. S.; Vieira H. L. Mitochondria and carbon monoxide: cytoprotection and control of cell metabolism–a role for Ca2+?. J. Physiol. 2016, 594, 4131–4138. 10.1113/JP270955. PubMed DOI PMC

Desmard M.; Boczkowski J.; Poderoso J.; Motterlini R. Mitochondrial and cellular heme-dependent proteins as targets for the bioactive function of the heme oxygenase/carbon monoxide system. Antioxid. Redox. Sign. 2007, 9, 2139–2156. 10.1089/ars.2007.1803. PubMed DOI

Wegiel B.; Gallo D.; Csizmadia E.; Harris C.; Belcher J.; Vercellotti G. M.; Penacho N.; Seth P.; Sukhatme V.; Ahmed A. Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. Cancer Res. 2013, 73, 7009–7021. 10.1158/0008-5472.CAN-13-1075. PubMed DOI PMC

Li Y.; Dang J.; Liang Q.; Yin L. Carbon monoxide (CO)-strengthened cooperative bioreductive anti-tumor therapy via mitochondrial exhaustion and hypoxia induction. Biomaterials 2019, 209, 138–151. 10.1016/j.biomaterials.2019.04.004. PubMed DOI

Romanski S.; Stamellou E.; Jaraba J.; Storz D.; Krämer B.; Hafner M.; Amslinger S.; Schmalz H.-G.; Yard B. Enzyme-triggered CO-releasing molecules (ET-CORMs): evaluation of biological activity in relation to their structure. Free Radical Bio. Med. 2013, 65, 78–88. 10.1016/j.freeradbiomed.2013.06.014. PubMed DOI

Pordel S.; Schrage B. R.; Ziegler C. J.; White J. K. Impact of steric bulk on photoinduced ligand exchange reactions in Mn (I) photoCORMs. Inorg. Chim. Acta 2020, 511, 11984510.1016/j.ica.2020.119845. DOI

Ling K.; Men F.; Wang W.-C.; Zhou Y.-Q.; Zhang H.-W.; Ye D.-W. Carbon monoxide and its controlled release: Therapeutic application, detection, and development of carbon monoxide releasing molecules (CORMs). J. Med. Chem. 2018, 61, 2611–2635. 10.1021/acs.jmedchem.6b01153. PubMed DOI

Motterlini R.; Otterbein L. E. The therapeutic potential of carbon monoxide. Nat. Rev. Drug Discovery 2010, 9, 728–743. 10.1038/nrd3228. PubMed DOI

Abeyrathna N.; Washington K.; Bashur C.; Liao Y. Nonmetallic carbon monoxide releasing molecules (CORMs). Org. Biomol. Chem. 2017, 15, 8692–8699. 10.1039/C7OB01674C. PubMed DOI

Weinstain R.; Slanina T.; Kand D.; Klan P. Visible-to-NIR-light activated release: From small molecules to nanomaterials. Chem. Rev. 2020, 120, 13135–13272. 10.1021/acs.chemrev.0c00663. PubMed DOI PMC

Zhang W.-Q.; Atkin A. J.; Thatcher R. J.; Whitwood A. C.; Fairlamb I. J. S.; Lynam J. M. Diversity and design of metal-based carbon monoxide-releasing molecules (CO-RMs) in aqueous systems: revealing the essential trends. Dalton Trans. 2009, 4351–4358. 10.1039/b822157j. PubMed DOI

Zhang W.-Q.; Whitwood A. C.; Fairlamb I. J. S.; Lynam J. M. Group 6 carbon monoxide-releasing metal complexes with biologically-compatible leaving groups. Inorg. Chem. 2010, 49, 8941–8952. 10.1021/ic101230j. PubMed DOI

Mishiro K.; Kimura T.; Furuyama T.; Kunishima M. Phototriggered active alkyne generation from cyclopropenones with visible light-responsive photocatalysts. Org. Lett. 2019, 21, 4101–4105. 10.1021/acs.orglett.9b01280. PubMed DOI

Palao E.; Slanina T.; Muchova L.; Solomek T.; Vitek L.; Kláan P. Transition-metal-free CO-releasing BODIPY derivatives activatable by visible to NIR light as promising bioactive molecules. J. Am. Chem. Soc. 2016, 138, 126–133. 10.1021/jacs.5b10800. PubMed DOI

Peng P.; Wang C.; Shi Z.; Johns V. K.; Ma L.; Oyer J.; Copik A.; Igarashi R.; Liao Y. Visible-light activatable organic CO-releasing molecules (PhotoCORMs) that simultaneously generate fluorophores. Org. Biomol. Chem. 2013, 11, 6671–6674. 10.1039/c3ob41385c. PubMed DOI

Allison R. R.; Sibata C. H. Oncologic photodynamic therapy photosensitizers: A clinical review. Photodiagnosis Photodyn. Ther. 2010, 7, 61–75. 10.1016/j.pdpdt.2010.02.001. PubMed DOI

Yuan Z.; Wang B.. Organic carbon monoxide prodrugs that release CO under physiological conditions. In Carbon monoxide in drug discovery 2022; p 232–258.

Pan Z.; Chittavong V.; Li W.; Zhang J.; Ji K.; Zhu M.; Ji X.; Wang B. Organic CO prodrugs: Structure–CO-release rate relationship studies. Chem.—Eur. J. 2017, 23, 9838–9845. 10.1002/chem.201700936. PubMed DOI PMC

Yang X.; Tripathi R.; Wang M.; Lu W.; Anifowose A.; Tan C.; Wang B. Toward “CO in a pill”: Silica-immobilized organic CO prodrugs for studying the feasibility of systemic delivery of CO via In situ gastrointestinal CO release. Mol. Pharmaceutics 2023, 20, 1850–1856. 10.1021/acs.molpharmaceut.2c01104. PubMed DOI PMC

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

Anderson S. N.; Larson M. T.; Berreau L. M. Solution or solid–it doesn’t matter: visible light-induced CO release reactivity of zinc flavonolato complexes. Dalton Trans. 2016, 45, 14570–14580. 10.1039/C6DT01709F. PubMed DOI

Stackova L.; Russo M.; Muchova L.; Orel V.; Vítek L.; Stacko P.; Klan P. Cyanine-flavonol hybrids for near-infrared light-activated delivery of carbon monoxide. Chem.—Eur. J. 2020, 26, 13184–13190. 10.1002/chem.202003272. PubMed DOI PMC

Ramundo A.; Janos J.; Muchova L.; Srankova M.; Dostal J.; Kloz M.; Vitek L.; Slavicek P.; Klan P. Visible-light-activated carbon monoxide release from porphyrin–flavonol hybrids. J. Am. Chem. Soc. 2024, 146, 920–929. 10.1021/jacs.3c11426. PubMed DOI PMC

Matsuura T.; Takemoto T.; Nakashima R. Photoinduced reactions—LXXI: Photorearrangement of 3-hydroxyflavones to 3-aryl-3-hydroxy-1, 2-indandiones. Tetrahedron 1973, 29, 3337–3340. 10.1016/S0040-4020(01)93485-4. 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

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

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

Brewer W. E.; Studer S. L.; Standiford M.; Chou P. T. Dynamics of the triplet state and the reverse proton transfer of 3-hydroxyflavone. J. Phys. Chem. 1989, 93, 6088–6094. 10.1021/j100353a029. DOI

Szakács Z.; Kállay M.; Kubinyi M. Theoretical study on the photooxygenation and photorearrangement reactions of 3-hydroxyflavone. RSC Adv. 2017, 7, 32185–32192. 10.1039/C7RA04590E. DOI

Ramundo A.; Hurtova M.; Bozek I.; Osifova Z.; Russo M.; Ngoy B. P.; Kren V.; Klan P. Multimodal carbon monoxide photorelease from flavonoids. Org. Lett. 2024, 26, 708–712. 10.1021/acs.orglett.3c04141. PubMed DOI PMC

Parthenopoulos D. A.; Kasha M. Ground state anion formation and picosecond excitation dynamics of 3-hydroxyflavone in formamide. Chem. Phys. Lett. 1990, 173, 303–309. 10.1016/0009-2614(90)85274-G. DOI

Sengupta P. K.; Kasha M. Excited state proton-transfer spectroscopy of 3-hydroxyflavone and quercetin. Chem. Phys. Lett. 1979, 68, 382–385. 10.1016/0009-2614(79)87221-8. DOI

Mughal E. U.; Sadiq A.; Ashraf J.; Zafar M. N.; Sumrra S. H.; Tariq R.; Mumtaz A.; Javid A.; Khan B. A.; Ali A.; Javed C. O. Flavonols and 4-thioflavonols as potential acetylcholinesterase and butyrylcholinesterase inhibitors: Synthesis, structure-activity relationship and molecular docking studies. Bioorg. Chem. 2019, 91, 10312410.1016/j.bioorg.2019.103124. PubMed DOI

Oyamada T. A new general method for the synthesis of flavonol derivatives. J. Chem. Soc. Jpn. 1934, 55, 1256–1261. 10.1246/nikkashi1921.55.12_1256. DOI

Algar J.; Flynn J. P. In Proc. Roy. Irish Acad., B; JSTOR: 1934; Vol. 42, p 1–8.

Dutta U.; Maity S.; Kancherla R.; Maiti D. Aerobic oxynitration of alkynes with t-BuONO and TEMPO. Org. Lett. 2014, 16, 6302–6305. 10.1021/ol503025n. PubMed DOI

Maligres P. E.; Waters M. S.; Fleitz F.; Askin D. A highly catalytic robust palladium catalyzed cyanation of aryl bromides. Tetrahedron Lett. 1999, 40, 8193–8195. 10.1016/S0040-4039(99)01707-4. DOI

Han X.; Whitfield S.; Cotten J. Synthesis, characterization and CO-releasing property of palladium (II) bipyridine flavonolate complexes. Transit. Met. Chem. 2020, 45, 217–225. 10.1007/s11243-019-00373-9. DOI

Khatoon H.; Abdulmalek E. A focused review of synthetic applications of Lawesson’s reagent in organic synthesis. Molecules 2021, 26, 6937.10.3390/molecules26226937. 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 p K a values by UV–visible spectroscopy and DFT calculations. J. Chem. Eng. Data 2013, 58, 1706–1716. 10.1021/je400153r. DOI

Perrin D. D.; B D.. Buffers for pH and metal ion control; Springer: Dordrecht, 1974.

Chou P.-T.; Martinez M. L.; Clements J. H. The observation of solvent-dependent proton-transfer/charge-transfer lasers from 4’-diethylamino-3-hydroxyflavone. Chem. Phys. Lett. 1993, 204, 395–399. 10.1016/0009-2614(93)89175-H. DOI

Chou P. T.; Martinez M. L.; Clements J. H. Reversal of excitation behavior of proton-transfer vs. charge-transfer by dielectric perturbation of electronic manifolds. J. Phys. Chem. 1993, 97, 2618–2622. 10.1021/j100113a024. DOI

Bi X.; Liu B.; McDonald L.; Pang Y. Excited-state intramolecular proton transfer (ESIPT) of fluorescent flavonoid dyes: A close look by low temperature fluorescence. J. Phys. Chem. B 2017, 121, 4981–4986. 10.1021/acs.jpcb.7b01885. PubMed DOI

Hansch C.; Leo A.; Taft R. A survey of Hammett substituent constants and resonance and field parameters. Chem. Rev. 1991, 91, 165–195. 10.1021/cr00002a004. DOI

Steer R.; Ramamurthy V. Photophysics and intramolecular photochemistry of thiones in solution. Acc. Chem. Res. 1988, 21, 380–386. 10.1021/ar00154a005. DOI

Zhao X.; Li X.; Liang S.; Dong X.; Zhang Z. 3-Hydroxyflavone derivatives: promising scaffolds for fluorescent imaging in cells. RSC Adv. 2021, 11, 28851–28862. 10.1039/D1RA04767A. PubMed DOI PMC

Wolfbeis O. S.; Knierzinger A.; Schipfer R. pH-dependent fluorescence spectroscopy XVII: First excited singlet state dissociation constants, phtootautomerism and dual fluorescence of flavonol. J. Photochem. 1983, 21, 67–79. 10.1016/0047-2670(83)80009-4. DOI

Valente J. V.; Buntine M. A.; Lincoln S. F.; David Ward A. UV–Vis and fluorimetric Al3+, Zn2+, Cd2+ and Pb2+ complexation studies of two 3-hydroxyflavones and a 3-hydroxythioflavone. Inorg. Chim. Acta 2007, 360, 3380–3386. 10.1016/j.ica.2007.04.011. DOI

You J.; Fu H.; Zhao D.; Hu T.; Nie J.; Wang T. Flavonol dyes with different substituents in photopolymerization. J. Photochem. Photobiol., A 2020, 386, 11209710.1016/j.jphotochem.2019.112097. DOI

Ormson S. M.; Brown R. G.; Vollmer F.; Rettig W. Switching between charge- and proton-transfer emission in the excited state of a substituted 3-hydroxyflavone. J. Photochem. Photobiol., A 1994, 81, 65–72. 10.1016/1010-6030(94)03778-7. 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

Ameer-Beg S.; Ormson S. M.; Brown R. G.; Matousek P.; Towrie M.; Nibbering E. T.; Foggi P.; Neuwahl F. V. Ultrafast measurements of excited state intramolecular proton transfer (ESIPT) in room temperature solutions of 3-hydroxyflavone and derivatives. J. Phys. Chem. A 2001, 105, 3709–3718. 10.1021/jp0031101. DOI

Sytnik A.; Gormin D.; Kasha M. Interplay between excited-state intramolecular proton transfer and charge transfer in flavonols and their use as protein-binding-site fluorescence probes. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 11968–11972. 10.1073/pnas.91.25.11968. PubMed DOI PMC

Falantin C.; Moncomble A.; Le Person A.; Cornard J. P. Chalcogen substitution: Effect of oxygen-by-sulfur exchange on structural and spectroscopic properties of flavonols. Spectrochim Acta A Mol. Biomol Spectrosc 2017, 187, 49–60. 10.1016/j.saa.2017.06.022. PubMed DOI

Pham T. C.; Heo S.; Nguyen V.-N.; Lee M. W.; Yoon J.; Lee S. Molecular design toward heavy-atom-free photosensitizers based on the C=S bond and their dual functions in hypoxia photodynamic cancer therapy and ClO–detection. ACS Appl. Mater. Interfaces 2021, 13, 13949–13957. 10.1021/acsami.0c22174. PubMed DOI

Wang C.-H.; Liu Z.-Y.; Huang C.-H.; Chen C.-T.; Meng F.-Y.; Liao Y.-C.; Liu Y.-H.; Chang C.-C.; Li E. Y.; Chou P.-T. Chapter open for the excited-state intramolecular thiol proton transfer in the room-temperature solution. J. Am. Chem. Soc. 2021, 143, 12715–12724. 10.1021/jacs.1c05602. PubMed 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

Dall’Acqua S.; Miolo G.; Innocenti G.; Caffieri S. The photodegradation of quercetin: relation to oxidation. Molecules 2012, 17, 8898–8907. 10.3390/molecules17088898. PubMed DOI PMC

Haag W. R.; Gassman E. Singlet oxygen in surface waters—Part I: Furfuryl alcohol as a trapping agent. Chemosphere 1984, 13, 631–640. 10.1016/0045-6535(84)90199-1. DOI

Li M.; Cline C.; Koker E.; Carmichael H.; Chignell C.; Bilski P. Quenching of singlet molecular oxygen (1O2) by azide anion in solvent mixtures. Photochem. Photobiol. 2001, 74, 760–764. 10.1562/0031-8655(2001)074<0760:QOSMOO>2.0.CO;2. PubMed DOI

Elisei F.; Lima J. C.; Ortica F.; Aloisi G. G.; Costa M.; Leitão E.; Abreu I.; Dias A.; Bonifacio V.; Medeiros J. Photophysical properties of hydroxy-substituted flavothiones. J. Phys. Chem. A 2000, 104, 6095–6102. 10.1021/jp000084y. DOI

Rao V. P.; Ramamurthy V. Mechanism of oxidation of α, β-unsaturated thiones by singlet oxygen. Tetrahedron 1985, 41, 2169–2176. 10.1016/S0040-4020(01)96589-5. DOI

Sanchez-Arroyo A. J.; Pardo Z. D.; Moreno-Jimenez F.; Herrera A.; Martín N.; García-Fresnadillo D. Photochemical oxidation of thioketones by singlet molecular oxygen revisited: Insights into photoproducts, kinetics, and reaction mechanism. J. Org. Chem. 2015, 80, 10575–10584. 10.1021/acs.joc.5b01710. PubMed DOI

Mali S. M.; Gopi H. N. Thioacetic acid/NaSH-mediated synthesis of N-protected amino thioacids and their utility in peptide synthesis. J. Org. Chem. 2014, 79, 2377–2383. 10.1021/jo402872p. PubMed DOI

Frank C. E. Hydrocarbon autoxidation. Chem. Rev. 1950, 46, 155–169. 10.1021/cr60143a003. PubMed DOI

Zoller U. In pursuit of stable, strained smallring sulfur heterocycles. Sulfur Reports 1997, 20, 173–195. 10.1080/01961779708047919. DOI

Utaka M.; Takeda A. Copper (II)-catalysed oxidation of quercetin and 3-hydroxyflavone. J. Chem. Soc., Chem. Commun. 1985, 1824–1826. 10.1039/c39850001824. DOI

Rajee R.; Ramamurthy V. Oxidation of thiones by singlet and triplet oxygen. Tetrahedron Lett. 1978, 19, 5127–5130. 10.1016/S0040-4039(01)85829-9. DOI

Herron J. T.; Huie R. E. Rate constants at 298 k for the reactions SO+SO+ M→(SO)2 + M and SO+(SO)2→ SO2+ S2O. Chem. Phys. Lett. 1980, 76, 322–324. 10.1016/0009-2614(80)87032-1. DOI

Jordán S.; Pajtás D.; Patonay T.; Langer P.; Kónya K. Synthesis of 6,7-dibromoflavone and its regioselective diversification via suzuki–miyaura reactions. Synthesis 2017, 49, 1983–1992. 10.1055/s-0036-1588376. DOI

Shen X.; Zhou Q.; Xiong W.; Pu W.; Zhang W.; Zhang G.; Wang C. Synthesis of 5-subsituted flavonols via the Algar-Flynn-Oyamada (AFO) reaction: The mechanistic implication. Tetrahedron 2017, 73, 4822–4829. 10.1016/j.tet.2017.06.064. DOI

Gunduz S.; Goren A. C.; Ozturk T. Facile syntheses of 3-hydroxyflavones. Org. Lett. 2012, 14, 1576–1579. 10.1021/ol300310e. PubMed DOI

Roy T.; Boateng S. T.; Banang-Mbeumi S.; Singh P. K.; Basnet P.; Chamcheu R.-C. N.; Ladu F.; Chauvin I.; Spiegelman V. S.; Hill R. A.; Kousoulas K. G.; Nagalo B. M.; Walker A. L.; Fotie J.; Murru S.; Sechi M.; Chamcheu J. C. Synthesis, inverse docking-assisted identification and in vitro biological characterization of Flavonol-based analogs of fisetin as c-Kit, CDK2 and mTOR inhibitors against melanoma and non-melanoma skin cancers. Bioorg. Chem. 2021, 107, 10459510.1016/j.bioorg.2020.104595. PubMed DOI PMC

Kucherak O. A.; Shvadchak V. V.; Kyriukha Y. A.; Yushchenko D. A. Synthesis of a fluorescent probe for sensing multiple protein states. Eur. J. Org. Chem. 2018, 2018, 5155–5162. 10.1002/ejoc.201800524. DOI

Weig A. W.; O’Conner P. M.; Kwiecinski J. M.; Marciano O. M.; Nunag A.; Gutierrez A. T.; Melander R. J.; Horswill A. R.; Melander C. A structure activity relationship study of 3,4′-dimethoxyflavone for ArlRS inhibition in Staphylococcus aureus. Org. Biomol. Chem. 2023, 21, 3373–3380. 10.1039/D3OB00123G. PubMed DOI PMC

Tran B. L.; Cohen S. M. Flavothionato metal complexes: implications for the use of hydroxyflavothiones as green pesticides. Chem. Commun. 2006, 203–205. 10.1039/B512185J. PubMed DOI

Su Y. Y.; Yang W. X.; Yang X.; Zhang R. L.; Zhao J. S. Visible light-induced CO-release reactivity of a series of ZnII-flavonolate complexes. Aust. J. Chem. 2018, 71, 549–558. 10.1071/CH18192. DOI

Borges M.; Romão A.; Matos O.; Marzano C.; Caffieri S.; Becker R. S.; Maçanita A. L. Photobiological properties of hydroxy-substituted flavothiones. Photochem. Photobiol. 2002, 75, 97–106. 10.1562/0031-8655(2002)075<0097:PPOHSF>2.0.CO;2. PubMed DOI

Carbon Monoxide-Releasing Activity of Plant Flavonoids