Naphthoquinones Oxidize H2S to Polysulfides and Thiosulfate, Implications for Therapeutic Applications

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dc.citation.articleNumber13293en_US
dc.citation.issueNumber21en_US
dc.citation.journalTitleInternational Journal of Molecular Sciencesen_US
dc.citation.volumeNumber23en_US
dc.contributor.authorOlson, Kenneth R.en_US
dc.contributor.authorClear, Kasey J.en_US
dc.contributor.authorDerry, Paul J.en_US
dc.contributor.authorGao, Yanen_US
dc.contributor.authorMa, Zhilinen_US
dc.contributor.authorCieplik, Nathaniel M.en_US
dc.contributor.authorFiume, Alyssaen_US
dc.contributor.authorGaziano, Dominic J.en_US
dc.contributor.authorKasko, Stephen M.en_US
dc.contributor.authorNarloch, Kathleenen_US
dc.contributor.authorVelander, Cecilia L.en_US
dc.contributor.authorNwebube, Ifeyinwaen_US
dc.contributor.authorPallissery, Collin J.en_US
dc.contributor.authorPfaff, Ellaen_US
dc.contributor.authorVilla, Brian P.en_US
dc.contributor.authorKent, Thomas A.en_US
dc.contributor.authorWu, Gangen_US
dc.contributor.authorStraub, Karl D.en_US
dc.date.accessioned2022-12-13T19:11:21Zen_US
dc.date.available2022-12-13T19:11:21Zen_US
dc.date.issued2022en_US
dc.description.abstract1,4-Napththoquinones (NQs) are clinically relevant therapeutics that affect cell function through production of reactive oxygen species (ROS) and formation of adducts with regulatory protein thiols. Reactive sulfur species (RSS) are chemically and biologically similar to ROS and here we examine RSS production by NQ oxidation of hydrogen sulfide (H2S) using RSS-specific fluorophores, liquid chromatography-mass spectrometry, UV-Vis absorption spectrometry, oxygen-sensitive optodes, thiosulfate-specific nanoparticles, HPLC-monobromobimane derivatization, and ion chromatographic assays. We show that NQs, catalytically oxidize H2S to per- and polysulfides (H2Sn, n = 2–6), thiosulfate, sulfite and sulfate in reactions that consume oxygen and are accelerated by superoxide dismutase (SOD) and inhibited by catalase. The approximate efficacy of NQs (in decreasing order) is, 1,4-NQ ≈ juglone ≈ plumbagin > 2-methoxy-1,4-NQ ≈ menadione >> phylloquinone ≈ anthraquinone ≈ menaquinone ≈ lawsone. We propose that the most probable reactions are an initial two-electron oxidation of H2S to S0 and reduction of NQ to NQH2. S0 may react with H2S or elongate H2Sn in variety of reactions. Reoxidation of NQH2 likely involves a semiquinone radical (NQ·−) intermediate via several mechanisms involving oxygen and comproportionation to produce NQ and superoxide. Dismutation of the latter forms hydrogen peroxide which then further oxidizes RSS to sulfoxides. These findings provide the chemical background for novel sulfur-based approaches to naphthoquinone-directed therapies.en_US
dc.identifier.citationOlson, Kenneth R., Clear, Kasey J., Derry, Paul J., et al.. "Naphthoquinones Oxidize H2S to Polysulfides and Thiosulfate, Implications for Therapeutic Applications." <i>International Journal of Molecular Sciences,</i> 23, no. 21 (2022) MDPI: https://doi.org/10.3390/ijms232113293.en_US
dc.identifier.digitalijms-23-13293-v2en_US
dc.identifier.doihttps://doi.org/10.3390/ijms232113293en_US
dc.identifier.urihttps://hdl.handle.net/1911/114104en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsThis article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleNaphthoquinones Oxidize H2S to Polysulfides and Thiosulfate, Implications for Therapeutic Applicationsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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