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

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dc.citation.articleNumber13293
dc.citation.issueNumber21
dc.citation.journalTitleInternational Journal of Molecular Sciences
dc.citation.volumeNumber23
dc.contributor.authorOlson, Kenneth R.
dc.contributor.authorClear, Kasey J.
dc.contributor.authorDerry, Paul J.
dc.contributor.authorGao, Yan
dc.contributor.authorMa, Zhilin
dc.contributor.authorCieplik, Nathaniel M.
dc.contributor.authorFiume, Alyssa
dc.contributor.authorGaziano, Dominic J.
dc.contributor.authorKasko, Stephen M.
dc.contributor.authorNarloch, Kathleen
dc.contributor.authorVelander, Cecilia L.
dc.contributor.authorNwebube, Ifeyinwa
dc.contributor.authorPallissery, Collin J.
dc.contributor.authorPfaff, Ella
dc.contributor.authorVilla, Brian P.
dc.contributor.authorKent, Thomas A.
dc.contributor.authorWu, Gang
dc.contributor.authorStraub, Karl D.
dc.date.accessioned2022-12-13T19:11:21Z
dc.date.available2022-12-13T19:11:21Z
dc.date.issued2022
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.
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.
dc.identifier.digitalijms-23-13293-v2
dc.identifier.doihttps://doi.org/10.3390/ijms232113293
dc.identifier.urihttps://hdl.handle.net/1911/114104
dc.language.isoeng
dc.publisherMDPI
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/).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleNaphthoquinones Oxidize H2S to Polysulfides and Thiosulfate, Implications for Therapeutic Applications
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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