The two-electron and two-proton p -hydroquinone/ p -benzoquinone (H 2 Q/BQ) redox couple has mechanistic parallels to the function of ubiquinone in the electron transport chain. This proton-dependent redox behavior has shown applicability in catalytic aerobic oxidation reactions, redox flow batteries, and co-electrocatalytic oxygen reduction. Under nominally aprotic conditions in non-aqueous solvents, BQ can be reduced by up to two electrons in separate electrochemically reversible reactions. With weak acids (AH) at high concentrations, potential inversion can occur due to favorable hydrogen-bonding interactions with the intermediate monoanion [BQ(AH) m ]˙ − . The solvation shell created by these interactions can mediate a second one-electron reduction coupled to proton transfer at more positive potentials ([BQ(AH) m ]˙ − + n AH + e − ⇌ [HQ(AH) (m+n)−1 (A)] 2− ), resulting in an overall two electron reduction at a single potential at intermediate acid concentrations. Here we show that hydrogen-bonded adducts of reduced quinones and the proton donor 2,2,2-trifluoroethanol (TFEOH) can mediate the transfer of electrons to a Mn-based complex during the electrocatalytic reduction of dioxygen (O 2 ). The Mn electrocatalyst is selective for H 2 O 2 with only TFEOH and O 2 present, however, with BQ present under sufficient concentrations of TFEOH, an electrogenerated [H 2 Q(AH) 3 (A) 2 ] 2− adduct (where AH = TFEOH) alters product selectivity to 96(±0.5)% H 2 O in a co-electrocatalytic fashion. These results suggest that hydrogen-bonded quinone anions can function in an analogous co-electrocatalytic manner to H 2 Q.
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Oxidation of Hydrogen Sulfide by Quinones: How Polyphenols Initiate Their Cytoprotective Effects
We have shown that autoxidized polyphenolic nutraceuticals oxidize H2S to polysulfides and thiosulfate and this may convey their cytoprotective effects. Polyphenol reactivity is largely attributed to the B ring, which is usually a form of hydroxyquinone (HQ). Here, we examine the effects of HQs on sulfur metabolism using H2S- and polysulfide-specific fluorophores (AzMC and SSP4, respectively) and thiosulfate sensitive silver nanoparticles (AgNP). In buffer, 1,4-dihydroxybenzene (1,4-DB), 1,4-benzoquinone (1,4-BQ), pyrogallol (PG) and gallic acid (GA) oxidized H2S to polysulfides and thiosulfate, whereas 1,2-DB, 1,3-DB, 1,2-dihydroxy,3,4-benzoquinone and shikimic acid did not. In addition, 1,4-DB, 1,4-BQ, PG and GA also increased polysulfide production in HEK293 cells. In buffer, H2S oxidation by 1,4-DB was oxygen-dependent, partially inhibited by tempol and trolox, and absorbance spectra were consistent with redox cycling between HQ autoxidation and H2S-mediated reduction. Neither 1,2-DB, 1,3-DB, 1,4-DB nor 1,4-BQ reduced polysulfides to H2S in either 21% or 0% oxygen. Epinephrine and norepinephrine also oxidized H2S to polysulfides and thiosulfate; dopamine and tyrosine were ineffective. Polyphenones were also examined, but only 2,5-dihydroxy- and 2,3,4-trihydroxybenzophenones oxidized H2S. These results show that H2S is readily oxidized by specific hydroxyquinones and quinones, most likely through the formation of a semiquinone radical intermediate derived from either reaction of oxygen with the reduced quinones, or from direct reaction between H2S and quinones. We propose that polysulfide production by these reactions contributes to the health-promoting benefits of polyphenolic nutraceuticals.
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- Award ID(s):
- 2012106
- NSF-PAR ID:
- 10270657
- Date Published:
- Journal Name:
- International Journal of Molecular Sciences
- Volume:
- 22
- Issue:
- 2
- ISSN:
- 1422-0067
- Page Range / eLocation ID:
- 961
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract The 1,4‐diacyloxylation of 1,3‐cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing
cis ‐selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2, which limit process sustainability and large‐scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ withtert ‐butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch fromtrans tocis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports highcis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large‐scale applications. -
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Abstract The 1,4‐diacyloxylation of 1,3‐cyclohexadiene (CHD) affords valuable stereochemically defined scaffolds for natural product and pharmaceutical synthesis. Existing
cis ‐selective diacyloxylation protocols require superstoichiometric quantities of benzoquinone (BQ) or MnO2, which limit process sustainability and large‐scale application. In this report, reaction development and mechanistic studies are described that overcome these limitations by pairing catalytic BQ withtert ‐butyl hydroperoxide as the stoichiometric oxidant. Catalytic quantities of bromide enable a switch fromtrans tocis diastereoselectivity. A catalyst with a 1:2 Pd:Br ratio supports highcis selectivity while retaining good rate and product yield. Further studies enable replacement of BQ with hydroquinone (HQ) as a source of cocatalyst, avoiding the handling of volatile and toxic BQ in large‐scale applications. -
1,4-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.more » « less
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Abstract Hydrogen sulfide (H2S) is a noxious, potentially poisonous, but necessary gas produced from sulfur metabolism in humans. In Down Syndrome (DS), the production of H2S is elevated and associated with degraded mitochondrial function. Therefore, removing H2S from the body as a stable oxide could be an approach to reducing the deleterious effects of H2S in DS. In this report we describe the catalytic oxidation of hydrogen sulfide (H2S) to polysulfides (HS2+n−) and thiosulfate (S2O32−) by poly(ethylene glycol) hydrophilic carbon clusters (PEG‐HCCs) and poly(ethylene glycol) oxidized activated charcoal (PEG‐OACs), examples of oxidized carbon nanozymes (OCNs). We show that OCNs oxidize H2S to polysulfides and S2O32−in a dose‐dependent manner. The reaction is dependent on O2and the presence of quinone groups on the OCNs. In DS donor lymphocytes we found that OCNs increased polysulfide production, proliferation, and afforded protection against additional toxic levels of H2S compared to untreated DS lymphocytes. Finally, in Dp16 and Ts65DN murine models of DS, we found that OCNs restored osteoclast differentiation. This new action suggests potential facile translation into the clinic for conditions involving excess H2S exemplified by DS.
- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.3390/ijms22020961
