The chemical biology of the persulfide (RSSH)/perthiyl (RSS·) redox couple and possible role in biological redox signaling

The recent finding that hydropersulfides (RSSH) are biologically prevalent in mammalian systems has prompted further investigation of their chemical properties in order to provide a basis for understanding their potential functions, if any. Hydropersulfides have been touted as hyper-reactive thiol-like species that possess increased nucleophilicity and reducing capabilities compared to their thiol counterparts. Herein, using persulfide generating model systems, the ability of RSSH species to act as one-electron reductants has been examined. Not unexpectedly, RSSH is relatively easily oxidized, compared to thiols, by weak oxidants to generate the perthiyl radical (RSS·). Somewhat surprisingly, however, RSS· was found to be stable in the presence of both O2 and NO and only appears to dimerize. Thus, the RSSH/RSS· redox couple is readily accessible under biological conditions and since dimerization of RSS· may be a rare event due to low concentrations and/or sequestration within a protein, it is speculated that the general lack of reactivity of individual RSS· species may allow this couple to be utilized as a redox component in biological systems. •Hydropersulfides (RSSH) are readily oxidized to the corresponding perthiyl radical (RSS·).•RSS· does not react with O2 or NO.•Hydropersulfides are superior reductants compared to thiols (RSH).•Perthiyl is less reactive than a thiyl (RS·) species.•The RSSH/RSS· redox couple is biologically accessible and possibly relevant.