Sulfide-mediated autocatalytic reduction of metmyoglobin

PALERMO, JUAN CRUZ; CARLLINNI COLOMBO, MELISA; SEMELAK, JONATHAN A; BOUBETA, FERNANDO M.; ESTRIN, DARÍO A.; BARI, SARA E.

Conferencia; XXI International Conference on Oxygen Binding and Sensing Proteins; 2022

The coordination of hydrogen sulfide, H2S, to ferric hemeproteins has been reported in morethan 40 examples, an d forms moderately stable hexacoordinated low spin complexes,[FeIII(SH-)].1 The metal centered reduction has been reported in some cases, with varyingtimescales. Subsequent aerobic reactivity of the metmyoglobin complex, MbFeIII(SH-) hasbeen reported and yields myoglobin, MbFeII, with the concomitant formation of thiosulfate,sulfite and polysulfides.2 Combining kineti c an d spectroscopic methods, we proposed amechanism for the reduction of MbFeIII by excess sulfide, under argon atmosphere. AsymmetricS-shaped time-traces for the formation of MbFeII, under varying sulfide concentrations orpH were observed, pointing to an autocatalytic behavior. Further analysis of the time-traces atselected times revealed a secondary sigmoidal dependence on the initial concentration ofsulfide, suggesting a full time-dose response. The slow initial phase is suggested to depend onthe resonant form FeII(SH*) of the starting complex, yielding minor quantities of MbFeII andsulfanyl radical, SH*. The overall rate of the reaction is augmented with increasing pH, pointingto hydrosulfide, SH-, as a critical species in the early steps. We propose the intermediacy of thedisulfanuidyl radical anion, HSS*2-, promoted under alkaline conditions by reaction of HS- andHS*, as a source of disulfane (HSS-).3 Significantly, the formation of MbFeII after the additionof HSS- to MbFeIII(SH-) is faster than the isolated addition of HS- or HSS- to MbFeIII(H2O),suggesting a synergistic effect, and pointing to HSS- as a key species in the steep increase ofthe reduction rate of MbFeIII by sulfide. Kinetic simulations of the sigmoidal traces assisted theevaluation of the proposed mechanism. The process has been termed reductive sulfhydration,after the well described reductive nitrosylation ; this denomination should be discussed, asferrous forms do not form stable complexes with sulfide.References(1) Boubeta, F. et al. Antioxid Redox Signal. 2020, 32(4), 247-257 (10.1089/ars.2019.7878).(2) Bostelaar, T. et al. J Am Chem Soc. 2016, 138 (27), 8476–8488 (10.1021/jacs.6b03456).(3) Mills, G. et al. J Phys Chem. 1987, 91 (6), 1590–1596 (10.1021/j100290a060).