Sulfide-mediated autocatalytic reduction of metmyoglobin

PALERMO, JUAN CRUZ; CARLLINNI COLOMBO, MELISA; SEMELAK, JONATHAN ALEXIS; BOUBETA, FERNANDO MARTÍN; ESTRIN, DARÍO ARIEL; BARI, SARA ELIZABETH

Roma

Congreso; International hybrid Conference on Oxygen Binding and Sensing Proteins; 2022

Universidad de Roma

The coordination of hydrogen sulfide, H2S, to ferric hemeproteins has been reported in more than 40 examples, and forms moderately stable hexacoordinated low spin complexes, [FeIII(SH-)].1 The metal centered reduction has been reported in some cases, with varying timescales. Subsequent aerobic reactivity of the metmyoglobin complex, MbFeIII(SH-) has been reported and yields myoglobin, MbFeII, with the concomitant formation of thiosulfate, sulfite and polysulfides.2 Combining kinetic and spectroscopic methods, we proposed a mechanism for the reduction of MbFeIII by excess sulfide, under argon atmosphere.Asymmetric S-shaped time-traces for the formation of MbFeII, under varying sulfide concentrations or pH were observed, pointing to an autocatalytic behavior. Further analysis of the time-traces at selected times revealed a secondary sigmoidal dependence on the initial concentration of sulfide, suggesting a full time-dose response. The slow initial phase is suggested to depend on the resonant form FeII(SH*) of the starting complex, yielding minor quantities of MbFeII and sulfanyl radical, SH*. The overall rate of the reaction is augmented with increasing pH, pointing to hydrosulfide, SH-, as a critical species in the early steps. We propose the intermediacy of the disulfanuidyl radical anion, HSS*2-, promoted under alkaline conditions by reaction of HS- and HS*, as a source of disulfane (HSS-).3 Significantly, the formation of MbFeII after the addition of HSSto MbFeIII(SH-) is faster than the isolated addition of HS- or HSSto MbFeIII(H2O), suggesting a synergistic effect, and pointing to HSS- as a key species in the steep increase of the reduction rate of MbFeIII by sulfide. Kinetic simulations of the sigmoidal traces assisted the evaluation of the proposed mechanism.The process has been termed reductive sulfhydration, after the well describedreductive nitrosylation; this denomination should be discussed, as ferrous forms donot form stable complexes with sulfide.