Autocatalytic Mechanism in the Anaerobic Reduction of Metmyoglobin by Sulfide Species

The mechanism of the metal centered reduction of metmyoglobin(MbFe(III)) by sulfide species (H2S/HS-) under an argon atmosphere has been studied by a combination ofspectroscopic, kinetic, and computational methods. Asymmetric S-shapedtime-traces for the formation of MbFe(II) at varying ratiosof excess sulfide were observed at pH 5.3 < pH < 8.0 and 25 & DEG;C, suggesting an autocatalytic reaction mechanism. An increasedrate at more alkaline pHs points to HS- as relevantreactive species for the reduction. The formation of the sulfanylradical (HS & BULL;) in the slow initial phase was assessedusing the spin-trap phenyl N-tert-butyl nitrone. This radical initiates the formation of S-Sreactive species as disulfanuidyl/ disulfanudi-idyl radical anionsand disulfide (HSSH & BULL;-/HSS & BULL;2- and HSS-, respectively). The autocatalysis hasbeen ascribed to HSS-, formed after HSSH & BULL;-/HSS & BULL;2- disproportionation, which behavesas a fast reductant toward the intermediate complex MbFe(III)(HS-). We propose a reaction mechanism for thesulfide-mediated reduction of metmyoglobin where only ferric hemeiron initiates the oxidation of sulfide species. Beside the chemicalinterest, this insight into the MbFe(III)/sulfide reactionunder an argon atmosphere is relevant for the interpretation of biochemicalaspects of ectopic myoglobins found on hypoxic tissues toward reactivesulfur species. Thesulfide-mediated reduction of metmyoglobin under anargon atmosphere is a pH-dependent autocatalytic process.

Automated summary

This study investigated the mechanism of metal centered reduction of metmyoglobin by sulfide species under an argon atmosphere. The formation of MbFe(II) at varying ratios of excess sulfide indicated an autocatalytic reaction mechanism. The reaction rate increased at higher alkaline pHs, suggesting HS- as the relevant reactive species for the reduction. The proposed reaction mechanism involves the formation of sulfanyl radical, disulfanuidyl/disulfanudi-idyl radical anions and disulfide, and the autocatalysis is attributed to the behavior of HSS- as a fast reductant.