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 of spectroscopic, kinetic, and computational methods. Asymmetric S-shaped time-traces for the formation of MbFe^II at varying ratios of excess sulfide were observed at pH 5.3 < pH < 8.0 and 25 °C, suggesting an autocatalytic reaction mechanism. An increased rate at more alkaline pHs points to HS^- as relevant reactive species for the reduction. The formation of the sulfanyl radical (HS^•) in the slow initial phase was assessed using the spin-trap phenyl N-tert-butyl nitrone. This radical initiates the formation of S-S reactive species as disulfanuidyl/ disulfanudi-idyl radical anions and disulfide (HSSH^•-/HSS^•2- and HSS^-, respectively). The autocatalysis has been ascribed to HSS^-, formed after HSSH^•-/HSS^•2- disproportionation, which behaves as a fast reductant toward the intermediate complex MbFe^III(HS^-). We propose a reaction mechanism for the sulfide-mediated reduction of metmyoglobin where only ferric heme iron initiates the oxidation of sulfide species. Beside the chemical interest, this insight into the MbFe^III/sulfide reaction under an argon atmosphere is relevant for the interpretation of biochemical aspects of ectopic myoglobins found on hypoxic tissues toward reactive sulfur species.