Autocatalytic Mechanism in the Anaerobic Reduction of Metmyoglobin by Sulfide Species

The mechanism of the metal centered reduction of metmyoglobin (MbFeIII) 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 MbFeII 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 MbFeIII(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 MbFeIII/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.