A Mechanistic Interpretation of Disulfane Oxidation by Ferric Myoglobin

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

Congreso; L Encuentro anual de la Sociedad Argentina de Biofísica; 2022

Sociedad Argentina de Biofísica

Dihydrogen disulfane, H2S2, is an endogenous gasotransmitter which has been recently proposed as an effector of the biochemical activity of hydrogen sulfide (H2S). As other gasotransmitters (NO, CO) it exerts physiological functions at low, regulated, concentrations, but is toxic above these values. Heme proteins are among the possible targets of this species and may provide a detoxification mechanism, by oxidizing the excess sulfane. In this work, we focused on the reactivity of dihydrogen disulfane, and its conjugated base hydrodisulfide, HS2–, towards ferric myoglobin (MbFeIII).We followed the reaction of variable excess concentrations of Na2S2 with MbFeIII, under argon atmosphere, at 7 ≤ pH ≤ 8 and 25°C, by UV - Vis spectroscopy. The formation of MbFeII was observed, suggesting the concomitant one - electron oxidation of H2S2/ HS2‾, to the radical disulfanyl HSS•. A biexponential behavior was verified when the formation of MbFeII was not interfered by the formation of sulfheme species. A two-steps mechanism for the metal centered reduction is proposed. The first step is assigned to the fast formation of a coordination complex intermediate, as has been previously reported for the reaction of H2S with MbFeIII. , This proposed intermediate slowly yields MbFeII and HSS•. A kinetic constant has been estimated for the metal - centered reduction, which does not depend on the initial disulfane concentration. Preliminarily, an increase in the rate of the second step is observed at higher pH. Higher polysulfides are detected in the final reaction mixture, resulting from the dimerization of HSS• and the subsequent chemistry of these sulfur species in aqueous solutions. The results point at ferric hemeproteins as efficient mediators of oxidative disulfane detoxification.