The mechanisms of hemoglobin autoxidation evidence for proton-assisted nucleophilic displacement of superoxide by anions

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Abstract

Human oxyhemoglobin (HbO2) in the presence of excess nucleophile (e.g., N3, SCN, F, Cl) is shown by visible and Soret spectra to form cleanly the oxidized metHb with the nucleophile as ligand. The rates, sensitive to pH and to both the concentration and the nucleophilicity of anionic nucleophile (N), follow the rate law: rate = k[HbO2][N][H+]. This autoxidation process thus appears to involve the nucleophilic displacement of superoxide from a protonated intermediate and can reasonably account for normal metHb formation in the erythrocyte where chloride can serve as the nucleophile. MetHb formation due to electron transfer agents (e.g. nitrite) which are normally not present can follow a different course such as direct electron transfer to bound dioxygen to form iron (III) peroxide. Abnormal amino acids or denaturation can provide increased access of nucleophile or electron transfer reactant and thus promote autoxidation.

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