Mechanism for the autoxidation of hemoglobin by phenols, nitrite and “oxidant” drugs. Peroxide formation by one electron donation to bound dioxygen

The reaction of HbO 2 with phenols to produce metHb shows inverse rate dependence upon [H +], direct dependence upon [HbO 2] and [phenol], and a rate that correlates with the electron donor characteristics of the reagents. Thus, the availability of an electron from an external agent permits facile reduction of O 2 to O 2 = and the reaction of HbO 2 with phenols gives rise to metHb and peroxide as reaction products. In contrast, with nucleophiles such as azide O 2 is displaced as superoxide. Since reduction of bound O 2 is seen to occur only by reductive displacement or by reaction with a single electron donor, Hb apparently owes its normal resistance to autoxidation to the isolation of the binding site from electron donors and nucleophiles and not to an unique kind of iron-O 2 bonding. Such reasoning explains the effects of structural abnormality that render M-type Hbs susceptible to oxidation. Also the oxidation of HbO 2 upon exposure to “oxidant drugs” is explicable in terms of the drugs acting as one electron reducing agents towards bound dioxygen.