Studies on the Reaction of Reduced Vitamin B12 Derivatives with the Nitrosyl Hydride (HNO) Donor Angeli's Salt: HNO Oxidizes the Transition-Metal Center of Cob(I)alamin

Although it is well established that nitrosyl hydride (nitroxyl, HNO) reduces transition metals including transition-metal centers of porphyrins and metalloproteins, oxidation of a metal center by HNO has yet to be reported. Kinetic and mechanistic studies on the Co-II vitamin B-12 form, cob(II)alamin [Cbl(II)], with the widely used HNO donor Angeli's salt (AS) have been carried out. The stoichiometry of the reaction is Cbl(II)/AS = 1:2, and AS decomposition to give HNO and nitrite is the rate-determining step. Separate studies on the reaction between cob(I)alamin [Cbl(I)(-)] and AS and experiments in the presence of excess nitrite or the efficient cob(III)alamin trapping agent cyanide support a mechanism in which HNO reduces Cbl(II) to Cbl(I)(-), being itself oxidized to NO. A second molecule of HNO then oxidizes Cbl(I)(-) back to Cbl(II), which reacts rapidly with NO to form nitroxylcobalamin [nitrosylcobalamin, NO--Cbl(III), NOCbl].