We report the first studies on the reaction between an HNO donor compound and vitamin B-12 complexes. Kinetic and mechanistic studies have been carried out on the reaction between the vitamin B-12 derivative aquacobalamin (H(2)OCbl(+)/ HOCbl; pK(a) = 7.8) and the HNO donor Angeli's salt. Studies were carried out with aquacobalamin in excess, since nitrite also reacts with aquacobalamin to form nitrocobalamin (NO(2)Cbl). At pH <9.90 aquacobalamin reacts directly with the monoprotonated form of Angeli's salt, HN2O3-, to form nitroxylcobalamin (NO--Cbl(III); NOCbl) and nitrite. At pH >10.80 the reaction instead switches predominantly to a mechanism in which spontaneous decomposition of Angeli's salt to give HNO and nitrite becomes the rate-determining step, followed by the rapid reaction between aquacobalamin and HNO/NO- to again give NOCbl. Both reactions proceed with a 1:1 stoichiometry and formation of nitrite is confirmed using the Griess assay.