Rates and mechanisms of dealkylations of coenzyme B-12, Ado-B-12, and of five related organocobalamin compounds, including 2',5'-dideoxyadenosyl, 3',5'-dideoxyadenosyl, 2',3',5'-trideoxyadenosyl, 1,5-dideoxyribofuranosyl, and tetrahydrofurfuryl complexes (2'dAdo-B-12, 3'dAdo-B-12, 2',3'ddAdo-B-12, 1dRF-B-12, and THFF-B-12, respectively), were determined in acidic solutions. In each case, competitive homolytic and acid-induced hydrolytic cobalt-carbon bond decomposition pathways were identified. Two mechanisms were observed for Co-C bond hydrolysis: the first, involving initial depurination followed by elimination from an organometallic intermediate, predominates for 2'dAdo-B-12 and 2',3'-ddAdoB(12); the second path, involving ring-opening protonation at the ribofuranosyl oxygen, analogous to hydrolyses of simple beta-hydroxy and beta-alkoxy complexes, predominates for the other four complexes. The rates of both hydrolysis pathways exhibited a marked dependence on the ligand functional groups. Ado-B-12, the most substituted and most stable of the complexes, decomposes nearly 10 000-fold more slowly than the least stable, unsubstituted THFF-B-12 complex. Systematic variation of the hydroxy and adenine substituents on the furanosyl ring afforded insights into the roles of these substituents in effecting this large stabilization toward hydrolysis. Because of the extreme hydrolytic stability of the coenzyme, biologically relevant homolytic dissociation of 5'-deoxyadenosyl radical is competitive with hydrolysis over a wide pH range where the unprotonated, base-on form is kinetically dominant. Determination of the pH dependence of the dealkylation rates of Ado-B-12, 2'dAdo-B-12, and 3'dAdo-B-12 afforded quantification of the competition between homolytic and hydrolytic paths. In contrast to hydrolysis, the limiting homolytic Co-C bond dissociation rate was found to be insensitive to hydroxy substitution. Finally, broader issues relevant to organocobalamin chemistry and also bearing on earlier observations, are considered, among them protonation equilibria and dealkylation kinetics of organocobalamins, and fitting procedures for axial base dissociation equilibria.