Dealkylation of Coenzyme B12 and Related Organocobalamins: Ligand Structural Effects on Rates and Mechanisms of Hydrolysis

Rates and mechanisms of dealkylations of coenzyme B12, Ado-B12, 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-B12, 3‘dAdo-B12, 2‘,3‘ddAdo-B12, 1dRF-B12, and THFF-B12, 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-B12 and 2‘,3‘-ddAdoB12; the second path, involving ring-opening protonation at the ribofuranosyl oxygen, analogous to hydrolyses of simple β-hydroxy and β-alkoxy complexes, predominates for the other four complexes. The rates of both hydrolysis pathways exhibited a marked dependence on the ligand functional groups. Ado-B12, the most substitut...