title: Reductive cleavage mechanism of methylcobalamin: elementary steps of Co-C bond breaking.
abstract: Density functional theory has been applied to the investigation of the reductive cleavage mechanism of methylcobalamin (MeCbl). In the reductive cleavage of MeCbl, the Co-C bond is cleaved homolytically, and formation of the anion radical ([MeCbl]*-) reduces the dissociation energy by approximately 50%. Such dissociation energy lowering in [MeCbl]*- arises from the involvement of two electronic states: the initial state, which is formed upon electron addition, has dominant pi*corrin character, but when the Co-C bond is stretched the unpaired electron moves to the sigma*Co-C state, and the final cleavage involves the three-electron (sigma)2(sigma*)1 bond. The pi*corrin-sigma*Co-C states crossing does not take place at the equilibrium geometry of [MeCbl]*- but only when the Co-C bond is stretched to 2.3 A. In contrast to the neutral cofactor, the most energetically efficient cleavage of the Co-C bond is from the base-off form. The analysis of thermodynamic and kinetic data provides a rationale as to why Co-C cleavage in reduced form requires prior departure of the axial base. Finally, the possible connection of present work to B12 enzymatic catalysis and the involvement of anion-radical-like [MeCbl]*- species in relevant methyl transfer reactions is discussed.
authors.affiliation: Department of Chemistry, University of Louisville, Louisville, KY 40292, USA. pawel@louisville.edu
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kozlowski
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Kuta
authors.forename: Wlodzimierz
authors.initials: W
authors.lastname: Galezowski
mesh_terms: D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003035:Cobalt / Q000737:chemistry*; D007700:Kinetics; D010084:Oxidation-Reduction; D013816:Thermodynamics; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003035:Cobalt; D002244:Carbon; C019476:mecobalamin; D014805:Vitamin B 12