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Reductive Cleavage Mechanism of Methylcobalamin:  Elementary Steps of Co−C Bond Breaking

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journal contribution
posted on 05.07.2007 by Pawel M. Kozlowski, Jadwiga Kuta, Wlodzimierz Galezowski
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 ∼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 π*corrin character, but when the Co−C bond is stretched the unpaired electron moves to the σ*Co-C state, and the final cleavage involves the three-electron (σ)2(σ*) bond. The π*corrin−σ*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 Å. 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.