Stabilization of the adenosyl radical in coenzyme B12 – a theoretical study

Density functional theory B3LYP calculations have been carried out on a large model for coenzyme B12. The dissociation curve for the homolytic cleavage of the Co–C bond has been studied for the free cofactor, in the gas phase and including the effect of a dielectric continuum with a dielectric constant of 4.00, as well as in the presence of some key residues present in methylmalonyl-CoA mutase, an enzyme that depends on coenzyme B12. We describe a hitherto unknown effect of the cofactor which facilitates the homolysis reaction: electrostatic interactions stabilize the radicals formed in this step. H-bonding to protein residues leads to further stabilization.