DFT calculations and in vitro experiments do show energy barriers reactions in
the methionine synthase process. By contrast, in vivo experiments suggest that
methionine synthase process reactions are running without any energy barriers.
We performed the MCSCF calculations of the Co-C cleavage reaction paths for one
electron reduced methylcobalamin cofactor systems with dimethylbenzimidazol
axial ligand substituted by histidine (base-on imidazol model) and for base-off
system. The basis set of the 6-31G** for cobalt and of the 6-31G for s,p-atoms was
used within all calculations. Our results show that the larger than 13 active electrons
and 13 active molecular orbitals of the Methylco(II)balamin cofactor species do
not lead to an observable modification of the calculated Co-C reaction paths
energy barriers. The MCSCF calculations of Methylco(II)balamin Co-C band rupture
reaction paths show 3.32 kcal/mol in the case of the methylcobalamin histidine
(imidazole) base-on model and 7.82 kcal/mol in the case of the base-off model
total energy barriers, respectively. We concluded that neither methylcobalamin
histidine base-on cofactor nor base-off methylcobalamin cofactor can participate
into Co-C bond cleavage SN1 reaction, making the SN1 mechanism for CH3
radical transfer from methylcobalamin cofactor to cysteine improbable. The
homocysteine negative ion and methylcobalamin cofactor common model lead
to the one electron transfer from homocysteine negative ion to methylcobalamin
cofactor, triggering the Co-C bond cleavage in the methionine synthase process.
In conclusion, the methyl-radical transfer from Methylco(II)balamin systems to
homocysteine is an SN2 reaction type.