Theoretical investigation of the mechanism for the reductive dehalogenation of methyl halides mediated by the Co^I-based compounds cobalamin and cobaloxime

Theoretical calculations focusing on the cleavage of the C–X bond in methyl halides (CH₃X; X = Cl, Br, I) as mediated by Co^I-based systems have been carried out using the hybrid functional ωB97-XD together with the basis set 6–311++G(2d,2p). A total of seven Co^I-based compounds were evaluated: cob[I]alamin (Co^ICbl) in its base-on form and cobaloxime (Co^ICbx) with either no ligand or different ligands (either pyridine (PYR), tributylphosphine (TBP), dimethyl sulfide (DMS), cyclohexylisocyanide (CI), or 5,6-dimethylbenzimidazole (DMB)) at the lower axial position. For the large Co^ICbl system, an ONIOM scheme was employed, where the high layer was described at the DFT level and the low layer was computed using the semi-empirical method PM6. A full DFT model was employed for the Co^ICbx cases. An S_N2-like mechanism was evaluated in all cases. The intrinsic reaction coordinate profiles suggested early transition states with activation energies of ≈ 12 kcal/mol, ≈ 10 kcal/mol, and ≈ 5 kcal/mol for C–Cl, C–Br, and C–I cleavage, respectively, which is consistent with the leaving group abilities of these halides. The evolutions of the atomic charges in and the bond orders of Co–C and C–X were computed, and the results confirmed the existence of early transition states (δB_av≈ 40%), where the polarization C^δ+–X^δ− (%E_v ≈ 43%) is the determining factor in the reaction process. Finally, a comparison of all the determined parameters showed that the reaction in the DMB–Co^ICbx system resembles the process that occurs in the larger Co^ICbl, suggesting that the former system could be a reliable model for the study of reductive dehalogenation mediated by vitamin B₁₂, which is key to the anaerobic microbiological treatment of halocarbon contaminants.