Theoretical analysis of C–F bond cleavage mediated by cob[I]alamin-based structures

In the present work, C–F bond cleavage mediated by the super-reduced form of cobalamin (i.e., Co^ICbl) was theoretically studied at the ONIOM(BP86/6-311++G(d,p):PM6) + SMD level of theory. Dispersion effects were introduced by employing Grimme’s empirical dispersion at the ONIOM(BP86-D/6-311++G(d,p):PM6) + SMD level. In the first stage of the study, cobalamin was characterized in terms of the coordination number of the central cobalt atom. The ONIOM(BP86/6-311++G(d,p):PM6) results showed that the base-off form of the system is slightly more stable than its base-on counterpart (ΔE = E_base-off – E_base-on ~ −2 kcal/mol). The inclusion of dispersive forces in the description of the system stabilizes the base-on form, which becomes as stable as its base-off counterpart. Moreover, in the latter case, the energy barrier separating both structures was found to be negligible, with a computed value of 1.02 kcal/mol. In the second stage of the work, the reaction Co^ICbl + CH₃F → MeCbl + F⁻ was studied considering the base-off and the base-on forms of Co^ICbl. The reaction that occurs in the presence of the base-on form of Co^ICbl was found to be kinetically more favorable (ΔE^≠ = 13.7 kcal/mol) than that occurring in the presence of the base-off form (ΔE^≠ = 41.2 kcal/mol). Further reaction-force analyses of the processes showed that the energy barrier to C–F bond cleavage arises largely due to structural rearrangements when the reaction occurs on the base-on form of the Co^ICbl complex, but is mainly due to electronic rearrangements when the reaction takes place on the base-off form of the complex. The latter behavior emerges from differences in the synchronicity of the bond strengthening/weakening processes along the reaction path; the base-on mode of Co^ICbl is able to decrease the synchronicity of the chemical events. This work gives new molecular-level insights into the role of Cbl-based systems in the cleavage of C–F bonds. These insights have potential implications for research into processes for degrading fluorine-containing pollutants.