Role of the Axial Base in the Modulation of the Cob(I)alamin Electronic Properties: Insight from QM/MM, DFT, and CASSCF Calculations

Quantum chemical computations are used to study the electronic and structural properties of the cob(I)alamin intermediate of the cobalamin-dependent methionine synthase (MetH). QM(DFT)/MM calculations on the methylcobalamin (MeCbI) binding domain of MetH reveal that the transfer of the methyl group to the substrate is associated with the displacement of the histidine axial base (His759). The axial base oscillates between a His-on form in the Me-cob(II)lamin:MetH resting state, where the Co-N(His759) distance is 2.27 angstrom, and a His-off form in the cob(l)alamin:MetH intermediate (2.78 angstrom). Furthermore, QM/MM and gas phase DFT calculations based on an unrestricted formalism show that the cob(I)alamin intermediate exhibits a complex electronic structure, intermediate between the Co (I) and Co (II)-radical corrin states. To understand this complexity, the electronic structure of Im center dot center dot center dot[Cob(I)alamin] is investigated using multireference CASSCF/QDPT2 calculations on gas phase models where the axial histidine is modeled by imidazole (Im). It is found that the correlated ground state wave function consists of a closed-shell Co-I (d(8)) configuration and a diradical contribution, which can be described as a Co-II (d(7))-radical corrin (pi*)(1) configuration. Moreover, the contribution of these two configurations depends on the Co-N-Im distance. At short Co-N-Im distances (<2.5 angstrom), the dominant electronic configuration is the diradical state, while for longer distances it is the closed-shell state. The implications of this finding are discussed in the context of the methyl transfer reaction between the Me-H(4)folate substrate and cob(I)alamin.