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

摘要

Quantum chemical computations are used to study the electronic and structural properties of the cob(I)alamin intermediateof the cobalamin-dependent methionine synthase (MetH). QM(DFT)/MM calculations on the methylcobalamin (MeCbl) binding domainof MetH reveal that the transfer of the methyl group to the substrate is associated with the displacement of the histidineaxial base (His759). The axial base oscillates between a His-on form in the Me-cob(III)lamin:MetH resting state, where theCo-N(His759) distance is 2.27 A, and a His-off form in the cob(I)alamin:MetH intermediate (2.78 A). Furthermore, QM/MM andgas phase DFT calculations based on an unrestricted formalism show that the cob(I)alamin intermediate exhibits a complexelectronic structure, intermediate between the Co(I) and Co(II)-radical corrin states. To understand this complexity, theelectronic structure of Im … [Cob(I)alamin] is investigated using multireference CASSCF/QDPT2 calculations on gas phasemodels where the axial histidine is modeled by imidazole (Im). It is found that the correlated ground state wave functionconsists 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 (π~*)~1 configuration. Moreover, the contribution of these two configurations depends on the Co-N_(Im)distance. At short Co-N_(Im) distances (<2.5 A), the dominant electronic configuration is the diradical state, while forlonger distances it is the closed-shell state. The implications of this finding are discussed in the context of the methyltransfer reaction between the Me-H4folate substrate and cob(I)alamin.