Density Functional Study on the Effect of the trans Axial Ligand of B₁₂ Cofactors on the Heterolytic Cleavage of the Co−C Bond

Abstract

Density functional theory (DFT) Becke3LYP calculations including full and restricted geometry optimizations are carried out on the complex [Co(Cor)(Benz)(CH3)]+ (Cor = corrin, Benz = benzimidazole), which is a model of B 12 cofactors, and on the products of the two possible heterolytic cleavages of the Co−C bond, [Co(Cor)(Benz)(CH3)], CH3 +, [Co(Cor)(Benz)(CH3)]2 +, and CH3 -. The thermodynamics of the heterolytic processes are found to depend very significantly on the distance of the axial ligand from the cobalt. The results are explained through simple molecular orbital reasonings, and their possible implications for the biological reactivity of adenosylcobalamin and methylcobalamin are discussed.

The effect of solvent on the electrode process of methylcobalamine as studied by cyclic voltammetry

“…All geometric optimizations were made to the default tolerances of Gaussian. Previously, DFT calculations have been made [23][24][25][26][27] for R-Cbl(III) compounds; however, there had been no calculations for the one-electron reduced products, the CH 3 -Cbl(II) species. Actually, this radical anion does not appear to have much Co(II) character since the singly occupied MO (SOMO) for the doublet species is mostly a corrin ring p * MO with only a little d yz character.…”

Electronic reorganization: Origin of sigma trans promotion effect

“…As discussed below, this may result in weak trans promotion effect, namely, the complex‐substrate binding affinity would be insensitive to changes in the trans ligand. A likely prominent example is the insensitivity of the homolytic bond dissociation energy of the strongly covalent but formally ionic Co(III)–alkyl bond to the properties of the trans ligand in corrinoid complexes relevant to coenzyme B12 and other systems of biochemical interest 168–170…”

Generation of adenosyl radical from S-adenosylmethionine (SAM) in biotin synthase

“…Density functional theory (DFT) calculations provided valuable insight into the structure and catalytic properties of adenosylcobalamin [19][20][21][22]. The Co-C bond dissociation energy of coenzyme B 12 has been estimated to be about 30 kcal/mol from DFT studies [23][24][25][26][27][28][29][30][31][32][33], which is in good agreement with experimental results [34,35]. QM/MM calculations of glutamate mutase [36] and methylmalonyl-CoA mutase [37,38] showed that the bond dissociation energy of the Co-C bond in the enzymes is significantly reduced by the geometrical distortion of the coenzyme.…”