Density Functional Theory Analysis of Stereoelectronic Properties of Cobalamins^†

Density functional theory (DFT) is applied to the calculation of the steric and electronic factors which might affect the Co−C_R bond activation in coenzyme B₁₂. The six-coordinate cobalamins (B−[Co^III(corrin)]−R, models of coenzyme B₁₂) include the actual corrin macroring as the equatorial ligand and imidazole (Im), dimethylbenzimidazole (DBI) or water (H₂O), as the α-trans ligand (B). The β axial ligand (R) represents a series of alkyl groups with different steric bulkiness ranging from −C⋮N, −C⋮CH through methyl, ethyl, isopropyl, tert-butyl to 5‘-deoxy-5‘-adenosyl. Each trans ligand (Im, DBI or H₂O) produces a positive correlation of the Co−C_R and Co−N_B bond lengths. The increasing complexity of the R group leads to two major structural correlations:  a positive correlation between the Co−C_R and Co−N_B bond lengths and an inverse correlation between the Co−C_R bond length and the flatness of the corrin ring. It is shown that stereoelectronic properties of cobalamins can only be explained on the basis of electronic considerations. Moreover, electron donation from axial ligands to the cobalt atom either by electron donating substituents or by a properly oriented external electric field caused by external electric charges is argued to be the main trigger for the activation of the Co−C_R bond.