Theoretical investigation of steric and electronic effects in coenzyme B₁₂ models

In this study, the first density functional theory calculations on Bit models that contain the entire corrin ring are presented to evaluate earlier findings by other groups. Eight octahedral corrin systems with various axial ligands have been subject to a full density functional theory (DFT) lacvp** geometry optimization in vacuo. The largest of these calculations included around 1000 basis functions. For energies of optimized structures, we increased the basis set to a triple-zeta valence type. The effects of the different axial substituents on the crucial Co-C. bond length and the corrin folding have been evaluated. We find a systematic cis-steric effect and a less systematic trans induction. The corrin framework is fairly inert toward the size of the axial R-ligands, which argues against a mechanochemical trigger mechanism. The HOMO-LUMO gap increases through the steric series via a lowering of the HOMO energy, making the corrins less susceptible to homolytic cleavage. Rather different equilibrium structures of adenosylcobalamin and methylcobalamin models are anticipated from this study, which also indicates that the former has ca. 5 kcal/mol higher HOMO and LUMO energy. This is a theoretical explanation why adenosylcobalamin is more easily homolyzed, whereas methylcobalamin is heterolyzed.