Theoretical investigation of steric and electronic effects in coenzyme B-12 models

In this study, the first density functional theory calculations on Bit mode ls that contain the entire corrin ring are presented to evaluate earlier fi ndings 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 incr eased the basis set to a triple-zeta valence type. The effects of the diffe rent axial substituents on the crucial Co-C. bond length and the corrin fol ding have been evaluated. We find a systematic cis-steric effect and a less systematic trans induction. The corrin framework is fairly inert toward th e size of the axial R-ligands, which argues against a mechanochemical trigg er mechanism. The HOMO-LUMO gap increases through the steric series via a l owering of the HOMO energy, making the corrins less susceptible to homolyti c cleavage. Rather different equilibrium structures of adenosylcobalamin an d methylcobalamin models are anticipated from this study, which also indica tes 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.