Semi-empirical studies of cobalamins, corrin models, and cobaloximes. The nucleotide loop does not strain the corrin ring in cobalamins

PM3(tm) semi-empirical geometry optimization was applied to a variety of corrins. Notably, we present here the first quantum-mechanical equilibrium structures of cobalamins. Adenosylcobalamin (AdoB12) and methylcobalamin (MeB12) in their native and 5,6-dimethylbenzimidazole (DMB)-off, imidazole-on forms, and cob(II)alamin were subjected to full geometry optimization. The study presents three levels of in vacuo B12 models: the cobalamins themselves, the corrins, and the cobaloximes. We compare PM3(tm) data for corrins with other kinds of theory and experiment. The cobaloximes were less good B12 models due to their charge and the flexibility of the bis(dimethylglyoximato) framework. We found that the nucleotide loop and the amide chains had minor effect on the corrin geometry. This suggests that corrins are suitable as B12 models and that cobalamins are not particularly strained in comparison to the simpler corrin analogues. We have evaluated the differential preference of the two coenzymes for the two axial ligands imidazole and 5,6-dimethylbenzimidazole. AdoB12 prefers the imidazole ligand relative to MeB12 by 27 kcal mol−1. Finally, calculated electron affinities indicate that DMB serves as a delocalization reservoir, increasing electron affinity by 59 kcal mol−1 relative to ammonia. Hence, apo-enzymatic control of the CoN(ax) bond length may be a means to govern the homolysis–heterolysis selectivity, rendering delocalization of the SOMO electron possible during homolysis.