Differential steric effects in the axial ligation of pyridine and imidazole to α- and β-alkylcobinamides

One subclass of B-12-requiring enzymes is now known to bind their B-12 coenzymes "base-off," with a histidine residue from the protein supplying an imidazole ligand to the cobalt center. Recent results from Sirovatka and Finke (J.M. Sirovatka and R.G. Finke, J.Am. Chem. Sec. 119, (1997) 3057) show that imidazole has an extraordinary trans effect on the mode of carbon-cobalt bond cleavage in coenzyme B-12 analogs, compared to pyridine or the natural 5,6-dimethylbenzimidazole ligand, and it was suggested that a differential steric effect could, in part, account for the uniqueness of the imidazole ligand. Such a differential steric effect for imidazole and pyridine is now demonstrated by studies of the thermodynamics of ligation of these ligands to the alpha and beta diastereomers of two alkylcobinamides (RCbi(+)s, derivatives of cobalamins which lack the normal axial nucleotide) based on the known differences in steric crowding of the a ("lower") and beta ("upper") axial ligand positions of cobalt corrinoids. Imidazole binds more tightly than pyridine to both diastereomers of NCCH(2)Cbi(+) and CF(3)Cbi(+), in all cases due to a more favorable entropy change, which is the result of lowered steric interference with corrin side chain thermal motions. (C) 1998 Elsevier Science Inc. All rights reserved.