The preparation of N-acetyl-Co(III)-microperoxidase-8 (NAcCoMP8) and its ligand substitution reactions: a comparison with aquacobalamin (vitamin B(12a))

Abstract

The synthesis of the Co(III) porphyrin octapeptide N-acetyl-Co(III) microperoxidase-8 (NAcCoMP8) is described. NAcCoMP8 provides a means of comparing and contrasting the chemistry of Co(III) porphyrins and corrins to assess the influence of the macrocycle. Log K values, and ΔH and ΔS, for the coordination of anionic (CN(-), N3(-), NO2(-), HSO3(-)) and neutral (pyridine, N-methylimidazole, methoxylamine and hydroxylamine) ligands by aquacobalamin (H2OCbl(+)) and NAcCoMP8 are reported. Anions bind more strongly to H2OCbl(+) than to NAcCoMP8 while the converse is true for the neutral ligands. Density Functional Theory (DFT) calculations and QTAIM analyses suggest the bonding between Co(III) and these ligands is predominantly ionic although anionic ligands induce a significant covalency, the extent of which is important for the stability of the complex. The CoL bond length (L=an anion) in a Co(III) corrin, while longer than in a Co(III) porphyrin, is shorter than might be expected as assessed from CoL bond lengths when L=neutral ligand. It is likely that this stems from coulombic interaction between L and the residual charge at the metal center (2+ in corrin; 1+ in porphyrin). Co(III) in H2OCbl(+) is more labile towards substitution by CN(-) than NAcCoMP8 but the converse is true when the entering ligand is neutral N-methylimidazole. The extent of participation of the incoming ligand in the transition state of the reaction is controlled by the log K value so the nature of the incoming ligand determines in which of these two macrocyclic systems Co(III) is the more labile.