Probing the nature of the Co(iii) ion in cobalamins: a comparison of the reaction of aquacobalamin (vitamin B12a) and aqua-10-chlorocobalamin with some anionic and N-donor ligands

Abstract

To probe the cis effect of the corrin macrocycle in vitamin B₁₂ derivatives, equilibrium constants for the substitution of coordinated H₂O in aquacobalamin (vitamin B_12a, H₂OCbl⁺) and in aqua-10-chlorocobalamin, H₂O-10-ClCbl⁺, (in which Cl has replaced the C10 H) by an exogenous ligand, L (L = an anion, NO₂⁻, SCN⁻, N₃⁻, OCN⁻, S₂O₃²⁻, NCSe⁻ or a neutral N-donor, CH₃NH₂, pyridine, imidazole) have been determined. The cis influence reported in the electronic spectra of the cobalamins is observed in the spectra of L-10-ClCbls as well. Anionic ligands bind more strongly to H₂O-10-ClCbl⁺ than to H₂OCbl⁺ with log K values between 0.10 and 0.63 (average 0.26) larger; the converse is true for the neutral N-donor ligands, where log K is between 0.17 and 0.3 (average 0.25) smaller. Semi-empirical molecular orbital (SEMO) calculations using the ZINDO/1 model on the hydroxo complexes show that charge density is delocalised from the axial donor atom to the metal and Cl. This explains why coordinated OH⁻ is a poorer base in HO-10-ClCbl than in HOCbl and the pK_a of H₂O-10-ClCbl⁺ is lower than that of H₂OCbl⁺. It further explains why, because of the ability of the metal in concert with the C10 Cl to accept charge density from the ligand, an anionic ligand will bind more strongly to Co(III) in H₂O-10-ClCbl⁺ than in H₂OCbl⁺. The kinetics of the replacement of coordinated H₂O by two probe ligand, pyridine and azide, were determined. The rate constants for substitution of H₂O in H₂O-10-ClCbl⁺ by pyridine show saturation, whilst those for substitution by N₃⁻ do not; this is inconsistent with a purely dissociative mechanism and the reactions proceed through an interchange mechanism. The values of the activation parameters are more positive for the reaction between these ligands and H₂OCbl⁺, than for their reaction with H₂O-10-ClCbl⁺. This is interpreted to mean that the transition state in the reaction of H₂O-10-ClCbl⁺ occurs earlier along the reaction coordinate. In the temperature range studied, H₂O-10-ClCbl⁺ reacts more slowly with py and N₃⁻ than does H₂OCbl⁺. SEMO calculations indicate that as the Co–O bond to the departing H₂O molecule is stretched, the charge density on Co in H₂OCbl⁺ is always lower than on Co in H₂O-10-ClCbl⁺. This suggests that the former is a better electrophile towards the incoming ligand, and offers an explanation for the kinetics observations.