Kinetics and equilibrium studies on the reaction of vitamin B12a with azoles

Abstract

The ligand substitution reactions of aquacobalamin (H₂Ocbl⁺) were studied for pyrazole, 1,2,4-triazole and N-acetylimidazole as entering nucleophiles. These nucleophiles displace the coordinated H₂O molecules in H₂Ocbl⁺ to form the six-coordinate product complex. The second order rate constants for the reaction of H₂Ocbl⁺ with pyrazole, 1,2,4-triazole and N-acetylimidazole at 25 °C were found to be 35.0 ± 0.8, 24.0 ± 0.4 and 6.6 ± 1.6 M⁻¹ s⁻¹, respectively. From temperature and pressure dependence studies, activation parameters (ΔH^≠, ΔS^≠ and ΔV^≠) for the reaction of H₂Ocbl⁺ and N-acetylimidazole were found to be 108 ± 12 kJ mol⁻¹, +135 ± 40 J K⁻¹ mol⁻¹ and +7.2 ± 0.3 cm³ mol⁻¹, respectively. In addition, ΔH^≠ and ΔS^≠ for the reaction with pyrazole were found to be 85 ± 4 kJ mol⁻¹ and +69 ± 13 J K⁻¹ mol⁻¹ and those for 1,2,4-triazole were 90 ± 2 kJ mol⁻¹ and +83 ± 6 J K⁻¹ mol⁻¹. Based on the reported kinetic and activation parameters, the substitution of coordinated H₂O by these five-membered heterocyclic azoles follows an I_d mechanism in which the entering nucleophile partially participates in the transition state.