Kinetic and thermodynamic studies on the cyanation reactions and base-on/base-off equilibria of alkyl-13-epicobalamins

Abstract

Ligand substitution equilibria of two different 13-epicobalamins (X-13-epiCbl, X = NCCH₂ and CN⁻) with cyanide have been studied. It was found that CN⁻ substitutes the 5,6-dimethylbenzimidazole (DMBz) moiety in the α-position to form X(CN)Cbl-13epi, which for X = NCCH₂ in the presence of CN⁻ subsequently gives (CN)₂Cbl-13epi. The kinetics of the displacement of DMBz by CN⁻ showed saturation behaviour at high cyanide concentration and the limiting rate constants are characterized by the activation parameters: X = NCCH₂, ΔH^≠ = 83 ± 1 kJ mol⁻¹, ΔS^≠ = +77 ± 4 J K⁻¹ mol⁻¹, ΔV^≠ = +13.3 ± 1.0 cm³ mol⁻¹; X = CN⁻, ΔH^≠ = 106 ± 1 kJ mol⁻¹, ΔS^≠ = +82 ± 4 J K⁻¹ mol⁻¹ and ΔV^≠ = +14.8 ± 0.5 cm³ mol⁻¹. These parameters are interpreted in terms of a limiting D mechanism. The rate constants for the displacement of DMBz in the case of the 13-epicobalamins were found to be slower than those obtained in the case of the analogous alkylcobalamins, and consequently, the thermodynamic equilibrium constants for the 13-epicobalamins were found to be smaller than those obtained in the case of the alkylcobalmins. This clearly shows the effect of the epimerization of the e-side chain attached to the C-13 of the corrin ring on the rate and equilibrium constants for these ligand displacement reactions.