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.