Detailed kinetic and thermodynamic studies on the cyanation of alkylcobalamins. A generalized mechanistic description

Abstract

Ligand substitution equilibria of different cobalamins (XCbl, X = Ado, CF3CH2, n-Pr, NCCH2 and CN−) with cyanide have been studied. It was found that CN− substitutes the 5,6-dimethylbenzimidazole (DMBz) moiety in the α-position in all cases. A reinvestigation of the reactions of coenzyme B12 (X = Ado) and CF3CH2Cbl with CN− and an investigation of the same reaction for X = n-Pr, demonstrate that the unfavorable formation constants in these cases require very high cyanide concentrations to produce the 1 ∶ 1 complex, which causes the kinetics of the displacement of DMBz by cyanide to be too fast to follow. The kinetics of the displacement of DMBz by CN− could be followed for X = β-NCCH2 and CN− to form NCCH2(CN)Cbl and (CN)2Cbl, respectively. Both reactions show saturation kinetics at high cyanide concentration and the limiting rate constants are characterized by the activation parameters: X = NCCH2, ΔH≠ = 85 ± 2 kJ mol−1, ΔS≠ = +97 ± 6 J K−1 mol−1, ΔV≠ = +12.7 ± 0.5 cm3 mol−1; X = CN−, ΔH≠ = 105 ± 2 kJ mol−1, ΔS≠ = +81 ± 6 J K−1 mol−1 and ΔV≠ = +13.1 ± 0.3 cm3 mol−1. These parameters are interpreted in terms of a limiting D mechanism. A complete analysis of the trans effect order of the substituent X is presented. The results enable the formulation of a general mechanism that can account for the substitution behavior of all the investigated alkylcobalamins.