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.