The Effect of Solvent on the Ligand Substitution Reactions of Aquacobalamin (Vitamin B_12a)

Abstract

The kinetics of the substitution of coordinated H₂O in aquacobalamin (H₂OCbl⁺, vitamin B_12a) by pyridine (py) were studied as a function of temperature in water and in 70% (v/v) ethanol–water at pH 7.0. Saturation kinetics is observed, in agreement with a dissociative interchange mechanism. The values of ΔH‡ for the rate constant for interchange of H₂O and py are 80(2) and 99(8) kJ mol^–1 in water and ethanol–water, respectively, while ΔS‡ values are 47(8) and 106(27) J K^–1 mol^–1, respectively. There is a compensation effect between the two activation parameters which is interpreted in terms of the position of the transition state along the reaction coordinate. The transition state occurs later in an ethanol–water mixture, probably because the outer sphere complex that precedes the ligand exchange is less favoured than in pure water. Despite this compensation, the ligand substitution reaction is slower below about 50°C in the mixed-solvent system than in water. The present results, together with those previously reported by others, suggest that thismaybe a general feature of the ligand substitution reactions ofH₂OCbl⁺ in mixed solvents.

KEY WORDS: Vitamin B_12a, solvent effects, ligand substitution, inorganic reaction mechanisms.