Thermodynamic and Kinetic Studies on the Reaction between the Vitamin B_(12) Derivative #beta#-(N-Methylimidazolyl)cobalamin and N-Methylimidazole: Ligand Displacement at the #alpha# Axial Site of Cobalamins

摘要

The equilibria and kinetics of substitution of the 5,6-din~thvlbenzimidazole at the a. site of/3-(N-methylimidazolyl)-cobalamin by N-methylimidazole have been investigated, and the product, bis(N-methylimidazolyl)cobalamin, has been characterized by visible and ‘H NMR spectroscopies. The equilibrium constant for (N-MeIm)Cbl~ + N-MeIm (N-MeIm)2Cb1~ was determined by ‘H NMR speczrosco.pv (9.6 ± 0.1 M’, 25.0 0C, I = 1.5 M (NaCIO4)). The observed rate constant for this reaction exhibits an unusual inverse dependence on N-methylimidazole concentration, and it is proposed that substitution occurs via a base-off solvent-bound intermediate. Activation parameters typical for a dis.~ciative ligand substitution mechanism are repoi-ted at two different N-MeIm.,. concentrations, 5.00 x l0-~ M &AH4 = 99 ± 2 kJ moL’. AS~ = 39 ± 5 J moL’ K’. AV5 = 15.0 ± 0.7 cm3 moL’, and 1.00 M (All4 = 109.4 ± 0.8 kJ mol~’, AS4 = 70 ± 3 J moL’ K’. AVr = 16.8 ± 1.1 cm3 moL’). According to the proposed mechanism, these parameters correspond to the aquarion of (N-MeIm)2Cbl~ and the ring-opening reaction of the a-DM.BI of (N-MeIm)Cbl~ to give the solvent-bound intermediate in both cases, respectively.