Kinetic and thermodynamic studies on ligand substitution reactions and base-on/base-off equilibria of cyanoimidazolylcobamide,a vitamin B_(12) analog with an imidazole axial nucleoside

摘要

Ligand substitution reactions of the vitamin B_(12) analog cyanoimidazolylcobamide,CN(Im)Cbl,with cyanide were studied.Cyanide substitutes imidazole (Im) in the a-position more slowly than it substitutes dimethylbenzimidazole in cyanocobalamin (vitamin B_(12)).The kinetics of the displacement of Im by CN~- showed saturation behaviour at high cyanide concentration;the limiting rate constant was found to be 0.0264 s~(-1) at 25 deg C and is characterized by the activation parameters:DELTAH~(not=) = 111 +- 2 kJ mol~(-1),DELTAS~(not=) = +97 +- 6 J K~(-1) mol~(-1),and DELTAV~(not=) = +9.3 +- 0.3 cm~3 mol~(-1).These parameters are interpreted in terms of an I_d mechanism.The equilibrium constant for the reaction of CN(Im)Cbl with CN~- was found to be 861 +- 75 M~(-1),which is significantly less than that obtained for the reaction of cyanocobalamin with CN~-(viz.10~4 M~(-1)).pK_(base_off) for the base-on/base-off equilibrium was determined spectrophotometrically and found to be 0.99 +- 0.05,which is about 0.9 pH units higher than that obtained previously in the case of cyanocobalamin.In addition,the kinetics of the base-on/base-off reaction was studied using a pH-jump technique and the data obtained revealed evidence for an acid catalyzed reaction path.The results obtained in this study are discussed in reference to those reported previously for cyanocobalamin.