Kinetic and thermodynamic studies on the cyanation reactions and base-on/base-off equilibria of alkyl-13-epicobalamins

Ligand substitution equilibria of two different 13-epicobalamins (X-13-epiCbl, X = NCCH2 and CN-) with cyanide have been studied. It was found that CN- substitutes the 5,6-dimethylbenzimidazole (DMBz) moiety in the (alpha)-position to form X(CN)Cbl-13epi, which for X = NCCH2 in the presence of CN- subsequently gives (CN)2Cbl-13epi. The kinetics of the displacement of DMBz by CN- showed saturation behaviour at high cyanide concentration and the limiting rate constants are characterized by the activation parameters: X = NCCH2, (delta)H(double dagger)= 83 (plus-minus) 1 kJ mol^-1, (delta)S(double dagger)=+77 (plus-minus) 4 J K^-1 mol^-1, (delta)V (double dagger)=+13.3 (plus-minus) 1.0 cm^3 mol^-1; X = CN-, (delta)H(double dagger)= 106 (plus-minus) 1 kJ mol^-1, (delta)S(double dagger)=+82 (plus-minus) 4 J K^-1 mol^-1 and (delta)V(double dagger)=+14.8 (plus-minus) 0.5 cm3 mol^-1. These parameters are interpreted in terms of a limiting D mechanism. The rate constants for the displacement of DMBz in the case of the 13-epicobalamins were found to be slower than those obtained in the case of the analogous alkylcobalamins, and consequently, the thermodynamic equilibrium constants for the 13-epicobalamins were found to be smaller than those obtained in the case of the alkylcobalmins. This clearly shows the effect of the epimerization of the e-side chain attached to the C-13 of the corrin ring on the rate and equilibrium constants for these ligand displacement reactions.