Equilibrium and kinetic studies on the reactions of alkylcobalamins with cyanide.

Ligand substitution equilibria of different alkylcobalamins (RCbl, R = Me, CH2Br, CH2CF3, CHF2, CF3) with cyanide have been studied. It was found that CN- first substitutes the 5,6-dimethylbenzimidazole (Bzm) moiety in the α-position, followed by substitution of the alkyl group in the β-position trans to Bzm. The formation constants KCN for the 1:1 cyanide adducts (R(CN)Cbl) were found to be 0.38 ± 0.03, 0.43 ± 0.03, and 123 ± 9 M-1 for R = Me, CH2Br, and CF3, respectively. In the case of R = CH2CF3, the 1:1 adduct decomposes in the dark with CN- to give (CN)2Cbl. The unfavorable formation constants for R = Me and CH2Br indicate the requirement of very high cyanide concentrations to produce the 1:1 complex, which cause the kinetics of the displacement of Bzm to be too fast to follow kinetically. The kinetics of the displacement of Bzm by CN- could be followed for R = CH2CF3 and CF3 to form CF3CH2(CN)Cbl and CF3(CN)Cbl, respectively, in the rate-determining step. Both reactions show saturation kinetics at ...