REACTIONS OF CYANIDE WITH COBALAMINS

Cyanide catalyzes the equilibration of α-aquo-β-cyanocobalamin and β-aquo-α-cyanocobalamin below pH 2 through the intermediate formation of α,β-dicyanocobalamin. Rate and equilibrium constants for the individual steps of the isomerization reaction were determined from the kinetics for equilibration and the rate constants for formation of the two isomers of cyanocobalamin from dicyanocobalamin. The rate of cyanide addition to cyanocobalamin becomes independent of cyanide concentration above a half-maximal value at 0.021 M CN-, indicating a dissociative mechanism with a pH-independent rate constant of 0.042 s-1 for dimethylbenzimidazole dissociation. The faster dissociation in acid solutions suggests that cleavage of the Co-N bond is also catalyzed by acid. The addition of cyanide to aquocobalamin proceeds through addition of CN- above pH 9 and a 3-fold slower addition of HCN between pH 6 and 8. Below pH 6 there is a change in rate-limiting step that is attributed to slow rotation of bound CN-. A 35-fold difference between the rate constants at low and at high pH implicates a similar reaction sequence for the addition of cyanide to cyanocobalamin. The rates of cyanide addition to aquocobalamin and cyanocobalamin show positive deviations in hydrochloric acid (up to 3-fold in 1 M HCl) that reflect an unusual H_acidity function for the ionization of HCN. All of the different kinetic patterns for the reactions of cyanide with cobalamin derivatives may be explained by a single underlying dissociative interchange mechanism. © 1979, American Chemical Society. All rights reserved.