Reaction Kinetics of Cyanide Binding to a Cobalt Schiff-Base Macrocycle Relevant to Its Mechanism of Antidotal Action.

The Co(II/III)-containing macrocycle, cobalt 2,12-dimethyl-3,7,11,17-tetraazabicyclo-[11.3.1]-heptadeca-1(17)2,11,13,15-pentaenyl cation, or CoN[11.3.1], is a potential cyanide-scavenging agent. The rate of reduction of Co(III)N[11.3.1] by ascorbate is reasonably facile under pseudo-first-order conditions; a second-order rate constant of 11.7(±0.4) M s was determined at 25 °C and pH 7.4, along with the activation parameters for the reaction (Δ = 53.9(±0.8) kJ mol; Δ -79(±3) J mol K). It follows that any cyanide-decorporating capability of the cobalt complex should depend more on the cyanide-binding characteristics of Co(II)N[11.3.1] than the oxidized form. The kinetics of the reaction of cyanide with Co(II)N[11.3.1] under anaerobic pseudo-first-order conditions is rapid and resulted in a linear dependence on the cyanide concentration, = 8 × 10 M s, with a nonlinear intercept of 420 s at 10 °C, pH 7.6. The observed reaction rate increases significantly with increasing pH. A rate law is suggested, = '[X] + ( + /[H])[HCN], where is estimated to be ∼2 × 10 M s. Activation parameters for the reaction with HCN (Δ = 10.7(±0.4) kJ mol; Δ = -153(±1) J mol K) suggest an associative mechanism. In the presence of excess oxygen, i.e., at higher levels than free oxygen , the reaction rate was too fast to be measured, and the final product was the oxidized complex, Co(III)N[11.3.1], where any cyanide ligands had been lost. This is much more rapid than the oxidation of the parent compound by oxygen, for which a second-order rate constant of 0.5(±0.02) M s at 25 °C was obtained. The study has gone some way toward enhancing our understanding of the reaction of Co(II)N[11.3.1] with cyanide. The fast reaction rate implies a high efficacy of the cyanide-scavenging capability of the complex and further supports the suggestion stemming from our previous work that Co(II)N[11.3.1] could prove to be a better and more cost-effective cyanide antidote than the FDA-approved hydroxocobalamin.