c-Lactone ring increases the reactivity of cyanocobalamins toward glutathione

Abstract

Here, we suggest a new method of increasing the reactivity of cyanocobalamin (CNCbl) and its meso-chlorinated and brominated derivatives (CNCbl-Cl,Br) toward glutathione (GSH) that facilitates their reductive decyanation. In particular, we found that introducing a [Formula: see text]-lactone ring to CNCbl or its halogenated versions substantially accelerates their reduction by GSH to a Co(II)-species. The highest rate of the reaction was observed in the case of CNCbl-Cl [Formula: see text]-lactone. The mechanism of CNCbl [Formula: see text]-lactone reduction by GSH involves the formation of intermediate complexes with GSH, which are further transformed into unstable Co(III)-thiolato species with detached 5,6-dimethylbenzimidazole (DMBI) decomposing to Co(II)-species and thiyl radical. In the case of the reaction involving CNCbl-Cl [Formula: see text]-lactone, a parallel reduction pathway involves direct DMBI substitution by GSH. Besides the formation of Co(II)-species, the reduction of lactone ring occurs in the course of reactions of CNCbl [Formula: see text]-lactones with GSH, giving species possessing lower reactivity toward GSH than initial [Formula: see text]-lactones.