Which Oxidation State Initiates Dehalogenation in the B12-Dependent Enzyme NpRdhA: CoII, CoI, or Co0?

Abstract

The quantum chemical cluster approach was used to elucidate the reaction mechanism of debromination catalyzed by the B12-dependent reductive dehalogenase NpRdhA. Various pathways, involving different oxidation states of the cobalt ion and different protonation states of the model, have been analyzed in order to find the most favorable one. We find that the reductive C–Br cleavage takes place exclusively at the CoI state via a heterolytic pathway in the singlet state. Importantly, the C–H bond formation and the C–Br bond cleavage proceeds via a concerted transition state, as opposed to the stepwise pathway suggested before. C–Br cleavage at the CoII state has a very high barrier, and the reduction of CoI to Co0 is associated with a very negative potential; thus, reductive dehalogenation at CoII and Co0 can be safely ruled out. Examination of substrates with different halogen substitutions (F, Cl, Br, I) shows that the dehalogenation reactivity follows the order C–I > C–Br > C–Cl > C–F, and the barrier for ...