Can Photolysis of the Co-C Bond in Coenzyme B12-Dependent Enzymes be Used to Mimic the Native Reaction ?

Abstract

Coenzyme B12 (Adenosylcobalamin = AdoCbl)-dependent enzymes catalyze complex molecular transformations where cleavage of the Co-C bond initiates the catalytic cycle. Alternatively, the Co-C bond can also be cleaved with light. In both cases, rupture of the Co-C bond results in the formation of Co(II)/Ado radical pair (RP). There has been a suspicion that the photolytic cleavage of the Co-C bond can be used to mimic the RP formation that occurs in enzymes. Within the field of B12 chemistry, there has been a lack of consensus as to whether or not photolytic cleavage can be used as a probe or a direct comparison to the native reaction. Herein, we seek to resolve what the connection between light-induced RP formation and the native catalytic cycle is. We used a combined QM/MM approach to construct PESs for AdoCbl-dependent ethanolamine ammonia-lyase (EAL) as a function of axial bonds to describe the reaction mechanism. We have found that there is no direct comparison that can be made between photolysis and enzymatic cleavage. However, we offer an alternative explanation which involves considering the reduced cofactor. The topology of the PES (D1) for the one electron reduced cofactor is very similar to the PES associated with photo-induced cleavage (S1). Both surfaces contain two energy minima that are, similarly, the result of two distinct electronic states. Thus, it can be concluded that the reaction mechanism associated with the D1 surface and the S1 surface are very similar, providing the connection between photolysis and the native reaction.