Theoretical study on the kinetics and reaction mechanism involved in the reduction of quinone by 1-benzyl-1,4-dihydronicotinamide

Abstract

Although it is well known that coenzyme NAD(P)H is involved in anabolic and catabolic reactions in the living organism, there is still significant controversy over the reaction mechanism involved in this biochemical transformation. Thus, 1-benzyl-1,4-dihydronicotinamide was used as a NAD(P)H model in the reduction reaction of 1,4-benzoquinone (Q), 2,3,5,6-tetrachloro-1,4-benzoquinone, and 2,3-dicyano-1,4-benzoquinone in acetonitrile medium. The kinetic calculations support that formal hydride transfer is the main mechanism promoting Q reduction, while the two-step process dominates 2,3-dicyano-1,4-benzoquinone reduction. Interestingly, only the single-electron transfer mechanism takes place when 2,3,5,6-tetrachloro-1,4-benzoquinone is used, affording the corresponding semiquinone derivative as the main product. This mechanistic behavior is related to the presence or absence of electron-withdrawing groups in the quinones used. Furthermore, the kinetic study results showed that calculated reaction rate constants are in close agreement with experimental results. The results support that formal hydride transfer on the reduction reaction of Q by 1-benzyl-1,4-dihydronicotinamide in acetonitrile proceeds through a hydrogen coupled electron transfer mechanism. This theoretical analysis provides valuable knowledge that can be extrapolated to study the reduction of quinones performed by NADH and NADPH in physiological media.