Theoretical Insight into a Nonadiabatic Proton-Coupled Electron Transfer Mechanism of Reduced Flavin Oxygenation

The oxygenation of reduced flavin has been a fascinating research hotspot in flavin-dependent proteins because it plays an indispensable role in cellular metabolism and has potential applications in biocatalysis. This spin-forbidden reaction of high efficiency is far from being fully understood. Although investigation on the flavin chemistry has been going on for more than 60 years, there are few mechanistic explanations for the reaction of the singlet-reduced flavin with triplet oxygen. In this paper, the reaction between oxygen and the model of free reduced flavin (reduced lumiflavin anion) was studied by density functional and multireference calculations in detail. The results reveal that the reaction proceeds by an electronically nonadiabatic proton-coupled electron transfer mechanism. The intersystem crossing point has been captured.