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

Abstract

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.

Proton-Coupled Electron-Transfer Reduction of Dioxygen: The Importance of Precursor Complex Formation between Electron Donor and Proton Donor

“…Moreover, ORR by most flavoenzymes studied in the past are conformed to undergo the initial single ET (ET-PT), , though the positive environment near the active site of enzymes can greatly accelerate the reaction rate . In contrast to that, recent theoretical research suggested that the initial single ET is coupled with a proton transfer for several specific flavoenzymes (CPET). − Our work discloses that organic hydrides are potential reagents for O 2 reduction via MS-CPET. In addition, Thorpe et al argued that the solvation and the local polarity within the active site of flavoproteins could affect O 2 reactivity, which is consistent with our experimental results observed.…”

Chemical Mechanism of Fireworm Bioluminescence – A Theoretical Proposition

“…Hence, INT - L 4– and 3 O 2 form RC on the T 1 -PES, then via an intersystem crossing (ISC) to generate INT1 . Although the current computational method is not able to optimize the ISC structure and multireference methods cannot handle such large system, similar ISC processes have been investigated and validated in simpler systems as well. − Following the formation of INT1 , geminal diol INT2 is produced via TS3 by nucleophilic attack, overcoming a low barrier of 1.9 kcal•mol –1 . Subsequently, INT2 is expected to transform into D 4– via TS4A .…”

Oxygen reduction reaction at conducting polymer electrodes in a wider context: Insights from modelling concerning outer and inner sphere mechanisms

“…In biological systems, metal-free flavindependent enzymes, molecular oxygen activation consists in electron transfer to O 2 from a closed-shell reduced flavin anion, chemisorption prior to charge transfer being clearly spin forbidden. [55] Quantum chemical modelling [56,57] further shows that coupled proton and electron transfer (CPET) is an important factor in making these transformations possible.…”