Unraveling the flavin-catalyzed photooxidation of benzylic alcohol with transient absorption spectroscopy from sub-pico- to microseconds

Abstract

Flavin-mediated photooxidations have been described for applications in synthetic organic chemistry for some time and are claimed to be a route to the use of solar energy. We present a detailed investigation of the involved photophysical and photochemical steps in methoxybenzyl alcohol oxidation on a timescale ranging from sub-picoseconds to tens of microseconds. The results establish the flavin triplet state as the key intermediate for the photooxidation. The initial step is an electron transfer from the alcohol to the triplet state of the flavin catalyst with, followed by a proton transfer in B6 ms. In contrast, the electron transfer involving the singlet state of flavin is a loss channel. It is followed by rapid charge recombination (t = 50 ps) without significant product formation as seen when flavin is dissolved in pure benzylic alcohol. In dilute acetonitrile/water solutions of flavin and alcohol the electron transfer is mostly controlled by diffusion, though at high substrate concentrations >100 mM we also find a considerable contribution from preassociated flavin-alcohol-aggregates. The model including a productive triplet channel and a competing singlet loss channel is confirmed by the course of the photooxidation quantum yield as a function of substrate concentration: We find a maximum quantum yield of 3% at 25 mM of benzylic alcohol and significantly smaller values for both higher and lower alcohol concentrations. The observations indicate the importance to perform flavin photooxidations at optimized substrate concentrations to achieve high quantum efficiencies and provide directions for the design of flavin photocatalysts with improved performance.

LED‐Illuminated NMR Studies of Flavin‐Catalyzed Photooxidations Reveal Solvent Control of the Electron‐Transfer Mechanism

“…This reaction profile is typical for the presence , and delayed formation of the twofold reduced flavin RFTA-H 2 is observed indicating a oneelectron-transfer process. Photo-CIDNP polarizations detected in the oxidized and fully reduced flavin species (g) in CD 3 CN in combination with the results from recent UV/Vis studies [2] in CD 3 CN/D 2 O (1:1) show that the product formation via triplet zwitterionic radical pairs is identical in the two solvents. However, the NMR reaction profiles reveal that the stabilization of these downstream intermediates controls the further reaction mechanism.…”

MRC review of 2014

“…The periplasmic chaperone Skp is a 51-kDa trimer, with a broad substrate range of more than 30 different Omps. [1,2] For its function, Skp has to fulfill two requirements, which stand in direct mechanistic contrast: Long lifetime for the complex during transport, but fast substrate release time to the downstream receptor.…”

“…By this new approach, we have the possibility to gain new insights in the reaction mechanism we were not able to access before. UV/Vis spectroscopy can detect excited states and the initial reaction steps on an ultrafast time scale, [1] while NMR spectroscopy can give information about structure, aggregation and solvent effects.…”

“…[1] [ Merck encompasses all phases of drug discovery and development, from lead identification and technology development through involvement in clinical development teams, and troubleshooting of manufacturing problems. Thomas holds a special interest in the elucidation of the structure and stereochemistry of complex molecules by NMR and the design of pulse sequences to help achieve these goals.…”

Oxidation of alkyl benzenes by a flavin photooxidation catalyst on nanostructured metal-oxide films

“…The photophysics and photooxidation of the flavins have been investigated earlier (18 In an alternate pathway, formation of an alkyl benzene radical in the presence of oxygen has the capability to initiate radical chains, as the peroxyl radicals are very reactive with their corresponding alkyl benzene form. As pointed out earlier, there is a possibility of contributions in overall catalysis from competitive pathways (26).…”