Thiourea‐Enhanced Flavin Photooxidation of Benzyl Alcohol

Abstract

Upon irradiation, flavin oxidises 4-methoxybenzyl alcohol to the corresponding aldehyde using aerial O(2) as the terminal oxidant. We have observed that this reaction is significantly accelerated by the presence of thiourea. A series of thiourea-functionalised flavins has been prepared from flavin isothiocyanates and their photocatalytic efficiencies have been monitored by NMR. The alcohol photooxidation proceeds rapidly and cleanly with high turnover numbers of up to 580, exceeding previously reported performances. A likely mechanistic rationale for the more than 30-fold acceleration of the photo-redox reaction by thiourea has been derived from spectroscopic, electrochemical, and kinetic studies. Thus, thiourea acts as an electron-transfer mediator for the initial photooxidation of 4-methoxybenzyl alcohol by the excited flavins. This mechanism has similarities to electron-relay mechanisms in flavoenzymes, for which cysteine sulfenic acid intermediates are proposed. The observation that thiourea mediates flavin photo-redox processes is valuable for the design of more sophisticated photocatalysts based on Nature's best redox chromophore.

MRC review of 2014

“…By the usage of advanced labeling schemes, backbone assignments, paramagnetic relaxation enhancements (PRE), and extensive relaxation measurements, we were able to provide the first complete structural and dynamical description of a 70-kDa chaperone-substrate protein complex at the atomic level by high-resolution NMR. [3] Further, we were able to show for this complexes formed by the periplasmic chaperone Skp and its substrates OmpX (outer membrane protein X) and OmpA that the Skp chaperone holds its substrate in a unique dynamic compacted ensemble state of fast interchanging conformers, which we termed 'fluid globule'. Analysis of the relaxation properties of substrate and chaperone revealed decoupling of the movements of the two proteins, highlighting the effects of reorientation of the substrate on the chaperone-binding-surface and of avidity accounting for the strong interaction resulting in a nanomolar binding affinity for this particular complex.…”

“…As a model system the photooxidation of para-methoxybenzyl alcohol to the corresponding aldehyde by riboflavin tetraacetate [2,3] was selected because of flavins optimal UV/Vis properties and the diamagnetic nature of starting material and products enabling both spectroscopies. The schematic mechanism is shown in the figure below.…”

“…Here, we introduce three new pulse sequences based on the EXSIDE experiments. The first, impEXSIDE, employs the IMPRESS technique [3,4] (improved resolution using symmetrically shifted pulses), which exploits Hadamard encoding in the F1 dimension. The other two pulse sequences apply the band selective homonuclear decoupling (bash) Pure Shift5 acquisition technique and are called EXSIDE_PS and bsEXSIDE_PS.…”

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

“…Riboflavinbased organocatalysis has been explored as a green and economic alternative to metal catalyzed reactions (10) in the photooxidation of alkyl benzenes, amino acids, phenols, saccharides, water, and other substrates (4,(11)(12)(13)(14)(15)(16)(17).…”

“…To circumvent H 2 O 2 as an intermediate, a number of strategies have been explored including the use of transition-metal disproportionation cocatalysts (15,29), surfactants (30), modification of the flavin (7), and others (11,31,32 …”