Which is the real oxidant in competitive ligand self-hydroxylation and substrate oxidation—a biomimetic iron(ii)-hydroperoxo species or an oxo-iron(iv)-hydroxy one?

Abstract

Nonheme iron(II)-hydroperoxo species (FeII-(η2-OOH)) 1 and the concomitant oxo-iron(IV)-hydroxyl one 2 are proposed as the key intermediates of a large class of 2-oxoglutarate dependent dioxygenases (e.g., isopenicillin N synthase). Extensive...

Dioxygen Reduction and Bioinspired Oxidations by Non-heme Iron(II)−α-Hydroxy Acid Complexes

“…Furthermore, theoretical calculations reveal that the substrate oxidation on a quintet spin state surface poses a lower energy barrier compared to intraligand hydroxylation, and the reaction environment contributes to the energy barrier. 45…”

“…The rate-determining proton transfer from the α-OH group of the α-hydroxy acid to the iron­(III)–superoxo species substantiates the role played by the α-hydroxy acid ligand in the generation of a quintet iron­(II)–OOH species (Scheme ). DFT calculations also predict a lower energy barrier on the quintet spin surface for the iron­(II)–hydroperoxo species . According to the calculations, conversion of the side on iron­(II)–hydroperoxo species ( Int I ) to the high-valent iron­(IV)–oxo-hydroxo intermediate ( Int II ) is an exothermic O–O bond heterolysis, whereas the involvement of any iron­(III)–hydroperoxo species is unfavorable, which is in line with the experimental findings.…”

“…Though no iron–oxygen oxidants could be trapped due to their extremely high reactivity, assigning the oxidant in the absence of any external additives was based on interception studies in the presence of external substrates and additives, labeling experiments, and overall electron count balance. This proposal has been supported by DFT calculations ( vide infra ) …”

“…Of note, iron(II)–OOH intermediates have been reported as intermediates in the non-heme iron enzymes isopenicillin N synthase (IPNS) and pterin-dependent hydroxylase . While synthetic iron(II)–OOH species have not been detected directly, indirect experimental evidence suggests their involvement in the generation of high-valent iron species on synthetic systems. ,, A recent theoretical study on the dioxygen reactivity of iron(II)–benzilate complex 2 provided detailed density functional theory (DFT) calculations on the mechanism, which further strengthens the proposed mechanism . The rate-determining proton transfer from the α-OH group of the α-hydroxy acid to the iron(III)–superoxo species substantiates the role played by the α-hydroxy acid ligand in the generation of a quintet iron(II)–OOH species (Scheme ).…”

“…Energy profile calculation for the dioxygen activation pathway on the iron(II)–benzilate complex further depicts a spin crossover from the quintet spin state surface to the triplet spin state via a putative σ-complex intermediate for intraligand hydroxylation in the absence of external substrates. Furthermore, theoretical calculations reveal that the substrate oxidation on a quintet spin state surface poses a lower energy barrier compared to intraligand hydroxylation, and the reaction environment contributes to the energy barrier …”