Mechanism of Oxidative Activation of Fluorinated Aromatic Compounds by N‐Bridged Diiron‐Phthalocyanine: What Determines the Reactivity?

Colomban, Cédric; Tobing, Anthonio H.; Mukherjee, Gourab; Sastri, Chivukula V.; Sorokin, Alexander B.; Visser, Sam P. de

doi:10.1002/chem.201902934

Cited by 44 publications

(45 citation statements)

References 71 publications

(46 reference statements)

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“…These structures and spin density distributions are similar to those found for the reaction of biomimetic iron(IV)-oxo species with halides that were found to proceed with a similar reaction mechanism and rates. [27] As seen in nonheme iron halogenase calculations, halide transfer is easier when the halide group is neutral rather than anionic. [28] It may very well be that haloperoxidases operate by a similar mechanism, whereby the halide loses electron density prior to a covalent bond formation step.…”

Section: Resultsmentioning

confidence: 99%

Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

Mubarak

Visser

2019

Israel Journal of Chemistry

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Heme haloperoxidases are unique enzymes in biology that react H 2 O 2 and halides on a heme center to generate hypohalide, which reacts with a substrate by halide transfer. We studied model complexes of the active site of heme haloperoxidase and investigated the reaction mechanism starting from an iron(III)-hydrogen peroxide-heme complex. We find two stepwise proton transfers by active site Glu and His residues to form Compound I and water, whereby the second proton transfer step is rate-determining. In a subsequent reaction with chloride the oxygen atom transfer is studied to form hypohalide. Overall, the free energy of activation of the second proton transfer and oxygen atom transfer to halide are similar in energy with free energies of activation of around 20 kcal mol À 1. The calculations show that during oxygen atom transfer from Compound I to halide, significant charge-transfer happens prior to the transition state. This implies that the reaction may be enhanced in polar environments and through secondcoordination sphere effects. The studies show that the conversion of H 2 O 2 and halide on a heme center is fast and few intermediates along the reaction mechanism will have a lifetime that is long enough to enable trapping and characterization with experimental methods. A range of active site models and density functional theory methods were tested, but little effect is seen on the mechanism and optimized geometries.

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Section: Resultsmentioning

confidence: 99%

Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

Mubarak

Visser

2019

Israel Journal of Chemistry

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“…To get deeper insight into this unusual reactivity, detailed DFT analysis of the mechanism of defluorination of hexafluorobenzene by µ-nitrido diiron oxo species were carried out [82].…”

Section: % Defluorination 54 % Organic Carbon Lossmentioning

confidence: 99%

From mononuclear iron phthalocyanines in catalysis to μ-nitrido diiron complexes and beyond

Sorokin

2021

Catalysis Today

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“…All calculations were done for the doublet and quartet spin states. These methods have previously been applied for the studies of enzymatic reaction mechanisms and shown to reproduce experimental rate constants, regioselectivities and kinetic isotope effects well [96][97][98][99][100][101].…”

Section: Qm/mm Calculationsmentioning

confidence: 99%

Bioengineering of Cytochrome P450 OleTJE: How Does Substrate Positioning Affect the Product Distributions?

et al. 2020

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The cytochromes P450 are versatile enzymes found in all forms of life. Most P450s use dioxygen on a heme center to activate substrates, but one class of P450s utilizes hydrogen peroxide instead. Within the class of P450 peroxygenases, the P450 OleTJE isozyme binds fatty acid substrates and converts them into a range of products through the α-hydroxylation, β-hydroxylation and decarboxylation of the substrate. The latter produces hydrocarbon products and hence can be used as biofuels. The origin of these product distributions is unclear, and, as such, we decided to investigate substrate positioning in the active site and find out what the effect is on the chemoselectivity of the reaction. In this work we present a detailed computational study on the wild-type and engineered structures of P450 OleTJE using a combination of density functional theory and quantum mechanics/molecular mechanics methods. We initially explore the wild-type structure with a variety of methods and models and show that various substrate activation transition states are close in energy and hence small perturbations as through the protein may affect product distributions. We then engineered the protein by generating an in silico model of the double mutant Asn242Arg/Arg245Asn that moves the position of an active site Arg residue in the substrate-binding pocket that is known to form a salt-bridge with the substrate. The substrate activation by the iron(IV)-oxo heme cation radical species (Compound I) was again studied using quantum mechanics/molecular mechanics (QM/MM) methods. Dramatic differences in reactivity patterns, barrier heights and structure are seen, which shows the importance of correct substrate positioning in the protein and the effect of the second-coordination sphere on the selectivity and activity of enzymes.

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Mechanism of Oxidative Activation of Fluorinated Aromatic Compounds by N‐Bridged Diiron‐Phthalocyanine: What Determines the Reactivity?

Cited by 44 publications

References 71 publications

Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

Computational Study on the Catalytic Reaction Mechanism of Heme Haloperoxidase Enzymes

From mononuclear iron phthalocyanines in catalysis to μ-nitrido diiron complexes and beyond

Bioengineering of Cytochrome P450 OleTJE: How Does Substrate Positioning Affect the Product Distributions?

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