CO₂ Reduction by an Iron(I) Porphyrinate System: Effect of Hydrogen Bonding on the Second Coordination Sphere

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(10), P. 4474 - 4481

Published: Feb. 26, 2024

Transforming CO2 into valuable materials is an important reaction in catalysis, especially because concentrations the atmosphere have been growing steadily due to extensive fossil fuel usage. From environmental perspective, reduction of should be catalyzed by environmentally benign catalyst and avoid use heavy transition-metal ions. In this work, we present a computational study novel iron(I) porphyrin for reduction, namely, with tetraphenylporphyrin ligand analogues. particular, investigated one meso-phenyl groups substituted o-urea, p-urea, or o-2-amide groups. These substituents can provide hydrogen-bonding interactions second coordination sphere bound ligands assist proton relay. Furthermore, our studies bicarbonate phenol as stabilizers donors mechanism. Potential energy landscapes double protonation porphyrinate are reported. The work shows that bridges urea/amide iron center provides tight bonding pattern strong facilitates easy delivery CO2. Specifically, low-energy shuttle mechanism form CO water efficiently. o-urea group locks orientation helps ideal transfer, while there more mobility lesser stability o-amide position instead. Our calculations show leads proton-transfer barriers, line experimental observation. We then applied electric-field-effect estimate effects on two steps reaction. describe perturbations enhance driving forces used make predictions about how catalysts further engineered enhanced processes.

Language: Английский

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Quantum Mechanical Cluster Models for Calculations on Enzymatic Reaction Mechanisms: Set‐Up and Accuracy

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(60)

Published: Aug. 7, 2024

Enzymes turnover substrates into products with amazing efficiency and selectivity as such have great potential for use in biotechnology pharmaceutical applications. However, details of their catalytic cycles the origins surrounding regio- chemoselectivity enzymatic reaction processes remain unknown, which makes engineering enzymes challenging. Computational modelling can assist experimental work field establish factors that influence rates product distributions. A popular approach is quantum mechanical cluster models take first- second coordination sphere enzyme active site consideration. These QM are widely applied but often results obtained dependent on model choice selection. Herein, we show give highly accurate reproduce distributions free energies activation within several kcal mol

Language: Английский

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Machine learning-aided engineering of a cytochrome P450 for optimal bioconversion of lignin fragments

Physical Chemistry Chemical Physics, Journal Year: 2024, Volume and Issue: 26(25), P. 17577 - 17587

Published: Jan. 1, 2024

Using molecular dynamics, machine learning, and density functional theory calculations we make predictions on engineered cytochrome P450 structures their product distributions.

Language: Английский

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Insights into Cytochrome P450 Enzyme Catalyzed Defluorination of Aromatic Fluorides

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(42)

Published: Aug. 29, 2023

Density functional calculations establish a novel mechanism of aromatic defluorination by P450 Compound I. This is achieved via either an initial epoxide intermediate or through 1,2-fluorine shift in electrophilic intermediate, which highlights that the P450s can defluorinate fluoroarenes. However, absence proton donor strong Fe-F bond be obtained as shown from calculations.

Language: Английский

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Defluorination of Fluorophenols by a Nonheme Iron(IV)‐Oxo Species: Observation of a New Intermediate Along the Reaction

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(39)

Published: April 17, 2023

High-valent iron(IV)-oxo intermediates are versatile oxidants in the biotransformation of various substrates by metalloenzymes and catalyze essential reactions for human health as well biodegradation toxic organic pollutants environment. Herein, we report a biomimetic system that efficiently reacts with halophenols through defluorination characterize short-lived along reaction mechanism. We study reactivity pattern nonheme species series trihalophenols (X=F, Cl, Br). A combined experimental computational reveals oxidative dehalogenation 2,4,6-trifluorophenol is initiated an H-atom abstraction from phenolic group resulting formation phenolate radical iron(III)-hydroxo species. This forms adduct oxidized substrate λmax at 558 nm which subsequently decays to give quinones products.

Language: Английский

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Computational Modeling of the Enzymatic Achmatowicz Rearrangement by Heme-Dependent Chloroperoxidase: Reaction Mechanism, Enantiopreference, Regioselectivity, and Substrate Specificity

Journal of Chemical Information and Modeling, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

The chloroperoxidase from Caldariomyces fumago (CfCPO) catalyzes the oxidative ring expansion of α-heterofunctionalized furans via Achmatowicz rearrangement, providing an elegant tool to convert furan rings into complex-prefunctionalized scaffolds. However, mechanism this transformation remains unclear. Herein, CfCPO-catalyzed reaction rac-1-(2-furyl)ethanol (1a) is studied by quantum chemical calculations and molecular dynamics simulations. reveal that conversion follows general reaction. Notably, binding 1a enzyme's active site influences Compound I (Cpd I) formation, (R)-1a enantiomer results in a lower barrier compared (S)-1a, explaining observed (R)-enantiopreference toward racemic substrate. Additionally, due weaker steric hindrance between porphyrin substrate, nucleophilic attack Cpd on core preferred at less-substituted C4=C5 bond, rationale for experimentally regioselectivity. Finally, bottleneck residues substrate delivery channel also surroundings are proposed be responsible specificity CfCPO. This study lays theoretical foundation rational design new CPOs catalyze rearrangement with broader spectrum or specific stereopreference.

Language: Английский

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Environmental contamination by bisphenols: from plastic production to modulation of the intestinal morphophysiology in experimental models

Food and Chemical Toxicology, Journal Year: 2025, Volume and Issue: unknown, P. 115280 - 115280

Published: Feb. 1, 2025

Language: Английский

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Defluorination of Fluorophenols by a Heme Dehaloperoxidase: Insights into the Defluorination Mechanism

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 3898 - 3912

Published: Feb. 19, 2025

Language: Английский

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Melatonin Activation by Cytochrome P450 Isozymes: How Does CYP1A2 Compare to CYP1A1?

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3651 - 3651

Published: Feb. 11, 2023

Cytochrome P450 enzymes are versatile found in most biosystems that catalyze mono-oxygenation reactions as a means of biosynthesis and biodegradation steps. In the liver, they metabolize xenobiotics, but there range isozymes with differences three-dimensional structure protein chain. Consequently, various react substrates differently give varying product distributions. To understand how melatonin is activated by P450s we did thorough molecular dynamics quantum mechanics study on cytochrome 1A2 activation forming 6-hydroxymelatonin N-acetylserotonin products through aromatic hydroxylation O-demethylation pathways, respectively. We started from crystal coordinates docked substrate into model, obtained ten strong binding conformations active site. Subsequently, for each orientations, long (up to 1 μs) simulations were run. then analyzed orientations respect heme all snapshots. Interestingly, shortest distance does not correspond group expected be activated. However, positioning gives insight residues it interacts with. Thereafter, chemical cluster models created pathways calculated density functional theory. These relative barrier heights confirm experimental distributions highlight why certain obtained. make detailed comparison previous results CYP1A1 identify their reactivity melatonin.

Language: Английский

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Mechanism of the Oxidative Ring-Closure Reaction during Gliotoxin Biosynthesis by Cytochrome P450 GliF

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8567 - 8567

Published: Aug. 6, 2024

During gliotoxin biosynthesis in fungi, the cytochrome P450 GliF enzyme catalyzes an unusual C-N ring-closure step while also aromatic ring is hydroxylated same reaction cycle, which may have relevance to drug synthesis reactions biotechnology. However, as details of mechanism are still controversial, no applications been developed yet. To resolve and gain insight into steps leading ring-closure, we ran a combination molecular dynamics density functional theory calculations on structure reactivity tested range possible mechanisms, pathways models. The show that, rather than hydrogen atom transfer from substrate Compound I, initial proton transition state followed by fast electron en route radical intermediate, hence non-synchronous abstraction takes place. intermediate then reacts OH rebound form biradical through between centers, gives products. Interestingly, energetics mechanisms appear little affected addition polar groups model predict that can be catalyzed other isozymes bind substrate. Alternative pathways, such pathway starting with electrophilic attack arene epoxide, high energy ruled out.

Language: Английский

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