Enhanced Reactivity through Equatorial Sulfur Coordination in Nonheme Iron(IV)–Oxo Complexes: Insights from Experiment and Theory

Satpathy, Jagnyesh K.; Yadav, Rolly; Bagha, Umesh K.; Kumar, Devesh; Sastri, Chivukula V.; de Visser, Sam P.

doi:10.1021/acs.inorgchem.4c00070

Cited by 2 publications

(1 citation statement)

References 138 publications

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“…Therefore, we employed the well-accepted B3LYP functional featuring a “balanced” HF exchange–correlation for the investigation of electronic structure and reactivity. We want to emphasize that DFT-B3LYP has been the method of choice for oxo–iron complexes, as it is known to produce reliable results for spin-state energetics, spectroscopic parameters, , and reactivity. ,, …”

Section: Resultsmentioning

confidence: 99%

Unraveling the Geometry-Driven C═C Epoxidation and C–H Hydroxylation Reactivity of Tetra-Coordinated Nonheme Iron(IV)–Oxo Complexes

Bhardwaj,

Mondal

2024

Inorg. Chem.

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The electronic structure and reactivity of tetracoordinated nonheme iron(IV)−oxo complexes have remained unexplored for years. The recent synthesis of a closed-shell iron(IV)−oxo complex [(quinisox)Fe IV (O)] + (1) has set up a platform to understand how such complexes compare with the celebrated open-shell iron−oxo chemistry. Herein, using density functional theory and ab initio calculations, we present an in-depth electronic structure investigation of the C�C epoxidation [oxygen atom transfer (OAT)] and C−H hydroxylation [hydrogen atom transfer (HAT)] reactivity of 1. Using a solvent-coordinated geometry of 1 (1′) and other potential tetra-coordinated iron-(IV)−oxo complexes bearing rigid ligands (2 and 3), we established the geometric origin of spin-state energetics and reactivity of 1. Complex 1 featuring a strong Fe−O bond exhibits OAT and HAT reactivity in its quintet state. The lowest quintet OAT pathway has a lower barrier by ∼4 kcal/mol than the quintet HAT pathway, corroborating the experimentally observed gas-phase OAT reactivity preference. A conventional HAT reactivity preference for 2 and a comparable OAT and HAT reactivity for 3 are observed. This further supports the geometry-driven reactivity preference for 1. Noncovalent interaction analyses reveal a pronounced π−π interaction between the substrate and ligand in the OAT transition state, rationalizing the origin of the observed reactivity preference for 1.

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Section: Resultsmentioning

confidence: 99%

Unraveling the Geometry-Driven C═C Epoxidation and C–H Hydroxylation Reactivity of Tetra-Coordinated Nonheme Iron(IV)–Oxo Complexes

Bhardwaj,

Mondal

2024

Inorg. Chem.

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

Qureshi,

Mokkawes,

Cao

et al. 2024

IJMS

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

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Enhanced Reactivity through Equatorial Sulfur Coordination in Nonheme Iron(IV)–Oxo Complexes: Insights from Experiment and Theory

Cited by 2 publications

References 138 publications

Unraveling the Geometry-Driven C═C Epoxidation and C–H Hydroxylation Reactivity of Tetra-Coordinated Nonheme Iron(IV)–Oxo Complexes

Unraveling the Geometry-Driven C═C Epoxidation and C–H Hydroxylation Reactivity of Tetra-Coordinated Nonheme Iron(IV)–Oxo Complexes

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

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