Molecular orbital study of the hydroxylation of benzene and monofluorobenzene catalysed by iron-oxo porphyrin π cation radical complexes

Zakharieva, O.; Grodzicki, Michael; Trautwein, Alfred X.; Veeger, C.; Rietjens, Ivonne M. C. M.

doi:10.1007/s007750050043

Cited by 29 publications

(27 citation statements)

References 3 publications

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“…All further products, phenol, ketone and epoxide, are generated by rearrangement of these r-complexes. This is supported by theoretical investigations [54][55][56] ruling out a concerted epoxidation as an initial step in aromatic hydroxylation. Recent DFT computations 56 showed that in contrast to aliphatic hydroxylation, benzene hydroxylation only occurs on the low-spin surface and proceeds predominantly through an electrophilic pathway via a cation-like r-complex intermediate.…”

Section: Benzene Hydroxylationmentioning

confidence: 54%

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Ridder²,

et al. 2004

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Cytochrome P450 enzymes play a central role in drug metabolism, and models of their mechanism could contribute significantly to pharmaceutical research and development of new drugs. The mechanism of cytochrome P450 mediated hydroxylation of aromatics and the effects of substituents on reactivity have been investigated using B3LYP density functional theory computations in a realistic porphyrin model system. Two different orientations of substrate approach for addition of Compound I to benzene, and also possible subsequent rearrangement pathways have been explored. The rate-limiting Compound I addition to an aromatic carbon atom proceeds on the doublet potential energy surface via a transition state with mixed radical and cationic character. Subsequent formation of epoxide, ketone and phenol products is shown to occur with low barriers, especially starting from a cation-like rather than a radical-like tetrahedral adduct of Compound I with benzene. Effects of ring substituents were explored by calculating the activation barriers for Compound I addition in the meta and para-position for a range of monosubstituted benzenes and for more complex polysubstituted benzenes. Two structure-reactivity relationships including 8 and 10 different substituted benzenes have been determined using (i) experimentally derived Hammett sigma-constants and (ii) a theoretical scale based on bond dissociation energies of hydroxyl adducts of the substrates, respectively. In both cases a dual-parameter approach that employs a combination of radical and cationic electronic descriptors gave good relationships with correlation coefficients R2 of 0.96 and 0.82, respectively. These relationships can be extended to predict the reactivity of other substituted aromatics, and thus can potentially be used in predictive drug metabolism models.

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Section: Benzene Hydroxylationmentioning

confidence: 54%

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Ridder²,

et al. 2004

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“…As discussed, the many theoretical studies reported so far have mainly focused on the reaction mechanism of P450. Although there have been some theoretical studies on the effect of axial ligands,24, 11, 49, 65–68 as far as we know, there have been no studies that directly compare the reactivity of Compound I by computing the entire potential energy surface of alkane hydroxylation. Recently, Ryde and coworkers have extensively studied, using the density functional theory, the effect of axial ligands on a model active‐site compound of several hemoproteins 49.…”

Section: Introductionmentioning

confidence: 99%

Effect of the axial cysteine ligand on the electronic structure and reactivity of high‐valent iron(IV) oxo‐porphyrins (Compound I): A theoretical study

Choe

Nagase

2005

J Comput Chem

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The effect of axial ligands on the reactivity of high-valent iron(IV) oxo-porphyrins (Compound I) was investigated using the B3LYP hybrid density functional method. We studied alkane hydroxylation using four models: Compound I with thiolate, imidazole, phenolate, and chloride anions as axial ligands. The first three ligands were employed as models for cysteinate, histidine, and tyrosinate, respectively. Our calculations show that anionic ligands and neutral ligands favor different electronic states for stationary points in the reaction coordinate, and the calculated energy barrier and energy of several reaction intermediates show similar values. A remarkable effect of axial ligands was found in the final product release step. Our calculations show that the thiolate ligand weakens a bond between heme and an alcohol. In contrast, the imidazole ligand significantly increases the interaction between heme and an alcohol, which causes the catalytic cycle to be less efficient.

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“…Other theoretical studies are the real position of the CO group in Fe(P)(Im)(CO) (Im = imidazole) complexes 14, 15, the position of the CN group in Fe(mdi) 2 (py)(CN) (mdi = malondialdiminate) complexes 16, the role of distal and proximal histidines (His) on the binding of O 2 in Hb 17–20, and structural aspects of the binding of O 2 and other ligands to heme 21–27. The amount of information obtained from the calculations is seriously limited by the size of the heme group itself, which has only recently allowed the appearance of theoretical studies on reactivity 28–33.…”

Section: Introductionmentioning

confidence: 99%

Nature of O₂, CO, and CN binding to hemoprotein models

Torrens

2004

Int J of Quantum Chemistry

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Parametrization of a molecular-mechanics program to include terms specific for five-and six-coordinate transition metal complexes results in computersimulated structures of hemo complexes. The principal new feature peculiar to five-and six-coordination is a term that measures the effect of electron-pair repulsion modified by the ligand electronegativity and takes into account the different structural possibilities. The work consists in the modification of program molecular mechanics for penta and hexacoordination. The model system takes into account the structural differences of the fixing center in the hemoglobin subunits. The customary proximal histidine is added. The macrocycle hemo IX is wholly considered in our model. The calculations show clearly that certain conformations are much more favorable that others for fixing O 2 . From the O 2 binding in hemoglobin and myoglobin and in simple Fe porphyrin models, it is concluded that the bent O 2 ligand is best viewed as bound superoxide, O 2 Ϫ .

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Molecular orbital study of the hydroxylation of benzene and monofluorobenzene catalysed by iron-oxo porphyrin π cation radical complexes

Cited by 29 publications

References 3 publications

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Effect of the axial cysteine ligand on the electronic structure and reactivity of high‐valent iron(IV) oxo‐porphyrins (Compound I): A theoretical study

Nature of O₂, CO, and CN binding to hemoprotein models

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Molecular orbital study of the hydroxylation of benzene and monofluorobenzene catalysed by iron-oxo porphyrin π cation radical complexes

Cited by 29 publications

References 3 publications

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Mechanism and structure–reactivity relationships for aromatic hydroxylation by cytochrome P450

Effect of the axial cysteine ligand on the electronic structure and reactivity of high‐valent iron(IV) oxo‐porphyrins (Compound I): A theoretical study

Nature of O2, CO, and CN binding to hemoprotein models

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Nature of O₂, CO, and CN binding to hemoprotein models