On the identity and reactivity patterns of the “second oxidant” of the T252A mutant of cytochrome P450cam in the oxidation of 5-methylenenylcamphor

Hirao, Hajime; Kumar, Devesh; Shaik, Sason

doi:10.1016/j.jinorgbio.2006.09.001

Cited by 26 publications

(35 citation statements)

References 62 publications

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“…48 We can tentatively deduce that were Cpd 0 the reactive species in the T252A mutant of CYP101, one would have expected to find alongside the epoxide of 2 also some of the corresponding 1,2-diol. This latter step involves significant electronic reorganization (C-H bond breaking, Fe=O bond breaking, C-O bond formation, and electron shift from the organic moiety to convert the Fe(IV) to Fe(III)), and therefore the corresponding barrier is large, ca.…”

Section: A Computational Assessment Of the Reactivity Of Cpd 0 Via Inmentioning

confidence: 88%

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Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

2007

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Covering: up to 2006 but not exhaustively This focused review discusses mechanisms of oxygenation of organic compounds by cytochrome P450, based on density functional theory (DFT) and hybrid DFT and molecular mechanics (DFT/MM). The reactivity of the active species, Compound I, generally involves two-state reactivity (TSR) and sometimes multi-state reactivity (MSR). The reactivity of the ferric-hydroperoxide species (Compound 0) is reviewed too. According to DFT calculations, Compound 0 must be silent in the presence of Compound I. Much of the experimental mechanistic data is shown to be accounted for by the TSR/MSR concept. 1 Introduction 2 The catalytic cycle of the enzyme 3 Unresolved issues in the chemistry of P450 enzymes 3.1 How many reactive oxidant species does the P450 have? 3.2 Unresolved issues in the mechanism of hydroxylation and epoxidation 4 Properties of Cpd I of P450 4.1 Electronic structure and geometries of low-lying states of Cpd I 4.2 Origins of two-and multi-state reactivity 5 Reactivity of Cpd I towards alkanes and olefins 5.1 The mechanism of C-H hydroxylation 5.2 The mechanism of double bond epoxidation 5.3 The mechanism of desaturation 6 Gauging the reactivity of Cpd 0 6.1 A computational assessment of the electrophilic reactivity of Cpd 0 6.2 A computational assessment of the reactivity of Cpd 0 via initial O-O homolysis 6.3 An assessment of the reactivity of the two oxidant of P450 7 Conclusions 8 Acknowledgements 9 References

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Section: A Computational Assessment Of the Reactivity Of Cpd 0 Via Inmentioning

confidence: 88%

“…1). 48 A process of reasoning that is often used in mechanistic research is based on the comparison of reactivities in model bimolecular reactions to those of P450. 31 Apparently, the two experiments are at odds with each other, and one may wonder if the photo-oxidative experiment indeed gave rise to Cpd I.…”

Section: Sason Shaik Hajime Hirao Devesh Kumarmentioning

confidence: 99%

Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

2007

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“…The electronic structure of Cpd I and the electron reorganization patterns of the substrate oxidation reactions of Cpd I have been discussed for several different spin states (Ogliaro et al, 2000a,b; Yoshizawa et al, 2001; de Visser et al, 2002; Himo and Siegbahn, 2003; Kamachi and Yoshizawa, 2003; Meunier et al, 2004; Hackett et al, 2005, 2007; Hirao et al, 2005; Shaik et al, 2005, 2007a,b, 2010a; Isobe et al, 2008, 2011, 2012; Shoji et al, 2008; Yamaguchi et al, 2009; Li et al, 2012; Rydberg et al, 2014). Computational studies to assess the reactivity of Cpd 0 have also been conducted (Ogliaro et al, 2002; Kamachi et al, 2003; Bach and Dmitrenko, 2006; Derat et al, 2006; Hirao et al, 2006b; Li et al, 2007). Overall, DFT calculations predicted that Cpd 0 is less reactive than Cpd I.…”

Section: Applications Of Dftmentioning

confidence: 99%

Applications of density functional theory to iron-containing molecules of bioinorganic interest

2014

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The past decades have seen an explosive growth in the application of density functional theory (DFT) methods to molecular systems that are of interest in a variety of scientific fields. Owing to its balanced accuracy and efficiency, DFT plays particularly useful roles in the theoretical investigation of large molecules. Even for biological molecules such as proteins, DFT finds application in the form of, e.g., hybrid quantum mechanics and molecular mechanics (QM/MM), in which DFT may be used as a QM method to describe a higher prioritized region in the system, while a MM force field may be used to describe remaining atoms. Iron-containing molecules are particularly important targets of DFT calculations. From the viewpoint of chemistry, this is mainly because iron is abundant on earth, iron plays powerful (and often enigmatic) roles in enzyme catalysis, and iron thus has the great potential for biomimetic catalysis of chemically difficult transformations. In this paper, we present a brief overview of several recent applications of DFT to iron-containing non-heme synthetic complexes, heme-type cytochrome P450 enzymes, and non-heme iron enzymes, all of which are of particular interest in the field of bioinorganic chemistry. Emphasis will be placed on our own work.

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“…Transition-state (TS) geometries at the B3 LYP/B1 level were initially optimized with Jaguar, and then located with Gaussian 03. We use this practice [36] since Gaussian has a more efficient frequency calculation module and gives more reliable energy values for TSs in some cases. The B3 LYP/B1 geometry optimization was followed by frequency calculations by Gaussian 03 at the same level to characterize local minima and TSs.…”

Section: Computational Detailsmentioning

confidence: 99%

A Two‐State Reactivity Rationale for Counterintuitive Axial Ligand Effects on the CH Activation Reactivity of Nonheme Fe^IVO Oxidants

Hirao

Que

Nam

et al. 2008

Chemistry A European J

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This paper addresses the observation of counterintuitive reactivity patterns of iron-oxo reagents, TMC(L)FeO(2+,1+); L=CH(3)CN, CF(3)CO(2) (-), N(3) (-), and SR(-), in O-transfer to phosphines versus H-abstraction from, for example, 1,4-cyclohexadiene. Experiments show that O-transfer reactivity correlates with the electrophilicity of the oxidant, but H-abstraction reactivity follows an opposite trend. DFT/B3 LYP calculations reveal that two-state reactivity (TSR) serves as a compelling rationale for these trends, whereby all reactions involve two adjacent spin-states of the iron(IV)-oxo species, triplet and quintet. The ground state triplet surface has high barriers, whereas the excited state quintet surface features lower ones. The barriers, on any single surface, are found to increase as the electrophilicity of TMC(L)FeO(2+,1+) decreases. Thus, the counterintuitive behavior of the H-abstraction reactions cannot be explained by considering the reactivity of only a single spin state but can be rationalized by a TSR model in which the reactions proceed on the two surfaces. Two TSR models are outlined: one is traditional involving a variable transmission coefficient for crossover from triplet to quintet, followed by quintet-state reactions; the other considers the net barrier as a blend of the triplet and quintet barriers. The blending coefficient (x), which estimates the triplet participation, increases as the quintet-triplet energy gap of the TMC(L)FeO(2+,1+) reagent increases, in the following order of L: CH(3)CN > CF(3)CO(2) (-) > N(3) (-) > SR(-). The calculated barriers predict the dichotomic experimental trends and the counterintuitive behavior of the H-abstraction series. The TSR approaches make a variety of testable predictions.

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On the identity and reactivity patterns of the “second oxidant” of the T252A mutant of cytochrome P450cam in the oxidation of 5-methylenenylcamphor

Cited by 26 publications

References 62 publications

Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

Applications of density functional theory to iron-containing molecules of bioinorganic interest

A Two‐State Reactivity Rationale for Counterintuitive Axial Ligand Effects on the CH Activation Reactivity of Nonheme Fe^IVO Oxidants

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On the identity and reactivity patterns of the “second oxidant” of the T252A mutant of cytochrome P450cam in the oxidation of 5-methylenenylcamphor

Cited by 26 publications

References 62 publications

Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

Reactivity patterns of cytochrome P450 enzymes: multifunctionality of the active species, and the two states–two oxidants conundrum

Applications of density functional theory to iron-containing molecules of bioinorganic interest

A Two‐State Reactivity Rationale for Counterintuitive Axial Ligand Effects on the CH Activation Reactivity of Nonheme FeIVO Oxidants

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A Two‐State Reactivity Rationale for Counterintuitive Axial Ligand Effects on the CH Activation Reactivity of Nonheme Fe^IVO Oxidants