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Metal-carbenesare common reaction intermediates in chemical catalysis;however, very few catalysts are known with a trimetal-carbene activecenter. In this work, we describea computational study into the chemical and catalytic properties ofa unique trimetal carbene containing a Ru2Pt-carbene core,[(CpRu)2(μ2-CH2)(μ3-NCH3)Pt(P(CH3)3)2], with and without bound CO. The chemical structure and individualorbital interactions are identified from a natural bond orbital analysis,and the reaction pathways for consecutive intramolecular CH3and H transfer (or vice versa) are investigated. The studies showthat CO binding has dramatic effects on the reaction mechanism andweakens the Ru–H bond strength. The reaction processes arerationalized by valence bond models and thermochemical bond strengthstudies. The work leads to suggestions on how to improve this chemicalsystem for enhanced alkane synthesis. [ABSTRACT FROM AUTHOR]

Cytochrome P450 enzymes are heme-containing mono-oxygenases that mainly react through oxygen-atom transfer. Specific features of substrate and oxidant that determine the reaction rate constant for oxygen atom transfer are still poorly understood and therefore, we did a systematic gas-phase study on reactions by iron(IV)-oxo porphyrin cation radical structures with arenes. We present herein the first results obtained by using Fourier transform-ion cyclotron resonance mass spectrometry and provide rate constants and product distributions for the assayed reactions. Product distributions and kinetic isotope effect studies implicate a rate-determining aromatic hydroxylation reaction that correlates with the ionization energy of the substrate and no evidence of aliphatic hydroxylation products is observed. To further understand the details of the reaction mechanism, a computational study on a model complex was performed. These studies confirm the experimental hypothesis of dominant aromatic over aliphatic hydroxylation and show that the lack of an axial ligand affects the aliphatic pathways. Moreover, a two-parabola valence bond model is used to rationalize the rate constant and identify key properties of the oxidant and substrate that drive the reaction. In particular, the work shows that aromatic hydroxylation rates correlate with the ionization energy of the substrate as well as with the electron affinity of the oxidant., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Cytochrome P450 enzymes are highly versatile biological catalysts in our body that react with a broad range of substrates. Key functions in the liver include the metabolism of drugs and xenobiotics. One particular metabolic pathway that is poorly understood relates to the P450 activation of aliphatic groups leading to either hydroxylation or desaturation pathways. A DFT and QM/MM study has been carried out on the factors that determine the regioselectivity of aliphatic hydroxylation over desaturation of compounds by P450 isozymes. The calculations establish multistate reactivity patterns, whereby the product distributions differ on each of the spin-state surfaces; hence spin-selective product formation was found. The electronic and thermochemical factors that determine the bifurcation pathways were analysed and a model that predicts the regioselectivity of aliphatic hydroxylation over desaturation pathways was established from valence bond and molecular orbital theories. Thus, the difference in energy of the OH versus the OC bond formed and the π-conjugation energy determines the degree of desaturation products. In addition, environmental effects of the substrate binding pocket that affect the regioselectivities were identified. These studies imply that bioengineering P450 isozymes for desaturation reactions will have to include modifications in the substrate binding pocket to restrict the hydroxylation rebound reaction., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Iron(IV)-oxo intermediates are involved in oxidations catalyzed by heme and nonheme iron enzymes, including the cytochromes P450. At the distal site of the heme in P450 Compound I (Fe(IV) -oxo bound to porphyrin radical), the oxo group is involved in several hydrogen-bonding interactions with the protein, but their role in catalysis is currently unknown. In this work, we investigate the effects of hydrogen bonding on the reactivity of high-valent metal-oxo moiety in a nonheme iron biomimetic model complex with trigonal bipyramidal symmetry that has three hydrogen-bond donors directed toward a metal(IV)-oxo group. We show these interactions lower the oxidative power of the oxidant in reactions with dehydroanthracene and cyclohexadiene dramatically as they decrease the strength of the OH bond (BDEOH ) in the resulting metal(III)-hydroxo complex. Furthermore, the distal hydrogen-bonding effects cause stereochemical repulsions with the approaching substrate and force a sideways attack rather than a more favorable attack from the top. The calculations, therefore, give important new insights into distal hydrogen bonding, and show that in biomimetic, and, by extension, enzymatic systems, the hydrogen bond may be important for proton-relay mechanisms involved in the formation of the metal-oxo intermediates, but the enzyme pays the price for this by reduced hydrogen atom abstraction ability of the intermediate. Indeed, in nonheme iron enzymes, where no proton relay takes place, there generally is no donating hydrogen bond to the iron(IV)-oxo moiety., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

There is a major controversy in cytochrome P450 chemistry regarding the nature of the active oxidant responsible for substrate monoxygenation. Part of this controversy originates from the fact that the later stages in the catalytic cycle of P450 enzymes proceed so fast that little experimental evidence is available. Early studies suggested an iron(IV)- oxo heme cation radical ([heme((+•))-Fe(IV)=O] or Compound I) as the active species able to abstract a hydrogen atom from a substrate and rebind the hydroxyl group to form an alcohol product. Such simplistic early models involving a single active species have subsequently been invalidated by several experimental studies which clearly indicates that there must be at least two active species of some description. Based on these and other data, a two-oxidant hypothesis was put forward where Compound I and its precursor in the catalytic cycle ([heme-Fe(III)-OOH]- or Compound 0) are competitive oxidants. Density functional theory studies, however, suggest an alternative hypothesis involving a two-state-reactivity scenario where Compound I has two close-lying spin states that react differently with substrates and masquerade as two distinct oxidants. These theoretical studies show that the two spin states of Compound I react with substrates via aliphatic and aromatic C-H hydroxylation, C=C epoxidation and sulfoxidation reactions, and explain experimentally observed product distributions and kinetic isotope effects. This review will give an overview of recent studies on the two-oxidant versus two-state-reactivity hypotheses and how theory contributes to the understanding of enzymatic reaction processes.