Hydrogen atom abstraction

About: Hydrogen atom abstraction is a research topic. Over the lifetime, 7059 publications have been published within this topic receiving 151781 citations.

Electronic structure of compound I in human isoforms of cytochrome P450 from QM/MM modeling.

Abstract: Human cytochromes P450 play a vital role in drug metabolism. The key step in substrate oxidation involves hydrogen atom abstraction or C=C bond addition by the oxygen atom of the Compound I intermediate. The latter has three unpaired electrons, two on the Fe-O center and one shared between the porphyrin ring and the proximal cysteinyl sulfur atom. Changes in its electronic structure have been suggested to affect reactivity. The electronic and geometric structure of Compound I in three important human subfamilies of cytochrome P450 (P450, 2C, 2B, and 3A) that are major contributors to drug metabolism is characterized here using combined quantum mechanical/molecular mechanical (QM/MM) calculations at the B3LYP:CHARMM27 level. Compound I is remarkably similar in all isoforms, with the third unpaired electron located mainly on the porphyrin ring, and this prediction is not very sensitive to details of the QM/MM methodology, such as the DFT functional, the basis set, or the size of the QM region. The presence of substrate also has no effect. The main source of variability in spin density on the cysteinyl sulfur (from 26 to 50%) is the details of the system setup, such as the starting protein geometry used for QM/MM minimization. This conformational effect is larger than the differences between human isoforms, which are therefore not distinguishable on electronic grounds, so it is unlikely that observed large differences in substrate selectivity can be explained to a large extent in these terms.

Reaction of Ethylene with Hydroxyl Radicals: A Theoretical Study†

Abstract: Ab initio calculations of portions of the C2H5O potential energy surface critical to the title reaction are presented. These calculations are based on QCISD geometries and frequencies and RQCISD(T) energies extrapolated to the complete-basis-set limit. Rate coefficients for the reaction of C2H4 with OH are calculated using this surface and the two transition-state model of Greenwald and co-workers [J. Phys. Chem. A 2005, 109, 6031] for the association of OH with C2H4. The present calculations reproduce most of the experimental data, including the temperature and pressure dependence of the rate coefficients, with only a small (0.4 kcal/mol) adjustment to the energy barrier for direct hydrogen abstraction. We confirm the importance of this channel above 800 K and find that a significant fraction of the total rate coefficient (∼10%) is due to the formation of vinyl alcohol above this temperature. Calculations of the vinyl alcohol channel are consistent with the recent observation of this molecule in low-pres...

Gas-phase radical formation during the reactions of methane, ethane, ethylene, and propylene over selected oxide catalysts

Abstract: The formation of surface-generated gas-phase radicals during the reactions of methane, ethane, ethylene, and propylene over Bi/sub 2/O/sub 3/, ..gamma..-Bi/sub 2/O/sub 3/ x MoO/sub 3/, PbO, MgO, and Li/MgO was examined by EPR matrix isolation spectroscopy. Allyl radicals were detected during the reaction of propylene over all of the oxides examined. Gas-phase methyl and ethyl radicals were detected during the reactions of methane and ethane, respectively, over MgO and Li/MgO while Bi/sub 2/O/sub 3/, ..gamma..-Bi/sub 2/O/sub 3/ x MoO/sub 3/, and PbO were essentially inactive. Gas-phase vinyl radicals were not detected during the reaction of ethylene over any of the oxides. These differences in reactivity are attributed to differences in reactivity of the oxide ions on these surfaces towards hydrogen atom abstraction. 28 references, 1 figure.

C-H activation by a mononuclear manganese(III) hydroxide complex: synthesis and characterization of a manganese-lipoxygenase mimic?

Abstract: Lipoxygenases are mononuclear non-heme metalloenzymes that regio- and stereospecifically convert 1,4-pentadiene subunit-containing fatty acids into alkyl peroxides. The rate-determining step is generally accepted to be hydrogen atom abstraction from the pentadiene subunit of the substrate by an active metal(III)-hydroxide species to give a metal(II)-water species and an organic radical. All known plant and animal lipoxygenases contain iron as the active metal; recently, however, manganese was found to be the active metal in a fungal lipoxygenase. Reported here are the synthesis and characterization of a mononuclear Mn(III) complex, [MnIII(PY5)(OH)](CF3SO3)2 (PY5 = 2,6-bis(bis(2-pyridyl)methoxymethane)pyridine), that reacts with hydrocarbon substrates in a manner most consistent with hydrogen atom abstraction and provides chemical precedence for the proposed reaction mechanism. The neutral penta-pyridyl ligation of PY5 endows a strong Lewis acidic character to the metal center allowing the Mn(III) compound...

Absolute Asymmetric Synthesis from Achiral Molecules in the Chiral Crystalline Environment

Abstract: The current status of absolute asymmetric synthesis in a chiral crystalline environment has been reviewed. A number of topochemically controlled four-center type photocycloadditions are described for a series of unsymmetrically substituted diolefin crystals and CT crystals. This concept has been applied to intramolecular photoreactions, and several successful absolute asymmetric syntheses have been achieved, involving Norrish Type II reaction, di-π-methane rearrangement, electrocyclization, thietane formation, oxetane formation, hydrogen abstraction by thiocarbonyl and alkenyl groups, and radical-pair intermediates.