Theoretical modeling of hydroxyl-radical-induced lipid peroxidation reactions

The OH-radical-induced mechanism of lipid peroxidation, involving hydrogen abstraction followed by O2 addition, is explored using the kinetically corrected hybrid density functional MPWB1K in conjunction with the MG3S basis set and a polarized continuum model to mimic the membrane interior. Using a small nonadiene model of linoleic acid, it is found that hydrogen abstraction preferentially occurs at the mono-allylic methylene groups at the ends of the conjugated segment rather than at the central bis-allylic carbon, in disagreement with experimental data. Using a full linoleic acid, however, abstraction is correctly predicted to occur at the central carbon, giving a pentadienyl radical. The Gibbs free energy for abstraction at the central C11 is approximately 8 kcal/mol, compared to 9 kcal/mol at the end points (giving an allyl radical). Subsequent oxygen addition will occur at one of the terminal atoms of the pentadienyl radical fragment, giving a localized peroxy radical and a conjugated butadiene fragment, but is associated with rather high free energy barriers and low exergonicity at the CPCM-MPWB1K/MG3S level. The ZPE-corrected potential energy surfaces obtained without solvent effects, on the other hand, display considerably lower barriers and more exergonic reactions.     

The "somersault" mechanism for the p-450 hydroxylation of hydrocarbons. The intervention of transient inverted metastable hydroperoxides

A series of model theoretical calculations are described that suggest a new mechanism for the oxidation step in enzymatic cytochrome P450 hydroxylation of saturated hydrocarbons. A new class of metastable metal hydroperoxides is described that involves the rearrangement of the ground-state metal hydroperoxide to its inverted isomeric form with a hydroxyl radical hydrogen bonded to the metal oxide (MO-OH --> MO....HO). The activation energy for this somersault motion of the FeO-OH group is 20.3 kcal/mol for the P450 model porphyrin iron(III) hydroperoxide [Por(SH)Fe(III)-OOH(-)] to produce the isomeric ferryl oxygen hydrogen bonded to an *OH radical [Por(SH)Fe(III)-O....HO(-)]. This isomeric metastable hydroperoxide, the proposed primary oxidant in the P450 hydroxylation reaction, is calculated to be 17.8 kcal/mol higher in energy than the ground-state iron(III) hydroperoxide Cpd 0. The first step of the proposed mechanism for isobutane oxidation is abstraction of a hydrogen atom from the C-H bond of isobutane by the hydrogen-bonded hydroxyl radical to produce a water molecule strongly hydrogen bonded to anionic Cpd II. The hydroxylation step involves a concerted but nonsynchronous transfer of a hydrogen atom from this newly formed, bound, water molecule to the ferryl oxygen with a concomitant rebound of the incipient *OH radical to the carbon radical of isobutane to produce the C-O bond of the final product, tert-butyl alcohol. The TS for the oxygen rebound step is 2 kcal/mol lower in energy than the hydrogen abstraction TS (DeltaE() = 19.5 kcal/mol). The overall proposed new mechanism is consistent with a lot of the ancillary experimental data for this enzymatic hydroxylation reaction.     

In vitro and in silico interaction of faba bean (Vicia faba L.) seed extract with xanthine oxidase and evaluation of antioxidant activity as a therapeutic potential

Acetone extract of faba bean (Vicia faba L.) was found to be highest total phenol and flavonoid content among all extracts. Antioxidant activity for inhibition percentage (free radical scavenging activity) had 86.47% for acetone extract, and 97.36% for ascorbic acid respectively. IC₅₀ value of ascorbic acid and acetone extact were found to be 9 μg/mL ± 0.20 and 30 μg/mL ± 0.21. Faba bean seeds had catechin, epicatechin, gallic acid and ellagic acid which on molecular docking study revealed that it binds effectively with xanthine oxidase by binding energy of –7.78, –6.11, –6.39, –5.78 kcal/mol respectively compared to allopurinol drug having binding energy of –4.94 kcal/mol. Gallic acid, ellagic acid, catechin, epicatechin (polyphenols) and allopurinol bind other than catalytic residues (Glu-1261) of xanthine oxidase. In vitro and in silico analysis recommended that mode of enzyme inhibition was mixed type.     

Wellenmechanische untersuchungen am 2-buten unter berücksichtigung aller elektronen

2-butene has been investigated for different nuclear positions taking all 32 electrons into account, using the SCF –MO –LC (LCGO ) method. The calculations show that the energy of the trans-form is 1.1 kcal/mol lower than that of the cis-form. The potential curve between these two forms is shown graphically. The ionization energy was estimated to be 9.0 eV.     

Oxidative Dehydrogenation of Propane over a VO2‐Exchanged MCM‐22 Zeolite: A DFT Study

The adsorption and the mechanism of the oxidative dehydrogenation (ODH) of propane over VO₂‐exchanged MCM‐22 are investigated by DFT calculations using the M06‐L functional, which takes into account dispersion contributions to the energy. The adsorption energies of propane are in good agreement with those from computationally much more demanding MP2 calculations and with experimental results. In contrast, B3LYP binding energies are too small. The reaction begins with the movement of a methylene hydrogen atom to the oxygen atom of the VO₂ group, which leads to an isopropyl radical bound to a HO? V? O intermediate. This step is rate determining with the apparent activation energy of 30.9 kcal mol^?1, a value within the range of experimental results for ODH over other silica supports. In the propene formation step, the hydroxyl group is the more reactive group requiring an apparent activation energy of 27.7 kcal mol^?1 compared to that of the oxy group of 40.8 kcal mol^?1. To take the effect of the extended framework into account, single‐point calculations on 120T structures at the same level of theory are performed. The apparent activation energy is reduced to 28.5 kcal mol^?1 by a stabilizing effect caused by the framework. Reoxidation of the catalyst is found to be important for the product release at the end of the reaction.     

The reaction of triplet flavin with indole. A study of the cascade of reactive intermediates using density functional theory and time resolved infrared spectroscopy

As a model for riboflavin, lumiflavin was investigated using density functional theory methods (B3LYP/6-31G* and B3LYP/6-31+G**) with regard to the proposed cascade of intermediates formed after excitation to the triplet state, followed by electron-transfer, proton-transfer, and radical[bond]radical coupling reactions. The excited triplet state of the flavin is predicted to be 42 kcal/mol higher in energy than the singlet ground state, and the pi radical anion lies 45.1 kcal/mol lower in energy than the ground-state flavin and a free electron in the gas phase. The former value compares to a solution-phase triplet energy of 49.8 kcal/mol of riboflavin. For the radical anion, the thermodynamically favored position to accept a proton on the flavin ring system is at N(5). A natural population analysis also provided spin density information for the radicals and insight into the origin of the relative stabilities of the six different calculated hydroflavin radicals. The resulting 5H-LF* radical can then undergo radical[bond]radical coupling reactions, with the most thermodynamically stable adduct being formed at C(4'). Vibrational spectra were also calculated for the transient species. Experimental time-resolved infrared spectroscopic data obtained using riboflavin tetraacetate are in excellent agreement with the calculated spectra for the triplet flavin, the radical anion, and the most stable hydroflavin radical.     

Periodic density functional theory study of methane activation over La(2)O(3): activity of O(2-), O(-), O(2)(2-), oxygen point defect,and Sr(2+)-doped surface sites

Results of gradient-corrected periodic density functional theory calculations are reported for hydrogen abstraction from methane at O(s)(2-), O(s)(-), O(2)(s)(2-) point defect, and Sr(2+)-doped surface sites on La(2)O(3)(001). The results show that the anionic O(s)(-) species is the most active surface oxygen site. The overall reaction energy to activate methane at an O(s)(-) site to form a surface hydroxyl group and gas-phase (*)CH(3) radical is 8.2 kcal/mol, with an activation barrier of 10.1 kcal/mol. The binding energy of hydrogen at an site O(s)(-) is -102 kcal/mol. An oxygen site with similar activity can be generated by doping strontium into the oxide by a direct Sr(2+)/La(3+) exchange at the surface. The O(-)-like nature of the surface site is reflected in a calculated hydrogen binding energy of -109.7 kcal/mol. Calculations indicate that surface peroxide (O(2(s))(2-)) sites can be generated by adsorption of O(2) at surface oxygen vacancies, as well as by dissociative adsorption of O(2) across the closed-shell oxide surface of La(2)O(3)(001). The overall reaction energy and apparent activation barrier for the latter pathway are calculated to be only 12.1 and 33.0 kcal/mol, respectively. Irrespective of the route to peroxide formation, the O(2)(s)(2-) intermediate is characterized by a bent orientation with respect to the surface and an O-O bond length of 1.47 A; both attributes are consistent with structural features characteristic of classical peroxides. We found surface peroxide sites to be slightly less favorable for H-abstraction from methane than the O(s)(-) species, with DeltaE(rxn)(CH(4)) = 39.3 kcal/mol, E(act) = 47.3 kcal/mol, and DeltaE(ads)(H) = -71.5 kcal/mol. A possible mechanism for oxidative coupling of methane over La(2)O(3)(001) involving surface peroxides as the active oxygen source is suggested.     

Density functional theory study of the oxidative dehydrogenation of propane on the (001) surface of V2O5

The density functional theory using a plane‐waves basis set and pseudopotential has been used to study the reaction pathways for ODH of propane on the V₂O₅(001) surface. The calculations indicated that propane adsoprtion step was initiated by the insertion of vanadyl oxygen O (1) into methylene C? H bond forming an iso‐propanol structure. This step is the rate‐determining step with an activation energy of 23.3 kcal/mol. The subsequent step involved the abstraction of the second hydrogen by O (1) site leading the formation of propene. This process had an activation energy of 22.5 kcal/mol. The elimination of surface bound water molecule at the O (1) was a barrierless process. The energy required for this process was compensated from O2 dissociative adsorption. Finally, the electronic density of state has been applied to prove the reality of the calculated results. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Quaternary ammonium room-temperature ionic liquid including an oxygen atom in side chain/lithium salt binary electrolytes: ab initio molecular orbital calculations of interactions between ions

Interactions of the lithium bis(trifluoromethylsulfonyl)amide (LiTFSA) complex with N, N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium (DEME), 1-ethyl-3-methylimidazolium (EMIM) cations, neutral diethylether (DEE), and the DEMETFSA complex were studied by ab initio molecular orbital calculations. An interaction energy potential calculated for the DEME cation with the LiTFSA complex has a minimum when the Li atom has contact with the oxygen atom of DEME cation, while potentials for the EMIM cation with the LiTFSA complex are always repulsive. The MP2/6-311G**//HF/6-311G** level interaction energy calculated for the DEME cation with the LiTFSA complex was -18.4 kcal/mol. The interaction energy for the neutral DEE with the LiTFSA complex was larger (-21.1 kcal/mol). The interaction energy for the DEMETFSA complex with LiTFSA complex is greater (-23.2 kcal/mol). The electrostatic and induction interactions are the major source of the attraction in the two systems. The substantial attraction between the DEME cation and the LiTFSA complex suggests that the interaction between the Li cation and the oxygen atom of DEME cation plays important roles in determining the mobility of the Li cation in DEME-based room temperature ionic liquids.     

Wellenmechanische absolutrechnung am HeHHe+

The wave function of the HeHHe⁺ molecule has been calculated by means of the GENERAL SCF –MO –LC (LCGO ) PROGRAM SYSTEM, taking all four electrons into account. The calculations were carried out for a number of linear equidistant, linear non-equidistant, and bent nuclear arrangements. The minimum energy of ?5.7930 a.u. was found for a linear equidistant configuration with a He? H distance of 0.939 Å. The corresponding ionization energy was 37.9 eV. An estimation of the energy of formation of HeHHe⁺ from HeH⁺ and He based on SCF -calculations on HeH⁺ and He gave 7.9 kcal/mole. The frequencies of the normal vibrations were calculated.     

Deactivation reactions in the modeled 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐mediated free‐radical polymerization of styrene: A comparative study with the 2,2,6,6‐tetramethyl‐1‐piperidinyloxy/acrylonitrile system

The competitiveness of the combination and disproportionation reactions between a 1‐phenylpropyl radical, standing for a growing polystyryl macroradical, and a 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) radical in the nitroxide‐mediated free‐radical polymerization of styrene was quantitatively evaluated by the study of the transition geometry and the potential energy profiles for the competing reactions with the use of quantum‐mechanical calculations at the density functional theory (DFT) UB3‐LYP/6‐311+G(3df, 2p)//(unrestricted) Austin Model 1 level of theory. The search for transition geometries resulted in six and two transition structures for the radical combination and disproportionation reactions, respectively. The former transition structures, mainly differing in the out‐of‐plane angle of the N? O bond in the transition structure TEMPO molecule, were correlated with the activation energy, which was determined to be in the range of 8.4–19.4 kcal mol^?1 from a single‐point calculation at the DFT UB3‐LYP/6‐311+G(3df, 2p)//unrestricted Austin Model 1 level. The calculated activation energy for the disproportionation reaction was less favorable by a value of more than 30 kcal mol^?1 in comparison with that for the combination reaction. The approximate barrier difference for the TEMPO addition and disproportionation reaction was slightly smaller for the styrene polymerization system than for the acrylonitrile polymerization system, thus indicating that a β‐proton abstraction through a TEMPO radical from the polymer backbone could diminish control over the radical polymerization of styrene with the nitroxide even more than in the latter system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 232–241, 2007     

Ab initio study of hydrogen bonding in the phenol–water system

Three hydrogen-bonded minima on the phenol-water, C₆H₅OH—H₂O, potential energy surface were located with 3–21G and 6–31G** basis sets at both Hartree–Fock and MP2 levels of theory. MP2 binding energies were computed using large “correlation consistent” basis sets that included extra diffuse functions on all atoms. An estimate of the effect of expanding the basis set to the triple-zeta level (multiple f functions on carbon and oxygen and multiple d functions on hydrogen) was derived from calculations on a related prototype system. The best estimates of the electronic binding energies for the three minima are –7.8, –5.0, and –2.0 kcal/mol. The consequences of uncertainties in the geometries and limitations in the level of correlation recovery are analyzed. It is suggested that our best estimates will likely underestimate the complete basis set, full CI values by 0.1–0.3 kcal/mol. Vibrational normal modes were determined for all three minima, including an MP2/6–31G** analysis for the most strongly bound complex. Computational strategies for larger phenol–water complexes are discussed. © John Wiley & Sons, Inc.     

An ab initio MO study of allene episulfide, cyclopropanethione and thioxyallyl

The electronic structures of allene episulfide, cyclopropanethione and thioxyallyl were examined by ab initio MO calculations and were compared with those of the corresponding oxygen compounds, allene oxide, cyclopropanone and oxyallyl. The difference in reactivities of allene episulfide and allene oxide was also speculatively estimated from the calculated electronic structures. The lowest singlet state of thioxyallyl was predicted to be the B₂ state, which corresponds to the σ, π-diradical. A small activation energy is required for the cyclization of the B₂ state to give allene episulfide. The A₁ singlet state lies 11 kcal mol⁻¹ higher than the B₂ singlet state and undergoes the disrotatory rotation of methylene groups to give cyclopropanethione with no activation energy.     

Quantum chemical study of low temperature oxidation mechanism of dibenzofuran

A density functional theory (DFT) study of the reaction of dibenzofuranyl radical with oxygen molecule has been made. The geometries, energies, and vibrational frequencies of the reactant, transition states, intermediates, and products have been calculated at the B3LYP/6-311+G(3df,2p)//B3LYP/6-31G(d) level of theory. The initial reaction of dibenzofuran (DBF) with molecular oxygen results in the formation of the 1-dibenzofuranylperoxy radical. The stability of this adduct toward decomposition at low to intermediate temperatures results in it undergoing several possible rearrangements. The lowest energy pathway with a barrier of 24.2 kcal/mol involves a rearrangement to the 1,1-dioxadibenzofuran radical. The next lowest energy pathway involves fission of the O-O linkage whose reaction energy was found to be 37.6 kcal/mol. Transition state theory (TST) calculations indicate that the lowest energy pathway should predominate at temperatures up to about 1200 K. Two other unimolecular reaction pathways with barriers of 45.5 and 91.1 kcal/mol have also been discovered. The latter pathway leads to the formation of a para-quinone (dibenzofuran quinone) which has been detected experimentally in the low-temperature oxidation of DBF [Marquaire, P. M.; Worner, R.; Rambaud, P.; Baronnet, F. Organohalogen Compd. 1999, 40, 519]. Our quantum calculations, however, do not support this latter pathway to quinone formation. Instead, the quinone is most probably formed as a consequence of recombination of the 1-dibenzofuranyloxy radical (produced by peroxy fission) with an O atom in the para position. Each of the unimolecular reaction pathways have been subjected to detailed quantum chemical investigation and transition states and intermediates leading to the final products (principally CO, CO2, and C2H2 with traces of benzofuran and benzene) have been identified. For certain stable intermediates, their possible reactions with molecular oxygen have been further investigated quantum chemically. The present work therefore presents a detailed quantum chemical investigation of the reaction pathways in the low-temperature oxidation mechanism of DBF. Since the dibenzofuran moiety is present in the polychlorinated DBFs, our conclusions should be generally applicable to this family of compounds.     

Ab initio calculations on small hydrides including electron correlation

The two lowest electronic states (³ B ₁ and ¹ A ₁) of the methylene radical (CH₂) are calculated both in SCF-approximation and with the IEPA-PNO method (including electron correlation). The influence of polarization functions and electronic correlation on the shape of the potential curves of the two states is discussed. The calculated equilibrium geometries agree very well with experiment, but the results for transition energies (e.g. ³ B ₁¹ A ₁ excitation energy=9.2 kcal/mole, total binding energy=187 kcal/mole) are more reliable than the existent experimental values.     

Amide–π interactions between formamide and benzene

High‐level ab initio calculations have been carried out using a formamide–benzene model system to evaluate amide–π interactions. The interaction energies were estimated as a sum of the CCSD(T) correlation contribution and the HF energy at the complete basis set limit, for the geometries of the model structures at the energy minimum obtained by potential energy surface (PES) scans. NH/π geometry in a face‐on configuration was found to be the most attractive among the various geometries considered, with interaction energy of ?3.75 kcal/mol. An interaction energy of ?2.08 kcal/mol was calculated for the stacked N/Center type geometry, where the nitrogen atom of formamide points directly toward the center of the aromatic ring. The weakest C?O/π geometry, where a carbonyl oxygen atom points toward the plane of the aromatic ring, was found to have energy minimum at an intermolecular distance of 3.67 Å from the PES, with a repulsive interaction energy less than 1 kcal/mol. However, if there are simultaneous attractive interactions with other parts of the molecule besides the amide group, the weak repulsion could be easily overcome, to give a C?O/π geometry interaction. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2009     

Theoretical Study of the Benzene Dimer by the Density‐Functional‐Theory Formalism Based on Electron‐Density Partitioning

The density‐functional approach based on the partition into subsystems was applied to study the benzene dimer. For several structures, the calculated interaction energy and intermolecular distance were compared with the previous theoretical results. A good agreement with high level ab initio correlated methods was found. For instance, the interaction energies obtained in this work and the CCSD(T) method agree within 0.1 – 0.6 kcal/mol depending on the structure of the dimer. The structure with the largest interaction energy is T‐shaped, in agreement with CCSD(T) results. The T‐shaped structure of benzene dimer was suggested by several experimental measurements. The calculated interaction energy of 2.09 kcal/mol agrees also well with experimental estimates based on the dissociation energy which ranges from 1.6±0.2 to 2.4±0.4 kcal/mol and the estimated zero‐point vibration energy of 0.3 – 0.5 kcal/mol.     

Dissociation of acetone radical cation (CH3COCH3(+*) --> CH3CO(+) + CH3(*)): an ab initio direct classical trajectory study of the energy dependence of the branching ratio

The nonstatistical dissociation of acetone radical cation has been studied by ab initio direct classical trajectory calculations at the MP2/6-31G(d) level of theory. A bond additivity correction has been used to improve the MP2 potential energy surface (BAC-MP2). The energy dependence of the branching ratio, dissociation kinetics, and translational energy distribution for the two types of methyl groups have been investigated using microcanonical ensembles and specific mode excitation. In each case, the dissociation favors the loss of the newly formed methyl group, in agreement with the experiments. For microcanonical ensembles, the branching ratios for methyl loss are calculated to be 1.43, 1.88, 1.70, and 1.50 for 1, 2, 10, and 18 kcal/mol of excess energy, respectively. The energy dependence of the branching ratio is seen more dramatically in the excitation of individual modes involving C-C-O bending. For modes 3 and 6, the branching ratio rises to 1.6 and 1.8-2.3 when 1 or 2 kcal/mol are added, respectively, but falls off when more energy is added. For mode 8, the branching ratio continues to rise monotonically from 1.5 to 2.76 when 1-8 kcal/mol of excess energy are added.     

Glycine interaction with carbon nanotubes: an ab initio study

The interaction of the glycine radical on the side walls of both armchair and zigzag single walled carbon nanotubes is investigated by density functional theory. It is found that the interaction potential of the N-centered glycine radical with the tubes has a minimum of 16.9 (armchair) and 20.2 (zigzag) kcal/mol with respect to the dissociation products. In contrast, the C-centered radical, which is 22.7 kcal/mol lower in energy than the N-centered radical, does not form stable complexes with both types of carbon nanotubes.     

Physico-chemical aspects of polyethylene processing in an open mixer. Part 32: Formal kinetics of γ-lactone formation from secondary products. Heterogeneous kinetics

Oxidation of aldehydes and γ-hydroxy-trans-vinylene groups can yield γ-lactones. These intermediates account for γ-lactone formation in the advanced stages of polyethylene processing in air. The acyl-peroxy radical formed on free radical induced oxidation of aldehydes can abstract intramolecularly a δ-hydrogen atom to yield a peracid. Reaction of the alkyl radical formed in this reaction with the hydroperoxide group of the peracid gives a γ-lactone with simultaneous release of a hydroxyl radical. The calculated rate of γ-lactone formation according to the mechanism envisaged decreases slightly with increasing temperature (activation energy of about −5 kcal/mol). It is in agreement with the experiments that do not show significant activation energy in the high temperature range for the advanced stages of polyethylene processing. The calculated rate of γ-lactone formation is found to increase by a factor of about 2.7 if the processing experiments are performed in pure oxygen instead of in air. This is close to the experimental factor of about 2.Peroxidation of γ-hydroxy-trans-vinylene groups can also yield γ-lactones. The first possibility involves addition of a peroxy radical to the double bond followed by oxygen addition to the alkyl radical. This reaction possibly yields an α-peroxy-hydroperoxide. Intramolecular decomposition involving the two reactive groups of the α-peroxy-hydroperoxide can give an ozonide that on thermal decomposition yields among others an acid group in 4-position to the alcohol. The activation energy calculated is strongly negative so that the rate should decrease strongly with increasing temperature. Hence, the mechanism cannot contribute significantly to γ-lactone formation in the whole temperature range of the experiments. This is so in spite of the fact that the rate is estimated to increase by a factor of about 1.7 on passing from air to pure oxygen, which is close to the experimental value of approximately 2. The second possibility of transformation of γ-hydroxy-trans-vinylene groups is based on stress-induced oxygen addition to the double bond. Acid catalyzed decomposition of the allylic hydroperoxide that is formed in the reaction yields a pair of aldehydes with one of the aldehyde groups in 4-position to the alcohol group. Peroxidation of the aldehyde pair can give an acid group in 4-position to the hydroxyl group so that a γ-lactone can be formed. The activation energy calculated for the process is very small and the effect of the oxygen concentration corresponds to an increase by a factor of approximately 4.5 on passing from air to pure oxygen. It is postulated that simultaneous contribution by different mechanisms might well account for the experimental value of about 2.The heterogeneous kinetics discussed in detail allows for complementary data interpretation. It is especially suited for the understanding of the advanced stages of polyethylene processing, after some induction time.