A theoretical study on the mechanism of camphor hydroxylation by compound I of cytochrome p450

Mechanistic and energetic aspects for the conversion of camphor to 5-exo-hydroxycamphor by the compound I iron-oxo species of cytochrome P450 are discussed from B3LYP DFT calculations. This reaction occurs in a two-step manner along the lines that the oxygen rebound mechanism suggests. The activation energy for the first transition state of the H atom abstraction at the C5 atom of camphor is computed to be more than 20 kcal/mol. This H atom abstraction is the rate-determining step in this hydroxylation reaction, leading to a reaction intermediate that involves a carbon radical species and the iron-hydroxo species. The second transition state of the rebound step that connects the reaction intermediate and the product alcohol complex lies a few kcal/mol below that for the H atom abstraction on the doublet and quartet potential energy surfaces. This energetic feature allows the virtually barrierless recombination in both spin states, being consistent with experimentally observed high stereoselectivity and brief lifetimes of the reaction intermediate. The overall energetic profile of the catalytic mechanism of camphor hydroxylation particularly with respect to why the high activation energy for the H atom abstraction is accessible under physiological conditions is also considered and calculated. According to a proton source model involving Thr252, Asp251, and two solvent water molecules (Biochemistry 1998, 37, 9211), the energetics for the conversion of the iron-peroxo species to compound I is studied. A significant energy over 50 kcal/mol is released in the course of this dioxygen activation process. The energy released in this chemical process is an important driving force in alkane hydroxylation by cytochrome P450. This energy is used for the access to the high activation energy for the H atom abstraction.     

QM/MM modeling of the hydroxylation of the androstenedione substrate catalyzed by cytochrome P450 aromatase (CYP19A1)

CYP19A1 aromatase is a member of the Cytochrome P450 family of hemeproteins, and is the enzyme responsible for the final step of the androgens conversion into the corresponding estrogens, via a three‐step oxidative process. For this reason, the inhibition of this enzyme plays an important role in the treatment of hormone‐dependent breast cancer. The first catalytic subcycle, corresponding to the hydroxilation of androstenedione, has been proposed to occur through a first hydrogen abstraction and a subsequent oxygen rebound step. In present work, we have studied the mechanism of the first catalytic subcycle by means of hybrid quantum mechanics/molecular mechanics methods. The inclusion of the protein flexibility has been achieved by means of Free Energy Perturbation techniques, giving rise to a free energy of activation for the hydrogen abstraction step of 13.5 kcal/mol. The subsequent oxygen rebound step, characterized by a small free energy barrier (1.5 kcal/mol), leads to the hydroxylated products through a highly exergonic reaction. In addition, an analysis of the primary deuterium kinetic isotopic effects, calculated for the hydrogen abstraction step, reveals values (～10) overpassing the semiclassical limit for the C? H, indicating the presence of a substantial tunnel effect. Finally, a decomposition analysis of the interaction energy for the substrate and cofactor in the active site is also discussed. According to our results, the role of the enzymatic environment consists of a transition state stabilization by means of dispersive and polarization effects. © 2015 Wiley Periodicals, Inc.     

Hydrogen by Deuterium Substitution in an Aldehyde Tunes the Regioselectivity by a Nonheme Manganese(III)–Peroxo Complex

Mononuclear nonheme Mn^III‐peroxo complexes are important intermediates in biology, and take part in oxygen activation by photosystem II. Herein, we present work on two isomeric biomimetic side‐on Mn^III‐peroxo intermediates with bispidine ligand system and reactivity patterns with aldehydes. The complexes are characterized with UV/Vis and mass spectrometric techniques and reaction rates with cyclohexane carboxaldehyde (CCA) are measured. The reaction gives an unusual regioselectivity switch from aliphatic to aldehyde hydrogen atom abstraction upon deuteration of the substrate, leading to the corresponding carboxylic acid product for the latter, while the former gives a deformylation reaction. Mechanistic details are established from kinetic isotope effect studies and density functional theory calculations. Thus, replacement of C?H by C?D raises the hydrogen atom abstraction barriers and enables a regioselectivity switch to a competitive pathway that is slightly higher in energy.     

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.     

The catalytic mechanism of mouse renin studied with QM/MM calculations

Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.     

Preparation and reactivity of [D3d]-octahedrane: the most stable (CH)12 hydrocarbon

The synthesis of the (CH)12 hydrocarbon [D(3d)]-octahedrane (heptacyclo[6.4.0.0(2,4).0(3,7).0(5,12).0(6,10).0(9,11)]dodecane) 1 and its selective functionalization retaining the hydrocarbon cage is described. The B3LYP/6-311+G* strain energy of 1 is 83.7 kcal mol(-1) (4.7 kcal mol(-1) per C-C bond) which is significantly higher than that of the structurally related (CH)16 [D(4d)]-decahedrane 2 (75.4 kcal mol(-1); 3.1 kcal mol(-1) per C-C bond) and (CH)20 [I(h)]-dodecahedrane 3 (51.5 kcal mol(-1); 1.7 kcal mol(-1) per C-C bond); the heats of formation for 1-3 computed according to homodesmotic equations are 52, 35, and 4 kcal mol(-1). Catalytic hydrogenation of 1 leads to consecutive opening of the two cyclopropane rings to give C2-bisseco-octahedrane (pentacyclo[6.4.0.0(2,6).0(3,11).0(4,9)]dodecane) 16 as the major product. Although 1 is highly strained, its carbon skeleton is kinetically quite stable: Upon heating, 1 does not decompose until above 180 degrees C. The B3LYP/6-31G* barriers for the S(R)2 attack of the tBuO. and Br3C. radicals on a carbon atom of one of the cyclopropane fragments (Delta(298) = 27-28 kcal mol(-1)) are higher than those for hydrogen atom abstraction. The latter barriers are virtually identical for the abstraction from the C1-H and C2-H positions with the tBuO. radical (DeltaG(298) = 17.4 and 17.9 kcal mol(-1), respectively), but significantly different for the reaction at these positions with the Br3C. radical (DeltaG(298) = 18.8 and 21.0 kcal mol(-1)). These computational results agree well with experiments, in which the chlorination of 1 with tert-butyl hypochlorite gave a mixture of 1- and 2-chlorooctahedranes (ratio 3:2). The bromination with carbon tetrabromide under phase-transfer catalytic (PTC) conditions (nBu4NBr/NaOH) selectively gave 1-bromooctahedrane in 43 % isolated yield. For comparison, the PTC bromination was also applied to 2,4-dehydroadamantane yielding 54 % 7-bromo-2,4-dehydroadamantane.     

QM/MM study of mechanisms for compound I formation in the catalytic cycle of cytochrome P450cam

In the catalytic cycle of cytochrome P450cam, after molecular oxygen binds as a ligand to the heme iron atom to yield a ferrous dioxygen complex, there are fast proton transfers that lead to the formation of the active species, Compound I (Cpd I), which are not well understood because they occur so rapidly. In the present work, the conversion of the ferric hydroperoxo complex (Cpd 0) to Cpd I has been investigated by combined quantum-mechanical/molecular-mechanical (QM/MM) calculations. The residues Asp(251) and Glu(366) are considered as proton sources. In mechanism I, a proton is transported to the distal oxygen atom of the hydroperoxo group via a hydrogen bonding network to form protonated Cpd 0 (prot-Cpd0: FeOOH(2)), followed by heterolytic O-O bond cleavage that generates Cpd I and water. Although a local minimum is found for prot-Cpd0 in the Glu(366) channel, it is very high in energy (more than 20 kcal/mol above Cpd 0) and the barriers for its decay are only 3-4 kcal/mol (both toward Cpd 0 and Cpd I). In mechanism II, an initial O-O bond cleavage followed by a concomitant proton and electron transfer yields Cpd I and water. The rate-limiting step in mechanism II is O-O cleavage with a barrier of about 13-14 kcal/mol. According to the QM/MM calculations, the favored low-energy pathway to Cpd I is provided by mechanism II in the Asp(251) channel. Cpd 0 and Cpd I are of similar energies, with a slight preference for Cpd I.     

Computational investigation of hydrogen abstraction from 2-aminoethanol by the 1,5-dideoxyribose-5-yl radical: a model study of a reaction occurring in the active site of ethanolamine ammonia lyase

Hydrogen abstraction from 2-aminoethanol by the 5'-deoxyadenosyl radical, which is formed upon Co--C bond homolysis in coenzyme B(12), was investigated by theoretical means with employment of the DFT (B3LYP) and ab initio (MP2) approaches. As a model system for the 5'-deoxyadenosyl moiety the computationally less demanding 1,5-dideoxyribose was employed; two conformers, which differ in ring conformation (C2- and C3-endo), were considered. If hydrogen is abstracted from "free" substrate by the C2-endo conformer of the 1,5-dideoxyribose-5-yl radical, the activation enthalpy is 16.7 kcal mol(-1); with the C3-endo counterpart, the value is 17.3 kcal mol(-1). These energetic requirements are slightly above the activation enthalpy limit (15 kcal mol(-1)) determined experimentally for the rate-determining step of the sequence, that is, hydrogen delivery from 5'-deoxyadenosine to the product radical. The activation enthalpy is lower when the substrate interacts with at least one amino acid from the active site. According to the computations, when a His model system partially protonates the substrate the activation enthalpy is 4.5 kcal mol(-1) for the C3-endo conformer and 5.8 kcal mol(-1) for the C2-endo counterpart. As hydrogen abstraction from the fully as well as the partially protonated substrate is preceded by the formation of quite stable encounter complexes, the actual activation barriers are around 13-15 kcal mol(-1). A synergistic interaction of 2-aminoethanol with two amino acids where His partially protonates the NH(2) group and Asp partially deprotonates the OH group of the substrate results in an activation enthalpy of 12.4 kcal mol(-1) for the C3-endo conformer and 13.2 kcal mol(-1) for the C2-endo counterpart. However, if encounter complexes exist in the active site, the actual activation barriers are much higher (>25 kcal mol(-1)) than that reported for the rate-determining step. These findings together with previous computations suggest that the energetics of the initial hydrogen abstraction decrease with an interaction of the substrate with only a protonating auxiliary, but for the rearrangement of the radical the synergistic effects of two auxiliaries are essential to pull the barrier below the limit of 15 kcal mol(-1).     

Theoretical study of the catalytic mechanism and metal-ion dependence of peptide deformylase

The reaction pathway of deformylation catalyzed by E. coli peptide deformylase (PDF) has been investigated by the density functional theory method of PBE1PBE on a small model and by a two-layer ONIOM method on a realistic protein model. The deformylation proceeds in sequential steps involving nucleophilic addition of metal-coordinated water/hydroxide to the carbonyl carbon of the formyl group, proton transfer, and cleavage of the C-N bond. The first step is rate-determining for the deformylation, which occurs through a pentacoordinated metal center. The estimated activation energies with the ONIOM method are about 23.0, 15.0, and 14.9 kcal/mol for Zn-, Ni-, and Fe-PDFs, respectively. These calculated barriers are in close agreement with experimental observations. Our results demonstrate that the preference for metal coordination geometry exerts a significant influence on the catalytic activity of PDFs by affecting the activation of the carbonyl group of the substrate, the deprotonation of the metal-coordinated water, and the stabilization of the transition state. This preference for coordination geometry is mainly determined by the ligand environment and the intrinsic electronic structures of the metal center in the active site of the PDFs.     

Cytochrome P450CAM enzymatic catalysis cycle: a quantum mechanics/molecular mechanics study

The catalytic pathway of cytochrome P450cam is studied by means of a hybrid quantum mechanics/molecular mechanics method. Our results reveal an active role of the enzyme in the different catalytic steps. The protein initially controls the energy gap between the high- and low-spin states in the substrate binding process, allowing thermodynamic reduction by putidaredoxin reductase and molecular oxygen addition. A second electron reduction activates the delivery of protons to the active site through a selective interaction of Thr252 and the distal oxygen causing the O--O cleavage. Finally, the protein environment catalyzes the substrate hydrogen atom abstraction step with a remarkably low free energy barrier ( approximately 8 kcal/mol). Our results are consistent with the effect of mutations on the enzymatic efficacy and provide a satisfactory explanation for the experimental failure to trap the proposed catalytically competent species, a ferryl Fe(IV) heme.     

A theoretical study of reactivity and regioselectivity in the hydroxylation of adamantane by ferrate(VI)

The conversion of adamantane to adamantanols mediated by ferrate (FeO(4)(2)(-)), monoprotonated ferrate (HFeO(4)(-)), and diprotonated ferrate (H(2)FeO(4)) is discussed with the hybrid B3LYP density functional theory (DFT) method. Diprotonated ferrate is the best mediator for the activation of the C-H bonds of adamantane via two reaction pathways, in which 1-adamantanol is formed by the abstraction of a tertiary hydrogen atom (3 degrees ) and 2-adamantanol by the abstraction of a secondary hydrogen atom (2 degrees ). Each reaction pathway is initiated by a C-H bond cleavage via an H-atom abstraction that leads to a radical intermediate, followed by a C-O bond formation via an oxygen rebound step to lead to an adamantanol complex. The activation energies for the C-H cleavage step are 6.9 kcal/mol in the 1-adamantanol pathway and 8.4 kcal/mol in the 2-adamantanol pathway, respectively, at the B3LYP/6-311++G level of theory, whereas those of the second reaction step corresponding to the rebound step are relatively small. Thus, the rate-determining step in the two pathways is the C-H bond dissociation step, which is relevant to the regioselectivity for adamantane hydroxylation. The relative rate constant (3 degrees )/(2 degrees ) for the competing H-atom abstraction reactions is calculated to be 9.30 at 75 degrees C, which is fully consistent with an experimental value of 10.1.     

Computational study on mechanistic details of the aminoethanol rearrangement catalyzed by the vitamin B12-dependent ethanolamine ammonia lyase: His and Asp/Glu acting simultaneously as catalytic auxiliaries

The rearrangement of aminoethanol catalyzed by ethanolamine ammonia lyase is investigated by computational means employing DFT (B3LYP/6-31G) and ab initio molecular orbital theory (QCISD/cc-pVDZ). The study aims at providing a detailed account on various crucial aspects, in particular a distinction between a direct intramolecular migration of the partially protonated NH(2) group vs elimination of NH(4)(+). Three mechanistic scenarios were explored: (i) According to the calculations, irrespective of the nature of the protonating species, intramolecular migration of the NH(3) group is energetically less demanding than elimination of NH(4)(+). However, all computed activation enthalpies exceed the experimentally derived activation enthalpy (15 kcal/mol) associated with the rate-determining step, i.e., the hydrogen abstraction from the 5'-deoxyadenosine by the product radical. For example, when imidazole is used as a model system for His interacting with the NH(3) group of the substrate, the activation enthalpy for the migration process amounts to 27.4 kcal/mol. If acetic acid is employed to mimic Asp or Glu, the activation enthalpy is somewhat lower, being equal to 24.2 kcal/mol. (ii) For a partial deprotonation of the substrate 2 at the OH group, the rearrangement mechanism consists of the dissociation of an NH(2) radical from C(2) and its association at C(1) atom. For all investigated proton acceptors (i.e., OH(-), HCOO(-), CH(3)COO(-), CH(2)NH, imidazole), the activation enthalpy for the dissociation step also exceeds 15 kcal/mol. Typical data are 20.2 kcal/mol for Ac(-) and 23.8 kcal/mol for imidazole. (iii) However, in a synergistic action of partial protonation of the NH(2) group and partial deprotonation of the OH group by the two conceivable catalytic auxiliaries Asp/Glu and His, the activation enthalpy computed is compatible with the experimental data. For imidazole and acetate as model systems, the activation enthalpy is equal to 13.7 kcal/mol. This synergistic action of the two catalytic groups is expected to take place in a physiologically realistic pH range of 6-9.5, and the present computational findings may help to further characterize the yet unknown structural details of the ethanolamine ammonia lyase's active site.     

Analysis of the reactivities of protein C-H bonds to H atom abstraction by OH radical

Ab initio and density functional theory calculations are used to monitor the process wherein a OH· radical is allowed to approach the various CH groups of a Leu dipeptide, with its CH(2)CH(CH(3))(2) side chain. After forming an encounter complex, the OH· abstracts the pertinent H atom, and the resulting HOH is then dissociated from the complex. The energy barriers for H· abstraction from the β, γ, and δ CH groups are all less than 8 kcal/mol, but a significantly higher barrier is computed for the C(α)H removal. This higher barrier is the result of the strong H-bonds formed in the encounter complex between the OH· and the NH and C═O groups of the peptide units that surround the C(α) atom. This low-energy complex represents a kinetic trap which raises the energy needed to surmount the ensuing H· transfer barrier.     

A QM/MM simulation study of transamination reaction at the active site of aspartate aminotransferase: Free energy landscape and proton transfer pathways

Transaminase is a key enzyme for amino acid metabolism, which reversibly catalyzes the transamination reaction with the help of PLP (pyridoxal 5^' -phosphate) as its cofactor. Here we have investigated the mechanism and free energy landscape of the transamination reaction involving the aspartate transaminase (AspTase) enzyme and aspartate-PLP (Asp-PLP) complex using QM/MM simulation and metadynamics methods. The reaction is found to follow a stepwise mechanism where the active site residue Lys258 acts as a base to shuttle a proton from α -carbon (CA) to imine carbon (C4A) of the PLP-Asp Schiff base. In the first step, the Lys258 abstracts the CA proton of the substrate leading to the formation of a carbanionic intermediate which is followed by the reprotonation of the Asp-PLP Schiff base at C4A atom by Lys258. It is found that the free energy barrier for the proton abstraction by Lys258 and that for the reprotonation are 17.85 and 3.57 kcal/mol, respectively. The carbanionic intermediate is 7.14 kcal/mol higher in energy than the reactant. Hence, the first step acts as the rate limiting step. The present calculations also show that the Lys258 residue undergoes a conformational change after the first step of transamination reaction and becomes proximal to C4A atom of the Asp-PLP Schiff base to favor the second step. The active site residues Tyr70* and Gly38 anchor the Lys258 in proper position and orientation during the first step of the reaction and stabilize the positive charge over Lys258 generated at the intermediate step.     

Regioselectivity of aliphatic versus aromatic hydroxylation by a nonheme iron(II)-superoxo complex

Many enzymes in nature utilize molecular oxygen on an iron center for the catalysis of substrate hydroxylation. In recent years, great progress has been made in understanding the function and properties of iron(IV)-oxo complexes; however, little is known about the reactivity of iron(II)-superoxo intermediates in substrate activation. It has been proposed recently that iron(II)-superoxo intermediates take part as hydrogen abstraction species in the catalytic cycles of nonheme iron enzymes. To gain insight into oxygen atom transfer reactions by the nonheme iron(II)-superoxo species, we performed a density functional theory study on the aliphatic and aromatic hydroxylation reactions using a biomimetic model complex. The calculations show that nonheme iron(II)-superoxo complexes can be considered as effective oxidants in hydrogen atom abstraction reactions, for which we find a low barrier of 14.7 kcal mol(-1) on the sextet spin state surface. On the other hand, electrophilic reactions, such as aromatic hydroxylation, encounter much higher (>20 kcal mol(-1)) barrier heights and therefore are unlikely to proceed. A thermodynamic analysis puts our barrier heights into a larger context of previous studies using nonheme iron(IV)-oxo oxidants and predicts the activity of enzymatic iron(II)-superoxo intermediates.     

Dehydrogenative α-Oxygenation of Cyclic Ethers by a High-Valent Manganese(IV)-Oxo Species

High-valent metal-oxo species are typical catalytic cycle intermediates in mono-oxygenases and dioxygenases and commonly react through oxygen atom transfer to substrates. In this work we study a biomimetic model complex with a 1,1’-bis((3,5-dimethylpyridin-2-yl)methyl)-2,2’-bipiperidine ligand system bound to a manganese(IV)-oxo(hydroxo) species and study its formation from manganese(II)-hydroxo and H₂O₂ as well as its reaction with (S)-1-phenylisochromane through dehydrogenative α-oxygenation. The work utilizes density functional theory methods to explore its catalytic cycle and its reactivity patterns. We show that the manganese(IV)-oxo(hydroxo) species is an active oxidant and preferentially the oxo group abstracts a hydrogen atom from substrate with barriers well lower in energy than those found for hydrogen atom abstraction by the hydroxo group. Interestingly, the rate-determining step is the OH rebound rather than the hydrogen atom abstraction, which would imply they would have limited kinetic isotope effect for the replacement of the transferring hydrogen atom by deuterium.     

Dynamics of H and D abstraction in the reaction of Cl atom with butane-1,1,1,4,4,4-d6

We report the primary (D-atom) and secondary (H-atom) abstraction dynamics of chlorine atom reaction with butane-1,1,1,4,4,4-d(6). The H- and D-atom abstraction channels were studied over a range of collision energies: 10.4 kcal mol(-1) and 12.9 kcal mol(-1); 5.2 kcal mol(-1) to 12.8 kcal mol(-1), respectively, using crossed molecular beam dc slice ion imaging techniques. Single photon ionization at 157 nm was used to probe the butyl radical products resulting from the H- and D-atom abstraction reactions. These two channels manifest distinct dynamics principally in the translational energy distributions, while the angular distributions are remarkably similar. The reduced translational energy distribution for the primary abstraction showed marked variation with collision energy in the backward direction, while the secondary abstraction showed this variation in the forward direction.     

Axial and equatorial cyclohexylacyl and tetrahydropyranyl-2-acyl radicals. An experimental and theoretical study

Axial and equatorial cyclohexylacyl and tetrahydropyranyl-2-acyl radicals gave distinct EPR spectra thanks to surprisingly large beta-hydrogen atom hyperfine splittings that enabled them to be characterized and monitored. DFT computations indicated that the axial species (X = CH(2)) had a higher barrier to rotation about the (O)C(alpha)-C(beta) bond. The computed difference Delta H degrees for the axial and equatorial radicals (R = H, X = CH(2)) was 0.8 kcal mol(-)(1).     

The reaction of tricarbon with acetylene: an ab initio/RRKM study of the potential energy surface and product branching ratios

Ab initio calculations of the potential energy surface for the C3(1Sigmag+)+C2H2(1Sigmag+) reaction have been performed at the RCCSD(T)/cc-pVQZ//B3LYP/6-311G(d,p) + ZPE[B3LYP/6-311G(d,p)] level with extrapolation to the complete basis set limit for key intermediates and products. These calculations have been followed by statistical calculations of reaction rate constants and product branching ratios. The results show the reaction to begin with the formation of the 3-(didehydrovinylidene)cyclopropene intermediate i1 or five-member ring isomer i7 with the entrance barriers of 7.6 and 13.8 kcal/mol, respectively. i1 rearranges to the other C5H2 isomers, including ethynylpropadienylidene i2, singlet pentadiynylidene i3, pentatetraenylidene i4, ethynylcyclopropenylidene i5, and four- and five-member ring structures i6, i7, and i8 by ring-closure and ring-opening processes and hydrogen migrations. i2, i3, and i4 lose a hydrogen atom to produce the most stable linear isomer of C5H with the overall reaction endothermicity of approximately 24 kcal/mol. H elimination from i5 leads to the formation of the cyclic C5H isomer, HC2C3, +H, 27 kcal/ mol above C3+C2H2. 1,1-H2 loss from i4 results in the linear pentacarbon C5+H2 products endothermic by 4 kcal/mol. The H elimination pathways occur without exit barriers, whereas the H2 loss from i4 proceeds via a tight transition state 26.4 kcal/mol above the reactants. The characteristic energy threshold for the reaction under single collision conditions is predicted be in the range of approximately 24 kcal/mol. Product branching ratios obtained by solving kinetic equations with individual rate constants calculated using RRKM and VTST theories for collision energies between 25 and 35 kcal/mol show that l-C5H+H are the dominant reaction products, whereas HC2C3+H and l-C5+H2 are minor products with branching ratios not exceeding 2.5% and 0.7%, respectively. The ethynylcyclopropenylidene isomer i5 is calculated to be the most stable C5H2 species, more favorable than triplet pentadiynylidene i3t by approximately 2 kcal/mol.     

Reaction mechanism between carbonyl oxide and hydroxyl radical: a theoretical study

The reaction mechanism of carbonyl oxide with hydroxyl radical was investigated by using CASSCF, B3LYP, QCISD, CASPT2, and CCSD(T) theoretical approaches with the 6-311+G(d,p), 6-311+G(2df, 2p), and aug-cc-pVTZ basis sets. This reaction involves the formation of H2CO + HO2 radical in a process that is computed to be exothermic by 57 kcal/mol. However, the reaction mechanism is very complex and begins with the formation of a pre-reactive hydrogen-bonded complex and follows by the addition of HO radical to the carbon atom of H2COO, forming the intermediate peroxy-radical H2C(OO)OH before producing formaldehyde and hydroperoxy radical. Our calculations predict that both the pre-reactive hydrogen-bonded complex and the transition state of the addition process lie energetically below the enthalpy of the separate reactants (DeltaH(298K) = -6.1 and -2.5 kcal/mol, respectively) and the formation of the H2C(OO)OH adduct is exothermic by about 74 kcal/mol. Beyond this addition process, further reaction mechanisms have also been investigated, which involve the abstraction of a hydrogen of carbonyl oxide by HO radical, but the computed activation barriers suggest that they will not contribute to the gas-phase reaction of H2COO + HO.