Direct-dynamics VTST study of the [1,7] hydrogen shift in 7-methylocta-1,3(Z),5(Z)-triene. A model system for the hydrogen transfer reaction in previtamin D3

Direct-dynamics canonical variational transition-state theory calculations with microcanonically optimized multidimensional transmission coefficient (CVT/muOMT) for tunneling were carried out at the MPWB1K/6-31+G(d,p) level to study the [1,7] sigmatropic hydrogen rearrangement in 7-methylocta-1,3(Z),5(Z)-triene. This compound has seven conformers, of which only one leads to products, although all of them have to be included in the theoretical treatment. The calculated CVT/muOMT rate constants are in good agreement with the available experimental data. To try to understand the role of tunneling in the hydrogen shift reaction, we have also calculated the thermal rate constants for the monodeuterated compound in the interval T = 333.2-388.2 K. This allowed us to evaluate primary kinetic isotope effects (KIEs) and make a direct comparison with the experiment. Our calculations show that both the large measured KIE and the large measured difference in the activation energies between the deuterated and root compounds are due to the quantum tunneling. The tunneling contribution to the KIE becomes noticeable only when the coupling between the reaction coordinate and the transverse modes is taken into account. Our results confirm previous experimental and theoretical works, which guessed that the obtained kinetic parameters pointed to a reaction with an important contribution due to tunneling. The above conclusion would be essentially valid for the case of the [1,7] hydrogen shift in previtamin D3 because of the similarity to the studied model system.     

Unravelling the details of vitamin D photosynthesis by non-adiabatic molecular dynamics simulations

We investigate the photodynamics of vitamin D derivatives by a fully analytical implementation of the linear response time-dependent density functional theory surface hopping method (LR-TDDFT-SH). Our study elucidates the dynamics of the processes involved in vitamin D formation at the molecular level and with femtosecond resolution. We explain the major experimental findings and provide new insights that cannot directly be obtained from experiments: firstly, we investigate the dynamics of the photoinduced ring-opening of provitamin D (Pro) and cyclohexadiene (CHD) and the subsequent rotational isomerization. In agreement with recent experiments and CC2 calculations, only the bright S(1) state is involved in the ring-opening reaction. Our calculations confirm the experimentally reported 5 : 1 ratio between the excited state lifetimes of Pro and CHD. The longer lifetimes of Pro are attributed to steric constraints of the steroid skeleton and to temperature effects, both emerging directly from our simulations. For CHD and Pro, we present an explanation of the biexponential decay recently reported by Sension and coworkers [Tang et al., J. Phys. Chem., 2011, 134, 104503]: our calculations suggest that the fast and slow components arise from a reactive and an unreactive reaction pathway, respectively. Secondly, we assess the wavelength dependent photochemistry of previtamin D (Pre). Using replica exchange molecular dynamics we sample the Pre conformers present at thermal equilibrium. Based on this ensemble we explain the conformation dependent absorption and the essential features of Pre photochemistry. Consistent with the experiments, we find ring-closure to occur mostly after excitation of the cZc conformers and at lower energies, whereas Z/E isomerization of the central double bond preferably occurs after excitation at higher energies. For the isomerization we provide the first theoretical evidence of the proposed hula-twist mechanism. Our results show that LR-TDDFT-SH is a highly valuable tool for studying the photochemistry of moderately large systems, even though challenges remain in the vicinity of conical intersections.     

Trapping of the OH radical by alpha-tocopherol: a theoretical study

The antioxidant activity of alpha-tocopherol against the damaging hydroxyl radical was analyzed theoretically by hybrid density functional theory, following the direct dynamics method, where the thermal rate constants were calculated using variational transition-state theory with multidimensional tunneling. We found that the OH radical is only slightly or not at all selective, attacking by different mechanisms at several positions of the alpha-tocopherol molecule, giving competitive reactions. The most favorable pathways are the hydrogen abstraction reaction from the phenolic hydrogen and the electrophilic addition onto the aromatic ring. We propose a final rate constant, the sum of the competitive hydrogen abstraction and addition reactions, > or =2.7 x 10(8) M(-1) s(-1) at 298 K, where the hydrogen abstraction reaction represents only 20% of the total OH radical reaction. This result indicates that, molecule by molecule, in an apolar environment, alpha-tocopherol is less effective than coenzyme Q (which presents a rate constant of 6.2 x 10(10) M(-1) s(-1) at 298 K) as a scavenger of OH radicals. It was also found that both mechanisms are not direct but pass through intermediates in the entry channel, with little or no influence on the dynamics of the reactions. The hydrogen abstraction reaction also presents another intermediate in the exit channel, which may have a significant role in preventing the pro-oxidant effects of alpha-tocopherol, although less important than with free radicals other than OH.     

Toward an analogue of the transition state of preD3-D3 isomerization: stereoselective synthesis of linearly fused 6-8-6 carbocyclic systems

[reaction: see text] A stereoselective synthesis of 6-8-6 fused carbocyclic systems based on enol alkylation, ketone allylation, RCM, and Heck cyclization was developed to obtain compounds with a carbon framework that mimics the putative transition structure of the isomerization of previtamin D3 to vitamin D3.     

Access to [6.4.0]carbocyclic systems by tandem metathesis of dienynes. A step toward the synthesis of a PreD3-D3 transition state analogue

[reaction: see text] A new approach to the synthesis of linearly fused 6-8-6 tricarbocyclic systems, tandem ring-closing metathesis of dienynes, allows access to compounds with a carbon framework analogous to the proposed transition state of the isomerization of previtamin D(3) to vitamin D(3).     

C2H3与CH3F氢抽提反应机理与动力学性质

采用双水平直接动力学方法对C₂H₃与CH₃F氢抽提反应进行了研究. 在QCISD(T)/6-311++G(d, p)//B3LYP/6-311G(d, p)水平上, 计算的三个反应通道R1、R2和R3的能垒(ΔE^≠)分别为43.2、43.9和44.1 kJ·mol^-1, 反应热为-38.2 kJ·mol^-1. 此外, 利用传统过渡态理论(TST)、正则变分过渡态理论(CVT)和包含小曲率隧道效应(SCT)的CVT, 分别计算了200-3000 K温度范围内反应的速率常数k^TST、k^CVT和k^CVT/SCT. 结果表明: (1) 三个氢抽提反应通道的速率常数随温度的增加而增大, 其中变分效应的影响可以忽略, 隧道效应则在低温段影响显著; (2) R1反应是主反应通道, 但随着温度的升高, R2反应的竞争力增大, 而R3反应对总速率常数的影响很小.     

Explanation of the unusual temperature dependence of the atmospherically important OH + H(2)S --> H(2)O + HS reaction and prediction of the rate constant at combustion temperatures

Rate constants for the OH + H2S --> H2O + HS reaction, which is important for both atmospheric chemistry and combustion, are calculated by direct dynamics with the M06-2X density functional using the MG3S basis set. Energetics are compared to high-level MCG3/3//MC-QCISD/3 wave function theory and to results obtained by other density functionals. We employ canonical variational transition-state theory with multidimensional tunneling contributions and scaled generalized normal-mode frequencies evaluated in redundant curvilinear coordinates with anharmonicity included in the torsion. The transition state has a quantum mechanically distinguishable, nonsuperimposable mirror image that corresponds to a separate classical reaction path; the effect of the multiple paths is examined through use of a symmetry number and by torsional methods. Calculations with the reference-potential Pitzer-Gwinn treatment of the torsional mode agree with experiment, within experimental scatter, and predict a striking temperature dependence of the activation energy, increasing from -0.1 kcal/mol at 200 K to 0.2, 1.0, 3.4, and 9.8 kcal/mol at 300, 500, 1000, and 2400 K. The unusual temperature dependence arises from a dynamical bottleneck at an energy below reactants, following an addition complex on the reaction path with a classical binding energy of 4.4 kcal/mol. As a way to check the mechanism, kinetic isotope effects of the OH + D2S and OD + D2S reactions have been predicted.     

Potential energy surface for asymmetrically substituted reactions of type CWXYZ + A. Kinetics study

The CHClF(2) + Cl --> ClH + CClF(2) gas-phase abstraction reaction was chosen as a model of asymmetrically substituted polyatomic reactions of type CWXYZ + A --> products. The analytical potential energy surface for this reaction was constructed with suitable functional forms to represent vibrational modes, and calibrated with respect to experimental thermal rate constants which are available over the temperature range 296-410 K. On this surface, the thermal rate constants were calculated using variational transition-state theory with semiclassical transmission coefficients over a wider temperature range, 200-2500 K, therefore obtaining kinetics information at lower and higher temperatures than are experimentally available. This surface was also used to analyze dynamical features, such as tunneling and reaction-path curvature. In the former, the influence of the tunneling factor was important since a light hydrogen atom passes through the barrier. In the latter, it was found that vibrational excitation of the C-F and C-Cl stretching modes can be expected in the exit channel.     

Multi-structural variational transition state theory: kinetics of the 1,5-hydrogen shift isomerization of the 1-butoxyl radical including all structures and torsional anharmonicity

We investigate the statistical thermodynamics and kinetics of the 1,5-hydrogen shift isomerization reaction of the 1-butoxyl radical and its reverse isomerization. The partition functions and thermodynamic functions (entropy, enthalpy, heat capacity, and Gibbs free energy) are calculated using the multi-structural torsional (MS-T) anharmonicity method including all structures for three species (reactant, product, and transition state) involved in the reaction. The calculated thermodynamic quantities have been compared to those estimated by the empirical group additivity (GA) method. The kinetics of the unimolecular isomerization reaction was investigated using multi-structural canonical variational transition state theory (MS-CVT) including both multiple-structure and torsional (MS-T) anharmonicity effects. In these calculations, multidimensional tunneling (MT) probabilities were evaluated by the small-curvature tunneling (SCT) approximation and compared to results obtained with the zero-curvature tunneling (ZCT) approximation. The high-pressure-limit rate constants for both the forward and reverse reactions are reported as calculated by MS-CVT/MT, where MT can be ZCT or SCT. Comparison with the rate constants obtained by the single-structural harmonic oscillator (SS-HO) approximation shows the importance of anharmonicity in the rate constants of these reactions, and the effect of multi-structural anharmonicity is found to be very large. Whereas the tunneling effect increases the rate constants, the MS-T anharmonicity decreases them at all temperatures. The two effects counteract each other at temperatures 385 K and 264 K for forward and reverse reactions, respectively, and tunneling dominates at lower temperatures while MS-T anharmonicity has a larger effect at higher temperatures. The multi-structural torsional anharmonicity effect reduces the final reverse reaction rate constants by a much larger factor than it does to the forward ones as a result of the existence of more low-energy structures of the product 4-hydroxy-1-butyl radical than the reactant 1-butoxyl radical. As a consequence there is also a very large effect on the equilibrium constant. The neglect of multi-structural anharmonicity will lead to large errors in the estimation of reverse reaction rate constants.     

H原子和(CH3)2SiH2抽提反应的理论研究

采用UMP2/6-31G(d)理论水平优化了H原子和(CH3)2SiH2抽提反应势能面上的所有驻点,并在此水平基础上进行了内禀反应坐标(IRC)的计算,得到该反应的反应途径(MEP)。应用变分过渡态理论及最小能量途径半经典绝热基态隧道效应校正(MEPSAG)、小曲率半经典绝热基态隧道效应校正(SCSAG)等方法对上述反应进行了动力学研究,期望从理论上提供一套温度范围较宽、精度较高的动力学数据,为阐明反应机理和解释实验结果提供理论依据。     

Atom Tunneling in Chemistry

Quantum mechanical tunneling of atoms is increasingly found to play an important role in many chemical transformations. Experimentally, atom tunneling can be indirectly detected by temperature‐independent rate constants at low temperature or by enhanced kinetic isotope effects. In contrast, the influence of tunneling on the reaction rates can be monitored directly through computational investigations. The tunnel effect, for example, changes reaction paths and branching ratios, enables chemical reactions in an astrochemical environment that would be impossible by thermal transition, and influences biochemical processes.     

Ground-state conformational equilibrium of previtamin D and its E-isomer: Effect on the absorption characteristics

The ground-state conformational analysis of previtamin D, its E-isomer, tachysterol, their 10-desmethyl analogues and 1-methyl-1-hydroxy-previtamins have been performed by force-field calculations. Differences in the absorption characteristics of these compounds are discussed in view of the chromophore geometry and abundance (%) of the calculated conformers according to a Boltzmann distribution at 298 K. On the basis of present calculations, the red shift of previtamin D low-temperature UV and CD spectra determined earlier is attributed to the shift of conformational equilibrium in favour of more stable cZc geometries. The effect of complex formation with simplest model cluster of silica surface ((H₃SiO)₃SiOH), on previtamin D and tachysterol conformational equilibria and on UV-absorbance maxima has been evaluated.     

Dual-level direct dynamics studies for the reactions of OH radical with bromine-substituted ethanes

The dynamic properties of the multichannel hydrogen abstraction reactions of CH(3)CH(2)Br + OH --> products and CH(3)CHBr(2) + OH --> products are studied by dual-level direct dynamics method. For each reaction, three reaction channels, one for alpha-hydrogen abstraction and two for beta-hydrogen abstractions, have been identified. The minimum energy paths (MEPs) of both the reactions are calculated at the Becke's half-and-half (BH&H)-Lee-Yang-Parr (LYP)/6-311G(d, p) level and the energy profiles along the MEPs are further refined with interpolated single-point energies (ISPE) method at the G2M(RCC5)//BH&H-LYP level. There are complexes with energies less than those of the reactants or products located at the entrance or exit channels, which indicates that the reactions may proceed via an indirect mechanism. By canonical variational transition-state theory (CVT) the rate constants are calculated incorporating the small-curvature tunneling (SCT) correction in the temperature range of 220-2000 K. The agreement of the rate constants with available experimental values for two reactions is good in the measured temperature range. The calculated results show that alpha-hydrogen abstraction channel is the major reaction pathway in the lower temperature for two reactions, while the contribution of beta-hydrogen abstraction will increase with the increase in temperature.     

Potential energy surface for the F(2P(3/2),2P(1/2)) + CH4 hydrogen abstraction reaction. kinetics and dynamics study

A modified and recalibrated potential energy surface (PES) is reported for the gas-phase F(2P(3/2),2P(1/2)) + CH4 reaction and its deuterated analogue. This semiempirical surface is completely symmetric with respect to the permutation of the four methane hydrogen atoms and is calibrated with respect to the updated experimental and theoretical stationary point properties and experimental thermal rate constants. To take into account the two spin-orbit electronic states of the fluorine atom, two versions of the surface were constructed, the PES-SO and PES-NOSO surfaces, which differ in the choice of the zero reference level of the reactants. On both surfaces, the thermal rate constants were calculated using variational transition-state theory with semiclassical transmission coefficients over a wide temperature range, 180-500 K. While the PES-SO surface overestimates the experimental rate constants, the PES-NOSO surface shows a better agreement, reproducing the experimental variation with temperature. The influence of the tunneling factor is negligible, due to the flattening of the surface in the entrance valley, and we found a direct dependence on temperature, and therefore positive and small activation energies, in agreement with experiment. The kinetic isotope effects calculated showed good agreement with the sparse experimental data at 283 and 298 K. Finally, on the PES-NOSO surface, other dynamical features, such as the coupling between the reaction coordinate and the vibrational modes, were analyzed. It was found qualitatively that the FH stretching and the CH3 umbrella bending modes in the products appear vibrationally excited. These kinetics and dynamics results seem to indicate that a single, adiabatic PES is adequate to describe this reaction.     

Synthesis of (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: compounds to probe vitamin D conformation in receptor complex by 19F-NMR

To study the interaction of vitamin D with its receptor by 19F-NMR, (5Z,10Z)- and (5Z,10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 were synthesized starting from vitamin D2 via electrophilic fluorination of vitamin D-SO2 adducts as the key step. Regio- and stereoselective electrophilic fluorination at C(19) of vitamin D-SO2 adducts was achieved under the conditions using (PhSO2)2NF and bulky bases. The stereochemistry of the addition and elimination of SO2 of various vitamin D derivatives was studied in detail. SO2 causes Z-E isomerization of the 5,6-double bond of vitamin D and adds to the resulting (5E)-isomer from the sterically less hindered side opposite to the substituent at C(1). Elimination of SO2 from 19-substituted vitamin D-SO2 adducts proceeded exclusively in a suprafacial manner with respect to the diene part under either thermal or reductive conditions. Dye-sensitized photochemical isomerization of 19-fluorovitamin D derivatives was studied in detail. The rapid isomerization at the 5,6-double bond was followed by the slow isomerization at the 10,19-double bond to yield the (5E,10Z)-isomer (by nomenclature of the 1-OH derivatives) as the major product. (10Z)- and (10E)-19-Fluorovitamin Ds were also interconverted thermally probably via the corresponding previtamin D by 1,7-sigmatropic isomerization.     

Theoretical study of the trapping of the OOH radical by coenzyme Q

The reactivity of the hydroperoxyl radical with coenzyme Q, as a prototypical chemical reaction involved in biological antioxidant actions, was studied theoretically. Two pathways were analyzed: the hydrogen abstraction reaction from the phenolic hydrogen on the reduced form (ubiquinol), and OOH addition on the oxidized form (ubiquinone). Optimized geometries, harmonic vibrational frequencies, and energies of the stationary points (reactants, intermediate complexes, transition states, and products) for each pathway were calculated at the BHandHLYP/6-31G level of theory. The reaction paths for the two mechanisms were traced independently, and the respective thermal rate constants were calculated using variational transition-state theory with multidimensional small-curvature tunneling. We found that the reactivity of the OOH radical is dominated by the hydrogen abstraction mechanism on ubiquinol, with a rate constant of 5.32 x 10(5) M(-1) s(-1), at 298 K. This result strongly contrasts with that, also obtained by our group, for the more reactive OH radical, which attacks ubiquinone by an addition mechanism, with a diffusion-controlled rate of 6.25 x 10(10) M(-1) s(-1), at 298 K.     

硝基胍H迁移异构化反应动力学的从头计算研究

Theoretical studies on the α- and β-forms nitroguanidine were carried out using ab initio theoretical methods, at the MP2/6-31G(d,p) level. The predicted geometrical parameters were in good agreement with the available theoretical values, which calculated by other author. The three C-N bond lengths in α-form nitroguanidine were different, the longest bond length was 1.430 A, the shortest was 1.283 A. But they were almost similar in β-form, the longest was 1.375 A, the shortest was 1.322 A. Therefore there were conjugative effects in β-form but not in α-form. The calculated results also show that the β-form is stable with respect to the α-form from energetically, lower 28.16 kJ/mol corrected with zero point vibrational energy. The transition-state for the unimolecular isomerization was conformed by the IRC calculation. The calculated energy barrier for the direct intramolecular hydrogen atom transfer isomerization process was 132.95 kJ/mol. The isomerization reaction, exothermal reaction, is a typical intramolecular hydrogen atom synfacial transfer reaction. Rate constants of the isomerization reaction were evaluated within the temperature range of 200-1773 K by the classical transition state theory. The rate constant was 1.99×10-11 s-1 and the equilibrium constant was 1.00×105 at 298 K. With the temperature increasing, the equilibrium value decayed and the reaction process was more difficult.     

On the importance of prereactive complexes in molecule-radical reactions: hydrogen abstraction from aldehydes by OH.

In this work, the OH + formaldehyde and OH + acetaldehyde reactions have been characterized using accurate ab initio methods with large basis sets. The results clearly indicate that the reaction occurs by hydrogen abstraction, and that the OH addition channel is unfavorable. Close to zero (for formaldehyde) and negative (for acetaldehyde) activation energy values are obtained, which are in excellent agreement with the experimentally observed values. The reaction rate constants, calculated using the classical transition-state theory as applied to a complex mechanism involving the formation of a prereactive complex, reproduce very well the reported experimental results. Consideration of the prereactive complex is shown to be essential for the determination of the height of the energy barrier and thus for the correct calculation of the tunneling factor.     

Direct dynamics study of the hydrogen-abstraction reaction of 1,1,2,2,3-fluorinated propane with the hydroxyl radical

The hydrogen abstraction reactions by a hydroxyl radical from 1,1,2,2,3-fluorinated propane (CF2HCF2CFH2) have been investigated by the dual-level direct dynamics method. Three equilibrium conformers (I, II, III) of CF2HCF2CFH2, one with Cs and two with C1 symmetries, are identified by the rotations of -CFH2 and -CF2H groups. Two transition states are located for the conformer I (Cs symmetry) + OH --> products (R1) reaction, and three distinct transition states are identified for conformers II and III (C1 symmetry) + OH --> products (R2 and R3). The optimized geometries and harmonic vibrational frequencies of all reactants, complexes, transition states, and products are calculated at the BB1K/6-31+G(d,p) level of theory. The single-point energy calculations are performed at the G3(MP2) level using the BB1K geometries. Using improved canonical variational transition-state theory (ICVT) with the small-curvature tunneling correction (SCT), the rate constants for each channel are calculated over a wide temperature range of 200-2000 K. It is found that the H-abstraction reaction from the -CFH2 group is the predominant product channel for three reactions. The total rate constant is evaluated by the Boltzmann distribution function, and the agreement between theoretical and experimental values is good.     

Direct ab initio dynamics studies on the hydrogen-abstraction reactions of OH radicals with HOX (X = F, Cl, and Br)

The hydrogen abstract reactions of OH radicals with HOF (R1), HOCl (R2), and HOBr (R3) have been studied systematically by a dual-level direct-dynamics method. The geometries and frequencies of all the stationary points are optimized at the MP2/6-311+G(2d, 2p) level of theory. A hydrogen-bonded complex is located at the product channel for the OH + HOBr reaction. To improve the energetics information along the minimum energy path (MEP), single-point energy calculations are carried out at the CCSD(T)/6-311++G(3df, 3pd) level of theory. Interpolated single-point energy (ISPE) method is employed to correct the energy profiles for the three reactions. It is found that neither the barrier heights (DeltaE) nor the H-O bond dissociation energies [D(H-O)] exhibit any clear-cut linear correlations with the halogen electronegative. The decrease of DeltaE and D(H-O) for the three reactions are in order of HOF > HOBr > HOCl. Rate constants for each reaction are calculated by canonical variational transition-state theory (CVT) with a small-curvature tunneling correction (SCT) within 200-2000 K. The agreement of the rate constants with available experimental values for reactions R2 and R3 at 298 K is good. Our results show that the variational effect is small while the tunneling correction has an important contribution in the calculation of rate constants in the low-temperature range. Due to the lack of the kinetic data of these reactions, the present theoretical results are expected to be useful and reasonable to estimate the dynamical properties of these reactions over a wide temperature range where no experimental value is available.