Solution Conformation of a Pentapeptide by NMR and Molecular Modeling Studies

High resolution NMR studies and molecular modeling calculations were performed on a linear pentapeptide BOC-Tyr-Gly-Gly-Pro-Leu-OMe. This molecule exhibits two conformations in the solution state. While the ¹³C spectrum in nonpolar solvents such as acetonitrile shows only one form, in DMSO-d₆ and MeOD there are two forms. The appearance of the major (M) and minor (m) resonances is attributed to cis-trans isomerization about the X-Pro bond.

The assignments of several proton resonances for the major conformer were made through the combined analysis of two dimensional (2D) homonuclear correlated spectroscopy (COSY) and available data on similar peptides. The solution conformation of the major moiety was probed using the distance constraints obtained from 2D-NOE spectroscopy (NOESY). In addition, other information such as presence of internal hydrogen bonds and dihedral angle values from coupling constants for the amide protons were also used.     

The isomerization of cytosine: Intramolecular hydrogen atom transfer mediated through formic acid

The catalytic ability of H₂O and HCOOH to facilitate the tautomerism of KA to KIt isomer has been studied. It is shown that the direct tautomerism (path A) is unlikely because of the high activation free energy, whereas the presence of H₂O and HCOOH (paths B and C) significantly contributes to decreasing the activation free energy. Meanwhile, the conventional transition state theory followed by Wigner tunneling correction is applied to estimate the rate constants. The rate constant with Wigner tunneling correction for direct tautomerization is obviously smaller than that of HCOOH‐mediated tautomerization, which is the most plausible mechanism. Finally, another important finding is that the ratio of reaction rates between direct tautomerism reaction and catalyst‐induced tautomerism increases with the increase of the catalyst concentration at a given temperature. The results of the present study demonstrate the feasibility of acid catalysis for DNA bases isomerization reaction that would otherwise be forbidden.     

Combined 1H NMR and DFT study of the solvent effects on the iron pentacarbonyl‐catalyzed photo‐assisted isomerization of allyl alcohol

The relative rates of iron pentacarbonyl‐catalyzed photo‐induced isomerization of allyl alcohol to propanal in various solvents have been measured using ¹H NMR spectroscopy. The reactions were run in linear and cyclic alkanes, alcohols, and amines in order to investigate solvent effects on the isomerization mechanism upon ultraviolet irradiation. The isomerization was efficient in nonane, hexane, cyclohexane, and benzene. The isomerization was very slow or completely suppressed in ethanol, propanol, isopropanol, triethylamine, and pyridine. Density functional theory calculations predicted thermodynamically favorable (ΔG^o < 0) formation of Fe(CO)₄–solvent compounds in the suppressing alcohol/amine solvents and unfavorable (ΔG^o > 0) formation in the hydrocarbon solvents. The strong solvent ligation likely prevents formation of Fe(CO)₃●(η²‐alkene) necessary for isomerization. Copyright © 2013 John Wiley & Sons, Ltd.     

Thermolysis kinetics of diethyl 2,3‐dicyano‐2,3‐di(p‐substituted phenyl)succinates

An experimental approach was developed to determine the intrinsic thermolysis rate constants of the central carbon–carbon bond during the dl/meso isomerization of diethyl 2,3‐dicyano‐2,3‐di(p‐substituted phenyl)succinates (G=H, Me, OMe, Cl, and NO₂) at temperatures ranging from 80 to 120 °C. The obtained rate constants are significantly affected by the polarity of the para substituents, in sharp contrast to their negligible effects on the dl/meso isomerization equilibrium constants. Moreover, the substituent effects on the activation enthalpies can be linearly correlated with the Hammett substituent resonance constants and the homolytic dissociation enthalpies (bond dissociation energies) of the benzylic C–H bonds of ethyl 2‐cyano‐2‐(p‐substituted phenyl)acetates. Copyright © 2011 John Wiley & Sons, Ltd.     

Theoretical Study on Mechanism of Cycloadditional Reaction Between Dichloro-Germylidene and Formaldehyde

用MP2/6-31G^*方法研究了单线态二氯亚甲基锗烯与甲醛环加成反应的反应机理,该反应有两条相互竞争的主反应通道,同时伴随着两中间体(INT3和INT4)副产物的生成. 第一条主反应通道所生成的物种为三员环中间体(INT1)和Ge-O顺位的四员环产物(P1);第二条主反应通道所生成的物种为Ge-O对位的扭曲四员环中间体(INT2)和氯迁移产物(P2);P1和INT2分别与甲醛(R2)的进一步作用而导致了两副产物的生成.     

Understanding the role of Zn2+ in the hydrolysis of glycylserine: a mechanistic study by using density functional theory

The hydrolysis mechanism of glycylserine in the presence of Zn²⁺ was theoretically studied by means of density functional theory calculations. Two possible reaction mechanisms are proposed for the hydrolysis reaction: (1) the first one involves a stepwise reaction with an initial attack of the serine –OH to the amide carbonyl group through a general base catalysis of a water molecule, which undergoes to a proton transfer to the carboxylate group to give a cyclic intermediate. Its further rearrangement finally forms an ester that hydrolyses to yield products. (2) The second mechanism involves a general base catalysis by the carboxylate group for the water attack to the amide carbonyl group to generate a tetrahedral intermediate. Upon comparison of both mechanisms, it is observed that the former is favoured; furthermore, its first step is the rate-limiting step in a bicyclic asynchronous transition state with evolution of 86% in C₍₁₎–O₍₂₎ bond. The crucial role of Zn²⁺ in this hydrolysis process can be rationalised in terms of the inductive effect and the formation of a rigid structure that increases the electrophilicity of the amide carbonyl group. The calculations presented in this report are in good agreement with reported values for the activation barrier.     

The Endo-Exo Isomerization of N-Phenyl-5-norbornene-2,3-dicarboximide

ENDO isomers of N-phenyl-5-norbornene-2,3-dicarboximide was converted to exo-isomers below retro-Diels-Alder temperature under various reaction conditions. The exo-endo yield ratio was studied by NMR and the ¹H and ¹³C NMR chemical shifts of the isomers are reported. While no intermediate could be isolated using several different radical trapping agents, the results show that 7,5 proton chemical shift is a possible isomerization mechanism.     

Mechanisms and Möbius strips: understanding dynamic processes in annulenes

Exploratory computational studies on annulenes with planar, Möbius, and two‐twist topologies have resulted in new mechanisms to explain facile thermal configuration change (cis‐trans isomerization) for medium‐sized annulenes ([12]‐ to [16]annulene). Möbius π‐bond shifting through both aromatic and antiaromatic transition states, two‐twist π‐bond shifting, and planar nondegenerate π‐bond shifting can all be invoked to explain experimental results. Moreover, a simple bond‐shift rule, which is based on the change in number of trans C?C double bonds (Δtrans), was developed that predicts the topology of the transition state(s) necessary to effect the desired cis‐trans isomerization. The bond‐shift rule was also applied to configuration change in dehydro[12]annulene. Finally, extensive investigation of the [14]annulene hypersurface revealed that numerous Möbius minima exist within 10 kcal/mol of the global minimum. Copyright © 2012 John Wiley & Sons, Ltd.     

3种药物分子的1H和13C NMR谱线全指定

应用1D和2D NMR技术,对3种药物分子：比卡鲁胺(Bicalutamide)、马来酸罗格列酮(Rosiglitazone Maleate)、氯吡格雷硫酸盐(Clopidogrel Hydrogensulfate)的¹H和¹³C NMR的谱峰进行了准确归属.     

2-硝基苯胺合成苯并氧化呋咱反应的密度泛函研究

用密度泛函理论在B3LYP/6-31G(d,p)计算水平下研究了次氯酸钠氧化邻硝基苯胺生成苯并氧化呋咱的环氧化反应．考虑溶剂化效应对反应的影响,使用极化连续反应场模型进行几何优化．计算了该反应的两种可能反应通道,它们都是分步反应,反应通道A经历氧化、移氢、脱水和环化四步反应,在反应通道B中,氢氧化钠的OH^-首先进攻邻硝基苯胺的胺基H原子,生成邻硝基苯亚胺负离子．计算结果表明,在反应通道A是可行的反应通道,1个水分子辅助进行分子内脱水反应是速控步骤．     

Application of Optically Detected EPR to Study the Stability of Sterically Hindered Amine Radical Cations to Proton Transfer Reaction

Optically detected electron paramagnetic resonance technique has been applied to study the stability of sterically hindered amine radical cations with respect to the ion–molecule proton transfer reaction in liquid squalane solutions. The reaction has proved very sensitive to the steric effect of bulky tertiary substituents at the nitrogen atom. It has been established that steric hindrance is able to efficiently block the N–H proton transfer reaction, while the H-bonding may stabilize the distonic intermediate complex of aminyl radical and cation of ammonium type.     

Nonlinear laser UV photochemistry of maleic acid in aqueous solution

This work deals with photochemical transformations of maleic acid in an aqueous solution under powerful picosecond fourth-harmonic pulses of a YAG-Nd³⁺ laser with λ=266 nm and nanosecond pulses of an excimer KrF laser with λ-248 nm. It has been found that by changing the irradiation intensity only it is possible to produce selectively different products with a high quantum yield resulting from the following reactions of the ?C=C? bond of the maleic acid molecule: 1) cis-trans isomerization at radiation intensities up to 10⁸ W/cm² as a result of linear photochemistry; 2) radical dimerization of the maleic acid withJ=10⁸÷10⁹ W/cm² and water addition to the ?C=C? bond of the maleic acid withJ?10⁹ W/cm² as a result of nonlinear photochemistry.     

Kinetics of pi‐complex isomerization during AlCl3‐catalyzed Friedel–Crafts reactions between linear olefins and p‐xylene

Rapid isomerization of pi‐complex intermediates results in the formation of multiple isomers of alkyl aromatics during AlCl₃‐catalyzed reactions between linear olefins and aromatic rings. The authors present results of a kinetic study of reactions between p‐xylene, 1‐dodecene, and linear tetradecenes. Product distributions are well predicted based on a model of reversible pi‐complex isomerization. Surprisingly, no double bond isomerization was observed in the linear olefins: All isomerization occurred in the pi‐complexes. Copyright © 2014 John Wiley & Sons, Ltd.     

Transformation of alkylbenzenes in an oxidizing medium on H-ZSM-5 catalyst under supercritical conditions

Reactions of the substituted benzenes toluene, p-xylene, fluorobenzene, phenol, cumene and styrene with nitrous oxide as an oxidant on H-ZSM-5 catalyst under supercritical conditions at 345–420°C and 70–150 atm were studied. It is shown that the products of disproportionation, isomerization and condensation that do not contain oxygen form predominantly. Only in the oxidation of toluene does the selectivity to the oxidation product (cresols) reach 35%. The yield of corresponding phenols in the oxidation of alkyl-, hydroxy- and fluorobenzenes is negligible. The double bond conjugated with the π-system of benzene rings (styrene), as well as the presence of branched alkyl substituents (in cumene) and hydroxyl-group (in phenol) hinder the formation of benzene ring oxidation products.     

Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP)

Hydrolytic reactions of cyclic bis(3′‐5′)diadenylic acid (c‐di‐AMP) have been followed by Reversed phase high performance liquid chromatography (RP‐HPLC) over a wide pH range at 90 °C. Under neutral and basic conditions (pH ≥ 7), disappearance of the starting material (first‐order in [OH^?]) was accompanied by formation of a mixture of adenosine 2′‐monophosphate and 3′‐monophosphate (2′‐AMP and 3′‐AMP). Under very acidic conditions (from H₀ = ?0.7 to 0.2), c‐di‐AMP undergoes two parallel reactions (first‐order in [H⁺]): the starting material is cleaved to 2′‐AMP and 3′‐AMP and depurinated to adenine (i.e., cleavage of the N‐glycosidic bond), the former reaction being slightly faster than the latter one. At pH 1–3, isomerization to cyclic bis(2′‐5′)diadenylic acid competes with the depurination. Copyright © 2012 John Wiley & Sons, Ltd.     

A comparative study on the gas‐phase and liquid‐phase thermal isomerization reaction of α‐pinene

In this paper, a method of preparation of ocimene is investigated, which is obtained from isomerization reaction of α‐pinene. Two kinds of experimental apparatus are established for the investigation of the thermal isomerization reaction of α‐pinene. The behavior of thermal isomerization reaction of α‐pinene is respectively discussed in the gas phase and in the liquid phase. Under gas phase conditions, the conversion of α‐pinene is 80% and the selectivity of ocimene is 30%–33%. Under liquid phase conditions, the conversion of α‐pinene is 60% and the selectivity of ocimene is 50%–54%. According to the kinetic‐molecular theory of ideal gases, two kinds of reaction models are proposed to visualize the reaction process. In addition, the mechanism and kinetics of thermal isomerization reaction of α‐pinene are respectively discussed. The conclusion is that the gas phase reaction temperature is calculated to be 390–450 °C and the liquid phase reaction temperature is calculated to be 450–550 °C. From a bond dissociation energy point of view, results support the hypothesis that the reaction involves biradical intermediates. Copyright © 2012 John Wiley & Sons, Ltd.     

吡啶酰胺类化合物中酰胺键异构化的变温核磁共振研究

合成了一系列六氢吡啶酰胺化合物以研究酰胺键的双键性质. 采用¹H 及¹³C NMR 技术确证了不同取代的酰胺化合物中酰胺键的双键性质. 进一步采用变温核磁共振技术对2-(3,5- dinitrophenyl)-1-(piperidin-1-yl)ethanone(化合物1)进行了¹H 及¹³C NMR研究. 结果表明,在20 ℃（293 K）时,a, b及c, d上的氢和碳原子具有不同的化学位移,且距酰胺键越近,化学位移的差异越大. 随着温度的升高,两种异构体的转换速率增加,酰胺双键的性质越来越不明显,导致化学位移的差异逐渐减小,直至融合为一个峰. 经计算,在融合温度下两种异构体的相互转换的速率常数是380 s-¹,能垒约为67 kJ&#8226; mol^-1.       

Kinetics of the geometric isomerization of cyclohexene in a stochastic bath

Rare-events molecular dynamics techniques are used to study the interconversion between the two half-chair isomers of cyclohexene (C₆H₁₀), in a solvent modelled through a stochastic bath, in order to investigate dynamic solvent effects on the isomerization rate. Adopting the torsional angle around the C-C sigma bond opposite to the double bond as the reaction coordinate, we calculate the equilibrium distribution of this coordinate (using umbrella sampling), and estimate the isomerization rate, including the transmission coefficient κ. The paper also contains methodological developments. A variant of Andersen's stochastic collision method (canonical ensemble sampling) is developed for molecules with constraints: by resampling Cartesian velocities of a localized subgroup of atoms of the molecule and leaving all other atomic velocity components unchanged, one mimics the collision of a virtual gas molecule with a subpart of the molecule of interest. To evaluate the transmission coefficient κ, the initial conditions for trajectories ‘crossing the top’ are automatically generated during the run, using a biased potential to obtain the probability of being at the saddle point.     

黑索金的电子结构和热解机理的从头算研究

利用从头算梯度修正密度泛函理论,我们在B3LYP/6-31G(d,p)水平上,计算了高能炸药黑索金(RDX)及其热解中间产物C3H6N5O4和NO2等的电子结构、能量、键级和一些热力学性质,并在此基础上,计算了键离解能和反应速率常数.此外,我们还分别从键级和键离解能角度,讨论了RDX的热解机理,所得结果与实验一致.     

Pyrolysis of amines: Infrared spectrum of allylimine

Infrared absorption spectrum of allylimine in the gas phase was measured for the first time. The spectrum consisted of two rotational isomers, cis and trans, around the CC bond. The relative population of the trans form was 70–80%, and the rest was for the cis form at room temperature. This intermediate molecule was produced by the thermal decomposition of diallylamine and by the isomerization of propargylamine. The vibrational assignments were made with the help of an ab initio MO calculation. The half-life in the absorption cell was about 20 min.