4-取代Fentanyl类化合物电子结构及构效关系研究

本文对十一个4-取代Fentanyl类化合物进行了量子化学(INDO)计算, 研究了它们的电子结构及构效关系. 结果表明, 这些化合物同其他Fentanyl类化合物在主要活性部位和电子结构趋势上基本相同. 酰胺氧原子是最重要的负电中心, 哌啶氮原子在季铵化后发挥正电中心作用. 4-取代基的极性基团可能以电荷转移作用或氢键接受体形式与受体极性部位结合, 并能影响其他活性部位电子密度. 另外, 4-取代基的立体因素与疏水因素同生物活性相关.     

Experimental and theoretical study of three new benzothiazole-fused carbazole derivatives

Three new D-π-A type compounds, each containing one benzothiazole ring as an electron acceptor and one N-ethylcarbazole group as electron donor, were synthesized and characterized by elemental analysis, NMR, MS and thermogravimetric analysis. The absorption and emission spectra of three compounds were experimentally determined in several solvents and were simultaneously computed using density functional theory (DFT) and time-dependent density functional theory (TDDFT). The calculated reorganization energy for hole and electron indicates that three compounds are in favor of hole transport than electron transport. The calculated absorption and emission wavelengths are well coincident with the measured data. The calculated lowest-lying absorption spectra can be mainly attributed to intramolecular charge transfer (ICT). And the calculated fluorescence spectra can be mainly described as originating from an excited state with intramolecular charge transfer (ICT) character. The results show that three compounds exhibited excellent thermal stability and high fluorescence quantum yields, indicating their potential applications as excellent optoelectronic material in optical field.     

丁吡吗啉与其苯基类似物的电子结构特征比较

通过化学合成获得丁吡吗啉及其苯基类似物,并对其杀菌活性进行了比较.借助X射线晶体衍射方法,对丁吡吗啉的结构进行了解析.进一步选择6-31G(2df,2pd)基组,利用密度泛函理论B3LYP方法对丁吡吗啉及其苯基类似物的空间几何结构进行优化,借助前线分子轨道、Mulliken电荷、自然键轨道(NBO)分析、表观静电势等对丁吡吗啉及其苯基类似物的电子结构与其杀菌活性相关性进行了理论探讨.结果表明吡啶环取代苯环后,一方面吡啶环上的N原子是一个负电中心,有利于与受体分子间形成氢键等相互作用;另一方面,吡啶环又是一个缺电子的芳环,与苯环相比,在与受体的π-π相互作用中能起到更好的电子接受体的作用.这两种因素使得丁吡吗啉更容易与受体结合,因而活性更高.     

4H-甲基咪唑苯二氮(艹卓)酮类抗HIV-1药物的量子化学研究

用分子力学MM3方法、量子化学MNDO法和从头算STO-3G基组计算了20个4H-甲基咪唑苯二氮(廿卓)酮HIV-1逆转录酶抑制剂的优势构型和电子结构,用逐步回归方法和BP神经网络方法得到其抗HIV-1活性与电子结构的定量构效关系.结果表明:(1)TIBO类衍生物的体积越大,极性越小,即流水性越大对抑制HIV-1活性越有利.(2)C环N上H原子可能是化合物的正电活性部位.(3)R′原子与受体作用时可能作为电子给予体,前线轨道中S的贡献比O大得多,故含S的TIBO化合物比含O化合物的活性高.(4)苯环上连接吸电子基团对活性有利,由于分子的正负电荷中心距离较近,极性较小,疏水性较大,故3位取代比2位取代活性更高.     

Interplay between hydrogen bond formation and multicenter pi-electron delocalization: intermolecular hydrogen bonds

The interplay between aromatic electron delocalization and intermolecular hydrogen bonding is thoroughly investigated using multicenter delocalization analysis. The effect on the hydrogen bond strength of aromatic electron delocalization within the acceptor and donor molecules is determined by means of the interaction energies between monomers, calculated at the B3LYP/6-311++G(d,p) level of theory. This magnitude is compared to variations of multicenter electron delocalization indices and covalent hydrogen bond indices, which are shown to correlate perfectly with the relative values of the interaction energies for the different complexes studied. The multicenter electron delocalization indices and covalent bond indices have been computed using the quantum theory of atoms in molecules approach. All the hydrogen bonds are formed with oxygen as the acceptor atom; however, the atom bonded to the donor hydrogen has been either oxygen or nitrogen. The water-water complex is taken as reference, where the donor and acceptor molecular environments are modified by substituting the hydrogens and the hydroxyl group by phenol, furan, and pyrrole aromatic rings. The results here shown match perfectly with the qualitative expectations derived from the resonance model.     

Detailed comparison of the pnicogen bond with chalcogen,halogen, and hydrogen bonds

The characteristics of the pnicogen bond are explored using a variety of quantum chemical techniques. In particular, this interaction is compared with its halogen and chalcogen bond cousins, as well as with the more common H‐bond. In general, these bonds are all of comparable strength. More specifically, they are strengthened by the presence of an electronegative substituent on the electron‐acceptor atom, and each gains strength as one moves down the appropriate column of the periodic table, for example, from N to P to As. These noncovalent bonds owe their stability to a mixture in nearly equal parts of electrostatic attraction and charge transfer, along with a smaller dispersion component. The charge transfer arises from the overlap between the lone pair of the electron donor and a σ* antibond of the acceptor. The angular characteristics of the equilibrium geometry result primarily from a compromise between electrostatic and induction forces. Angular distortions of the H‐bond are typically less energetically demanding than comparable bends of the other noncovalent bonds. © 2012 Wiley Periodicals, Inc.     

Molecular quantum similarity analysis of estrogenic activity

The main objective of this study was to evaluate the capability of 120 aromatic chemicals to bind to the human alpha estrogen receptor (hER alpha) by the use of quantum similarity methods. The experimental data were segregated into two categories, i.e., those compounds with and without estrogenicity activity (active and inactive). To identify potential ligands, semiquantitative structure-activity relationships were developed for the complete set correlating the presence or lack of binding affinity to the estrogen receptor with structural features of the molecules. The structure-activity relationships were based upon molecular similarity indices, which implicitly contain information related to changes in the electron distributions of the molecules, along with indicator variables, accounting for several structural features. In addition, the whole set was split into several chemical classes for modeling purposes. Models were validated by dividing the complete set into several training and test sets to allow for external predictions to be made.     

Structure, spectroscopy, and reactivity properties of porphyrin pincers: a conceptual density functional theory and time-dependent density functional theory study

Porphyrin and pincer complexes are both important categories of compounds in biological and catalytic systems. The idea to combine them is computationally investigated in this work. By employment of density functional theory (DFT), conceptual DFT, and time-dependent DFT approaches, structure, spectroscopy, and reactivity properties of porphyrin pincers are systematically studied for a selection of divalent metal ions. We found that the porphyrin pincers are structurally and spectroscopically different from their precursors and are more reactive in electrophilic and nucleophilic reactions. A few quantitative linear/exponential relationships have been discovered between bonding interactions, charge distributions, and DFT chemical reactivity indices. These results are implicative in chemical modification of hemoproteins and understanding chemical reactivity in heme-containing and other biologically important complexes and cofactors.     

Carbon-13 NMR study of 1-methyl-3-phenyl-4-diazo-5-benzoylamidopyrazole and other model pyrazole compounds

A ¹³C nmr study of a diazo, of two diazonium salts and of some other model pyrazole compounds is reported. It is found that the C-4 diazo carbon is more shielded than the normal sp² pyrazole hybridized carbon, while its diazonium salt is more deshielded. The electron density on the C-4 of the diazopyrazole is probably due to the positive charge on the terminal nitrogen. Thus the ¹³C chemical shift values allowed us to understand the chemical behaviour of a compound of potential antitumor activity.     

石房蛤毒素(STX)衍生物的电子结构与毒性-结构关系研究

本文对十个石房蛤毒素(Saxitoxin,STX)衍生物进行了量子化学(INDO)计算,得到了多种电子结构信息。据此研究了它们的电子结构特征,确定了它们的活性部位。通过构效关系研究,发现某些电子结构指数与毒性之间存在较好的相关关系。这些结果为讨论该类化合物的作用机理、与受体之间的相互作用及进一步的分子设计提供了有价值的信息。     

Investigation of the inclusion complex of tolfenamic acid with β-cyclodextrin: Geometry and NBO analysis

Quantum chemical calculations were carried out to investigate geometry and driving forces for inclusion complexes of tolfenamic acid (TA) into β-CD (at 1:1 stoichiometry). Two possible orientations of TA in the β-CD cavity were considered. Both PM3MM and ONIOM2 method evidence that TA is encapsulated in the β-CD cavity for A and B orientation. Finally, charge transfer between the donor and acceptor orbitals of each TA and β-CD play an important role to stabilize the inclusion complex.     

推/拉电子取代基对PCBM结构及光谱性质影响的理论研究

应用密度泛函理论(DFT)方法计算[6,6]-苯基-C₆₁-丁酸甲酯(PCBM)及其苯环对位取代得到的4种衍生物的几何和电子结构. 采用第一激发能校正了分子的最低未占据分子轨道(LUMO)能级, 探讨了推/拉电子基团对分子前线轨道的影响. 在全优化几何构型的基础上, 采用含时密度泛函理论(TD-DFT)方法研究了电子吸收光谱特征和电荷转移态性质, 并讨论了推/拉电子基团对体系电子吸收光谱性质的影响. 通过对重组能和电子亲和势的计算, 预测了PCBM与4种衍生物的电子能力及电子迁移率大小的关系. 结果表明, 在PCBM中, 在苯环的对位引入推电子基团可以提高分子的前线轨道能级, 改变前线轨道电子云分布, 明显增强可见光范围内的吸收强度, 增加可见光范围内的电荷转移吸收, 且激发态的电荷转移随着引入基团推电子能力的增加而增强. 化合物5的激发态分子内电荷转移性质最强, 且具有较独特的光伏性质. 而在同样位置引入拉电子基团, 则降低了分子前线轨道能级对电子吸收光谱的影响.     

Photoinduced intramolecular charge transfer (ICT) reaction in trans-methyl p-(dimethylamino) cinnamate: A combined fluorescence measurement and quantum chemical calculations

The photophysical behaviour of trans-methyl p-(dimethylamino) cinnamate (t-MDMAC) donor–acceptor system has been investigated by steady-state absorption and emission spectroscopy and quantum chemical calculations. The molecule t-MDMAC shows an emission from the locally excited state in non-polar solvents. In addition to weak local emission, a strong solvent dependent red shifted fluorescence in polar aprotic solvents is attributed to highly polar intramolecular charge transfer state. However, the formation of hydrogen-bonded clusters with polar protic solvents has been suggested from a linear correlation between the observed red shifted fluorescence band maxima with hydrogen bonding parameters (). Calculations by ab initio and density functional theory show that the lone pair electron at nitrogen center is out of plane of the benzene ring in the global minimum ground state structure. In the gas phase, a potential energy surface along the twist coordinate at the donor (–NMe₂) and acceptor (–CH = CHCOOMe) sites shows stabilization of S₁ state and destabilization S₂ and S₀ states. A similar potential energy calculation along the twist coordinate in acetonitrile solvent using non-equilibrium polarized continuum model also shows more stabilization of S₁ state relative to other states and supports solvent dependent red shifted emission properties. In all types of calculations it is found that the nitrogen lone pair is delocalized over the benzene ring in the global minimum ground state and is localized on the nitrogen centre at the 90° twisted configuration. The S₁ energy state stabilization along the twist coordinate at the donor site and localized nitrogen lone pair at the perpendicular configuration support well the observed dual fluorescence in terms of proposed twisted intramolecular charge transfer (TICT) model.     

Integration of Graph Theory and Quantum Chemistry for Structure-Activity Relationships

Abstract

The objective of this article is to outline both graph-theoretically based and quantum chemically based structural indices of potential use in quantitative structure activity correlations. We consider graph-theoretical indices such as the connectivity index, topological index, Wiener index and molecular ID indices. Several structural and geometry-dependent indices can be derived from semiempirical and ab initio quantum calculations based on the charge densities, overlap matrices, frontier orbitals, molecular hardness, free valence, density matrices, quantum spectral difference indices, quantum spectral indices and bond matrices. Finally, the use of electrostatic potentials and charge densities for the prediction of reactive sites will be discussed.     

二苯二硫和二苄二硫润滑性能的量子化学研究

The molecular geometries optimization and electronic structures of diphenyl disulfide (DPDS) and dibenzyl disulfide (DBDS) compounds were investigated by density functional theory (DFT) and ab initio method at the 6-31G basis set level. The active atoms and bonds of reaction were provided by frontier molecular orbital theory. The molecular orbital parameters of DPDS and DBDS compounds and iron atom cluster were calculated by using density functional theory. The interaction pattern between the organic disulfide compounds and iron atom cluster was discussed based on the approximate rule of orbital energy. Some parameters characterizing the action strength between the organic disulfide compounds and iron atom cluster, including the bonding strength, reactive strength and static action strength, were analyzed by using frontier electron density, super de-localizability, net atomic charge and the interaction energy of chemical adsorption as criteria. The results indicate that S-S chemical bond and C-S chemical bond of the compounds are inclined to be broken when DPDS and DBDS interact with the metal. The anti wear ability order of DPDS and DBDS compounds is DPDS>DBDS, and the extreme pressure ability order of DPDS and DBDS compounds is DBDS>DPDS, and the prediction results based on quantum chemistry calculations are in good accordance with the friction and wear test results.     

有机二硫化物润滑添加剂抗磨极压性能的密度泛函理论研究

用量子化学的密度泛函理论计算了12种有机二硫化物和铁原子簇的分子轨道指数及其与铁原子簇的化学吸附作用能, 探讨了这种作用能与抗磨性能的关系; 运用轨道能量近似原则讨论了有机二硫化物与铁原子的作用方式; 以前线电子密度、超离域性指数和原子净电荷作为判据分析了12种有机二硫化物与铁原子间键合的强弱、反应性的大小等表征有机二硫化物与金属作用强弱的参数。结果表明: 有机二硫化物与铁接触时, 在较缓和条件下, SS键优先断裂与金属发生化学吸附形成配位键, 起到抗磨作用; 在高负荷下, 与金属发生常规条件下不能发生的化学反应, 即CS键断裂生成无机膜, 起到极压作用; 且随着碳链的增长, 有机二硫化物的抗磨性能愈来愈好, 但极压性能愈来愈差; 运用量子化学计算得到的预测结果与摩擦学试验结果具有良好的一致性, 可为同类极压添加剂化合物的分子设计提供较为可靠的参考依据和理论方法。