腺苷酸琥珀酸合成酶与其抑制剂的分子机制研究

利用密度泛函B3LYP方法选择6-31G(d)基组对腺苷酸琥珀酸合成酶(AdSS)天然抑制剂及其衍生物的结构进行优化,并对其稳定性进行了分析,同时采用Mulliken键序、原子电荷分布、表观静电势等对AdSS抑制剂及其衍生物电子结构与其生物活性相关性进行了理论研究.基于腺苷酸琥珀酸合成酶(AdSS)与其底物肌苷单磷酸(IMP)复合物的晶体结构以及获得的天然抑制剂衍生物稳定构象,利用分子对接、分子力学优化及常温分子动力学模拟对AdSS酶与天然抑制剂及其衍生物的相互作用复合物结构进行理论预测.结果表明,AdSS酶的系列抑制剂中磷酸根基团和乙内酰脲(Hydantoin)官能团构成药效团模型,识别过程中范德华相互作用能的贡献大于静电相互作用能.     

4-二羟基硼苯丙氨酸(BPA)及其多羟基衍生物BPA(OH)n(n=1,2,4)的电子结构的理论研究

使用密度泛函方法对硼中子捕获疗法药物4-二羟基硼苯丙氨酸(BPA)及其多羟基衍生物BPA(OH)和BPA(OH)2, BPA(OH)4的电子结构进行了理论计算, 探讨了BPA药物作用的可能机制及其羟基衍生物具有良好水溶性的主要因素. 研究结果表明, BPA的HOMO主要分布在苯环上, 而BPA(OH), BPA(OH)2和BPA(OH)4的HOMO主要位于多羟基基团与BPA母体的结合部位的C, N和O原子附近, 羟基衍生物的这种HOMO轨道特性、 结构中极性基团数量的增多及分子极性的增大等可能是它们具有良好水溶性的主要因素. 计算结果与实验结果一致.     

溶剂效应和取代基效应对2-(2-氨基苯基)苯并噻唑光谱性质及激发态分子内质子转移的影响

合成了多种2-(2-氨基苯基)苯并噻唑(APBT)氨基氢原子被供电子及吸电子基团取代的衍生物, 并用紫外光谱﹑荧光光谱等方法和密度泛函理论(DFT)计算研究了溶剂效应和取代基效应对衍生物的光谱性质及激发态分子内质子转移(ESIPT)的影响规律. 结果表明, 相比于非极性溶剂环己烷, 随溶剂极性的增加及APBT-溶剂分子间氢键的形成, APBT的紫外-可见最大吸收峰和荧光最大发射峰均发生了一定程度的红移, 并对APBT的ESIPT产生了影响. 在APBT分子的氨基氮原子上引入不同的吸电子或斥电子取代基, 对氮原子的电荷性质有较大的影响. 在环己烷溶剂中, 甲基取代后的APBT仅有单重荧光发射峰, 体系未发生ESIPT过程; 而COCH₂Cl等吸电子基团能促进APBT的ESIPT, 其荧光发射光谱出现了明显的双重峰, 表明体系发生了激发态分子内质子转移反应. 量子化学的理论计算较好地验证了光谱实验结果.     

[Ru(bpy)2(phen)]^2+主配体上双取代效应DFT法研究

对钌联吡啶菲咯啉配合物[Ru(bpy)2(phen)]^2+及其主配体(phen)上5,6-双取代衍生物,用密度泛函(DFT)法在B3LYP/LanL2DZ水平上进行理论计算研究。探讨供电子基团(OH)和拉电子基团(F)在主配体上的取代对配合物的电子结构及相关性质,如配合物前沿分子轨道的能量、组成、光谱性质、原子的净电荷布居及配位键长键角等的影响规律。计算结果表明,取代基对该系列取代衍生物的电子结构,特别是第一激发态的电子云分布影响较大,拉电子基团(F)能活化主配体,钝化辅助配体;而代电子基团(OH)则相反。无认是供电子基团(OH),还是拉电子基团(F)都导致取代衍生物的电子基谱带红移。此外,用基于极性交替规律及极性叠加概念的多系列箭头的图示方法对主配体上的原子净电荷布居的特征作了讨论。计算结果能较好地解释有关的实验现象与规律。     

计算烷烃异构体生成焓的新方法

基于作者提出的诱导极性叠加原理,设计了包括与诱导极性叠加总量要关的能量项的烷烃异构体的标准生成焓估算的新方法。与前人方法比较,它具有较高的计算精度,较少的参数,各参数物理意义明确,而且理论上可以推广到含多种杂原子的衍生物的标准生成焓的计算。     

原子转移自由基聚合方法在纤维素及其衍生物改性方面的应用Ⅱ

原子转移自由基聚合反应(atom transfer radical polymerization,ATRP)是纤维素及其衍生物进行修饰改性的一种有效途径。通过ATRP对纤维素及其衍生物进行改性,可以得到不包含相应均聚物的纯接枝产物,且接枝链的长度及分子量分布均可控。通过ATRP不仅可对纤维素进行本体改性,还可对其进行表面改性。原子转移自由基聚合方法在纤维素及其衍生物改性方面的应用Ⅰ″一文介绍了通过ATRP对纤维素及其衍生物进行本体改性的研究进展。本文概述了通过ATRP对纤维素及其衍生物进行表面改性的研究进展。     

密度泛函理论和从头算方法对四唑负离子的比较研究

运用多种密度泛函理论(DFT)方法和从头算(abinitio)方法研究了四唑负离子的分子几何、电子结构、红外光谱和热力学性质.结果表明,B3LYP-DFT法与MP2-abinitio法计算结果较吻合,故可用于对四唑衍生物及其配合物的系统研究.     

联二萘酚配合物催化的不对称异原子Diels-Alder反应研究进展

光学活性的联二萘酚及其衍生物作为优良的手性配体在不对称催化反应中的研究已经取得重大进展,本文概述了近些年来以联二萘酚及其衍生物为手性配体和各种金属盐形成的配合物作为手性催化剂在不对称催化的异原子Diels-Alder反应中的应用.总结了各种基于联二萘酚及其衍生物的用于异原子Diels-Alder反应的新的催化剂,以及能有效不对称催化该反应的新条件及新方法.     

通过F取代调节BDT衍生物给体材料的光伏性能

设计了3个由不同数量的F原子取代的苯并[1,2-b;4,5-b′]二塞吩(BDT)衍生物及其二聚体,采用密度泛函理论研究其电子结构和轨道能级,着重探讨了F原子取代对开路电压的影响.采用含时密度泛函理论模拟了光谱性质,明确了F原子取代对短路电流的影响;同时采用跃迁密度矩阵探讨了它们的激子耦合能力,进而推测F原子取代对光电转换效率的影响,为设计合成新型高效有机太阳能电池给体材料提供了重要的理论依据.     

1,3,4-噻二唑衍生物合成及其生物活性研究进展

1,3,4-噻二唑是含有N、S杂原子的五元杂环化合物,具有多种生物活性。目前,1,3,4-噻二唑及其衍生物广泛用于生物、医药等领域,尤其在抗菌、抗肿瘤、抗癌等方面的研究已取得重大突破。由于1,3,4-噻二唑结构的特殊性以及优越的生物活性,对其进行研究有重要意义。本文主要概述了近年来1,3,4-噻二唑衍生物的几种合成方法以及其在抗菌、抗肿瘤、抗癌方面的研究进展。     

Determination of the Structure and Effective Dielectric Constant of Hydrated Ions

Abstract

Debye's equation for the salting in or out of nonpolar compounds, such as benzene, in aqueous salt solutions was expanded so as to determine the effective dielectric decrement and constant of the hydrated domain of an ion. For ions having an electrostatic charge per surface area less than or equal to that of the K⁺ or Cl^? ions, this domain consists of a single layer of water molecules loosely or negatively hydrated to the ion; i.e., the domain consists of a mono-molecular B region. For ions having an electrostatic charge per unit surface area approximately equal to that of the Na⁺ and F^? ions, there exists no B region and only one layer of tightly bound or positively hydrated water (a monomolecular A region). Since the electrostatic field does not appreciably influence water molecules beyond this A region, such ions have an effective dielectric constant that is near zero, as in relatively inert molecules such as hydrocarbons. For all other ions, such as H⁺, Li⁺, Mg²⁺⁰,Cr²⁺, Sr²⁺, Ba²⁺, and other multivalent ions, there exists only one monomolecular A region followed by one monomolecular B region. The effective value of the dielectric constant of such an ion is obtained from its B region, since its A region cannot be penetrated. The effective dielectric decrement or constant of any B region as measured by benzene solubility goes through a maximum as the electrostatic charge per unit surface area (C/A) is decreased because a large C/A restricts the orientation of the hydrated water molecules and a low value of C/A allows competitive interaction between surrounding water molecules. Thus both small and large values of C/A decrease the solubility of benzene, i.e., decrease i t s ability to penetrate into the medium. A decrease in the macroscopic dielectric constant of water upon the addition of salt is due to the destruction of the clusters of water by the ions, or to the addition of ions which have effective dielectric constants less than that of water, or both. All hydrated ions o r molecules which salt-in or salt -out benzene have, respectfully, effective dielectric constants greater or less than that of water.     

Nature of the aqueous hydroxide ion probed by X-ray absorption spectroscopy

X-ray absorption spectra of aqueous 4 and 6 M potassium hydroxide solutions have been measured near the oxygen K edge. Upon addition of KOH to water, a new spectral feature (532.5 eV) emerges at energies well below the liquid water pre-edge feature (535 eV) and is attributed to OH- ions. In addition to spectral changes explicitly due to absorption by solvated OH- ions, calculated XA spectra indicate that first-solvation-shell water molecules exhibit an absorption spectrum that is unique from that of bulk liquid water. It is suggested that this spectral change results primarily from direct electronic perturbation of the unoccupied molecular orbitals of first-shell water molecules and only secondarily from geometric distortion of the local hydrogen bond network within the first hydration shell. Both the experimental and the calculated XA spectra indicate that the nature of the interaction between the OH- ion and the solvating water molecules is fundamentally different than the corresponding interactions of aqueous halide anions with respect to this direct orbital distortion. Analysis of the Mulliken charge populations suggests that the origin of this difference is a disparity in the charge asymmetry between the hydrogen atoms of the solvating water molecules. The charge asymmetry is induced both by electric field effects due to the presence of the anion and by charge transfer from the respective ions. The computational results also indicate that the OH- ion exists with a predominately "hyper-coordinated" solvation shell and that the OH- ion does not readily donate hydrogen bonds to the surrounding water molecules.     

Study on the Film Properties and Recognition for Metal Ions of Calix[4]arenes Derivative by Langmuir Monolayer

Calixarene molecules are very powerful ligand for ions and small molecules, and have been studied with several techniques as models for host‐guest systems. In this approach, the formation of Langmuir monolayer properties of three kinds calix[4]arene derivative were characterized and one of them, p‐tert‐butylthiacalix[4]arene (TCA), was chosen as object to study its Langmuir monolayer affected by different subphase conditions. The purpose of this study is to investigate the molecular recognition ability of TCA for metal ions at the water‐air interface. Changing the composition of aqueous subphase (containing various metal ion solutions respectively) produced strong variations on the monolayer parameters, indicating a different selectivity of the TCA ligand for the different metal cations. In particular, high selectivity for transition metal ions was found. Limiting area values are discussed in relation to the orientation of the cone‐shaped molecules at the water‐air interface.     

Quantum chemical studies of the chemisorption of water and of unhydrated and hydrated halide ions on mercury

Local structures on electrode interfaces can be explored by quantum chemical investigation of medium-sized systems consisting of a cluster of substrate (metal) atoms, one or several solvent molecules, and/or at least one ion to be adsorbed at the interface. For the study of water adsorption and halide ion adsorption (unhydrated as well as hydrated) on a mercury surface, we have used the standard CNDO method together with geometrical optimization of the atom positions.In this paper, the following topics have been treated: (a) adsorption of a single water molecule in different positions on a close-packed plane cluster of seven mercury atoms; (b) adsorption of unhydrated halide ions (Cl^?, Br^?, I^?) in the “on-top” or hollow position on the mercury surface; (c) adsorption of monohydrated halides on the mercury surface. Further studies including solvation by six water molecules are discussed.The calculations provide information about minimum-energy geometries, energetic data, and local charges. Furthermore, they allow some conclusions about water mobility and reorientation on a close-packed metal surface, water orientation under the combined influence of an adsorbed ion and the metal surface, and trends of charge distribution in the halide series to be drawn. Calculations are critically discussed in the light of experimental and other quantum chemical data.     

某些噻唑偶氮苯酚类试剂结构与性能关系的理论研究

噻唑偶氮试剂广泛应用于分析化学,近十来年发展较快,迄今已有170余种,但其结构和性能关系的理论研究报导较少。本文选取2-(2-噻唑偶氮)苯酚(简称TAP)及其九种甲基取代衍生物(见表1),用CNDO/2方法研究其结构与碱性关系,讨论这些试剂与金属离子螯合的可能位置,其结果和实验基本一致。计算分子构型所用TAP骨架取由文献,甲基用标准构型。原子编号见图1,计算在IBM PC/AT微机上完成。     

A first principles molecular dynamics study of lithium atom solvation in binary liquid mixture of water and ammonia: structural, electronic, and dynamical properties

The preferential solvation of solutes in mixed solvent systems is an interesting phenomenon that plays important roles in solubility and kinetics. In the present study, solvation of a lithium atom in aqueous ammonia solution has been investigated from first principles molecular dynamics simulations. Solvation of alkali metal atoms, like lithium, in aqueous and ammonia media is particularly interesting because the alkali metal atoms release their valence electrons in these media so as to produce solvated electrons and metal counterions. In the present work, first principles simulations are performed employing the Car-Parrinello molecular dynamics method. Spontaneous ionization of the Li atom is found to occur in the mixed solvent system. From the radial distribution functions, it is found that the Li(+) ion is preferentially solvated by water and the coordination number is mostly four in its first solvation shell and exchange of water molecules between the first and second solvation shells is essentially negligible in the time scale of our simulations. The Li(+) ion and the unbound electron are well separated and screened by the polar solvent molecules. Also the unbound electron is primarily captured by the hydrogens of water molecules. The diffusion rates of Li(+) ion and water molecules in its first solvation shell are found to be rather slow. In the bulk phase, the diffusion of water is found to be slower than that of ammonia molecules because of strong ammonia-water hydrogen bonds that participate in solvating ammonia molecules in the mixture. The ratio of first and second rank orientational correlation functions deviate from 3, which suggests a deviation from the ideal Debye-type orientational diffusion. It is found that the hydrogen bond lifetimes of ammonia-ammonia pairs is very short. However, ammonia-water H-bonds are found to be quite strong when ammonia acts as an acceptor and these hydrogen bonds are found to live longer than even water-water hydrogen bonds.     

药物水溶解度的QSAR研究和VolSurf参数

药物的水溶解度与其吸收密切相关。本文利用一种新的计算方法,VolSurf,预测药物的水溶解度并测定有利于药物水溶解度的主要分子特征。被测化合物包括26个结构不同的药物,通过偏最小二乘分析法,对药物水溶解度实验值与分子特征进行相关,得到较好的模型(r2=0.90,q2=0.77)。将化合物分为训练集和预测集进行相关分析,结果表明以18个化合物所建立的训练集模型对其余8个化合物有较好的预测能力,预测的标准偏差(SDEP)为0.59。参数分析表明分子与水相互作用的3个局部能量最小值越小,且它们之间的距离越大,对其水溶解度越有利;亲水性占主导因素的分子有高的水溶解度;分子的疏水性越强,在水中的溶解性越弱;大分子的溶解度较小分子溶解度低。     

How ions affect the structure of water

We model ion solvation in water. We use the MB model of water, a simple two-dimensional statistical mechanical model in which waters are represented as Lennard-Jones disks having Gaussian hydrogen-bonding arms. We introduce a charge dipole into MB waters. We perform (NPT) Monte Carlo simulations to explore how water molecules are organized around ions and around nonpolar solutes in salt solutions. The model gives good qualitative agreement with experiments, including Jones-Dole viscosity B coefficients, Samoilov and Hirata ion hydration activation energies, ion solvation thermodynamics, and Setschenow coefficients for Hofmeister series ions, which describe the salt concentration dependence of the solubilities of hydrophobic solutes. The two main ideas captured here are (1) that charge densities govern the interactions of ions with water, and (2) that a balance of forces determines water structure: electrostatics (water's dipole interacting with ions) and hydrogen bonding (water interacting with neighboring waters). Small ions (kosmotropes) have high charge densities so they cause strong electrostatic ordering of nearby waters, breaking hydrogen bonds. In contrast, large ions (chaotropes) have low charge densities, and surrounding water molecules are largely hydrogen bonded.     

Palladium cluster catalysts supported on chelate resin-metal complexes

The dry beads of chelate resin-metal complexes have been prepared from metal ions and the chelate resin containing iminodiacetic acid moieties. The surface area of the chelate resin can be increased both by washing with an organic solvent miscible with water and by complexing with multi-valent cations. Palladium clusters are supported on the chelate resin-metal complexes by two methods, in which the order is reversed between “complexing of metal ions” and “supporting of palladium clusters”. The supported palladium clusters catalyze the hydrogenation of C=C bonds, and the catalytic activity greatly depends on the metal ions used for the complexation. In the case of typical metal ions, the complexing of metal ions after supporting of palladium clusters makes the surface area of the resin increase, but makes the catalytic activity decrease compared with the reverse order. In the case of lanthanoid ions, on the other hand, the same order makes both the surface area and the catalytic activity increase.     

Mass spectrometry in structural and stereochemical problems—CCIV. Spectra of hydantoins II. Electron impact induced fragmentation of some substituted hydantoins

The mass spectral decomposition modes of hydantoin and derivatives containing alkyl and phenyl substituents have been investigated using isotopic labeling techniques. The loss of carbon monoxide from the molecular ions of these compounds was shown to preferentially involve the C-4 carbonyl group. Other fragmentation processes characteristic of the hydantoin ring system and the effect on this of alkyl and phenyl substitution are described.