含偶氮苯主-客体复合物的光致异构化反应对结合能与几何构象的影响

在分子尺度上构建光驱动的人工分子机器是超分子化学研究的一个热点。偶氮苯是一类具有双稳态的光致开关分子,能够完成高效、可逆的反式(E)$\to $顺式(Z)的光致异构化过程,因而可以作为人工分子机器的功能单元。本文采用密度泛函理论(DFT)和反应分子动力学(RMD)模拟,研究了含偶氮苯封端基团的互锁型超分子体系中冠醚主体与二烷基铵客体间结合强度,模拟了偶氮苯Z$\to $E异构化反应的动态过程,讨论了异构化反应对主客体分子构象的影响。在偶氮苯封端基团通过发生Z$\to $E异构化实现体系单向可控运动时,较强的主-客体间结合能力是保证互锁型超分子体系稳定的必要前提。顺式客体与主体大环氢键相互作用比反式客体更强,因此顺式复合异构体具有比反式异构体更大的结合强度。偶氮苯基团发生E$\to $Z光致异构化引入位阻效应,使得顺式复合物只能从环戊基准封端处进行脱环。主客体复合过程对偶氮苯基团的几何结构没有明显影响。偶氮苯光致异构化发生的速度快于客体脱环的速度是实现单向运动的动力学上的必要条件。在异构化反应后的500 ps内,大环会经历一个明显的结构驰豫过程。冠醚大环主体的柔性构象有助于实现在偶氮苯光致异构化发生过程中主客体间持续稳定的结合。各种超分子体系中,尽管客体组成各不相同,但是包含相似的主客体识别位点的超分子体系具有相似的结合能,显示了机械互锁型复合体系中各种功能性构建单元间主客体相互作用具有正交性。引入双稳态的偶氮苯功能基团对客体其他部分的几何结构影响很小。理论计算结果有助于理性设计更复杂的刺激响应性人工分子机器。     

The Binding Energy Distribution Analysis Method (BEDAM) for the Estimation of Protein-Ligand Binding Affinities

The Binding Energy Distribution Analysis Method (BEDAM) for the computation of receptor-ligand standard binding free energies with implicit solvation is presented. The method is based on a well established statistical mechanics theory of molecular association. It is shown that, in the context of implicit solvation, the theory is homologous to the test particle method of solvation thermodynamics with the solute-solvent potential represented by the effective binding energy of the protein-ligand complex. Accordingly, in BEDAM the binding constant is computed by means of a weighted integral of the probability distribution of the binding energy obtained in the canonical ensemble in which the ligand is positioned in the binding site but the receptor and the ligand interact only with the solvent continuum. It is shown that the binding energy distribution encodes all of the physical effects of binding. The balance between binding enthalpy and entropy is seen in our formalism as a balance between favorable and unfavorable binding modes which are coupled through the normalization of the binding energy distribution function. An efficient computational protocol for the binding energy distribution based on the AGBNP2 implicit solvent model, parallel Hamiltonian replica exchange sampling and histogram reweighting is developed. Applications of the method to a set of known binders and non-binders of the L99A and L99A/M102Q mutants of T4 lysozyme receptor are illustrated. The method is able to discriminate without error binders from non-binders, and the computed standard binding free energies of the binders are found to be in good agreement with experimental measurements. Analysis of the results reveals that the binding affinities of these systems reflect the contributions from multiple conformations spanning a wide range of binding energies.     

Determination of Binding Strengths of Host-Guest Complexes in Deep Eutectic Solvents Using Spin Probe Methodology

Electron paramagnetic resonance (EPR) and spin probe methodologies have been employed to study the complexation properties of cyclodextrins (CDs) and cucurbit[n]urils (CB[n]s) in the deep eutectic solvent (DES) choline chloride-urea. In the presence of γ-CD an affinity constant very similar to that measured in water was measured in DES with benzyl-tert-butyl nitroxide (BTBN). With β-CD, complexation of BTBN is significantly depressed, although still maintained. Complexation of TEMPO radical probe by CB[7] or CB[8] was instead almost entirely cancelled in DES. In addition, this methodology enabled for the first time to measure the single rate constants for the association and dissociation processes with CDs in DES.     

毛细管电泳测定主客分子相互作用的结合常数

在２５℃下,用毛细管区带电泳测定了主管体分子（配体和溶质分子）β－环糊精（β－ＣＤ）和心得舒（ａｌｐｒｅｎｏｌｏ）在ｐＨ值为２．５,浓度为１００ｍｍｏｌ／Ｌ的磷酸盐缓冲溶液下的结合常数,并对４种求解方法既非线性拟合法,双倒数法,ｙ－倒数法和ｘ－倒数法的结果进行了比较,所得值分别是３０７．２、４０８．４、３３１．４和３４３．１Ｌ／ｍｏｌ,同时获得了结合物的迁移率。该方法可用于测定结合比为１：１的各种     

Quantum-Mechanical Proof of a Redheffer Inequality

An alternate proof, with minor restrictions, of the Weyl-type inequality of Redheffer is given using tools of chemists' quantum mechanics and Hilbert space instead of mathematicians' real analysis.     

Binding of Ionic Species: A General Approach To Measuring Binding Constants and Assessing Affinities

Bound together : The association of receptors with ionic species cannot be assimilated to the binding of neutral guests. When dealing with salts, both ion pairing and binding to the free and the ion‐paired ionic guest determine the actual association pattern (see figure). The general issue of measuring association constants and assessing affinities for ions is addressed and validated in two cases of anion binding.

     

金属卟啉对杂环及DNA分子识别研究进展

介绍了近几年国内外关于组装金属卟啉对杂环分子、DNA碱基以及RNA的分子识别的研究进展, 并简述了本课题组对金属卟啉与杂环及药物分子复合物的理论研究工作. 金属卟啉广泛存在于自然界和生物体中, 此识别过程对研究和模拟生命体中各种细胞之间的相互作用具有重要意义. 组装后的金属卟啉可通过轴向配位、氢键及π-π堆积作用等识别杂环分子. 金属卟啉对DNA的识别主要有四种作用方式, 而金属卟啉对DNA以及RNA分子的识别主要靠疏水作用力、静电力以及自堆叠作用. 卟啉阳离子与DNA的结合位点受主体侧链取代基的空间结构影响. 金属卟啉对药物分子的识别靠配位键和氢键进行, 以配位键结合的复合物通常具有更高的结合能.     

Prediction of the Atomic Electron Affinities Using a Wavelet Neural Network

Atomicelectronaffinity(EA)isimportantnotonlyinpurechemistrybutalsoinastro-physicalproblems,low-temperatureplasmas,tandemaccelerators,andelectron-capturedetectors.l'2Uptonow,itstillremainsdifficulttomeasuretheaccuratevaluesofEAexperimentally.I'2Theoreticalmethods,includingabinilioquantummechanicalcalcula-tions3-9andvarioussemi-empiricalextrapolationtechniques,,',,'havebeenextensivelystudied.However,thecalculationofEAofevensmallatomsisnotoriouslytime-consuminganditisstilldifficulttocalculateE…     

蛋白质相互作用: 界面分析, 结合自由能计算与相互作用设计

蛋白质相互作用在生命活动中起着重要作用. 研究蛋白质间相互作用的本质有助于了解生命活动中这些基本单元的作用. 本文主要综述了近期蛋白质相互作用研究的进展, 包括蛋白质相互作用界面的基本性质, 蛋白质结合自由能的计算方法, 不同相互作用在蛋白质结合/解离中的角色和差异, 以及上述知识在蛋白质相互作用设计中的应用. 蛋白质相互作用界面的特性, 例如界面大小、保守性以及结构的动态性质, 使得具有生物功能的蛋白质相互作用界面区别于非特异性的晶体堆积界面. 生物功能界面的一个重要结构特征是界面上存在着关键残基以及相对独立的相互作用模块. 利用多种方法, 如MM-PBSA、统计平均势以及不同的相互作用自由能模型, 可以在不同的精度上计算蛋白质相互作用自由能. 利用蛋白质相互作用界面的特点, 从不同的角度进行蛋白质相互作用对的设计与改造, 近年来已经有了不少成功的例子, 但还存在着很大的挑战. 我们认为在今后的蛋白质相互作用设计中, 考虑各种因素对蛋白质结合与解离的动力学过程的影响将有助于提高人类控制蛋白质相互作用的能力.     

多溴二苯醚取代特征对其芳香烃受体结合能力的效应分析

以已知18种多溴二苯醚（polybrominated diphenyl ethers,PBDEs）芳香烃受体结合能力实验值为因变量,构建基于取代基参数的PBDEs芳香烃受体结合能力定量构效关系模型以补足PBDEs芳香烃受体结合能力值,借助全析因实验的分析方法研究不同取代位置对PBDEs芳香烃受体结合能力的主效应及二阶交互效应,并分别从总取代基数、两苯环取代相似性、同一苯环取代基分布性综合研究PBDEs取代特征对芳香烃受体结合能力的影响规律.研究表明： PBDEs芳香烃受体结合能力受各取代位置主效应和二阶交互效应的显著影响,邻位取代基可显著降低PBDEs芳香烃受体结合能力,对位取代基则显著增强,间位取代基主效应较弱,主要通过与邻对位取代基间的二阶交互效应影响PBDEs芳香烃受体结合能力;总取代基数、两苯环取代相似性与PBDEs芳香烃受体结合能力无显著相关性,而同一苯环上取代基间分散性越大,同系物芳香烃受体结合能力越小.     

Synthesis of Glutamic Acid-based Cluster Galactosides and Their Binding Affinities with Liver Cells

Structurally well defined di-, tri- and tetra-valent cluster galactosides were synthesized in a convenient way.Oligo-glutamic acids were assembled as scaffolds. The presence of amine groups in these three ligands is expected to couple with drugs or genes for delivery. The binding affinities of these cluster galactoses to liver cells were determined by in vitro binding studies. Among them, the tetravalent cluster galactose (19) showed the highest affinity to liver cell. It is therefore a promising targeting device for the specific delivery of drugs or genes to parenchymal liver cells.     

最弱受约束电子势模型理论下使用双广义拉盖尔多项式计算氦原子基态能量

计算了在最弱受约束电子势模型理论下使用双广义拉盖尔多项式的氦原子基态能量. 给出了氦原子基态能量期望值的表达式. 通过搜索它的极小, 找到了氦原子基态能量的极小值. 将我们的结果与双灼(zeta)函数的Hartree-Fock(HF)方法的结果进行比较后发现, 我们的结果略优于双灼(zeta)函数的Hartree-Fock(HF)方法的结果. 如此表明线性组合技术可以应用在最弱受约束电子势模型理论中.     

Dimensional Matching versus Induced-Fit Distortions: Binding Affinities of Planar and Curved Polyaromatic Hydrocarbons with a Tetragold Metallorectangle

A tetragold(I) rectangle-like metallocage containing two pyrene-bis-imidazolylidene ligands and two carbazolyl-bis-alkynyl linkers is used for the encapsulation of a series of polycyclic aromatic hydrocarbons (PAHs), including corannulene. The binding affinities obtained for the encapsulation of the planar PAHs guests in CD₂Cl₂ are found to exponentially increase with the number of π-electrons of the guest (1.3 > logK >6.6). For the bowl-shaped molecule of corannulene, the association constant is much lower than the expected one according to its number of electrons. The molecular structure of the host–guest complex formed with corannulene shows that the molecule of the guest is compressed, while the host is expanded, thus showing an interesting case of artificial mutual induced-fit arrangement.     

Sm2Fe17N3晶体的价电子结构分析和结合能、最强键能计算

由EET理论直接建立了Sm2Fe17N3晶体的价电子结构,同时计算并筛选了晶体的结合能和最强键能,分别为EC^0=14716.8±13.7kJ·mol^-1和Eα=110.1311 kJ·mol^-1。分析计算结果表明:Sm2Fe17N3晶体内共价电子数主要分布在12对由Fe(c1),Fe(c2)和Fe(c3)参与形成的最强键能的键上,由这3种Fe晶位原子形成的共价键键距普遍小于0.3 nm,共价键较强对晶体结合能作主要贡献;并且其结合能相比Sm2Fe17晶体的小得多,解释了Sm2Fe17合金在低温和非真空状态条件下易氧化而经过渗氮后得到的Sm2Fe17N3则表现出常温下结构稳定、化学性能好的特性;计算出N原子参与形成的成键原子对的理论键能值普遍在1 kJ·mol^-1左右,反映出Sm2Fe17N3化合物内在渗氮特性,分析了制备钐铁氮永磁材料过程中Sm2Fe17合金较低温渗氮难、渗氮不稳定和渗氮不均匀的缺陷。     

TATB/氟聚物PBX力学性能、结合能和爆炸性能的模拟计算

Molecular dynamics （MD） method was used to simulate 1,3,5-triamino-2,4,6-trinitrobenzene （TATB） coated with fluorine containing polymers. The mechanical properties and binding energies of PBXs were obtained. It was found that when the number of chain monomers of fluorine containing polymers was the same, the elasticity of TATB/F2314 was increased more greatly than others and the binding energy of TATB/F2311 was the largest among four PBXs. Detonation heat and velocity of such four PBXs were calculated according to theoretical and empirical formulas. The results show that the order of detonation heat is TATB〉TATB/PVDF〉TATB/F2311〉TATB/ F2314 〉 TATB/PCTFE while the order of detonation velocity is TATB/PVDF 〈 TATB/F2311 〈 TATB/F2314 〈 TATB/PCTFE 〈TATB.     

Synthetic dsDNA‐Binding Peptides Using Natural Compounds as Model

We have developed a series of short DNA‐binding peptides containing newly synthesized, unnatural as well as natural amino acid building blocks. By a combinatorial‐library approach, oligopeptides were developed with moderate dsDNA‐binding affinities. Two strategies were used to further enhance the binding affinity of the lead peptides: Ac‐Arg‐Ual‐Sar‐Chi‐Chi‐Chi‐Arg‐NH₂ and Ac‐Arg‐Cbg‐Cha‐Chi‐Chi‐Tal‐Arg‐NH₂. Site‐selective amino acid substitutions increased the binding affinities up to 2 × 10^?5 M . Further enhancement of the binding affinities could be achieved by coupling of an acridine intercalating unit, using linker arms of different length and flexibility. With the introduction of a new lysine‐based acridine unit, different types of oligopeptide–acridine conjugates were designed using known dsDNA‐binding ligands as model compounds. The binding capacities of these new oligopeptide–acridine conjugates have been investigated by a fluorescent intercalator (ethidium bromide) displacement (FID) assay. With the synthesis of the dipeptide–acridine conjugates, binding affinities in the low micromolar range were obtained (6.4 × 10^?6 M ), which is similar to the binding strength of the well‐known DNA binder Hoechst 33258.     

三原子分子振动光谱的相互作用模式计算

Using the quantum self-trapping theory, the interaction model (IM) for calculation of vebrational spectroscopy for tri-atomic molecules has been devoloped, and the results for 16O3, 18 O3, SO2, HCN and DCN are in good agreement with the experirnental data. It shows that this method is superior to the NM and LM methods, and it is applicable to the calculation of high-excited vibrational states especially.     

静电势能模型对类水滑石结构与性能的理论研究

The electrostatic potential energy model of hydrotalcites was based on the theory of crystallography. The anionic potential energy of MgAl-hydrotalcites, with 20 layers and 2107 anions per layer, was calculated, and the anionic stability of the hydrotalcites was investigated. The charge density of the layer and the distance between the adjacent anions varied with the molar ratio of Al3+/(Mg2+ +Al3+). Anionic potential energy depended on the charge and size of the anions. Calculation results remained consistent with thermal stability and the ion exchange ability reported. This model is able to predict anionic stability of the hydrotalcites.