三七素对映异构体的计算机模拟研究

三七主要用于跌打损伤、内伤出血等内外出血症.用量子化学法,采用B3LYP方法,6-31+G(d,p)基组计算三七素对映异构体的分子结构及能量等数据,结果表明S-三七素的能量略比R-三七素高.以S-三七素为模板分子,分别选甲基丙烯酸(MAA)、三氟甲基丙烯酸(TFMAA)、丙烯酰胺(AM)、N-乙烯基吡咯烷尉(NVP)、2.乙烯基吡啶(2-VP)、4-乙烯基吡啶(4-VP)6种物质为功能单体,模拟并探讨不同功能单体对S-三七素的选择性,模拟计算分子印迹聚合的过程中,模板分子、功能单体及聚合物构型复杂,分子量大,全用PM3半经验法.采用结合能来反映S-三七素和不同单体之间的相互作用,比较模板分了与功能单体相互作用的强弱,以选择功能单体.结果证明AM的印迹效应最好而NVP最差.该模型稳定性和预测能力俱佳,从而为S-三七素的拆分及检测实验打下理论基础.     

呋喃西林分子印迹聚合物的分子模拟与验证

以呋喃西林(Nitrofurazone,NFZ)为模板分子,甲基丙烯酸(MAA)、丙烯酰胺(AM)、2-乙烯基吡啶(2-VP)、甲基丙烯酸甲酯(MMA)为功能单体,通过LC-WPBE/6-31G(d,p)方法方法模拟计算了呋喃西林与不同功能单体间的分子印迹的自组装,对形成的四种印迹复合物进行结构、能量、成键情况、NBO电荷、结合能的分析。计算结果表明NFZ分子印迹聚合物最佳的功能单体为甲基丙烯酸,且其与模板分子比例为6:1时,印迹效果最佳。同时,根据理论计算的结果制备聚合物,并通过吸附动力学实验、平衡结合实验和选择性实验对合成的聚合物进行了表征,结果表明模拟结果与实验结果一致。     

苯氧基乙酸印迹聚合物的选择性研究

该文以苯氧基乙酸为模板分子,制备了苯氧基乙酸印迹聚合物.采用柱吸附并结合紫外-可见分光光度法研究了苯氧基乙酸印迹聚合物对苯氧基乙酸、对氯苯氧基乙酸和2,4-二氯苯氧基乙酸的选择性,同时与空白聚合物进行了比较.研究了印迹聚合物作为固定相的柱分离特性.研究了分别以甲基丙烯酸和4-乙烯基吡啶为功能单体的苯氧基乙酸印迹聚合物的选择性能,结果表明苯氧基乙酸印迹聚合物相比空白聚合物有较好的选择性,并且选择性还与功能单体有关.     

酪胺分子印迹聚合物最佳功能单体筛选计算机模拟研究

酪胺广泛存在于发酵食品中,高浓度可引发偏头疼。用量子化学法,采用Gaussian软件中Hartre-Fock方法的6-31G(d)基组计算酪胺和甲基丙烯酸(MAA)、丙烯酸(AA)、甲基丙烯酸甲酯(MMA)和对乙烯基苯甲酸(P-VBA)4种功能单体的能量,模拟并探讨不同功能单体对酪胺的选择性。用模板分子和不同功能单体形成复合物的结合能(四大小来反映酪胺与不同功能单体之间的相互作用,比较模板分子与功能单体相互作用的强弱,选择最佳功能单体。计算机模拟结果表明MAA和P-VBA与模板分子的结合能(△E)最小,作用力较强,且最佳反应比为1:3,从而为合成高亲和性的酪胺分子印迹聚合物,实现酪胺快速检测提供理论基础。     

邻苯二甲酸酯类分子印迹聚合物预组装体系的分子模拟计算

以邻苯二甲酸二异癸酯(T1)及2个衍生分子T2、T3为模板分子,以α-甲基丙烯酸(MAA)、丙烯酰胺(AM)和3-氨丙基三乙氧基硅烷(APTES)为功能单体,三氯甲烷、甲醇、乙醇及乙腈为致孔剂,运用量子化学方法模拟模板分子与不同功能单体的分子印迹聚合物预组装体系的构型、能量及复合反应的结合能ΔE,以及单体与模板分子在不同溶剂中的溶剂化能。结果表明,APTES与T3以1:1摩尔比结合时形成更为稳定的复合物,最大结合能达到103.6 KJ·mol~(-1);模板分子和功能单体在三氯甲烷中的溶剂化能最小,因此三氯甲烷更适合作为溶剂。通过模拟计算,有助于揭示分子印迹聚合物识别原理,为邻苯二甲酸二异癸酯类的分子印迹聚合物制备提供理论参考。     

不同功能单体制备水杨酸分子印迹聚合物的分子模拟研究

采用分子模拟技术,研究水杨酸分子制备印迹聚合物过程中,水杨酸(SA)与不同功能单体之间的结合能.作者等先计算水杨酸与常用功能单体之间的结合能,再选出适合制备水杨酸分子印迹聚合物的功能单体.其次详细讨论丙烯酰胺(AM)和甲基丙烯酸(MAA)与SA的结合能以及聚合物与水杨酸分子之问的结合能.发现,(1)制备分子印迹聚合物过程中,水杨酸的作用功能基团是-COOH,AM、MAA的作用功能基团分别是-NH2、-COOH.(2)SA与AM形成的复合物结合能大于与MAA形成复合物的结合能.由此,推断以AM为功能单体的水杨酸分子印迹聚合物,比以MAA为功能单体的水杨酸分子印迹聚合物的吸附量大,与实验结果一致.     

分子印迹聚合物预组装体系计算机模拟

使用Gaussian 03软件研究了以苯丙氨酸为模板,甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,三氟乙酸为助溶剂的分子印迹预组装体系。通过计算机模拟考察了功能单体浓度、交联剂浓度和助溶剂浓度对模板-功能单体复合物浓度的影响,从理论上计算了苯丙氨酸分子印迹聚合物的最佳合成条件。通过模拟,有助于解释实验现象以及合成高特异性和亲和性分子印迹聚合物。     

Leu-Phe分子印迹预组装体系热力学平衡的计算模拟

使用Gaussian03软件研究以Leu-Phe为模板,甲基丙烯酸为功能单体,乙二醇二甲基丙烯酸酯为交联剂,三氟乙酸为助溶剂的分子印迹预组装体系.计算了功能单体、助溶剂和交联剂加入量对各种模板复合物浓度的影响,进而确定了Leu-Phe分子印迹聚合物的合成条件.按条件合成聚合物后考察其识别性能,并结合计算模拟和实验结果解释实验现象.计算模拟可能有助于合成高特异性和亲和性分子印迹聚合物,探讨了分子印迹聚合物的分子识别机理.     

采用量化计算和预实验的方法优化大黄酚印迹聚合物的合成

在研究大黄酚分子印迹聚合物制备过程中,为选择合适的功能单体,首先采用 PM3 量化计算方法,得出大黄酚与 4-乙烯吡啶、甲基丙烯酸之间的结合能分别为-768.91 kJ/mol 和-14.78 kJ/mol,表明4-乙烯吡啶与大黄酚的作用力更强,是较好的功能单体;又采用紫外预组装的实验方法优化选择功能单体,得出与上述一致的结论;同时实验确定大黄酚与4-乙烯吡啶最佳反应比为1:4.因此,以此单体和反应比去合成大黄酚印迹(MIP)和非印迹聚合物(NMIP),采用平衡吸附实验表征 MIP 的吸附性能和选择性,并推测其作用机理.结果表明:MIP 对大黄酚及结构相似物的分配系数均大于 NMIP;MIP 对大黄酚的结合容量大大高于 NMIP,对大黄酚的分配系数大于其结构类似物;由此说明:合成的 MIP 具有一定的印迹效果,4-乙烯吡啶与大黄酚(及其类似物)的作用可能产生于羟基蒽醌骨架上.研究表明:实验结果和量化计算具有一致性,量化计算方法对分子印迹聚合物合成时功能单体的选择具有很好的指导作用.     

甲基多巴对映异构体计算机模拟的研究

甲基多巴是具有旋光性的多巴类物质,其中S-甲基多巴是1种广泛应用的降压药物,而甲基多巴的外消旋体需要2倍剂量方可达到正常的降压作用.运用量子化学法,计算甲基多巴对映异构体的分子结构及能量,证明S-甲基多巴的能量比R-甲基多巴略高.分别以甲基多巴对映异构体为模板分子,甲基丙烯酸(MAA)和丙烯酰胺(AM)为功能单体,模拟和探讨不同功能单体对甲基多巴的选择性,结果显示MAA和AM的印迹效应都比较好,MAA与模板分子所形成复合物其结合能较AM略大.该模型稳定性和预测能力俱佳,它为混旋甲基多巴的拆分打下理论基础.     

Preparation of a photoresponsive molecularly imprinted polymer containing fluorine-substituted azobenzene chromophores

The primary objective of this work is to explore the photoresponsive molecular recognition directed by fluorine-fluorine interaction. A new kind of fluorine-substituted photoresponsive functional monomer, (4-methacryloyloxy) nonafluoroazobenzene (MANFAB), was designed and synthesized, and a photoresponsive molecularly imprinted polymer containing a fluorine-substituted azobenzene chromophore (MIPF) was then fabricated using MANFAB as the monomer and 2,3,4,5,7,8,9,10-octafluorophenazine (PAF) as the model template. The photoisomerization process of MIPF materials is reversible. The release and uptake of PAF from toluene is photoregulated by alternate irradiation at 315 nm and 440 nm, indicating that photoresponsive molecular recognition directed by fluorine-fluorine interaction is possible. The binding strength of the imprinted receptor sites in MIPF for PAF is 4.67 × 10⁴ M⁻¹. The density of receptor sites in the MIPF material is 1.26 μmol/g-MIPF.     

Numerical and experimental LDL transport through arterial wall

Atherosclerosis develops from oxidized low-density lipoprotein molecules (LDL). When oxidized LDL evolves in plaque formations within an artery wall, a series of reactions occur to repair the damage to the artery wall caused by oxidized LDL. Aim of this study was to compare experimental data of LDL transport through isolated blood vessel with computational results of bounding of oxidized LDL receptor-1 (LOX-1) for endothelial cells with numerical discrete methods such as dissipative particle dynamics (DPD) and lattice Boltzmann (LB) method. Experiments of LDL transport were performed on the isolated rabbit common carotid arteries acquired from fifteen rabbits after 12 weeks of high-fat diet. Oxidative LDL molecule is built and used for docking with LOX-1 receptor. Energies that give the best binding are computed, and the energy with greatest probability of attachment for oxidative LDL molecule and glutamine acid is further used in numerical simulations. Simulations using DPD and LB method use the computed binding energy to calculate the force necessary for binding of LDL molecule to the endothelial blood vessel layer. Experimental results have shown large uptake for shear stress below 1 dyn/cm². Computational results for both discrete methods DPD and LB have shown good accuracy with experimental data. Calculation of the interactive molecule forces from computational chemistry open a new avenue for multiscale modeling methods, which will give better insight for the understanding and the prediction of LDL transport through the arterial wall for the medical community.     

Theoretical study of aluminum arsenide clusters: equilibrium geometries and electronic structures of Al(n)As(n) (n=1-4)

The geometry, electronic configurations, harmonic vibrational frequencies and stability of the structural isomers of Al(n)As(n) clusters (n=1-4) have been investigated using density functional theory. For dimers and trimers, the lowest energy structures are planar cumulenic rings (IIs, VIs) with D(nh) symmetry. The caged structure with T(d) symmetry (IXs) lie lowest in energy among the tetramers. The AlAs bond dominates the structures for many isomers so that one preferred dissociation channel is loss of the AlAs monomer. The atomic charges, hybridization and chemical bonding in the different structures are also discussed. Comparisons with valence-isoelectronic Si(2n), Al(n)P(n) and Ga(n)As(n) clusters of same size, the properties of the aluminum arsenide clusters are analogous to those of their corresponding Al(n)P(n), Si(2n) counterparts. The results can explain the modification and refinement of Si phase in AlSi alloy in the molecular level.     

Conserved water mediated H-bonding dynamics of Ser117 and Thr119 residues in human transthyretin–thyroxin complexation: Inhibitor modeling study through docking and molecular dynamics simulation

Transthyretin (TTR) is a protein whose aggregation and deposition causes amyloid diseases in human beings. Amyloid fibril formation is prevented by binding of thyroxin (T4) or its analogs to TTR. The MD simulation study of several solvated X-ray structures of apo and holo TTR has indicated the role of a conserved water molecule and its interaction with T4 binding residues Ser117 and Thr119. Geometrical and electronic consequences of those interactions have been exploited to design a series of thyroxin analogs (Mod1–4) by modifying 5′ or 3′ or both the iodine atoms of thyroxin. Binding energy of the designed ligands has been calculated by docking the molecules in tetrameric structure of the protein. Theoretically investigated pharmacological parameters along with the binding energy data indicate the potentiality of 3′,5′-diacetyl-3,5-dichloro-l-thyronine (Mod4) to act as a better inhibitor for TTR-related amyloid diseases.     

Three- and four-body corrected fragment molecular orbital calculations with a novel subdividing fragmentation method applicable to structure-based drug design

We develop an inter-fragment interaction energy (IFIE) analysis based on the three- and four-body corrected fragment molecular orbital (FMO3 and FMO4) method to evaluate the interactions of functional group units in structure-based drug design context. The novel subdividing fragmentation method for a ligand (in units of their functional groups) and amino acid residues (in units of their main and side chains) enables us to understand the ligand-binding mechanism in more detail without sacrificing chemical accuracy of the total energy and IFIEs by using the FMO4 method. We perform FMO4 calculations with the second order Møller-Plesset perturbation theory for an estrogen receptor (ER) and the 17β-estradiol (EST) complex using the proposed fragmentation method and assess the interaction for each ligand-binding site by the FMO4-IFIE analysis. When the steroidal EST is divided into two functional units including “A ring” and “D ring”, respectively, the FMO4-IFIE analysis reveals their binding affinity with surrounding fragments of the amino acid residues; the “A ring” of EST has polarization interaction with the main chain of Thr347 and two hydrogen bonds with the side chains of Glu353 and Arg394; the “D ring” of EST has a hydrogen bond with the side chain of His524. In particular, the CH/π interactions of the “A ring” of EST with the side chains of Leu387 and Phe404 are easily identified in cooperation with the CHPI program. The FMO4-IFIE analysis using our novel subdividing fragmentation method, which provides higher resolution than the conventional IFIE analysis in units of ligand and each amino acid reside in the framework of two-body approximation, is a useful tool for revealing ligand-binding mechanism and would be applicable to rational drug design such as structure-based drug design and fragment-based drug design.     

PVP/Pd/IrO2电化学修饰电极的研究及其应用

本文研制了一种新型的 PVP/Pd/IrO_2电化学修饰电极。在 Pt 电极表面先后修饰 PVP(Poly VinylPyridine)及 Pd/IrO_2,该修饰电极对 HSO_3~-有良好的催化氧化作用;同时,在恒电位+0.6V 条件下,以该修饰电极与 Ag/AgCl 电极,Pt 对电极组成的气体传感器,对 SO_2也有良好的响应,预计在环境监测及环境保护等领域有应用前景。     

聚甘油脂肪酸酯QSPR的研究

采用量子化学MOPAC-AM1和单点能方法计算聚甘油脂肪酸酯的分子结构参数,然后用逐步线性回归方法建立聚甘油脂肪酸酯HLB值的定量结构性质(QSPR)模型,所得的预测模型中包含4个参数[单位质量分子所含氧原子数Xo、生成热fHm、电子能Ee和水合能Eh,预测值及外部检验的复相关系数(R2)和标准偏差(SD)分别为0.9553、0.73722和0.9678、6.34426。结果表明,量子化学方法计算简单,对聚甘油脂肪酸酯结构的表征能力较强,所建定量结构性质模型具有能较好的预测能力和较强的稳健性,并在一定程度上阐明了聚甘油脂肪酸酯HLB值与其分子结构之间的关系。     

氯霉素分子印迹聚合物预组装过程的分子动力学研究

以氯霉素(CAP)为模板分子,甲基丙烯酸(MAA)、丙烯酸(AA)、丙烯酰胺(AM)、甲基丙烯酸甲酯(MMA)为功能单体,采用分子动力学方法研究了不同预组装体系中CAP与功能单体的相互作用,考察了溶剂(氯仿、甲醇、乙腈)对预组装体系的影响,并采用试验方法验证模拟结果,最后研究了预组装体系中CAP与功能单体相互作用距离。结果表明:模拟结果与实验结果一致,在甲醇溶剂中,CAP与功能单体相互作用强弱顺序为MAA>AA>AM>MMA;乙腈溶剂中顺序为AM>MAA>AA>MMA。CAP与功能单体相互作用基团的距离在1.8~5.0,两者间可能存在较强的非共价结合作用。     

(OsB)_n(n=1-6)团簇结构与稳定性的第一性原理研究

基于第一性原理,采用密度泛函理论(DFT)中的广义梯度近似(GGA)对(OsB)_n(n=1-6)团簇各种可能的构型进行了几何结构优化,得出了各团簇的最稳定构型,并对最稳定构型的能量、结合能、二阶能量差分、能隙等性质进行了理论研究。研究结果表明:n=2、3时,体系的基态结构分别为棱形和锅盖形;n=4时,体系的基态结构是对称性为T_d的立方体形状,是本文对称性最高的构型;从n=4开始立方体构型主导着团簇基态结构的生长行为,表明团簇的稳定性不仅与团簇的尺寸大小有关,还与团簇的对称性有关。团簇(OsB)_4的能隙、结合能与能量的二阶差分比邻近的值都大,说明团簇(OsB)_4有较高的稳定性,n=4是团簇的幻数。