胆固醇酯转运蛋白抑制剂的3D-QSAR模型

利用VolSurf参数和比较分子场分析(CoMFA)方法对N,N-二取代三氟-3-氨基-2-丙醇衍生物类胆固醇酯转运蛋白抑制剂进行了三维定量构效关系(3D-QSAR)模型研究, 均得到较好的结果, 训练集模型具有良好的预测能力. VolSurf参数分析表明抑制活性高的分子必须具有合适的亲水性、多的氢键给体和少的氢键受体; 在一定范围内, 分子量大、表面光滑且非球性高的分子抑制活性高; 高疏水性以及质量中心与疏水区中心的高不平衡性对活性是不利因素. CoMFA结果表明, 立体作用对活性的影响较静电作用稍强, N-苯基取代基苯氧基的间位体积大且正电性强的基团对活性有利, N-苄基取代基的间位体积大且合适的电负性对活性有利, 而苄基的对位立体位阻的增加则对活性不利. VolSurf参数提供了分子整体性质信息, CoMFA提供了取代基信息, 两者互为补充, 对该类抑制剂新化合物的设计具有指导意义.     

反气相色谱技术与汉森溶解参数法测定咪唑基醋酸盐类离子液体的溶解度参数

采用反气相色谱技术在353.15~393.15 K温度范围内测定了4种咪唑基醋酸盐离子液体的溶解度参数.结果表明,在实验温度范围内,反气相色谱技术测定的离子液体的溶解度参数值随温度的升高而线性减小.通过外推法得到333.15 K时4种离子液体的溶解度参数分别为26.14,24.38,23.60和23.04 MPa~(1/2).采用Hansen溶解度参数软件在333.15 K时对4种离子液体的溶解度参数进行模拟计算,结果分别为26.52,23.99,23.45和22.00 MPa~(1/2).2种方法测定结果在±1.05 MPa~(1/2)的误差范围内一致,说明2种方法均适用于咪唑基醋酸盐溶解度参数的测定.     

离子液体中AM/AMPS/N8AM三元共聚物的合成及溶液性能

以丙烯酰胺(AM)和2-丙烯酰胺基-2-甲基丙磺酸(AMPS)为亲水单体, 以N-辛基丙烯酰胺(N8AM)为疏水单体, 在离子液体[bmim]BF4中实现了疏水缔合丙烯酰胺三元共聚物的合成.     

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。     

离子液体1-丁基-3-三甲基硅咪唑六氟磷酸盐萃取细胞色素C

建立了疏水性离子液体1-丁基-3-三甲基硅咪唑六氟磷酸盐(BtmsimPF6)萃取细胞色素C(Cyt-c)的新方法.在萃取条件为pH 1.0,Cyt-c溶液体积3 mL,BtmsimPF6体积400 μL,萃取时间30 min时,5 mg/L Cyt-c的萃取效率为85%.萃取机理研究表明:在酸性条件下,Cyt-c发生构型转变,肽链伸展,使疏水性基团外露,增加了Cyt-c在疏水性离子液体中的溶解性;同时,当pH＜2.0时,血红素基团中的Fe与Met-80的配位断裂,空出第六个配位空间,离子液体咪唑阳离子进入到肽链孔穴与Fe发生配位,形成新的配位键,从而被萃取到离子液体中.     

具有除草活性的吡唑啉并四嗪酮衍生物的设计、合成与定量构效关系的研究

设计合成了一系列未见文献报道的4-乙氧羰基-1,7-二氢-1-取代苯基-5-(未)取代吡唑啉[5,1-d][1,2,3,5]四嗪-7-酮衍生物, 其结构均经过¹H NMR、IR和元素分析表征. 生测结果显示, 与已报道的化合物相比, 它们表现出较好的除草活性. 定量的结构与活性关系研究表明, 它们的除草活性与取代基的立体效应参数和疏水性参数呈现很好的相关性, 相关系数r大于0.8. 当作用对象为油菜时, 化合物的活性可能主要与取代基R¹的摩尔分子折射和取代基R²的疏水性参数有关. 当取代基R¹的摩尔分子折射参数为1.452时, 相应化合物可能具有对油菜最高的除草活性; 当作用对象为稗草时, 化合物的活性主要与取代基R²疏水性参数和Taft (Es)参数有关.     

两亲性嵌段共聚物的合成及其在离子液体中的自组装行为

采用阴离子开环聚合法合成了两亲性嵌段共聚物PLA-PEG-PLA.用FT-IR,1H NMR和GPC等手段对嵌段共聚物的结构组成进行了表征.两亲性嵌段共聚物在离子液体1-丁基-3-甲基咪唑六氟磷酸盐中能自组装成胶束,用透射电子显微镜观察了聚合物在离子液体中形成胶束的纳米结构.当疏水链长固定时,胶束的自组装形状主要依赖于亲水链的长度.两亲性共聚物在离子液体中可自组装成可控制结构的纳米胶束,这种纳米结构胶束在很多领域具有广泛的应用前景.     

取代基物化参数及其在药物定量构效关系中的应用

把取代基电性、立体及疏水性物化参数组合建立一种新取代基描述方法, 对环尿素类和N,N-二甲基-2-溴苯乙胺类衍生物进行结构表征. 对训练样本集通过逐步回归筛选变量, 所建多元线性回归方程R2分别为0.853和0.960, 留一法交互检验Rcv2分别为0.723和0.901；用预测集样本作外部预测, 所得Qext2分别为0.7617和0.7653. 结果显示：环尿素类化合物结构中苯环邻位立体、间位疏水、对位疏水及立体因素对该类药物抗HIV活性产生阻抑作用； N,N-二甲基-2-溴苯乙胺类苯环上取代基立体因素及对位给电子效应有利于提高肾上腺素能阻断活性.     

反气相色谱测定非对称双阳离子型离子液体的溶解度参数

在343.15~363.15 K下采用反气相色谱法对实验室合成的3种非对称双阳离子型离子液体[PyC₅Pi]NTf₂]₂、[MpC₅Pi]NTf₂]₂和[PyC₆Pi]NTf₂]₂的溶解度参数进行了测定。以正辛烷、正癸烷、正十二烷、正十四烷和正十六烷作为探针溶剂,计算了在不同温度下探针溶剂在3种离子液体中的特性保留体积(V_g⁰)、摩尔吸收焓(ΔH₁^S)、无限稀释摩尔混合焓(ΔH_l^∞)、摩尔蒸发焓(ΔH_v)、无限稀释活度系数(Ω₁^∞)以及探针溶剂与3种离子液体的Flory-HuggirIs相互作用参数(χ₁₂^∞),得到了室温下3种离子液体的溶解度参数(δ₂)为28.52~32.66 (J·cm^-3)^1/2。分子结构中含有4-甲基吗啉比含有吡啶时溶解度参数更大。随着两个阳离子间连接基碳数的增加,溶解度参数增大。这一结果对研究离子液体的溶液性质和应用有指导作用。     

轻度交联环糊精聚合物包结诱导自组装胶束的研究

合成了含β-环糊精的多取代单体(GMA)x-CD,经自由基聚合得到轻度交联的或高度支化的聚合物P(GMA)x-CD;同时由自由基共聚得到含有金刚烷侧基的疏水聚合物PtBA-ADA.研究表明,他们可在碱性水中通过β-CD和ADA间的包结络合作用形成胶束.当改变聚合物浓度比时,胶束尺寸在150~300 nm范围变化.TEM和AFM研究表明胶束具有核壳结构,核为疏水PtBA-ADA,壳为亲水(GMA)x-CD.通过对胶束壳CD基的化学交联,将胶束结构进一步固定化.     

Synthesis and characterization of dicationic ionic liquids that contain both hydrophilic and hydrophobic anions

A series of dicationic ionic liquids, in which each dication is associated with both a hydrophobic anion and a hydrophilic anion, are synthesized. The thermal properties and solubility in organic solvents of these ILs are characterized. The ionic liquids show interesting properties, which are different from those of dicationic ionic liquids, in which each dication is associated with two identical anions.     

Study of ionic liquids by the method of voltammetry at the interface between two immiscible electrolytes

Ionic liquids were studied as the organic phase in the method of voltammetry between two immiscible electrolytes. The polarization of the interface between ionic liquid and water was studied; the dependence of the polarization range (potential window) on the solubility of ionic liquid in water was shown. It was established that the interface between H₂O and ionic liquid based on hydrophobic substituted phosphonium cation and tris(pentafluoroethyl)-trifluorophosphate anion is polarized in the range of potential of about 500 mV, which creates the possibility of determining the concentration of some union, in particular perchlorate and nitrate, even in when they are both present, as well as to measure the solubility of more hydrophilic ionic liquids in water.     

Ionic Liquids Can Permanently Modify Porous Silicon Surface Chemistry

To develop ionic liquid/porous silicon (IL/pSi) microarrays we have contact pin‐printed 20 hydrophobic and hydrophilic ionic liquids onto as‐prepared, hydrogen‐passivated porous silicon (ap‐pSi) and then determined the individual IL spot size, shape and associated pSi surface chemistry. The results reveal that the hydrophobic ionic liquids oxidize the ap‐pSi slightly. In contrast, the hydrophilic ionic liquids lead to heavily oxidized pSi (i.e., ox‐pSi). The strong oxidation arises from residual water within the hydrophilic ILs that is delivered from these ILs into the ap‐pSi matrix causing oxidation. This phenomenon is less of an issue in the hydrophobic ILs because their water solubility is substantially lower.     

QSAR Study and VolSurf Characterization of Human Intestinal Absorption of Druge

The prediction of human intestinal absorption is a major goal in the design,optimization,and selection of candidates for the develoment of oral drugs.In this study,a computerized method(VolSurf with GRID) was used as a novel tool for predicting human intestinal absorption of test compound,and for determining the critical molecular properties needed for human intestinal absorption.The tested molecules consisted of 20 diverse drug-like compounds.Partial least squares(PLS) discriminant analysis was used to correlate the experimental data with the theoretical molecular properties of human intestinal absorption.A good correlation(r^2=0.95,q^2=0.86) between the molecular modeling results and the experimental data demonstrated that human intestinal absorption could be predicted from the three-dimensional(3D) molecular structure of a compound .Favorable structureal properties identified for the potent intestinal absorption of drugs included strong imbalance between the center of mass of a molecule and the barycentre of its hydrophilic and hydrophobic regions and a definitive hydrophobic region as well as less hydrogen bonding donors and acceptors in the molecule.     

Solubilities of p-coumaric and caffeic acid in ionic liquids and organic solvents

The solubilities of two cinnamic acid derivatives, namely p-coumaric acid and caffeic acid, in six 1-alkyl-3-methyl imidazolium based ionic liquids composed of the PF₆⁻, BF₄⁻, TFO⁻ and TF₂N⁻ anions, and in two organic solvents, t-pentanol and ethyl acetate, have been measured at the temperature range of about (303 to 317) K. The p-coumaric acid was found to be more soluble than caffeic acid in all studied solvents. Higher solubilities of both acids were observed in the ionic liquids composed of the BF₄⁻ and TFO⁻ anions. The increase of the alkyl chain length on the cation invokes a decrease in solubility in the case of hydrophilic ionic liquids composed of BF₄⁻ anion, while in the case of hydrophobic ones composed of PF₆⁻ anion an increase in the solubility is observed. Between the two organic solvents t-pentanol is better solvent than ethyl acetate for both acids. Moreover, using the van’t Hoff equations the apparent Gibbs energy, enthalpy, and entropy of solution were calculated. Finally, successful correlation of the experimental data was achieved with the UNIQUAC and the NRTL activity coefficient models, while poor predictions of the solubility of the two acids in the organic solvents were obtained with two UNIFAC models.     

聚离子液体材料在分离科学中的研究进展

离子液体作为新型离子化试剂,具有诸多优越的物理化学性质,比如:良好的溶解性、导电性、热稳定性、生物相容性及低蒸气压和不易燃等特点,近年来在分析化学领域得到广泛关注。聚离子液体材料结合了离子液体和聚合物的双重性质,已经成为分离科学研究的前沿领域。本文详细讨论了离子液体与目标物之间的多种作用机制,比如亲/疏水作用、氢键作用、离子交换、π - π 堆积及静电吸附作用等等,总结了聚离子液体材料在固相萃取、液相色谱、气相色谱、毛细管电泳及毛细管电色谱等领域的研究进展;最后,对聚离子液体材料的发展前景进行了展望。     

Improving carbon dioxide solubility in ionic liquids

Previously we showed that CO2 could be used to extract organic molecules from ionic liquids without contamination of the ionic liquid. Consequently a number of other groups demonstrated that ionic liquid/CO2 biphasic systems could be used for homogeneously catalyzed reactions. Large differences in the solubility of various gases in ionic liquids present the possibility of using them for gas separations. More recently we and others have shown that the presence of CO2 increases the solubility of other gases that are poorly soluble in the ionic liquid phase. Therefore, a knowledge and understanding of the phase behavior of these ionic liquid/CO2 systems is important. With the aim of finding ionic liquids that improve CO2 solubility and gaining more information to help us understand how to design CO2-philic ionic liquids, we present the low- and high-pressure measurements of CO2 solubility in a range of ionic liquids possessing structures likely to increase the solubility of CO2. We examined the CO2 solubility in a number of ionic liquids with systematic increases in fluorination. We also studied nonfluorinated ionic liquids that have structural features known to improve CO2 solubility in other compounds such as polymers, for example, carbonyl groups and long alkyl chains with branching or ether linkages. Results show that ionic liquids containing increased fluoroalkyl chains on either the cation or anion do improve CO2 solubility when compared to less fluorinated ionic liquids previously studied. It was also found that it was possible to obtain similar, high levels of CO2 solubility in nonfluorous ionic liquids. In agreement with our previous results, we found that the anion frequently plays a key role in determining CO2 solubility in ionic liquids.