离子液体的毒性

离子液体因其特有的物化性质受到越来越多的关注,并被认为是环境友好的"绿色产品"。但是有关离子液体的潜在毒性一直被人们所忽视,直到最近才有少量报道。本文综述了离子液体毒性研究的相关情况：详细介绍了离子液体毒性研究的各种方法及优缺点;离子液体对各类生物的急性毒性和慢性毒性;离子液体的各部分组成,尤其是阳离子核种类、取代烷基碳链长度和阴离子种类对离子液体毒性的影响情况,以及SAR理论在离子液体毒性研究中的应用情况。在此基础上提出今后离子液体毒性研究的发展方向。     

分子电性距离矢量用于三嗪类化合物的构效关系研究

采用分子电性距离矢量(Molecular Electronegativity Distance Vector,MEDV)表征了三嗪类化合物的分子结构,并运用多元线性回归(Multiple Linear Regression,MLR)建立了该类化合物结构与其发光菌和大型蚤毒性的定量结构-毒性相关(Quanti-tative Structure-Toxicity Relationship,QSTR)模型,同时采用留一法交互检验对所建模型进行了分析和验证,建模计算值的相关系数R分别为0.970和0.952,留一法交互检验预测值的相关系数RLOO分别为0.917和0.921,并进一步阐述了结构与毒性之间的关系。结果表明,三嗪环上π电子离域程度减小有利于毒性增加,侧链N上取代基数目增加,化合物毒性减小。为进一步预测该类化合物的毒性,进行药物筛选提供了有效的理论依据。     

三嗪类化合物溶解度参数及毒性构－效关系

测定了１２种三嗪类化合物的水溶解度，辛醇水分配系数和对发光菌的毒性，并用分子连结性指数建立了预测三嗪类化合物的溶解度，辛醇水分配系数及对发光菌毒性的定量结构活性相关方程，其中１０种化合物文献中未见报道。     

三嗪类化合物溶解度参数及毒性构—效关系

测定了１２种三嗪类化合物的水溶解度，辛醇水分配系数和对发光菌的毒性，并用分子连结性指数建立了预测三嗪类化合物的溶解度，辛醇水分配系数及对发光菌毒性的定量结构活性相关方程，其中１０种化合物献中未见报道。e     

Recent Research Progress on the Toxicity of Ionic Liquids

作为一种新型的“绿色”溶剂,离子液体以其低挥发、溶解性好、性质稳定等特点而得到较多的研究,并已在化学、生物、环境和化工等领域得到广泛的应用。然而,有关离子液体潜在毒性的研究工作却很少,不利于离子液体的深入研究、开发与应用。本文综述了有关离子液体毒性研究的最新进展,介绍了离子液体毒性的研究方法与特性参数,论述了离子液体对生物体的毒性和对生态环境的破坏作用,讨论了影响离子液体毒性的各因素,并展望了离子液体的未来研究方向。     

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.     

Artificial Neural Networks Applied to the Quantitative Structure-Activity Relationship Study of Para-substituted Phenols

The artificial neural network (ANN) model with back-propagation of error is used to study the quantitative structure-activity relationship of para-substituted phenol derivatives between the biological activity and the physicochemical property parameters. Network parameters are optimized, and an empirical rule for dynamically adjusting the network's learning rate is proposed to improve the network's performance. The results showthat the three-layer ANN model gives satisfactory performance, with f(x)=1/(1+exp(-x)) as the network node's input-output transformation function and the number of hidden nodes 10. The network gives the mean square error (rose) of 0.036 when predicting the biological activity of 26 para-substituted phenol derivatives. This result compares favourably with that obtained by the conventional methods.     

Study on the Surface Property of Surfactant Ionic Liquids Solutions

The surfactant TX-100 can be dissolved in ionic liquid bmimPF6 and decrease the surface tension of 1-buty1-3-methylimidazolium hexafluorophosphate (bmimPF6) solutions. Here, we confirmed that in this new system, the pure solvents need rearrangement at the air-wate rinterface at the initial stage. The dynamic surface tension (DST) study shows that at the initial adsorption stage, the adsorption model of surfactant accords with the diffusion-controlled adsorption mechanism, and the dilute ionic liquids solutions is further close to the diffusion-controlled adsorption.     

GPR40 受体苯丙酸类激动剂三维定量构效关系研究

苯丙酸类化合物是G蛋白偶联受体40(GPR40)潜在的生物活性药物。本文基于比较分子力场分析法(Co MFA)和比较分子相似性指数分析法(CoMSIA),分别建立了40个已知活性的GPR40受体苯丙酸类激动剂的三维定量构效关系(3D-QSAR)模型,研究该类激动剂与生物活性之间的关系。CoMFA和CoMSIA模型的交叉验证系数(q~2)分别为0. 527和0. 500,拟合验证系数(r~2)分别为0. 901和0. 860,两个3D-QSAR模型预测值与实验值基本一致,表明模型具有良好的可信度和预测能力。根据两个3D-QSAR模型提供的立体场、静电场、疏水场、氢键供体场和氢键受体场所提供的信息提出优化该类抑制剂结构的药物设计思路,为指导设计更高活性的GPR40激动剂以及GRR40新分子激动活性的预测提供理论依据。     

Broadband NMR Relaxometry as a Powerful Technique to Study Molecular Dynamics of Ionic Liquids

Fast field cycling nuclear magnetic resonance (FFC NMR) relaxometry technique has been demonstrated to be a useful analytical tool to investigate molecular dynamics in very diverse systems during the last decades. Of particular importance has been its application in studying ionic liquids, upon which this review article is based. Some of the research carried out on ionic liquids during the last ten years using this technique is highlighted in this article with the aim of promoting the favorable features of FFC NMR applied toward understanding dynamics of complex systems.     

Spectroscopic and Chemical Properties of Ionic Liquids: Computational Study

A brief account is given of highlights of our computational efforts – often in collaboration with experimental groups – to understand spectroscopic and chemical properties of ionic liquids (ILs). Molecular dynamics, including their inhomogeneous character, responsible for key spectral features observed in dielectric absorption, infra-red (IR) and fluorescence correlation spectroscopy (FCS) measurements are elucidated. Mechanisms of chemical processes involving imidazolium-based ILs are illustrated for CO₂ capture and related reactions, transesterification of cellulose, and Au nanocluster-catalyzed Suzuki cross-coupling reaction with attention paid to differing roles of IL ions. A comparison with experiments is also made.     

一种新三维描述子用于Nevirapine类抗艾滋病药物定量构效关系的研究

运用三维全息原子场作用矢量(3D-HoVAIF)对33个Nevirapine类抗艾滋病药物进行了定量构效关系(QSAR)研究。采用偏最小二乘回归(PLSR)建立定量构效关系模型,同时采用内部及外部双重验证的方法对所得模型稳定性能进行深入分析和检验,所建模型的复相关系数(Rcum2)、留一法(LOO)交互校验(CV)复相关系数(Qcum2)和外部样本校验复相关系数(Qext2)分别为0·835、0·530和0·518。结果表明,3D-HoVAIF能较好表征Nevirapine类抗艾滋病药物分子结构信息,且所建模型具有较好稳定性能和预测能力。     

苯乙酮肟醚类化合物的合成及基于定量构效关系研究的分子设计

由于肟醚结构的特殊性质, 因而很多农药和医药化合物中包含该结构. 介绍苯乙酮肟醚类化合物的合成、瓜类白粉病抑制活性的定量构效关系(QSAR)研究以及基于QSAR研究结果的新化合物设计、合成和生测, 尝试了农药先导合理设计流程在具有瓜类白粉病抑制活性的苯乙酮肟醚类化合物设计中的应用. 初步的结果显示, 介绍的工作模式既充分利用了原来的工作基础, 又降低了失败的风险、污染和成本.     

Theoretical-Computational Modeling of Gas-State Thermodynamics in Flexible Molecular Systems: Ionic Liquids in the Gas Phase as a Case Study

A theoretical-computational procedure based on the quasi-Gaussian entropy (QGE) theory and molecular dynamics (MD) simulations is proposed for the calculation of thermodynamic properties for molecular and supra-molecular species in the gas phase. The peculiarity of the methodology reported in this study is its ability to construct an analytical model of all the most relevant thermodynamic properties, even within a wide temperature range, based on a practically automatic sampling of the entire conformational repertoire of highly flexible systems, thereby bypassing the need for an explicit search for all possible conformers/rotamers deemed relevant. In this respect, the reliability of the presented method mainly depends on the quality of the force field used in the MD simulations and on the ability to discriminate in a physically coherent way between semi-classical and quantum degrees of freedom. The method was tested on six model systems (n-butane, n-butane, n-octanol, octadecane, 1-butyl-3-methylimidazolium hexafluorophosphate and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ionic pairs), which, being experimentally characterized and already addressed by other theoretical-computational methods, were considered as particularly suitable to allow us to evaluate the method’s accuracy and efficiency, bringing out advantages and possible drawbacks. The results demonstrate that such a physically coherent yet relatively simple method can represent a further valid computational tool that is alternative and complementary to other extremely efficient computational methods, as it is particularly suited for addressing the thermodynamics of gaseous systems with a high conformational complexity over a large range of temperature.     

抗癌性吲哚喹唑啉衍生物的定量构效关系

用量子化学密度泛函理论(DFT)、分子力学(MM＋)及回归分析方法,对一系列抗癌性吲哚喹唑啉衍生物进行了定量构效关系(QSAR)的研究.通过回归分析,筛选了影响抗癌活性的主要因素,建立了定量构效关系方程.结果表明,化合物的最低未占据分子轨道(LUMO)与最高占据分子轨道(HOMO)之间的能量差(ΔεL-H)、分子的疏水性(lgP)以及环D上的总电荷(ΣQD)和环D上R1取代基的第一个原子的净电荷(QFR1)是影响化合物抗癌活性的主要因素.所得模型对化合物抗癌活性有较好的预测效果. 同时, 与ΔεL-H密切相关的LUMO轨道能量及共轭平面面积对药物的DNA-结合及其活性起着十分重要的作用,可通过选取具有较强的拉电子性质同时又能与本系列化合物的骨架形成更大共轭体系的取代基R1,设计抗癌活性较高的化合物.     

Effects of Cationic Structure on Cellulose Dissolution in Ionic Liquids: A Molecular Dynamics Study

In recent years, great progress has been made in the dissolution of cellulose with ionic liquids (ILs). However, the mechanism of cellulose dissolution, especially the role the IL cation played in the dissolution process, has not been clearly understood. Herein, the mixtures of cellulose with a series of imidazolium‐based chloride ionic liquids and 1‐butyl‐3‐methyl pyridinium chloride ([C₄mpy]Cl) were simulated to study the effect that varying the heterocyclic structure and alkyl chain length of the IL cation has on the dissolution of cellulose. It was shown that the dissolution of cellulose in [C₄mpy]Cl is better than that in [C₄mim]Cl. For imidazolium‐based ILs, the shorter the alkyl chain is, the higher the solubility will be. In addition, an all‐atom force field for 1‐allyl‐3‐methyl imidazolium cation ([Amim]⁺) was developed, for the first time, to investigate the effect the electron‐withdrawing group within the alkyl chain of the IL cation has on the dissolution of cellulose. It was found that the interaction energy between [Amim]⁺ and cellulose was greater than that between [C₃mim]⁺ and cellulose, indicating that the presence of electron‐withdrawing group in alkyl chain of the cation enhanced the interaction between the cation and cellulose due to the increase of electronegativity of the cations. These findings are used to assess the cationic effect on the dissolution of cellulose in ILs. They are also expected to be important for rational design of novel ILs for efficient dissolution of cellulose.     

HLA-A*0201限制性CTL表位定量结构与活性研究

采用VHSE氨基酸结构描述子表征HLA-A*0201限制性表位结构, 以遗传算法和偏最小二乘相结合(GA-PLS)对102个训练集进行定量构效关系建模. 剔除3个异常样本后, 据候选模型交互检验及50个外部测试集预测结果, 筛选得到最优偏最小二乘模型(A＝2), 其R², Q²和 分别为0.755, 0.621和0.680. 构效研究显示: CTL表位活性主要与1, 2, 7, 8, 9位氨基酸残基疏水、1, 2位立体及6位残基电性等性质密切相关.     

碱性离子液体的合成及其在Baylis-Hillman 反应中的应用

采用正交实验优化合成了碱性离子液体氢氧化1-丁基-4-二甲氨基吡啶盐, 以其为反应溶剂, 在催化剂DABCO(1,4-二氮杂二环[2.2.2]辛烷)作用下进行了芳香醛与丙烯酸甲酯的Baylis-Hillman 反应研究. 实验结果表明, 在该离子液体的存在下, 芳香醛与丙烯酸甲酯以较快的反应速度和较高产率生成目标化合物. 在此基础上, 进一步研究了水-离子液体复合体系对Baylis-Hillman 反应的影响, 取得了更快的速率及更高的产率.     

基于QSAR模型的有机磷化合物毒性预测

随着有机磷化合物(OPs)的广泛应用,其在越来越多的环境介质中被检测出来。大多数OPs具有毒性,但人们缺乏快速且有效的预测手段来对毒性进行评估。本文将结合E-Dragon软件计算的分子描述符,采用不同的QSAR模型对36个OPs的毒性进行预测。文中采用后退法作为描述符筛选方法,以均方根误差(RMSE)作为评价标准,共找到14个对线性核函数支持向量机(SVM)模型贡献较大的描述符;在最终得到的SVM模型交叉验证结果中,计算值与实际值的相关系数为0. 913,均方根误差为0. 388;外部测试验证结果中,平均相对误差为9. 10%。此外,采用多元线性回归(MLR)、人工神经网络(ANN)以及偏最小二乘回归(PLS)模型对OPs的毒性进行预测,交叉验证结果显示,三个模型的计算值与实际值的相关系数分别为0. 878、0. 686与0. 620,没有SVM模型的预测能力好。因此采用线性核函数的SVM模型对OPs进行毒性预测是一个行之有效的方法。