分子亲脂-亲水性的量子化学描述II. 氨基酸侧链的亲水指标和亲脂指标

在启发式亲脂势HMLP (heuristic molecular lipophilicity potential)的基础上提出了分子、分子片段和原子的亲水指标和亲脂指标. 计算出了20个天然氨基酸侧链的亲水、亲脂指标和亲水、亲脂表面积, 并用线性自由能函数表达氨基酸侧链的溶剂化自由能, ΔG_sol,i^θ＝b₀＋b₁L_i＋b₂H_i＋b₃S_i^＋＋b₄S_i^－. . 应用线性自由能函数和氨基酸侧链的亲水和亲脂指标, 计算了20个氨基酸残基的3种相转移自由能(蒸气-水、蒸气-正辛醇、正辛醇-水)和正辛醇-水分配系数logP_ow, 取得了与实验值高度一致的良好效果. HMLP的亲水和亲脂指标是HMLP的指标化, 扩展了这一方法的使用范围. 氨基酸侧链的亲水、亲脂指标和线性自由能函数有望用于生物大分子受体与配体的结合自由能的估算、蛋白质的结构与功能、蛋白-蛋白相互作用和识别的研究.     

分子亲脂-亲水性的量子化学描述(Ⅰ)--分子的亲脂和亲水表面

给出基于分子结构的“启发式”亲脂-亲水势HMLP(Heuristic molecular lipophilicity-hydrophilicity potential)的理论分析和有说服力的算例.用量子化学计算其分子表面的静电势V(r)的分布,通过与周围原子表面静电势的比较,构造表达分子静电势的极性和大小的函数L(r).亲脂势L(r)保留了静电势V(r)描述分子静电作用的能力,并把应用范围扩展到疏水性的描述.HMLP不使用原子的经验参数,但在L(r)的构造中使用了经验的函数形式.经参数化和指标化后,HMLP有望用于蛋白质结构与功能的研究和药物分子配体与生物大分子受体结合自由能的估算.     

微乳液的热力学性质 I: 芳烃类的侧链链长对微乳液热力学函数影响

本文研究以非离子型表面活性剂-正辛醇-水-芳烃类所组成的微乳液, 探讨醇从油相转移到界面相时的自由能变化, 以及温度对自由能的影响。计算出熵和焓的变化, 发现在实验范围内, 上述热力学函数的对数值与芳烃侧链的碳原子数(n)呈线性关系。这些关系式对微乳液的构成和稳定性的讨论是重要的, 还对几种芳烃异构体所构成的微乳液的热力学函数进行了实验和讨论。     

微乳液的热力学性质 I: 芳烃类的侧链链长对微乳液热力学函数影响

本文研究以非离子型表面活性剂-正辛醇-水-芳烃类所组成的微乳液, 探讨醇从油相转移到界面相时的自由能变化, 以及温度对自由能的影响。计算出熵和焓的变化, 发现在实验范围内, 上述热力学函数的对数值与芳烃侧链的碳原子数(n)呈线性关系。这些关系式对微乳液的构成和稳定性的讨论是重要的, 还对几种芳烃异构体所构成的微乳液的热力学函数进行了实验和讨论。     

气相色谱保留值与疏水亲脂参数的关系

 ]本文利用数理统计方法，研究了分子结构参数与气相色谱保留行为的关系，重点考察了疏水亲脂参数logP以及结合诱导效应指数F和分子连通性指数1X，对于极性和非极性物质色谱保留值的不同贡献。并通过对保留值的预测，证明了它们的密切相关性。     

α,ω-双(4-硝基苯氰基)直链烷烃的溶剂效应

在许多化学和生物体系的变化过程中,溶剂性质起着重要的作用.在一些含水的有机溶剂中,大的有机化合物分子由于疏水亲脂相互作用倾向于簇集和自挠曲,从而大大影响分子的化学反应性能和物理性质.这种相互作用也应存在于生命体的细胞中,而表现出生理上的变化.蒋锡夔等曾报导含水量不同溶剂对一系列长链分子化学反应性的影响。     

碳酸酯把手改构Wang树脂及其性能

基于碳酸酯结构易于亲核脱除的原理, 使用氯甲酸氯甲酯改构Wang树脂, 并探究了改构树脂与首位氨基酸的缩合效率. 实验结果表明, 改构后的Wang树脂与20种Fmoc保护氨基酸均能达到70%以上的缩合效率; 且对于带有较大侧链基团的Fmoc保护氨基酸, 通过降低树脂取代度或延长反应时间可提高其连接率. 为了验证改构后的碳酸酯型树脂在裂解时侧链未受到影响, 设计合成了3种模型肽, 并用温和裂解剂3-吡啶甲醛肟铯盐进行裂解. 实验结果表明, 利用改构树脂能得到侧链全保护的肽片段, 可初步应用到长链困难肽的合成中.     

两亲性梳形聚合物胶束行为的Monte Carlo模拟

采用二维和三维格子模型用Monte Carlo法模拟两亲性梳形聚合物的胶束行 为. 模拟时采用动态算法结合链的reptation运动并且编制了三维结构显示程序及获得了体系的Monte Carlo自由能. 结果表明: 约化相互作用能的选取对胶束及乳液体系的形态结构有重大影响; 三维模拟可以得到体系形态结构更为直观的结果; 亲油主链亲水侧链型梳形聚合物在水相中的胶束比在油相的胶束有更低的能量.     

固体的表面能及其亲水/疏水性

固体表面的亲水/疏水性质与表面分子与水之间的固/液界面相互作用自由能以及水介质中表面分子与空气之间的固/(液)/气界面相互作用自由能密切相关.水介质中固体表面与水之间存在范德华引力或疏水引力,与气泡之间存在范德华斥力、疏水引力以及静电斥力.在Lifshitz-范德华(LW)相互作用自由能、Lewis酸-碱(AB)相互作用自由能以及静电(EL)相互作用自由能3者之中,AB相互作用自由能比其它两者要大2～3个数量级以上.与固体表面能Lewis酸-碱分量相关的亲水指数√r_s~++√r_s~-可以成为衡量固体表面亲水/疏水性质的重要判据,水介质中固体表面疏水的必要条件是√r_s~++√r_s~-＜5mJ~(1/2)/m,指数大于或接近5mJ~(1/2)/m的表面必然是亲水的.     

两亲聚合物表面的反相气相色谱分析

采用反相气相色谱探针技术研究了苯乙烯－氧乙烯－苯乙烯三嵌段两亲聚合物的表面物理化学性质。包括表面吸附热力学函数,表面能的色散分量以及表面分子链与探针的分子间相互作用,。探讨了共聚物中亲油性链段聚苯乙烯（PS）和亲水性链段聚氧乙烯（PEO）的组成比例与其表面性质的关系。结果表明共聚物表面组成中随PEO含量的增加,其表面能增大,表面分子链与探针分子的相互作用增强,表面吸附能力也增强。     

Heuristic molecular lipophilicity potential (HMLP): lipophilicity and hydrophilicity of amino acid side chains

Heuristic molecular lipophilicity potential (HMLP) is applied in the study of lipophilicity and hydrophilicity of 20 natural amino acids side chains. The HMLP parameters, surface area S(i), lipophilic indices L(i), and hydrophilic indices H(i) of amino acid side chains are derived from lipophilicity potential L(r). The parameters are correlated with the experimental data of phase-transferring free energies of vapor-to-water, vapor-to-cyclohexane, vapor-to-octanol, cyclohexane-to-water, octanol-to-water, and cyclohexane-to-octanol through a linear free energy equation DeltaG(0)(tr,i) = b(0) + b(1)S(i) (+) + b(2)S(i) (-) + b(3)L(i) + b(4)H(i). For all above six phase-transfer free energies, the HMLP parameters of 20 amino acid side chains give good calculation results using linear free energy equation. HMLP is an ab initio quantum chemical approach and a structure-based technique. Except for atomic van der Waals radii, there are no other empirical parameters used. The HMLP has clear physical and chemical meaning and provides useful lipophilic and hydrophilic parameters for the studies of proteins and peptides.     

Heuristic molecular lipophilicity potential (HMLP): a 2D-QSAR study to LADH of molecular family pyrazole and derivatives

The quantum chemical and structure-based technique heuristic molecular lipophilicity potential (HMLP) is used in the liver alcohol dehydrogenase (LADH) study of molecular family pyrazole and derivatives. The molecular lipophilic index LM, molecular hydrophilic index HM, lipophilic indices lss, and hydrophilic indices hss of the substitutes (fragments), and atomic lipophilicity indices las are constructed and used in QSAR study. The HMLP indices are correlated with bioactivities of 18 pyrazole derivatives according to the 2D QSAR procedure. The multiple linear regression equation between the bioactivities of pyrazole derivatives and HMLP indices are built using partial least square (PLS) with the optimal statistical quantity (r=0.987, s=0.479, F=47.19). The inhibition mechanism of LADH of the pyrazole derivatives is explained according to the physical meaning of HMLP indices. During the HMLP calculations for the 2D QSAR, the only input parameters are the atomic van der Waals radius without the need to resort to any empirical parameters. Accordingly, HMLP can provide a rigorous theoretical approach with a crystal clear physical meaning for the 2D QSAR.     

Heuristic lipophilicity potential for computer-aided rational drug design

In this contribution we suggest a heuristic molecular lipophilicitypotential (HMLP), which is a structure-based technique requiring noempirical indices of atomic lipophilicity. The input data used in thisapproach are molecular geometries and molecular surfaces. The HMLP is amodified electrostatic potential, combined with the averaged influences fromthe molecular environment. Quantum mechanics is used to calculate theelectron density function (r) and the electrostatic potential V(r), andfrom this information a lipophilicity potential L(r) is generated. The HMLPis a unified lipophilicity and hydrophilicity potential. The interactions ofdipole and multipole moments, hydrogen bonds, and charged atoms in amolecule are included in the hydrophilic interactions in this model. TheHMLP is used to study hydrogen bonds and water–octanol partitioncoefficients in several examples. The calculated results show that the HMLPgives qualitatively and quantitatively correct, as well as chemicallyreasonable, results in cases where comparisons are available. Thesecomparisons indicate that the HMLP has advantages over the empiricallipophilicity potential in many aspects. The HMLP is a three-dimensional andeasily visualizable representation of molecular lipophilicity, suggested asa potential tool in computer-aided three-dimensional drug design.     

Structure-Lipophilicity and Structure-Polarity relationships of amino acids and peptides

The objectives of this study were to gain insights into the structure-lipophilicity relationships of peptides and to propose an improved model for estimating their lipophilicity. First, existing databases were extended to obtain the distribution coefficients of a total of 208 free or protected peptides (di- to pentapeptides). The polarity parameters (Λ) of 23 free amino acids and 19 protected amino acids (AcNH? CHR? CONH₂) and of their side chains were calculated from experimental distribution coefficients and computed molecular volumes. An analysis of the polarity parameters revealed that the hydrophobicity of the amino-acid side chains is largely reduced due to the polar field of the backbone. The polarity parameters of the peptides were then obtained in a similar manner and shown to be highly correlated with the sum of the polarity parameters of their side chains, i.e., the lipophilicity of peptides can be calculated from their molecular volume and the sum of their side-chain polarities using the regression established for each individual series of peptides (Fig. 1). This last restriction is essential since the polarity and lipophilic increment of a NH? C*H? CO unit were shown to decrease with increasing length of backbone.     

Investigating the Influence of (Deoxy)fluorination on the Lipophilicity of Non‐UV‐Active Fluorinated Alkanols and Carbohydrates by a New log P Determination Method

Property tuning by fluorination is very effective for a number of purposes, and currently increasingly investigated for aliphatic compounds. An important application is lipophilicity (log P) modulation. However, the determination of log P is cumbersome for non‐UV‐active compounds. A new variation of the shake‐flask log P determination method is presented, enabling the measurement of log P for fluorinated compounds with or without UV activity regardless of whether they are hydrophilic or lipophilic. No calibration curves or measurements of compound masses/aliquot volumes are required. With this method, the influence of fluorination on the lipophilicity of fluorinated aliphatic alcohols was determined, and the log P values of fluorinated carbohydrates were measured. Interesting trends and changes, for example, for the dependence on relative stereochemistry, are reported.     

Sulfonated carbon materials with hydrophilic and lipophilic properties

Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for the etherification of isopentene with methanol to produce tert amyl methyl ether （TAME） in toluene solution （lipophilic system）. Microcalorimetric adsorptions of water and benzene showed that the HS-C was highly hydrophilic without the lipophilicity, while the H-PRC exhibited both the hydrophilicity and lipophilicity. Thus, the HS-C was well dispersed in aqueous solution and difficult to separate from it. On the other hand, the H-PRC was highly active, more active than the acidic resin （D008） and sulfuric acid, for the synthesis of DMM in aqueous solution. The H-PRC was also highly active, more active than the HS-C, for the etherification of isopentene with methanol to produce TAME in toluene solution, probably owing to its amphiphilic surface property as well as its strong surface acidity as measured by the microcalorirnetric adsorption of NH3.     

Conformational Space of a Polyphilic Molecule with a Fluorophilic Side Chain Integrated in a DPPC Bilayer

We investigate the conformational space of a polyphilic molecule with hydrophilic, lipophilic and fluorophilic parts inserted as a transmembrane agent into a dipalmitoylphosphatidylcholine bilayer by means of all‐atom molecular dynamics simulations. Special focus is put on the competing structural driving forces arising from the hydrophilic, lipophilic and fluorophilic side chains and the aromatic backbone of the polyphile. We observe a significant difference between the lipophilic and the fluorophilic side chains regarding their intramembrane distribution. While the lipophilic groups remain membrane‐centered, the fluorophilic parts tend to orient toward the phosphate headgroups. This trend is important for understanding the influence of polyphile agents on the properties of phospholipid membranes. From a fundamental point of view, our computed distribution functions of the side chains are related to the interplay of sterical, enthalpic and entropic driving forces. Our findings illustrate the potential of rationally designed membrane additives which can be exploited to tune the properties of phospholipid membranes. © 2017 Wiley Periodicals, Inc.