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The Construction of the System Predicting Oil/Water Partition Coefficient

油水分配系数预测系统的构建

基本信息

批准号：
62860015
负责人：
FUJITA Toshio
金额：
$ 6.21万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62860015/
关键词：
Partition Coefficient Oil water partition coefficient Heterocyclic compounds Peptides System predicting log P HPLC Log P database Log P log P 計算システム高速液体クロマトグラフ log Pデータベース

项目摘要

The index of the hydrophobicity, the 1-octanol/water partition coefficient (P) of therapeutic drugs and agrochemicals is considered to be one of the most important properties in controlling their behaviors in bioorganisms and environment. one of the useful features of log P values is their additive-constitutive nature. Thus, one can calculate log P values of complex molecules from the values of suitable reference molecules and pi values which correspond the substituent hydrophobicity. The pi for a given substituent, however, varies from one solute system to others, even though the variance for similar systems is not great. Analyses of the log P values of compounds, which have more than two substituents in a molecule or neighboring polar groups, with intrinsic substituent hydrophobicity and other physicochemical parameters should be necessary to estimate log P. From this point of view, the log P values of heterocyclic compounds, oligopeptides, benzoylphenylureas, and pyrethroids were measured and analyzed by means of free-energy-related substituent constants and the multiple regression technique. Most of pi values for monosubstituted diazines were positive and larger than the corresponding benzene-pi values because the electron withdrawing property of the diazine ring causes the change in the hydrogen bonding behavior on the substituent as well as on the ring-N atoms. The log P value of peptides was controlled by the steric effect of amino acid side chains and the conformational effect of peptide skeleton as well as the hydrophobicity of side chains and peptide bonds. The log b values of benzoylphenylureas and pyrethroids had good correlation with log k' by HPLC method. After establishing empirical correlation equations for each series of compounds, we have constructed a prototype version for a software system to predict log P values of a variety of compounds.

治疗药物和农药的疏水性指标- 1-辛醇/水分配系数(P)被认为是控制其在生物有机体和环境中的行为的最重要的性质之一。logp值的一个有用的特征是它们的加性-本构性。因此，可以从合适的参考分子的值和对应取代基疏水性的pi值计算复杂分子的log P值。然而，一个给定取代基的π在不同的溶质体系中是不同的，尽管在相似的体系中变化不大。对于具有两个以上取代基或相邻极性基团的化合物，若要估算log P值，必须分析其固有取代基疏水性等理化参数的log P值。为此，我们采用自由能相关取代基常数和多元回归技术对杂环化合物、寡肽、苯甲酰苯基脲类化合物和拟除虫酯类化合物的log P值进行了测量和分析。单取代嘧啶的pi值大多为正，且大于相应的苯-pi值，这是因为嘧啶环的吸电子性质导致取代基和环n原子上的氢键行为发生了变化。多肽的logp值受氨基酸侧链的立体效应、肽骨架的构象效应以及侧链和肽键的疏水性控制。高效液相色谱法测定苯甲酰苯脲类和拟除虫菊酯类化合物的log b值与log k′具有良好的相关性。在建立了每个系列化合物的经验相关方程后，我们构建了一个软件系统的原型版本，用于预测各种化合物的log P值。