The Construction of the System Predicting Oil/Water Partition Coefficient

治疗药物和农药的疏水性指数、正辛醇/水分配系数(P)被认为是控制它们在生物和环境中行为的最重要的属性之一。对数P值的有用特征之一是它们的加性-本构性质。因此，人们可以根据合适的参考分子的值和与取代基疏水性相对应的pi值来计算复杂分子的logP值。然而，给定取代基的pi在不同的溶质体系之间是不同的，即使类似体系的变化不大。一个分子或相邻的极性基团中含有两个以上取代基的化合物具有固有的取代基疏水性和其他物理化学参数，这些化合物的logP值是估算logP所必需的。从这个角度出发，利用自由能相关的取代基常数和多元回归技术，对杂环化合物、寡肽、苯甲酰基苯脲和拟除虫菊酯的logP值进行了测定和分析。单取代二氮杂环的pi大多为正值，且大于相应的苯基pi值，这是因为二氮杂环的吸电子性质导致了取代基和环-N原子上氢键行为的变化。多肽的logP值受氨基酸侧链的空间效应、多肽骨架的构象效应以及侧链和多肽键的疏水性控制。用高效液相色谱法测定，苯甲酰基苯脲和拟除虫菊酯的对数b值与对数k‘有很好的相关性。在建立了每一系列化合物的经验关联方程后，我们构建了一个用于预测各种化合物的logP值的软件系统的原型版本。

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.