| Project/Area Number |
62860015
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| Research Category |
Grant-in-Aid for Developmental Scientific Research
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| Allocation Type | Single-year Grants |
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| Research Field |
製造化学・食品
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
FUJITA Toshio Kyoto Univ., Fac. of Agriculture, Professor, 農学部, 教授 (90026427)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGAMI Chisako Kobe Women's College of Pharmacy, Associate Professor, 助教授 (20140410)
AKAMATSU Miki Kyoto Univ., Fac. of Agriculture, Researcher, 農学部, 教務職員 (70183134)
NISHIOKA Takaaki Kyoto Univ., Chem. Research Institute, Associate Professor, 化学研究所, 助教授 (80026559)
NISHIMURA Keiichiro Kyoto Univ., Fac. of Agriculture, Research Associate, 農学部, 助手 (70026558)
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| Project Period (FY) |
1987 – 1989
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| Project Status |
Completed (Fiscal Year 1989)
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| Budget Amount *help |
¥9,700,000 (Direct Cost: ¥9,700,000)
Fiscal Year 1989: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1988: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1987: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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