B. Tehan, E. J. Lloyd, M. Wong, W. Pitt, E. Gancia, D. Manallack
{"title":"用半经验分子轨道法估计pKa。第二部分:胺类、苯胺类及各种含氮杂环化合物的应用。","authors":"B. Tehan, E. J. Lloyd, M. Wong, W. Pitt, E. Gancia, D. Manallack","doi":"10.1002/1521-3838(200211)21:5<473::AID-QSAR473>3.0.CO;2-D","DOIUrl":null,"url":null,"abstract":"The pK a of a compound directly influences its biopharmaceutical profile. This article describes the development of a method for estimating pK a values for a number of nitrogen containing chemical structures using semiempirical QM properties derived from frontier electron theory. Typically, the property giving the best correlation with pK d was the electrophilic superdelocalisability of the nitrogen atom resulting in regression equations with r 2 values up to 0.94. The advantages of this technique are in the simplicity of the models and the speed of calculation, suggesting that this method could be widely applied to the estimation of pK a values. The success of this approach is discussed in relation to other methods.","PeriodicalId":20818,"journal":{"name":"Quantitative Structure-activity Relationships","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2002-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"63","resultStr":"{\"title\":\"Estimation of pKa Using Semiempirical Molecular Orbital Methods. Part 2: Application to Amines, Anilines and Various Nitrogen Containing Heterocyclic Compounds.\",\"authors\":\"B. Tehan, E. J. Lloyd, M. Wong, W. Pitt, E. Gancia, D. Manallack\",\"doi\":\"10.1002/1521-3838(200211)21:5<473::AID-QSAR473>3.0.CO;2-D\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The pK a of a compound directly influences its biopharmaceutical profile. This article describes the development of a method for estimating pK a values for a number of nitrogen containing chemical structures using semiempirical QM properties derived from frontier electron theory. Typically, the property giving the best correlation with pK d was the electrophilic superdelocalisability of the nitrogen atom resulting in regression equations with r 2 values up to 0.94. The advantages of this technique are in the simplicity of the models and the speed of calculation, suggesting that this method could be widely applied to the estimation of pK a values. The success of this approach is discussed in relation to other methods.\",\"PeriodicalId\":20818,\"journal\":{\"name\":\"Quantitative Structure-activity Relationships\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2002-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"63\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Quantitative Structure-activity Relationships\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/1521-3838(200211)21:5<473::AID-QSAR473>3.0.CO;2-D\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Quantitative Structure-activity Relationships","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/1521-3838(200211)21:5<473::AID-QSAR473>3.0.CO;2-D","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Estimation of pKa Using Semiempirical Molecular Orbital Methods. Part 2: Application to Amines, Anilines and Various Nitrogen Containing Heterocyclic Compounds.
The pK a of a compound directly influences its biopharmaceutical profile. This article describes the development of a method for estimating pK a values for a number of nitrogen containing chemical structures using semiempirical QM properties derived from frontier electron theory. Typically, the property giving the best correlation with pK d was the electrophilic superdelocalisability of the nitrogen atom resulting in regression equations with r 2 values up to 0.94. The advantages of this technique are in the simplicity of the models and the speed of calculation, suggesting that this method could be widely applied to the estimation of pK a values. The success of this approach is discussed in relation to other methods.