B. Tehan, E. J. Lloyd, M. Wong, W. Pitt, J. Montana, D. Manallack, E. Gancia
{"title":"Estimation of pKa Using Semiempirical Molecular Orbital Methods. Part 1: Application to Phenols and Carboxylic Acids.","authors":"B. Tehan, E. J. Lloyd, M. Wong, W. Pitt, J. Montana, D. Manallack, E. Gancia","doi":"10.1002/1521-3838(200211)21:5<457::AID-QSAR457>3.0.CO;2-5","DOIUrl":null,"url":null,"abstract":"The electronic properties of small molecules can be calculated quickly and with a reasonable degree of accuracy using semiempirical QM methods. In this study a set of QM properties derived from frontier electron theory have been used to produce a predictive model of the dissociation constants of phenols, benzoic acids and aliphatic carboxylic acids. The pK a values and structures of nearly 500 compounds were extracted from the Physprop database for this purpose. Multiple linear regression was used to search for relationships between pK a and the calculated QM properties. In most cases only a single independent variable, electrophilic superdelocalisability, was needed to produce a good model of pK a . The advantages of our approach are in the speed of calculation and the simplicity of the resultant models. The merits of using semiempirical methods to predict pK a are discussed in relation to previous studies.","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":"101","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Quantitative Structure-activity Relationships","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/1521-3838(200211)21:5<457::AID-QSAR457>3.0.CO;2-5","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 101
Abstract
The electronic properties of small molecules can be calculated quickly and with a reasonable degree of accuracy using semiempirical QM methods. In this study a set of QM properties derived from frontier electron theory have been used to produce a predictive model of the dissociation constants of phenols, benzoic acids and aliphatic carboxylic acids. The pK a values and structures of nearly 500 compounds were extracted from the Physprop database for this purpose. Multiple linear regression was used to search for relationships between pK a and the calculated QM properties. In most cases only a single independent variable, electrophilic superdelocalisability, was needed to produce a good model of pK a . The advantages of our approach are in the speed of calculation and the simplicity of the resultant models. The merits of using semiempirical methods to predict pK a are discussed in relation to previous studies.