Quantifying hydrogen bonding in QSAR and molecular modeling.
Quantitative descriptions of hydrogen bonding for use in QSAR and molecular modeling by means of H-bond descriptors have been analyzed in detail in this paper. Ten new H-bond surface and enthalpy integral descriptors were proposed. The usefulness of these new descriptors, as well as previously developed descriptors was verified using a set of 154 drugs for which data for intestinal absorption in humans were available. The results showed that descriptors such as the number of H-bond acceptor and donor atoms and polar surface area (PSA) did not sufficiently describe the actual H-bonding ability of atoms in molecules. Thus, to enable successful modeling it was necessary to introduce descriptors directly related to the experimental thermodynamics of hydrogen bonding.
Raevsky
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OA
Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, The Russian Academy of Sciences, Chernogolovka, 142432, Moscow, Russia. raevsky@ipac.ac.ru
Skvortsov
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D006801:Humans; D006860:Hydrogen Bonding; D007408:Intestinal Absorption; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D013816:Thermodynamics
D004364:Pharmaceutical Preparations