QSPR analysis of the partitioning of vaporous chemicals in a water-gas phase system and the water solubility of liquid and solid chemicals on the basis of fragment and physicochemical similarity and hybot descriptors.
QSPR analyses of the solubility in water of 558 vapors, 786 liquids and 2045 solid organic neutral chemicals and drugs are presented. Simultaneous consideration of H-bond acceptor and donor factors leads to a good description of the solubility of vapors and liquids. A volume-related term was found to have an essential negative contribution to the solubility of liquids. Consideration of polarizability, H-bond acceptor and donor factors and indicators for a few functional groups, as well as the experimental solubility values of structurally nearest neighbors yielded good correlations for liquids. The application of Yalkowsky's "General Solubility Equation" to 1063 solid chemicals and drugs resulted in a correlation of experimental vs calculated log S values with only modest statistical criteria. Two approaches to derive predictive models for solubility of solid chemicals and drugs were tested. The first approach was based on the QSPR for liquids together with indicator variables for different functional groups. Furthermore, a calculation of enthalpies for intermolecular complexes in crystal lattices, based on new H-bond potentials, was carried out for the better consideration of essential solubility- decreasing effects in the solid state, as compared with the liquid state. The second approach was based on a combination of similarity considerations and traditional QSPR. Both approaches lead to high quality predictions with average absolute errors on the level of experimental log S determination.
Raevsky
O
O
Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds of Russian Academy of Sciences, Severnii proezd, 1, Chernogolovka, Moscow region, 142432, Russia. raevsky@ipac.ac.ru
Andreeva
E
E
Raevskaja
O
O
Skvortsov
V
V
Schaper
K
K
D015195:Drug Design; D005740:Gases / Q000737:chemistry; D009930:Organic Chemicals / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D012984:Software; D012995:Solubility; D014835:Volatilization; D014867:Water / Q000737:chemistry
D005740:Gases; D009930:Organic Chemicals; D004364:Pharmaceutical Preparations; D014867:Water