title: Introduction of solvent-accessible surface area in the calculation of the hydrophobicity parameter log P from an atomistic approach.
abstract: A conventional atomistic approach of estimating molecular hydrophobicity (log P) was improved by taking into account the proximity effect of substituent groups as well as the importance of solute-solvent interaction in the partition phenomena. The new method reassigns atomic parameters when the molecule is fully exposed to surrounding solvent. Each atom in a molecule contributes to the log P by an amount of its atomic parameter multiplied by the degree of exposure to the surrounding solvent. This degree of exposure is calculated from the solvent-accessible surface area (SASA). In carrying out actual calculations, the necessary parameters were determined with the log P values of 500 compounds that were used as training data. This method, which may be called SASA-scaled atomistic method, gave satisfactory results when compared with the original method of estimating log P from atomic parameters. The ability of the new method to predict log P for compounds other than those used as the training data was also tested. The newly proposed SASA-scaled atomistic method was also compared with other methods available for the calculation of log P. The SASA-scaled atomistic method gave better estimations from fewer training data. Finally, the ability of the proposed method to predict differences in log P for steric isomers was tested. The new method was superior to other methods, including CLOGP, a widely accepted method of estimating log P for a variety of compounds.
authors.affiliation: Faculty of Pharmaceutical Sciences, Osaka University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Masuda
authors.forename: T
authors.initials: T
authors.lastname: Jikihara
authors.forename: K
authors.initials: K
authors.lastname: Nakamura
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Takagi
authors.forename: H
authors.initials: H
authors.lastname: Fujiwara
mesh_terms: D002626:Chemistry, Pharmaceutical; D012997:Solvents; D013499:Surface Properties
chemical_list: D012997:Solvents