title: The contribution of the hydrogen bond acidity on the lipophilicity of drugs estimated from chromatographic measurements.
abstract: The influence of the hydrogen bond acidity when the 1-octanol/water partition coefficient (log P(o/w)) of drugs is determined from chromatographic measurements was studied in this work. This influence was firstly evaluated by means of the comparison between the Abraham solvation parameter model when it is applied to express the 1-octanol/water partitioning and the chromatographic retention, expressed as the solute polarity p. Then, several hydrogen bond acidity descriptors were compared in order to determine properly the log P(o/w) of drugs. These descriptors were obtained from different software and comprise two-dimensional parameters such as the calculated Abraham hydrogen bond acidity A and three-dimensional descriptors like HDCA-2 from CODESSA program or WO1 and DRDODO descriptors calculated from Volsurf+software. The additional HOMO-LUMO polarizability descriptor should be added when the three-dimensional descriptors are used to complement the chromatographic retention. The models generated using these descriptors were compared studying the correlations between the determined log P(o/w) values and the reference ones. The comparison showed that there was no significant difference between the tested models and any of them was able to determine the log P(o/w) of drugs from a single chromatographic measurement and the correspondent molecular descriptors terms. However, the model that involved the calculated A descriptor was simpler and it is thus recommended for practical uses.
authors.affiliation: Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Pallicer
authors.affiliation: ESTEVE, Av. Mare de Déu de Montserrat, 221, 08041 Barcelona, Spain.
authors.forename: Rosalia
authors.initials: R
authors.lastname: Pascual
authors.affiliation: ESTEVE, Av. Mare de Déu de Montserrat, 221, 08041 Barcelona, Spain.
authors.forename: Adriana
authors.initials: A
authors.lastname: Port
authors.affiliation: Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Rosés
authors.affiliation: Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Ràfols
authors.affiliation: Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain. Electronic address: e.bosch@ub.edu.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bosch
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D000465:Algorithms; D001185:Artificial Intelligence; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D020003:1-Octanol