title: Limits of rapid log P determination methods for highly lipophilic and flexible compounds.
abstract: Lipophilicity is of crucial importance in many fields including pharmaceutical, environmental, cosmetic and food industries. Whereas different experimental strategies have been developed for rapid lipophilicity determination of new chemical entities, log P determination of highly lipophilic compounds is always challenging. In this study, three published chromatographic methods have been compared on a series of phenylalkanoic acids including the pro-perfume HaloscentD (HD-C12). Different log P values were obtained depending on the chromatographic method used for log P estimation. Molecular modelling suggested that log P variations may be due to the chromatographic conditions applied (isocratic or gradient mode, ratio methanol/water in the mobile phase), responsible of specific conformations of the molecule in solution. Thus, for flexible compounds, published methods have to be used with caution and considered as a good tool to estimate a log P range, depending on the molecular conformational state.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martel
authors.affiliation: Firmenich SA, Corporate R&D Division, Route des Jeunes 1, 1211 Geneva, Switzerland. Electronic address: frederic.begnaud@firmenich.com.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Begnaud
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: William
authors.initials: W
authors.lastname: Schuler
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Gillerat
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: Nils
authors.initials: N
authors.lastname: Oberhauser
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland. Electronic address: alessandra.nurisso@unige.ch.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nurisso
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Quai Ernest Ansermet 30, 1211 Geneva 4, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
mesh_terms: D002851:Chromatography, High Pressure Liquid; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular
chemical_list: D008055:Lipids
keywords: Chromatographic-based measurement; Conformational search; Flexible compounds; High lipophilicity