title: Development of a simple proton nuclear magnetic resonance-based procedure to estimate the approximate distribution coefficient at physiological pH (logD7.4): Evaluation and comparison to existing practices.
abstract: In drug discovery, lipophilicity is a key parameter for drug optimization. Lipophilicity determinations can be both work and time consuming, especially for non-UV active compounds. Herein, an improved and simple 1H NMR-based method is described to estimate the lipophilicity at physiological pH (logD7.4) in 1-octanol and D2O buffer. The method can be applied to both UV and non-UV active compounds. In addition, neither calibration curves nor internal/external standards are needed. We have demonstrated that logD7.4can be accurately measured using 1H NMR for compounds within the logD7.4interval between 0.7 and 3.3. The method was also compared to a previously described HPLC method.
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: E Johanna L
authors.initials: EJL
authors.lastname: Stéen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Nyberg
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Lehel
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
authors.forename: Valdemar L
authors.initials: VL
authors.lastname: Andersen
authors.affiliation: Dipartimento di Farmacia e Scienze del Farmaco, Università degli Studi di Bari A. Moro, Via Orabona, 4, 70125 Bari, Italy.
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Di Pilato
authors.affiliation: Center for Integrated Molecular Brain Imaging and University of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
authors.forename: Gitte M
authors.initials: GM
authors.lastname: Knudsen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark.
authors.forename: Jesper L
authors.initials: JL
authors.lastname: Kristensen
authors.affiliation: Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark; Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark; Center for Integrated Molecular Brain Imaging and University of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark. Electronic address: matthias.herth@sund.ku.dk.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Herth
mesh_terms: D020003:1-Octanol / Q000737:chemistry; D017666:Deuterium Oxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D066244:Proton Magnetic Resonance Spectroscopy
chemical_list: D004364:Pharmaceutical Preparations; D017666:Deuterium Oxide; D020003:1-Octanol
keywords: Distribution coefficient; Lipophilicity; LogD(7.4); NMR