title: Prediction of Phospholipid-Water Partition Coefficients of Ionic Organic Chemicals Using the Mechanistic Model COSMOmic.
abstract: The partition coefficient of chemicals from water to phospholipid membrane, K(lipw), is of central importance for various fields. For neutral organic molecules, log K(lipw) correlates with the log of bulk solvent-water partition coefficients such as the octanol-water partition coefficient. However, this is not the case for charged compounds, for which a mechanistic modeling approach is highly necessary. In this work, we extend the model COSMOmic, which adapts the COSMO-RS theory for anisotropic phases and has been shown to reliably predict K(lipw) for neutral compounds, to the use of ionic compounds. To make the COSMOmic model applicable for ionic solutes, we implemented the internal membrane dipole potential in COSMOmic. We empirically optimized the potential with experimental K(lipw) data of 161 neutral and 75 ionic compounds, yielding potential shapes that agree well with experimentally determined potentials from the literature. This model refinement has no negative effect on the prediction accuracy of neutral compounds (root-mean-square error, RMSE = 0.62 log units), while it highly improves the prediction of ions (RMSE = 0.70 log units). The refined COSMOmic is, to our knowledge, the first mechanistic model that predicts K(lipw) of both ionic and neutral species with accuracies better than 1 log unit.
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Bittermann
authors.affiliation: Ecotoxicology Group, Swiss Federal Research Station (Agroscope) , Schloss 1, CH-8820 Wädenswil, Switzerland.|COSMOlogic GmbH&COKG, Imbacher Weg 46, 51379 Leverkusen, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Spycher
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig, Germany.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Endo
authors.affiliation: COSMOlogic GmbH&COKG, Imbacher Weg 46, 51379 Leverkusen, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Pohler
authors.affiliation: COSMOlogic GmbH&COKG, Imbacher Weg 46, 51379 Leverkusen, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Huniar
authors.affiliation: UFZ - Helmholtz Centre for Environmental Research, Permoserstr. 15, D-04318 Leipzig, Germany.|Institute of Chemistry, University of Halle-Wittenberg , Kurt Mothes Str. 2, D-06120 Halle, Germany.
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Goss
authors.affiliation: COSMOlogic GmbH&COKG, Imbacher Weg 46, 51379 Leverkusen, Germany.|Department of Physical and Theoretical Chemistry, University of Regensburg , 93040 Regensburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Klamt
mesh_terms: D007477:Ions; D008564:Membrane Potentials; D008956:Models, Chemical; D009930:Organic Chemicals / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D007477:Ions; D009930:Organic Chemicals; D010743:Phospholipids; D014867:Water