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Titel (primär) Prediction of phospholipid−water partition coefficients of ionic organic chemicals using the mechanistic model COSMOmic
Autor Bittermann, K.; Spycher, S.; Endo, S.; Pohler, L.; Huniar, U.; Goss, K.-U.; Klamt, A.;
Journal / Serie Journal of Physical Chemistry B
Erscheinungsjahr 2014
Department AUC;
Band/Volume 118
Heft 51
Sprache englisch;
POF III (gesamt) T42;
Keywords partition coefficients; lipid membranes; ions; membrane dipole potential; COSMO-RS
UFZ Querschnittsthemen RU3;
Abstract The partition coefficient of chemicals from water to phospholipid membrane, Klipw, is of central importance for various fields. For neutral organic molecules, log Klipw 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 Klipw 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 Klipw 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 Klipw of both ionic and neutral species with accuracies better than 1 log unit.
ID 15718
dauerhafte UFZ-Verlinkung https://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=15718
Bittermann, K., Spycher, S., Endo, S., Pohler, L., Huniar, U., Goss, K.-U., Klamt, A. (2014):
Prediction of phospholipid−water partition coefficients of ionic organic chemicals using the mechanistic model COSMOmic
J. Phys. Chem. B 118 (51), 14833 - 14842