| Autor: |
Schwöbel JAH; BIOVIA, Dassault Systèmes Deutschland GmbH, Imbacher Weg 46, D-51379 Leverkusen, Germany., Ebert A; UFZ-Helmholtz Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany.; Institute of Biophysics, Johannes Kepler University, Gruberstraße 40, 4020 Linz, Austria., Bittermann K; UFZ-Helmholtz Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany., Huniar U; BIOVIA, Dassault Systèmes Deutschland GmbH, Imbacher Weg 46, D-51379 Leverkusen, Germany., Goss KU; UFZ-Helmholtz Centre for Environmental Research, Permoserstraße 15, D-04318 Leipzig, Germany.; Institute of Chemistry, University of Halle-Wittenberg, Kurt Mothes Str. 2, D-06120 Halle, Germany., Klamt A; BIOVIA, Dassault Systèmes Deutschland GmbH, Imbacher Weg 46, D-51379 Leverkusen, Germany.; Institute of Physical and Theoretical Chemistry, University of Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany. |
| Abstrakt: |
We present a new and entirely mechanistic COSMO perm method to predict passive membrane permeabilities for neutral compounds, as well as anions and cations. The COSMO perm approach is based on compound-specific free energy profiles within a membrane of interest from COSMO-RS (conductor-like screening model for realistic solvation) calculations. These are combined with membrane layer-specific diffusion coefficients, for example, in the water phase, the polar head groups, and the alkyl tails of biochemical phospholipid bilayers. COSMO-RS utilizes first-principle quantum chemical structures and physically sound intermolecular interactions (electrostatic, hydrogen bond, and van der Waals). For this reason, it is unbiased toward different application scenarios, such as in cosmetics and industrial chemical or pharmaceutical industries. A fully predictive calculation of passive permeation through phospholipid bilayer membranes results in a performance of r 2 = 0.92; rmsd = 0.90 log 10 units for neutral compounds and anions, as compared to gold standard black lipid membrane experiments. It will be demonstrated that new membrane types can be generated by the related COSMO plex method and directly used for permeability studies by COSMO perm . |
