Schwoebel, Johannes A. H. and Ebert, Andrea and Bittermann, Kai and Huniar, Uwe and Goss, Kai-Uwe and Klamt, Andreas (2020) COSMOperm: Mechanistic Prediction of Passive Membrane Permeability for Neutral Compounds and Ions and Its pH Dependence. JOURNAL OF PHYSICAL CHEMISTRY B, 124 (16). pp. 3343-3354. ISSN 1520-6106, 1520-5207
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We present a new and entirely mechanistic COSMOperm method to predict passive membrane permeabilities for neutral compounds, as well as anions and cations. The COSMOperm 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 COSMOplex method and directly used for permeability studies by COSMOperm.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIPID-BILAYER-MEMBRANES; WATER PARTITION-COEFFICIENTS; PHOSPHOLIPID-BILAYERS; PROTON TRANSPORT; IN-VITRO; MODEL; RS; PERMEATION; ACCUMULATE; DIFFUSION; |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Mar 2021 08:41 |
| Last Modified: | 26 Mar 2021 08:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/44711 |
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