Kleemiss, Florian and Puylaert, Pim and Duvinage, Daniel and Fugel, Malte and Sugimoto, Kunihisa and Beckmann, Jens and Grabowsky, Simon (2021) Ibuprofen and sila-ibuprofen: polarization effects in the crystal and enzyme environments. ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS, 77. pp. 892-905. ISSN , 2052-5206
Full text not available from this repository. (Request a copy)Abstract
Sila-ibuprofen is a new potential nonsteroidal anti-inflammatory drug which deviates from its parent ibuprofen in terms of the electrostatic potential around the carbon/silicon-switched C/Si-H group. Therefore, sila-ibuprofen is more water soluble and has a lower melting enthalpy. However, its binding and inhibition properties of cyclooxygenases appear to be very similar to regular ibuprofen. Therefore, in this study, intermolecular interactions and interaction densities of both ibuprofen and sila-ibuprofen in their biologically active forms, i.e. deprotonated and as the pure S-enantiomers are investigated. Quantum-crystallographically refined salts with argininium and 1-phenylethan-1-amoninium (PEA) counter-cations as crystalline models of the interactions with the guanidine functional group of arginine inside cyclooxygenases are presented. The similarities and differences between the polarization of ibuprofen and silaibuprofen in the crystal, enzyme, solvent and isolated environments are discussed based on quantum-chemical calculations. For the explicit crystal and enzyme environments, specifically, molecular dynamics simulations starting from the crystal models were combined with QM/MM calculations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERMOLECULAR INTERACTIONS; DENSITY; ACID; REFINEMENT; MOLECULES; MECHANISM; FIELDS; ATOMS; quantum crystallography; ibuprofen; cyclooxygenase; interaction density; electrostatic potential; sila-ibuprofen; polarization |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Analytische Chemie, Chemo- und Biosensorik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Sep 2022 10:03 |
| Last Modified: | 20 Sep 2022 10:03 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47650 |
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