Kleemiss, Florian; Puylaert, Pim; Duvinage, Daniel; Fugel, Malte; Sugimoto, Kunihisa; Beckmann, Jens; Grabowsky, Simon (2021). Ibuprofen and sila-ibuprofen: polarization effects in the crystal and enzyme environments. Acta crystallographica Section B, 77(6), pp. 892-905. International Union of Crystallography 10.1107/S2052520621009379
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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-amoni-nium (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 sila-ibuprofen 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: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Kleemiss, Florian, Grabowsky, Simon |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
2052-5206 |
Publisher: |
International Union of Crystallography |
Language: |
English |
Submitter: |
Simon Grabowsky |
Date Deposited: |
01 Feb 2022 15:20 |
Last Modified: |
05 Dec 2022 16:03 |
Publisher DOI: |
10.1107/S2052520621009379 |
BORIS DOI: |
10.48350/164385 |
URI: |
https://boris.unibe.ch/id/eprint/164385 |
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