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Ibuprofen and sila‐ibuprofen: polarization effects in the crystal and enzyme environments
Author(s) -
Kleemiss Florian,
Puylaert Pim,
Duvinage Daniel,
Fugel Malte,
Sugimoto Kunihisa,
Beckmann Jens,
Grabowsky Simon
Publication year - 2021
Publication title -
acta crystallographica section b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.604
H-Index - 33
ISSN - 2052-5206
DOI - 10.1107/s2052520621009379
Subject(s) - ibuprofen , chemistry , enthalpy , crystal (programming language) , crystallography , intermolecular force , molecular dynamics , computational chemistry , polymorphism (computer science) , stereochemistry , organic chemistry , thermodynamics , molecule , biochemistry , medicine , physics , computer science , genotype , gene , pharmacology , programming language
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 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.