Ibuprofen and sila-ibuprofen: polarization effects in the crystal and enzyme environments (original) (raw)
2021, Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials
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. Quantumcrystallographically 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. quantum crystallography Acta Cryst. (2021). B77, 892-905 Florian Kleemiss et al. Ibuprofen and sila-ibuprofen 903 Figure 15 Bar plots of the cumulative R RS values for the common bonds present in ibuprofen (top) and sila-ibuprofen (bottom). quantum crystallography 904 Florian Kleemiss et al. Ibuprofen and sila-ibuprofen Acta Cryst. (2021). B77, 892-905 quantum crystallography Acta Cryst. (2021). B77, 892-905 Florian Kleemiss et al. Ibuprofen and sila-ibuprofen 905
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