Topological and electrostatic properties of diclofenac molecule as a non-steroidal anti-inflammatory drug: An experimental and theoretical study

Diclofenac is a Non-Steroidal Anti-Inflammatory Drug (NSAID), which highly inhibits the lipoxygenase pathways and reduces the formation of leukotriene lipids. In this work, we report on measurements and calculations of the electron density of Diclofenac, obtained from high resolution experimental X-ray diffraction data at 110 K and theoretical calculations. The supramolecular structure is dominated by the formation of a dimer through COOH homo-synthon. The analysis of the molecular electron density (by means of quantum theory of atoms in molecules), the electrostatic potential, the crystal packing and intermolecular interactions (through Hirshfeld surface analysis) enables gaining more insight into the nature of the molecule and its ability to interact with other molecules. Furthermore, the topological properties of the dimer interactions in both the crystal phase and human transthyretin protein environment were identified. The electrostatic potential map shows that the high electronegative regions appear around the carboxyl group of the diclofenac molecule in both the crystal and protein environment. This study is complemented by a molecular dynamics simulation of the interaction of diclofenac with transthyretin protein, which enables to test the hypothesis made with the charge density analysis.