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

Abstract

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 110K and theoretical calculations. The supramolecular structure is dominated by the formation of a dimer through COOH homosynthon. 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 2 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.

Physicochemical Modeling of the Adsorption of Pharmaceuticals on MIL-100-Fe and MIL-101-Fe MOFs

“…The molecular area of least reactivity (blue color) was identified in the hydroxyl group of the carboxyl (mainly in the H atom), and the most reactive area (red color) was found on the oxygen atom attached to the carbon from the carboxyl group. The rest of this molecule showed an intermediate reactivity (i.e., yellow zones) [76, 77]. Finally, the highest reactivity zone of NAP molecule was the oxygen of the methoxyl and -COOH groups, while the less reactivity zone was identified in the hydrogen of the -COOH group.…”

Understanding Hygroscopicity of Theophyllineviaa Novel Cocrystal Polymorph: A Charge Density Study

“…Common themes across recent cocrystal studies have investigated the physical property enhancement of cocrystallization but the chemical explanation for the property alteration has largely not been identified. Charge density studies may provide the necessary tools to highlight weak interaction patterns across organic structures; − future coformer selection requires a strong understanding of how the physical properties are influenced by these interactions. ,, …”

The Cocktail Effects on the Acute Cytotoxicity of Pesticides and Pharmaceuticals Frequently Detected in the Environment

“…The exact effects how these compounds with varying mode of actions impact the non-target organism is still unclear. Furthermore, there is a possibility of various unpredictable chemical interactions between these compounds at the molecular level, influencing toxicity [ 63 , 64 ]. Ecotoxicological testing is necessary to assess the cumulative biological effects of chemical cocktails including the changed biological effects due to molecular reactions between the compounds.…”