A new series of pyrazoles-based compounds: synthesis, HOMO–LUMO analysis, MEP, quantum reactivity, and in silico covid-19 activity

Abstract

In the present study, we synthesized four new pyrazole-based compounds with yields of 80%, 70%, 56% and 60% for compounds 2–5, respectively. All compounds were characterized by spectroscopic methods. Density functional theory (DFT) calculations were performed to investigate the electronic and quantum chemical properties of the newly synthesized compounds. The optimized geometries obtained from DFT analysis were used to examine the active sites of the compounds through MEP diagrams. Furthermore, the differences in the HOMO–LUMO energy levels were analyzed to assess the biological activity, chemical reactivity, and stability of the molecules. Additional quantum reactivity descriptors were evaluated based on the molecular orbital energies. In parallel, an in silico docking study was conducted to explore the biological activity of the synthesized compounds against the COVID-19 receptor. Among the synthesized compounds, compound 3 not only showed the most favorable electronic properties (smallest energy gap: 1.17 eV and highest ω: 23.31 eV) but also exhibited the lowest binding energy (–4.43 kcal/mol) in docking studies, indicating strong and stable binding to the 6LU7 protease active site. The combined results from DFT calculations, docking studies and ADME-Tox profiling provide valuable insights into the electronic properties, reactivity, and potential biological applications of the synthesized compounds.