Theoretical studies, spectroscopic investigation, molecular docking, molecular dynamics and MMGBSA calculations with 2‐hydrazinoquinoline

ABSTRACT

• Spectral and theoretical characterization of 2-Hydrazinoquinoline. • Studies on Vibrational analysis, MEP surface, ELF diagram, NBO and NHO analysis. • Exploration of Fukui functions, Thermodynamic Properties and Hirshfield surface. • TD-DFT for UV–Vis studies along with FMO analysis. • ADME properties prediction and Molecular Docking with four different targets. • 200ns Molecular Dynamics Simulation followed by MMGBSA calculation. We report a comprehensive account on the theoretical and spectroscopic study of 2-hydrazinoquinoline. Computational studies have been performed using density functional theory (DFT) via B3LYP functional and 6-311++G (d,p) basis set. The theoretically predicted spectra showed good agreement with the experimentally obtained IR, NMR and UV spectra. TD-DFT provided information regarding the electronic transition probabilities. Calculation of the energy and structures of the FMO helped in understanding the stability, reactivity and other vital molecular properties. The NBO analysis afforded the insights on the various donor–acceptor interactions at the orbital level, that are responsible for stabilizing the molecule. The distribution of electron density across the molecule was studied using molecular electrostatic potential (MEP). The ELF studies were used to identify the electronic localization within the molecule. The pharmaco-kinetic properties along with the drug-likeness was analyzed as a part of understanding the therapeutic potential of the molecule. Molecular docking studies with four macromolecular targets (COVID-19 viral main protease, FABG4 enzyme, Cruzain and RIP2 Kinase) revealed reasonably good binding affinities. The stability of the best two docked-complexes were investigated using 200ns molecular dynamics simulation followed by effective free energy calculation using MMGBSA. [Display omitted] [ FROM AUTHOR]