Molecular docking, DFT calculations, and molecular dynamics simulations in the computational investigation of hydrazone derivative potential as a COVID-19 receptor inhibitor

The ongoing quest for multifunctional organic molecules that exhibit both pharmaceutical and optoelectronic potential has intensified interest in heterocyclic compounds. Among them, hydrazone derivatives stand out for their diverse biological activities, including antimicrobial, antiviral, and anticancer properties, as well as their tunable electronic and optical properties. The presence of the –C N–NH– linkage enables effective conjugation and charge transfer, enhancing their chemical reactivity, stability, and nonlinear optical (NLO) behaviour. Owing to these versatile features, the design and synthesis of novel hydrazone-based heterocycles have gained prominence for potential applications in drug development and advanced material science. This study focuses on the design, synthesis, and characterization of a novel hydrazone derivative, N′-((2,3-dihydrobenzo[ b ][1,4]dioxin-6-yl)methylene)furan-2-carbohydrazide (DDMF). The compound combines furan and benzo dioxane moieties to enhance conjugation and biological activity. Its structural, electronic, and reactive properties were examined using FT-IR, ¹H NMR, ¹ ³C NMR, and DFT-based quantum chemical analyses. In addition, molecular docking and ADMET studies were performed to evaluate its binding affinity, drug-likeness, and pharmacokinetic behaviour, providing insight into its potential pharmaceutical and optoelectronic applications. The DDMF compound was synthesized and structurally confirmed using FT-IR, ¹H NMR, and ¹ ³C NMR spectroscopy. Theoretical investigations were carried out using Density Functional Theory (DFT) to study molecular geometry, electronic structure, and reactivity descriptors. Frontier Molecular Orbital (FMO), Natural Bond Orbital (NBO), and Molecular Electrostatic Potential (MEP) analyses were performed to assess charge distribution and reactive sites. In addition, UV-Vis, NLO, and molecular docking studies were conducted alongside ADMET and drug-likeness evaluations. The optimized geometry showed excellent correlation with experimental data, exhibiting minimal RMSD in bond lengths (0.020 Å) and bond angles (5.20°). FMO analysis revealed moderate reactivity and effective charge transfer, while NBO and MEP confirmed significant electron delocalization. The compound exhibited strong NLO activity and consistent NMR spectral agreement (¹H RMSD = 0.437 ppm; ¹³C RMSD = 1.24 ppm). UV-Vis spectra indicated distinct π→π* transitions at 275 and 350 nm. Docking studies showed stable interactions of DDMF with SARS-CoV-2 targets, supported by stable RMSD (∼1–2.5 Å) and low RMSF values. The compound demonstrated excellent intestinal absorption (94.63 %), favorable ADMET profiles, and high drug-likeness (MW 272.26 g/mol, LogP 1.84, TPSA 73.06 Ų). The combined experimental and theoretical investigations unequivocally confirm the successful synthesis, structural integrity, and stability of the DDMF molecule. The compound exhibits favorable electronic configuration, optical responsiveness, and pharmacological potential, as evidenced by its consistent spectroscopic characteristics, strong charge-transfer behaviour, and stable molecular interactions with biological targets. The integration of computational and spectroscopic analyses establishes DDMF as a structurally robust and functionally versatile molecule, making it a promising candidate for future advancements in both optoelectronic device fabrication and therapeutic drug development. • Synthesis of novel hydrazone derivative. • Investigation of electronic properties through DFT-based analysis. • Molecular docking analysis to evaluate the inhibitory potential of the synthesized compound. • Molecular dynamics simulation conducted over a 100 ns period to examine the dynamic interactions between the protein and ligand.