Experimental and Theoretical Investigation of 6‐Nitropiperonal Through Structural, Electronic, and Biological Perspectives

ABSTRACT This study explores the structural, electronic, and biological properties of 6‐nitropiperonal (6NP), a nitro‐substituted derivative of piperonal with potential biomedical relevance. The crystalline nature of 6NP was confirmed by powder x‐ray diffraction (PXRD), while FT‐IR and FT‐Raman analyses provided detailed vibrational insights. UV–vis spectroscopy revealed absorption bands at 325.3 and 408.7 nm, attributed to π–π* and n–π* transitions. Density functional theory (DFT) calculations at the B3LYP/6‐311++G(d,p) level yielded optimized geometry and a HOMO–LUMO gap of 3.92 eV, indicating moderate electronic stability and potential for controlled charge‐transfer interactions. Reactivity analyses using molecular electrostatic potential (MEP), natural bond orbital (NBO), and Fukui functions identified clear electrophilic and nucleophilic regions within the molecule. ADMET predictions suggested favorable oral bioavailability and low toxicity, supporting its drug‐likeness profile. Molecular docking against the antibacterial target protein (1JIJ) showed a binding affinity of −6.6 kcal/mol, further supported by 100 ns molecular dynamics simulations confirming stable ligand–protein interactions. Experimental assays demonstrated notable antioxidant activity (DPPH IC50 = 39.04 µg/mL), along with moderate antibacterial activity against Staphylococcus aureus and Escherichia coli, as well as antifungal activity against Candida albicans and Aspergillus flavus. These findings establish a clear structure–property–activity relationship and highlight 6NP as a promising bioactive candidate.