Synthesis, characterization, and in‐depth molecular docking studies of 2‐naphthol derivatives with <i>Escherichia coli</i> receptors, coupled with comprehensive evaluation of antibacterial and antioxidant activities

Abstract Antibiotic resistance and oxidative stress represent two major public health challenges of the 21st century, with their interplay contributing to the emergence of drug‐resistant bacterial strains. Naphthol derivatives have attracted significant attention due to their dual antibiotic and antioxidant properties. In this study, we have synthesized two 2‐naphthol derivatives, NHNP‐NMA and 4Cl‐HNP‐NMA, by reacting substituted benzaldehydes with N ‐methylacetamide under solvent‐free conditions, catalyzed by trichloroacetic acid or montmorillonite K10 clay. The yields of the synthesized compounds were 82% for NHNP‐NMA and 79% for 4Cl‐HNP‐NMA. The compounds have been characterized through UV–visible, ¹H‐NMR, FT‐IR, and mass spectral techniques, and their molecular structures were optimized using DFT/B3LYP calculations. Further computational analyses such as frontier molecular orbital (FMO) evaluation, Mulliken charge distribution, molecular electrostatic potential (MEP) mapping, and theoretical UV–visible along with vibrational spectral analyses were carried out. For NHNP‐NMA, the HOMO energy was computed to be −6.01 eV and the LUMO energy to be −1.43 eV, whereas 4Cl‐HNP‐NMA displayed a HOMO energy of −6.14 eV and a LUMO of −1.56 eV. Although the chlorine substitution lowered both the HOMO and LUMO energies, both compounds exhibited an identical bandgap of 4.58 eV. Docking simulations indicated potential activity against Escherichia coli , which was corroborated by in vitro experiments. The antioxidant activity of both compounds was evaluated using the DPPH radical scavenging assay, showing significant results for both derivatives.