Synthesis and Bioevaluation of Terephthalic Dihydrazide and a Benzidine‐Based Terephthalamide: Antioxidant, Antimicrobial, and Antibiofilm Activities With Computational Insights

Two structurally distinct terephthaloyl‐derived compounds were synthesized by nucleophilic acyl substitution of terephthaloyl dichloride. Reaction with hydrazine hydrate afforded terephthalic dihydrazide (benzene‐1,4‐dicarbohydrazide; PA‐1) in 80% yield, whereas reaction with benzidine afforded N 1 ,N 4 ‐bis(4′‐amino‐[1,1′‐biphenyl]‐4‐yl)terephthalamide (PA‐2) in 77% yield. The compounds were characterized by Fourier‐transform infrared (FT‐IR) and nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM), powder X‐ray diffraction (PXRD), ultraviolet–visible (UV–Vis) spectroscopy, and thermogravimetric analysis (TGA). At 50 μg/mL, PA‐2 showed 82.49% ± 1.35% DPPH and 82.80% ± 1.50% ABTS radical‐scavenging activity, compared with 59.49% ± 1.54% and 58.44% ± 0.59%, respectively, for PA‐1. PA‐2 also displayed stronger antibacterial activity, with MIC values of 10–20 μg/mL against the tested bacterial strains, and greater biofilm inhibition (51.89%–57.61%) than PA‐1. Molecular docking and molecular dynamics (MD) simulations consistently predicted more favorable and stable interactions for PA‐2, while density functional theory (DFT) calculations showed a smaller HOMO‐LUMO gap for PA‐2 (2.437 eV) than for PA‐1 (3.271 eV). These combined results support a structure–property–bioactivity relationship in which the extended benzidine‐derived π‐conjugated architecture of PA‐2 is associated with enhanced electronic responsiveness and improved multifunctional biological performance.