Biologically Active Organic Antioxidants: Synthesis, Analysis, and Mechanistic Insights via <scp>DFT</scp> Calculations, Crystallographic Analysis, and Molecular Docking Techniques

ABSTRACT Three novel Schiff base compounds—KAT [2‐[(3‐methyl‐thiophen‐2‐ylmethylene)‐amino]‐phenol], KMT [4‐methyl‐2‐[(3‐methyl‐thiophen‐2‐ylmethylene)‐amino]‐phenol], and KNT [2‐[(3‐methyl‐thiophen‐2‐ylmethylene)‐amino]‐4‐nitro‐phenol]—were synthesized from biologically relevant precursors. The structures of the compounds were thoroughly characterized using elemental analysis, FT‐IR, UV–Vis spectroscopy, mass spectrometry, and both 1 H and 13 C NMR spectroscopy, which were further validated by single‐crystal X‐ray diffraction (SC‐XRD). The antioxidant potential of these Schiff bases was assessed via in vitro radical scavenging activity using the DPPH method, benchmarked against the standard antioxidant, butylated hydroxyanisole (BHA). To deepen our understanding of their antioxidant properties, comprehensive theoretical studies based on density functional theory (DFT) were performed. Moreover, the influence of various solvents on antioxidant efficiency was explored, revealing the critical role of solvent polarity and hydrogen bonding interactions. Molecular docking studies were conducted to assess the enzyme inhibitory potential of the Schiff bases, particularly targeting human peroxiredoxin enzyme 5 (PDB: 1HD2). These findings, supported by cell viability assays, underscore the promise of the synthesized Schiff bases as potent pharmacophores with low toxicity to healthy cells.