Aromatic amino acid based Schiff base copper(II) complexes as potential lung cancer therapeutics: Biological and antioxidant activity, DNA/BSA interaction, mesogenic properties, molecular docking and DFT study.

Three new copper(II) complexes, Cu(L1)₂, Cu(L2)₂, and Cu(L3)₂, derived from aromatic amino acid based Schiff base ligands, potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-phenylpropanoate (HL1), potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(4-hydroxyphenyl) propanoate (HL2) and potassium (E)-2-((4-hexadecyloxy)-2-hydroxybenzylidene)amino)-3-(1H-indol-2-yl)propanoate (HL3) were synthesized and characterized by using elemental analysis and the spectroscopic techniques viz., UV-visible, 13C NMR, 1H NMR, FT-IR spectroscopy. All three complexes interact effectively with calf thymus-deoxyribonucleic acid (CT-DNA) and Bovine serum albumin (BSA), as evidenced from spectroscopic studies. Among them, Cu(L3)₂ exhibited the strongest biomolecular binding affinity, highest cytotoxic activity against lung adenocarcinoma (A-549) cells, and superior antioxidant capacity in the DPPH (2,2-diphenyl-1-picryhydrazyl) assay. Molecular docking simulations were carried out to evaluate the binding affinity and interaction profiles of aromatic amino acid-based Schiff base Cu(II) complexes with Human Serum Albumin (HSA). The results revealed selective binding at Sudlow's site I, with the binding of Cu(L3)₂ with HSA exhibiting the highest affinity (-5.81 kcal mol-1). The parent ligands HL1, HL2 and HL3 exhibit blue photoluminescence, and the presence of their long alkyl chain substituents induced mesomorphic behaviour with distinct nematic, smectic C, and mosaic textures, respectively. Density functional theory (DFT) calculations supported the experimental findings, revealing optimized geometries and HOMO-LUMO band gaps consistent with their reactivity trends. On the whole, Cu(L3)₂ emerges as the most promising candidate for biomedical applications, while the ligands themselves show potential for functional mesogenic material.