Synthesis and Biological Evaluation of π‐Conjugated Ir(III) Complexes: Cytotoxic Potential, DNA/HSA Binding, Thermodynamics, and Antioxidant Activity

Metal‐based complexes have greatly advanced anticancer therapy, but limitations of traditional drugs like cisplatin have driven the search for more stable and targeted metallodrugs. In this study, two novel Ir(III) complexes, PNIC and PNIT, incorporating a rigid Schiff base ligand (PNN) derived from 1,10‐phenanthroline‐5,6‐dione and N,N‐bis(4‐formylphenyl)‐N, N‐diphenylbenzidine, were synthesized and characterized by NMR, FT‐IR, HRMS, and UV–Vis spectroscopy. Both complexes exhibited large Stokes shifts (60 and 47 nm), high stability in GSH and PBS, and strong binding affinity toward DNA and HSA through hydrophobic and hydrogen bonding interactions. They also exhibited notable antioxidant activity and potent cytotoxicity against A549 lung cancer cells, with IC 50 values of 19.69 µM for PNIC and 16.86 µM for PNIT, and good selectivity toward normal HEK293 cells (SI = 10.5 and 13.6, respectively). These findings highlight the potential of both PNIC and PNIT as multifunctional Ir(III)‐based anticancer candidates possessing excellent bio‐stability and target selectivity.