Synthesis, Characterization, and Anticancer Activity of Rhodium (III) Complexes with Bidentate and Tridentate N‐Donor Ligands

Abstract A series of five novel rhodium(III) complexes of the type [Rh(tpy)(N^N)Cl](PF 6 ) 2 , incorporating a tridentate 2,2′:6′,2′′‐terpyridine (tpy) ligand and various bidentate N‐donor ligands, were synthesized and fully characterized. The single‐crystal X‐ray diffraction analysis of complex 5 [Rh(tpy)(dppz)Cl](PF 6 ) 2 (dppz = dipyrido[3,2‐a:2′,3′‐ c ]phenazine) confirmed its octahedral geometry. Cytotoxicity assays revealed potent antiproliferative activity against four human cancer cell lines (AGS, MCF‐7, HeLa, and HepG2). Notably, complex 5 demonstrated enhanced selectivity and cytotoxicity toward AGS cells compared to cisplatin. Molecular docking studies indicated that complexes 3 and 5 effectively insert into the minor groove of calf thymus DNA (ctDNA), supported by favorable steric and electrostatic interactions. Mechanistic studies further confirmed that complex 5 induces apoptosis, causes S‐phase cell cycle arrest, and elevates intracellular ROS levels in AGS cells. Collectively, these results highlight the potential of terpyridine‐based Rh(III) complexes as promising scaffolds for metal‐based anticancer drug development.