Synthesis, Characterization, and Biological Activity of New 4‘‐Functionalized Bis‐Terpyridine Ruthenium(II) Complexes: Anti‐Inflammatory Activity Advances

Abstract Ruthenium complexes incorporating 2,2′ : 6′,2′′‐terpyridine ligands have emerged as promising candidates due to their versatile biological activities including DNA‐binding, anti‐inflammatory, antimicrobial, and anticancer properties. In this study, three new 4′‐functionalized bis(terpyridine) Ru(II) complexes were synthesized. These complexes feature one ligand as 4‐(2,2′ : 6′,2′′‐terpyridine‐4′‐yl) benzoic acid and the second ligand as either 4′‐(2‐thienyl)‐2,2′ : 6′,2′′‐terpyridine, 4′‐(3,4‐dimethoxyphenyl)‐2,2′ : 6′,2′′‐terpyridine, or 4′‐(4‐dimethylaminophenyl)‐2,2′ : 6′,2′′‐terpyridine. Besides the chemical characterization by 1 H and 13 C NMR, mass spectrometry, and absorption and emission spectroscopy, the complexes were tested for their biological activity as anti‐inflammatory, anticancer, and antimicrobial agents. Moreover, the toxicity of the Ru(II) complexes was assessed and benchmarked against diclofenac potassium and ibuprofen using a haemolysis assay. Biological evaluations demonstrate that these ruthenium complexes exhibit promising therapeutic potential with reduced haemolytic activity compared to standard drugs. They demonstrate substantial anti‐inflammatory effects through inhibition of albumin denaturation along with moderate cytotoxicity against cancer cell lines and broad‐spectrum antimicrobial activity. These findings highlight the multifaceted biomedical applications of 4′‐functionalized bis(terpyridine) Ru(II) complexes, suggesting their potential for further development as effective and safe therapeutic agents.