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

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 ¹H and ¹³C 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.