Synthesis, characterization, cytotoxic and antimicrobial activity of ruthenium(II) arene complexes with N,N-bidentate ligands

Abstract

Three new complexes, [(η⁶-C₆H₆)RuCl(C₅H₄N-2-CH=N-Ar)]PF₆ (Ar = phenylmethylene (1), (4-methoxyphenyl)methylene (2), phenylhydrazone (3)), are prepared by reacting [(η⁶-C₆H₆)Ru(μ-Cl)Cl]₂ with N,Nʹ-bidentate ligands in a 1:2 ratio. Full characterization of the complexes was accomplished using ¹H and ¹³C NMR, elemental and thermal analyses, UV-Vis and IR spectroscopy and single crystal X-ray structures. Single crystal structures confirmed a pseudo-octahedral three-legged, piano-stool geometry around Ru(II), with the ligand coordinated to the ruthenium(II) through two N atoms. The cytotoxicity of the mononuclear complexes was established against the human ovarian cancer cell lines and selectivity was also tested against non-cancerous human epithelial kidney (HEK 293) cells. The compounds were selective towards the tumor cells in contrast to the known anti-cancer drug 5-flouro uracil which was not selective between the tumor cells and non-tumor cells. All the compounds showed moderate activity against MCF7 (human breast adenocarcinoma), but showed low antiproliferative activity against Caco-2 and HepG2. Also, antimicrobial activities of the complexes were tested against a panel of antimicrobial-susceptible and -resistant Gram-negative and Gram-positive bacteria. Of special interest is the anti-mycobacterial activity of all three synthesized complexes against M. smegmatis, and bactericidal activity against resistant E. faecalis and methicillin-resistant S. aureus ATCC 43300.