Synthesis and Characterization of Ruthenium-Paraphenylene-Cyclopentadienyl Full-Sandwich Complexes: Cytotoxic Activity against A549 Lung Cancer Cell Line and DNA Binding Properties.

Novel full-sandwich (-Cp)-Ru-paraphenylene complexes with the general formula [(-Cp)Ru(-L)](PF) where n = 1-3 and L = biphenyl, -terphenyl and -quaterphenyl, were synthesized and characterized by means of spectroscopic and analytical techniques. The structures of the complexes [(-Cp)Ru(-biphenyl)](PF) (), [(-Cp)Ru(-terphenyl)](PF) () and [(-Cp)Ru(-terphenyl)](PF) () was determined by X-ray single crystal methods. The interaction of the complexes [(-Cp)Ru(-quaterphenyl)]Cl, ()Cl, and [(-Cp)Ru(-quaterphenyl)]Cl, ()Cl, with the DNA duplex d(5'-CGCGAATTCGCG-3') was studied using NMR techniques. The results showed that both complexes interacted non-specifically with both the minor and major grooves of the helix. Specifically, ()Cl exhibited partial binding through intercalation between the T7 and T8 bases of the sequence without disrupting the C-G and A-T hydrogen bonds. Fluorometric determination of the complexes' binding constants revealed a significant influence of the number of connected phenyl rings in the paraphenylene ligand (L) on the binding affinity of their complexes with the d(5'-CGCGAATTCGCG-3'). The complexes ()Cl and ()Cl were found to be highly cytotoxic against the A549 lung cancer cell line, with complex () being more effective than () (IC for ()Cl: 17.45 ± 2.1 μΜ, IC for ()Cl: 65.83 ± 1.8 μΜ) and with a selectivity index (SI) (SI for ()Cl: 1.1 and SI for ()Cl: 4.8).