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 ( η 5 -Cp)-Ru-paraphenylene complexes with the general formula [( η 5 -Cp) n Ru( η 6 -L)](PF 6 ) n where n = 1-3 and L = biphenyl, p -terphenyl and p -quaterphenyl, were synthesized and characterized by means of spectroscopic and analytical techniques. The structures of the complexes [( η 5 -Cp)Ru( η 6 -biphenyl)](PF 6 ) ( 1 ), [( η 5 -Cp)Ru( η 6 -terphenyl)](PF 6 ) ( 3 ) and [( η 5 -Cp) 2 Ru( η 6 -terphenyl)](PF 6 ) 2 ( 4 ) was determined by X-ray single crystal methods. The interaction of the complexes [( η 5 -Cp)Ru( η 6 -quaterphenyl)]Cl, ( 6 )Cl, and [( η 5 -Cp) 2 Ru( η 6 -quaterphenyl)]Cl 2 , ( 7 )Cl 2 , with the DNA duplex d(5'-CGCGAATTCGCG-3') 2 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, ( 6 )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') 2 . The complexes ( 6 )Cl and ( 7 )Cl 2 were found to be highly cytotoxic against the A549 lung cancer cell line, with complex ( 6 ) being more effective than ( 7 ) (IC 50 for ( 6 )Cl: 17.45 ± 2.1 μΜ, IC 50 for ( 7 )Cl 2 : 65.83 ± 1.8 μΜ) and with a selectivity index (SI) (SI for ( 6 )Cl: 1.1 and SI for ( 7 )Cl 2 : 4.8).