How half sandwich ruthenium compounds interact with DNA while not being hydrolyzed; a comparative study

The non-coordinative interactions between the compounds [(η6-cym)Ru(pqx)Cl]Cl, (1)Cl, [(η6-cym)Ru(pbqx)Cl]Cl, (2)Cl (cym is 1-methyl-4-(1-methylethyl)benzene, pqx is 2-(2′-pyridyl)quinoxaline and pbqx is 2-(2′-pyridyl)benzo[g]quinoxaline), with the self-complementary oligonucleotide duplex d(5′-CGCGCG-3′)2 in 100mM phosphates buffer and 50mM NaCl, were studied by means of NMR spectroscopic techniques. The compounds (1)Cl and (2)Cl were found to be stable in aqueous media without being hydrolyzed, preserving their saturated coordination sphere (η6-arene-2N-Cl). Based on NMR techniques it was found that both (1) and (2) interact with the hexamer with the outer side of the chelating ligand L, causing elongation or disruption of the oligonucleotide Watson-Crick (W-C) hydrogen bonds. Since both compounds are highly cytotoxic, it can be concluded that their cytotoxic activity could be owed to this type of interactions, or non-coordinative interactions with other biomolecules. The cytotoxic compounds [(η6-cym)Ru(pqx)Cl]Cl and [(η6-cym)Ru(bpqx)Cl]Cl, (cym is 1-methyl-4-(1-methylethyl)benzene, pqx is 2-(2′-pyridyl)quinoxaline and pbqx is 2-(2′-pyridyl)benzo[g]quinoxaline), bind to the self-complementary oligonucleotide duplex d(5′-CGCGCG-3′)2 non-coordinatively, preserving their saturated coordination sphere (η6-arene-2N-Cl), causing elongation or disruption of the oligonucleotide Watson-Crick (W-C) hydrogen bonds. [Display omitted] •The compounds [(η6-cym)Ru(L)Cl]Cl (L=pqx and pbqx) are stable in aqueous media.•cym=p-cymene, pqx=2-(2′-pyridyl)quinoxaline, and pbqx=2-(2′-pyridyl)benzo[g]quinoxaline•They bound non-coordinatively to the oligonucleotide duplex d(5′-CGCGCG-3′)2.•They cause elongation or disruption of the d(5′-CGCGCG-3′)2, Watson-Crick hydrogen bonds.•Their cytotoxicity may be attributed to non-coordinative interactions with DNA.