Coordination of 9-Ethylguanine to the Mixed-Ligand Compound α-[Ru(azpy)(bpy)Cl2] (azpy = 2-Phenylazopyridine and bpy = 2,2‘-Bipyridine). An Unprecedented Ligand Positional Shift, Correlated to the Cytotoxicity of This Type of [RuL2Cl2] (with L = azpy or bpy) Complex

Publisher Website
Google Scholar
Abstract
The striking difference in cytotoxic activity between the inactive cis-[Ru(bpy)2Cl2] and the recently reported highly cytotoxic α-[Ru(azpy)2Cl2] (α indicating the isomer in which the coordinating Cl atoms, pyridine nitrogens, and azo nitrogens are in mutual cis, trans, cis orientation) encouraged the synthesis of the mixed-ligand compound cis-[Ru(azpy)(bpy)Cl2]. The synthesis and characterization of the only occurring isomer, i.e., α-[Ru(azpy)(bpy)Cl2], 1 (α denoting the isomer in which the Cl ligands are cis related to each other and the pyridine ring of azpy is trans to the pyridine ring of bpy), are described. The solid-state structure of 1 has been determined by X-ray structure analysis. The IC50 values obtained for several human tumor cell lines have indicated that compound 1 shows mostly a low to moderate cytotoxicity. The binding of the DNA model base 9-ethylguanine (9-EtGua) to the hydrolyzed species of 1 has been studied and compared to DNA model base binding studies of cis-[Ru(bpy)2Cl2] and α-[Ru(azpy)2Cl2]. The completely hydrolyzed species of 1, i.e., α-[Ru(azpy)(bpy)(H2O)2]2+, has been reacted with 9-EtGua in water at room temperature for 24 h. This resulted in the monofunctional binding of only one 9-EtGua, coordinated via the N7 atom. The product has been isolated as α-[Ru(azpy)(bpy)(9-EtGua)(H2O)](PF6)2, 2, and characterized by 2D NOESY NMR spectroscopy. The NOE data show that the 9-EtGua coordinates (under these conditions) at the position trans to the azo nitrogen atom. Surprisingly, time-dependent 1H NMR data of the 9-EtGua adduct 2 in acetone-d6 show an unprecedented positional shift of the 9-EtGua from the position trans to the azo nitrogen to the position trans to the bpy nitrogen atom, resulting in the adduct α‘-[Ru(azpy)(bpy)(9-EtGua)(H2O)](PF6)2 (α‘ indicating 9-EtGua is trans to the bpy nitrogen). This positional isomerization of 9-EtGua is correlated to the cytotoxicity of 1 in comparison to both the cytotoxicity and 9-EtGua coordination of cis-[Ru(bpy)2Cl2], α-[Ru(azpy)2Cl2], and β-[Ru(azpy)2Cl2]. This positional isomerization process is unprecedented in model base metal chemistry and could be of considerable biological significance.

This publication has 23 references indexed in Scilit: