DNA Interactions of Monofunctional Organometallic Ruthenium(II) Antitumor Complexes in Cell-free Media

Modifications of natural DNA in a cell-free medium by antitumor monodentate Ru(II) arene compounds of the general formula [(eta 6-arene)Ru(en)Cl]+ (arene ) biphenyl, dihydroanthracene, tetrahydroanthracene, p-cymene, or benzene; en ) ethylenediamine) were studied by atomic absorption, melting behavior, transcription mapping, circular and linear dichroism, plasmid unwinding, competitive ethidium displacement, and differential pulse polarography. The results indicate that these complexes bind preferentially to guanine residues in double-helical DNA. The data are consistent with DNA binding of the complexes containing biphenyl, dihydroanthracene, or tetrahydroanthracene ligands that involves combined coordination to G N7 and noncovalent, hydrophobic interactions between the arene ligand and DNA, which may include arene intercalation and minor groove binding. In contrast, the single hydrocarbon rings in the p-cymene and benzene ruthenium complexes cannot interact with double-helical DNA by intercalation. Interestingly, the adducts of the complex containing p-cymene ligand, which has methyl and isopropyl substituents, distort the conformation and thermally destabilize double-helical DNA distinctly more than the adducts of the three multiring ruthenium arene compounds. It has been suggested that the different character of conformational alterations induced in DNA, and the resulting thermal destabilization, may affect differently further “downstream” effects of damaged DNA and consequently may result in different biological effects of this new class of metal-based antitumor compounds. The results point to a unique profile of DNA binding for Ru(II) arene compounds, suggesting that a search for new anticancer compounds based on this class of complexes may also lead to an altered profile of biological activity in comparison with that of metal-based antitumor drugs already used in the clinic or currently on clinical trials

Synthesis and Characterization of Tetrahedral Ru3O Clusters with Intrinsic Framework Chirality: A Chiral Probe of the Intact Cluster Catalysis Concept

To bring evidence for or against the hypothesis of catalytic hydrogenation by intact trinuclear arene ruthenium clusters containing an oxo cap, cationic Ru3O clusters with three different arene ligands (intrinsically chiral tetrahedra) have been synthesized as racemic mixtures. By introduction of a chiral auxiliary substituent at one of the three different arene ligands, the separation of the two diastereomers was possible. The chiral Ru3O framework was evidenced by X-ray crystallography, by circular dichroism in the UV and IR regions, and by chiral shift reagents in the NMR spectra. The catalytic hydrogenation of the prochiral substrate methyl 2-acetamidoacrylate using a chiral Ru3O cluster showed no asymmetric induction, suggesting that the catalytically active species is not the intact Ru3O cluster

Relevance of the ligand exchange rate and mechanism of fac-[(CO)3M(H2O)3]+ (M = Mn, Tc, Re) complexes for new radiopharmaceuticals

Copyright © 2006 American Chemical SocietyPascal V. Grundler, Lothar Helm, Roger Alberto, and André E. Merbac