Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Non-covalent DNA-binding ruthenium anticancer drugs

The research work described in this thesis concerns metal-based anticancer drugs with an emphasis on non-covalent DNA-binding supramolecular assemblies. The project involves the preparation of a series of mono- and bi-metallic ruthenium complexes with a primary focus on fluorescent dinuclear triple-stranded helicates with different structural topographies. Emphasis is then directed towards an investigation of the DNA binding characteristics of these molecules and an evaluation of their anticancer properties in human cancer cell lines. Attention is brought to the significance that the cylinder-building moieties and their structural characteristics have to these features. The studies also include an examination of the effects of chirality of the investigated supramolecular systems and the impact they have on molecular recognition. This is addressed via studies of the interaction of optical isomers of ruthenium triple-stranded helicates with DNA as a biomolecular target system and with Δ-TRISPHAT as a representative small chiral molecule