Design and development of polynuclear ruthenium and platinum polypyridyl complexes in search of new anticancer agents

The research described in this Ph.D. Thesis has been devoted to the design and development of polynuclear polypyridyl ruthenium and ruthenium-platinum complexes in search of new anticancer agents. A variety of polynuclear ruthenium and ruthenium-platinum complexes has been synthesized with a long and flexible linker. The complexes are characterized and have been studied for anticancer activity. The ruthenium unit of the dinuclear complexes varies in molecular structure, which may result in different interactions with DNA, the target of anticancer platinum and ruthenium antitumor compounds. The monofunctional ruthenium unit coordinates to the DNA-model base 9-ethylguanine. Variable temperature 1H NMR experiments prove that the base is hindered in its free rotation at room temperature. The crystal structure of a dinuclear ruthenium-platinum complex shows that the platinum unit is capable of intercalation and coordination (in)to DNA. Trinuclear and tetranuclear ruthenium and ruthenium-platinum complexes show higher activity than the dinuclear derivatives. A tetranuclear ruthenium complex displays interesting biological features. Human ovarian cisplatin sensitive carcinoma cells adhere together and form clots upon incubation of the complex. The effect possibly indicates antimetastatic activity. Dinuclear and trinuclear ruthenium-platinum complexes of short and semi-rigid linkers do not show significant activity against different cancer cell lines.