Synthesis and reactivity of new diplatinum (III) complexes

Research in the field of bioinorganic chemistry has been stimulated by the worldwide success of the anticancer drug cisplatin. A considerable progress in platinum chemistry was achieved upon the synthesis of kinetically inert platinum(IV) compounds. At an early stage following the discovery of the antitumor activity of cisplatin, it became evident that DNA binding of the drug was crucial for its effect. A detailed understanding of the reactions between platinum complexes and model nucleobases contributes significantly to the interpretation of interactions of these compounds with nucleic acids. As far as diplatinum(III) complexes containing pyrimidine nucleobases are concerned, the discovery of a class of Pt antitumor agents called "platinum pyrimidine blues" was instrumental in developing the +3 oxidation state platinum compounds. It has been found that some of diplatinum(III) complexes selectively bind guanine nucleobases via their N(7) positions. There is the need to learn more about reactivity of diplatinum(III) compounds in respect to four common nucleobases. Therefore, the synthesis and reactivity of new platinum complexes with uncommon oxidation states of platinum centers are suggested as a particular interest of this research plan proposal. In detail, the proposed research programme is focused on the following main fundamental problems: 1) Synthesis and characterization of novel diplatinum(III) complexes; 2) Study of ligand substitution reactions/redox reactions of novel diplatinum(III) complexes prepared in accord with the project, including particularly reactions with guanine and the guanosine derivative 5`-dGMP. The obtained results should contribute significantly to the understanding of the details on the mechanism underlying the action of metal-containing antitumor drugs and might provide new knowledge that should lead to synthesis of new antitumor active compounds.