The chemistry of phosphates has long been an important area of research in biochemistry, and the chemistry of platinum in biological systems receives a great deal of attention due to the anti-tumor activity of cis-Pt(NH3)2Cl2 (cisplatin) and other platinum complexes. The research proposed here will produce fundamental results where these two areas cross. The research will begin with the synthesis of a series of phosphato complexes of platinum, including complexes of platinum(IV), for which the synthesis of new complexes has not been extensively investigated. Each of these new complexes will be carefully characterized in order to provide a basis for other workers to interpret the behavior of platinum complexes in the presence of phosphates. The characterization will include examination by phosphorus-31 NMR and, collaboratively, by X-ray crystallography. The complexes which will be most vigorously sought are those which should have characteristics which will make them candidates to be tested for anti-cancer activity: neutrality at physiological pH, ammine ligands, and cis position for leaving groups. Such complexes will be submitted to the National Cancer Institute for evaluation. The rates of formation and dissociation of the complexes will be studied so that the extent of reaction of platinum complexes with phosphates in biological systems can be estimated. In addition, the rates of hydrolysis of the coordinated phosphates will be studied in order to increase our understanding of the role that metal ions play in the enzyme-catalyzed hydrolysis of phosphates.
