THE PROVEN CLINICAL EFFECTIVENESS OF CISPLATIN AS WELL AS SEVERAL SECOND GENERATION ANALOGS HAS ESTABLISHED THE ROLE OF METAL COORDINATION COMPOUNDS IN CANCER CHEMOTHERAPY.

THE PROVEN CLINICAL EFFECTIVENESS OF CISPLATIN AS WELL AS SEVERAL SECOND GENERATION ANALOGS HAS ESTABLISHED THE ROLE OF METAL COORDINATION COMPOUNDS IN CANCER CHEMOTHERAPY. COMPLEXES OF METALS OTHER THAN PLATINUM HAVE BEEN OFTEN POORLY DESIGNED BECAUSE THEY WERE MODELED AFTER THE ACTIVE PLATINUM COMPLEXES WITHOUT CONSIDERING THEIR DIFFERENT THERMODYNAMIC AND KINETIC PARAMETERS. IN PARTICULAR, PALLADIUM ANALOGS OF ACTIVE PLATINUM COMPLEXES HAVE EXHIBITED MARGINAL ACTIVITY BECAUSE OF THEIR SUBSTITUTION LABILITY. BY DECREASING THIS LABILITY, THIS INVESTIGATOR HAS DEVELOPED PALLADIUM COMPLEXES EXHIBITING ANTINEOPLASTIC ACTIVITY IN VIVO. IT IS THE OBJECT OF THIS PROJECT TO FULLY CHARACTERIZE THE INTERRELATIONSHIP AMONG PALLADIUM COMPLEX STABILITY, LIGAND BASICITY, AND ANTITUMOR ACTIVITY OF PALLADIUM COMPLEXES TOWARD THE DESIGN OF MORE ACTIVE COMPLEXES. TO DETERMINE IF ENHANCING STABILITY WILL INCREASE EFFECTIVENESS, THIS INVESTIGATOR WILL SYNTHESIZE PALLADIUM COMPLEXES WITH LIGANDS OF VARYING BASICITY. AROMATIC LIGANDS WILL BE STUDIED AND THEIR BASICITY WILL BE VARIED BY ELECTRON-DONATING SUBSTITUENTS. THE EFFECT OF BASICITY OF ALIPHATIC CARBOXYLIC ACID LIGANDS ON THE STABILITY OF PD-0 BOND WILL ALSO BE INVESTIGATED. IT IS EXPECTED THAT ENHANCEMENT IN STABILITY OF PALLADIUM COMPLEXES WILL BE OBSERVED WITH INCREASED INDUCTIVE RELEASE OF ELECTRONS BY THE LIGANDS.