DIRECTED RADIATION SENSITIZERS FROM RH AND PT DIMERS

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The intent of this study is to: a) correlated the radiation sensitization by rhodium and platinum dimers in S, typhimurium cells with the range of one and two-electron reduction potentials established by cyclic voltammetry; b) synthesize a family of rhodium and platinum dimers designed to provide a range of one and two electron reduction potentials, and electrochemically characterize the few rhodium and platinum dimers commercially available, for subsequent sensitizer testing; c) determine for selected dimers the sensitizer efficiency as affected by oxygen and specific scavengers of the hydroxyl radical and the hydrated electron. Predictive correlations between sensitizer efficiency and one- and two-electron reduction potentials have been reported. However, the importance of reduction potential as a predictor of metal-induced radiation sensitization has not yet been studied, hence the objectives of this proposed work. The manipulation of reduction potentials within a related family of metal complexes requires carful selection of material. The family of tetracarboxylate- and pyrimidine-bridged rhodium and platinum dimer species is chasen here. Variatin of axial ligands may effect reduction potential by variation of inductive effects upon other complex-ligands containing a combination of sigma- and pi-donating effects. Variation of axial ammine ligands in the Rh2(CH3CO2)4 dimer system witll therefore be explored. Further, the Rh(II) and Pt(II) dimers lend themselves to high valemce manipulations, with expected concomitant variation of reduction potentials. Therefore, Pt(III) dimers, Rh (III) dimers, and mixed Rh(II)/Rh(III) dimers will be synthesized and tested for radiation sensitization. These metal dimers may find use as radiation sensitizers and antitumor drugs in mammalian systems. Ultimately, clinical benefit may be realized for certain of these complexes as combined modality agents interfaced with radiation therapy. The model for this possibility is cisplatin, that was initially shown to be a radiation sensitizer in bacterial systems and is now suggestive in a few clinical cancer trials as enhancing local tumor control when combined with radiation therapy.