Rhodium(III) complexes as genotoxic agents: photochemical effects and their implications

The genetic toxicology of coordination compounds of transition metals has been of considerable interest since the application of cis-platinum(II) to the therapy of solid tumors. The nature of reactions of such compounds with DNA is still unclear, despite intensive investigation. In this study, several coordination compounds of rhodium(III) were tested for DNA-damaging activity and mutagenicity in bacterial assays in an attempt to understand both the chemical species involved in interactions with DNA and any structural requirements for such interactions. For several complexes it appears that dissociation of a ligand from the complex precedes reactions with DNA. This conclusion stems from the finding that photosensitive complexes of rhodium(III) are often many times more toxic to repair-deficient bacterial stains of E. coli K12 when incubated in the light than when incubated in the dark. Similar responses were seen for mutagenicity in S. typhimurium strain TA100. However, reversion of strain TA102 was largely independent of light exposure. Comparisons between mutagenicity and DNA-damaging activity revealed that the 3 activities measured sorted with some independence among the different compounds tested. Thus, the profiles for crosslink formation and/or generation of oxidative mutagens (mutagenicity in S. typhimurium strain TA102), mutagenicity in TA100 and DNA-damaging activity for the various groups of complexes showed many of the theoretically possible combinations of response in the assays. It is possible, then, that there are different structural requirements for DNA-damaging activity and mutagenicity respectively. This may indicate that synthesis of coordination compounds with specific genotoxic properties is possible. Such syntheses may provide complexes for study of DNA-metal interactions and could, later, direct an approach to the design of new antitumor agents.