This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The antitumor activity of rhodium(II) carboxylates, [Rh2(RCOO)4], was discovered in 1976;however, its rather high toxicity relative to cisplatin, Pt(NH3)2Cl2, has prevented it from becoming clinically approved. This class of dirhodium(II) compounds can interact with both DNA and proteins: they can form complexes with the DNA nucleotide bases, interrupting the DNA replication process, or bind to the amino acid residues of proteins. Earlier studies suggest that reaction of rhodium(II) carboxylates with free thiol (-SH) containing groups, such as aminoacid cysteine, results in decomposition of the dirhodium complex, breaking the Rh-Rh bond and releasing CO2. It has been proposed that such a reaction with free thiol group(s) at or near the active center of an enzyme, such as DNA polymerase, can lead to inactivation of the enzyme;this view is in parallel with the toxicity effects of the rhodium(II) carboxylates. Pnematikakis et al. investigated complexes formed between rhodium(II) acetate, [Rh2(CH3COO)4], with L-cysteine, cysteine methyl-ester and D- penicillamine (3,3'-dimethyl cysteine) in the solid state, using IR and EPR spectroscopic methods, and concluded that these ligands form (N,S)- bound monomeric Rh(II) complexes. However, no details about the local structure around Rh(II) ions in these complexes, i.e. metal-ligand bond distances, is available.
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