More than half of all cancer patients receive a platinum-based drug such as cisplatin as part of their chemotherapy. But the compounds have dangerous side effects and many tumors develop resistance to the drugs, prompting chemists to seek out less toxic and more selective alternatives.
In one of the latest examples, Amanda David, a graduate student in chemistry professor Kim R. Dunbar’s group at Texas A&M University, described a family of promising dirhodium complexes during a symposium on bioinorganic chemistry sponsored by the Division of Inorganic Chemistry at the American Chemical Society meeting in San Francisco this week.
The Texas A&M team developed the dirhodium complexes with Claudia Turro at Ohio State University. In cell culture experiments, the compounds exhibited lower toxicities and were as effective or better than cisplatin against lung cancer cells
The new dirhodium compound [Rh2(μ-O2CCH3)2(η1-O2CCH3)(phenbodipy)(H2O)3][O2CCH3] (1), which incorporates a bodipy fluorescent tag, was prepared and studied by confocal fluorescence microscopy in human lung adenocarcinoma (A549) cells. It was determined that 1 localizes mainly in lysosomes and mitochondria with no apparent nuclear localization in the 1–100 μM range. These results support the conclusion that cellular organelles rather than the nucleus can be targeted by modification of the ligands bound to the Rh24+ core. This is the first study of a fluorophore-labeled metal–metal bonded compound, work that opens up new venues for the study of intracellular distribution of dinuclear transition metal anticancer complexes.
Syn of cisplatin
The synthesis of cisplatin is a classic in inorganic chemistry. Starting from potassium tetrachloroplatinate(II), K2[PtCl4], the first NH3 ligand is added to any of the four equivalent positions, but the second NH3 could be added cis or trans to the bound amine ligand. Because Cl− has a larger trans effect than NH3, the second amine preferentially substitutes trans to a chloride ligand, and therefore cis to the original amine. The trans effect of the halides follows the order I–>Br–>Cl–, therefore the synthesis is conducted using [PtI4]2− to ensure high yield and purity of the cis isomer, followed by conversion of the PtI2(NH3)2 into PtCl2(NH3)2, as first described by Dhara.
2 Dhara SC (1970). Indian Journal of Chemistry 8: 193–134.