Cellular accumulation and localization of rhodium metalloinsertors

Polypyridyl rhodium complexes bearing the sterically expansive chrysene diimine ligand are known to bind selectivity to mismatched base pairs in duplex DNA through insertion via the minor groove. These complexes are selectively cytotoxic in cell cultures bearing the microsatellite instability (MSI) phenotype, a marker for deficiencies in mismatch repair. The MSI phenotype has been found in a variety of carcinomas including hereditary nonpolyposis colorectal cancer, ovarian cancer, and treatment-related secondary leukemia. The effects of ancillary ligand substitution on the cellular accumulation and cytotoxicity were explored using a variety of H-bonding, anionic, or aliph. substituted ancillary ligands. Variations in the biol. activity are discussed in the context of uptake and localization of the complexes.