Photolabile Ruthenium(II)–Purine Complexes: Phototoxicity, DNA Binding, and Light-Triggered Drug Release

Abstract

Photoactivated chemotherapy is gaining increasing interest as a potentially selective treatment of cancer, and bacterial and viral infections. In this approach a therapeutic can be administered as a nontoxic prodrug and then converted to its active form in the diseased tissue by the localized application of light. Here we report the first example of a photolabile ruthenium prodrug that releases a purine ligand when irradiated with visible light. A series of ruthenium(II) polypyridyl complexes were prepared with the anticancer agent 6-mercaptopurine as a ligand. The nature of the polypyridyl ligand was found to strongly influence the properties of the complexes, including absorbance maxima, photostability, and the binding mode of 6-mercaptopurine. The lead complex is stable in solution in the dark but releases 6-mercapoturine when irradiated with visible light, leading to a significant increase in toxicity towards breast cancer cells.