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.