Fluorination on non-photolabile dppz ligands for improving Ru(ii) complex-based photoactivated chemotherapy

Abstract

Ru(II) polypyridine complexes which can undergo photo-induced ligand dissociation and subsequent DNA covalent binding may potentially serve as photoactivated chemotherapeutic (PACT) agents. In this paper, three fluorinated dppz ligand coordinated Ru(II) complexes (2–4) containing four monodentate pyridine ligands were studied. All complexes released one pyridine and covalently bound to DNA upon 470 nm irradiation. Compared with the parent complex [Ru(dppz)(py)₄]²⁺ (1), 2–4 displayed enhanced phototoxicity but diminished dark cytotoxicity, more favorable for PACT application. Complex 3 is the most efficient one with IC₅₀ values of about 8 μM toward HeLa and SKOV-3 cell lines, and also has a much higher IC₅₀ value toward normal L-02 cells. Our results indicate that fluorination on the retaining ligand may be an efficient way to improve the drug activity of Ru(II) PACT agents.