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

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 48; no. 32; pp. 12177 - 12185
• Main Authors: Boerhan, Rena, Sun, Weize, Tian, Na, Wang, Youchao, Lu, Jian, Li, Chao, Cheng, Xuexin, Wang, Xuesong, Zhou, Qianxiong
• Format: Journal Article
• Language: English
• Published: England Royal Society of Chemistry 28.08.2019
• Subjects: Absorption spectra; Apoptosis; Chemotherapy; Coordination compounds; Electrophoresis; Flow cytometry; Fluorination; Ligands; Mass spectra; NMR; Nuclear magnetic resonance; Ruthenium compounds; Toxicity
• ISSN: 1477-9226; 1477-9234
• DOI: 10.1039/c9dt01594a

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 IC 50 values of about 8 μM toward HeLa and SKOV-3 cell lines, and also has a much higher IC 50 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. Fluorination on the retaining ligand of Ru( ii ) PACT agents enhanced phototoxicity but diminished dark cytotoxicity compared with the parent complex, more favorable for PACT application.