Novel 6F-Iridium(III) complexes as potent theranostic agents: Hypoxia probing, radiosensitization and antiviral functionalities

Two novel cyclometalated iridium(III) complexes containing fluorinated phenylpyridine (TFPPy)(2)IrPic or phenylquinoline (TFPQ)(2)IrPic with pyridine-2-carboxylate as chelating ligands were synthesized and fully characterized. These complexes displayed hypoxia sensing and therapeutical activities. As hypoxia probes these two complexes achieved S/B ratio of 7.125; 8.156. Besides the anti-proliferation activities against Cisplatinresistant cancer cells, radiosensitization effect with SER value 1.742-1.941 were observed even in radioresistant cell lines after treatment with these complexes, mechanism confirmed via typical G2 phase arrest. Furthermore, the two complexes have shown antiviral activity against both HSV-1 and HSV-2 virus strands. Molecular docking calculation have revealed that this type of Ir(III) complex forms stable hydrogen bond and hydrophobic interactions to the major groove of the double helix of HSV. These findings demonstrated (TFPPy)(2)IrPic and (TFPQ)(2)IrPic as promising candidates for further evaluation as a novel prodrug platform for combination therapy (RT-CT). (c) 2020 Elsevier B.V. All rights reserved.