A new family of luminescent iridium complexes: synthesis, optical, and cytotoxic studies

Abstract

By using N,N-dibutyl-2,2′-bipyridine-4,4′-dicarboxamide as a diimine (dbbpy) and distinctive cyclometalated groups, this work reports a new family of cationic phosphorescent Ir(III) cyclometalated [Ir(C^N)₂(N^N)]X compounds [C^N = difluorophenylpyridine (dfppy) a, 2,6-difluoro-3-(pyridin-2-yl)benzaldehyde (CHO-dfppy) b, and 2,6-difluoro-3-pyridin-2-yl-benzoic acid (COOH-dfppy) c; X = Cl⁻2a,b,c-Cl; X = PF₆⁻2b,c-PF₆]. For comparative purposes, the related complex [Ir(dfppy)₂(H₂dcbpy)]⁺ (3a-PF₆) incorporating 3,3′-dicarboxy-2,2′-bipyridine as an auxiliary ligand (N^N = H₂dcbpy) is also presented. All complexes have been fully characterized and their photophysical properties were investigated in detail. The theoretically calculated results obtained by density functional theory (DFT) and time-dependent density functional theory (TD-DFT) studies indicate that luminescence is derived from mixed ³ML′CT (Ir → N^N)/³LL′CT (C^N → N^N) excited states with the predominant metal-to-diimine charge transfer character. Their antineoplastic activity against tumour cell lines A549 (lung carcinoma) and HeLa (cervix carcinoma), as well as the nontumor BEAS-2B (bronchial epithelium) cell line was assessed and fluorescence microscopy studies were performed for their cellular localization. Among them, 2a-Cl exhibited the most potent anticancer activity, being higher than cisplatin. However, 2b-Cl and 2c-Cl,-PF₆ were the least toxic, while 2b-PF₆ and 3a-PF₆ exhibited only moderate activity. Confocal microscopy studies for 2a-Cl suggest that complexes localize preferentially in the lysosomes and to a lesser extent in the cytoplasm, but ultimately causing damage to the mitochondria. Finally, the potential photodynamic behaviour of scarcely toxic complexes 2b-Cl, 2b-PF₆, 2c-Cl and 3a-PF₆ was also studied.