Nuclear targeting terpyridine iron(II) complexes for cellular imaging and remarkable photocytotoxicity

Abstract

Iron(II) complexes [Fe(L)2]2+ as perchlorate (1–3) and chloride (1a-3a) salts, where L is 4′-phenyl-2,2′:6′,2″-terpyridine (phtpy in 1, 1a), 4′-(9-anthracenyl)-2,2′:6′,2″-terpyridine (antpy in 2, 2a) and 4′-(1-pyrenyl)-2,2′:6′,2″-terpyridine (pytpy in 3, 3a), were prepared and their photocytotoxicity studied. The diamagnetic complexes 1–3 having an FeN6 core showed an Fe(III)–Fe(II) redox couple near 1.0 V vs. saturated calomel electrode in MeCN-0.1 M tetrabutylammonium perchlorate. Complexes 2 and 3, in addition, displayed a quasi-reversible ligand-based redox process near 0.0 V. The redox and spectral properties are rationalized from the theoretical studies. The complexes bind to DNA in a partial intercalative mode. The pytpy complex efficiently photo-cleaves DNA in green light via superoxide and hydroxyl radical formation. The antpy and pytpy complexes exhibited a remarkable photocytotoxic effect in HeLa cancer cells (IC50, ~ 9 μM) in visible light (400–700 nm), while remaining essentially nontoxic in dark (IC50, ~ 90 μM). Formation of reactive oxygen species (ROS) inside the HeLa cells was evidenced from the fluorescence enhancement of dichlorofluorescein upon treatment with the pytpy complex followed by photo-exposure. The antpy and pytpy complexes were used for cellular imaging. Confocal imaging and dual staining study using propidium iodide (PI) showed nuclear localization of the complexes.