title: A nonemissive iridium(III) complex that specifically lights-up the nuclei of living cells.
abstract: A nonemissive cyclometalated iridium(III) solvent complex, without conjugation with a cell-penetrating molecular transporter, [Ir(ppy)(2)(DMSO)(2)](+)PF(6)(-) (LIr1), has been developed as a first reaction-based fluorescence-turn-on agent for the nuclei of living cells. LIr1 can rapidly and selectively light-up the nuclei of living cells over fixed cells, giving rise to a significant luminescence enhancement (200-fold), and shows very low cytotoxicity at the imaging concentration (incubation time <10 min, LIr1 concentration 10 μM). More importantly, in contrast to the reported nuclear stains that are based on luminescence enhancement through interaction with nucleic acids, complex LIr1 as a nuclear stain has a reaction-based mode of action, which relies on its rapid reaction with histidine/histidine-containing proteins. Cellular uptake of LIr1 has been investigated in detail under different conditions, such as at various temperatures, with hypertonic treatment, and in the presence of metabolic and endocytic inhibitors. The results have indicated that LIr1 permeates the outer and nuclear membranes of living cells through an energy-dependent entry pathway within a few minutes. As determined by an inductively coupled plasma atomic emission spectroscopy (ICP-AEC), LIr1 is accumulated in the nuclei of living cells and converted into an intensely emissive adduct. Such novel reaction-based nuclear staining for visualizing exclusively the nuclei of living cells with a significant luminescence enhancement may extend the arsenal of currently available fluorescent stains for specific staining of cellular compartments.
authors.affiliation: Joint Center of Biomedical Imaging (BMI) of Department of Chemistry & Institute of Biomedical Science & Cancer Hospital, Laboratory of Advanced Materials, Fudan University, Shanghai 200433, P. R. China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.forename: Mengxiao
authors.initials: M
authors.lastname: Yu
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.forename: Yongquan
authors.initials: Y
authors.lastname: Wu
authors.forename: Chunhui
authors.initials: C
authors.lastname: Huang
authors.forename: Fuyou
authors.initials: F
authors.lastname: Li
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000737:chemistry / Q000648:ultrastructure*; D002470:Cell Survival; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry* / Q000378:metabolism; D049449:Luminescence; D011506:Proteins / Q000302:isolation & purification
chemical_list: D000596:Amino Acids; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D011506:Proteins; D007495:Iridium