title: Cell-trappable quinoline-derivatized fluoresceins for selective and reversible biological Zn(II) detection.
abstract: The synthesis and spectroscopic characterization of two new, cell-trappable fluorescent probes for Zn(II) are presented. These probes, 2-(4,5-bis(((6-(2-ethoxy-2-oxoethoxy)quinolin-8-yl)amino)methyl)-6-hydroxy-3-oxo-3H-8 xanthen-9-yl)benzoic acid (QZ2E) and 2,2'-((8,8'-(((9-(2-carboxyphenyl)-6-hydroxy-3-oxo-3H-xanthene-4,5-diyl)bis(methylene))bis(azanediyl))bis(quinoline-8,6-diyl))bis(oxy))diacetic acid (QZ2A), are poorly emissive in the off-state but exhibit dramatic increases in fluorescence upon Zn(II) binding (120 ± 10-fold for QZ2E, 30 ± 7-fold for QZ2A). This binding is selective for Zn(II) over other biologically relevant metal cations, toxic heavy metals, and most first-row transition metals and is of appropriate affinity (K(d1)(QZ2E) = 150 ± 100 μM, K(d2)(QZ2E) = 3.5 ± 0.1 mM, K(d1)(QZ2A) = 220 ± 30 μM, K(d2)(QZ2A) = 160 ± 80 μM, K(d3)(QZ2A) = 9 ± 6 μM) to reversibly bind Zn(II) at physiological levels. In live cells, QZ2E localizes to the Gogli apparatus where it can detect Zn(II). It is cell-membrane-permeable until cleavage of its ester groups by intracellular esterases produces QZ2A, a negatively charged acid form that cannot cross the cell membrane.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Lindsey E
authors.initials: LE
authors.lastname: McQuade
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D001692:Biological Transport; D002470:Cell Survival; D015195:Drug Design; D019793:Fluorescein / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D057054:Molecular Imaging; D011804:Quinolines / Q000737:chemistry*; D013057:Spectrum Analysis; D013379:Substrate Specificity; D015032:Zinc / Q000032:analysis* / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D011804:Quinolines; C037219:quinoline; D015032:Zinc; D019793:Fluorescein