Cell-trappable quinoline-derivatized fluoresceins for selective and reversible biological Zn(II) detection

Inorg Chem. 2010 Oct 18;49(20):9535-45. doi: 10.1021/ic1012507.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Transport
  • Cell Survival
  • Drug Design
  • Fluorescein / chemical synthesis
  • Fluorescein / chemistry*
  • Fluorescein / metabolism*
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism*
  • HeLa Cells
  • Humans
  • Molecular Imaging
  • Quinolines / chemistry*
  • Spectrum Analysis
  • Substrate Specificity
  • Zinc / analysis*
  • Zinc / chemistry

Substances

  • Fluorescent Dyes
  • Quinolines
  • quinoline
  • Zinc
  • Fluorescein