Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications

Inorg Chem. 2006 Nov 27;45(24):9748-57. doi: 10.1021/ic061137e.

Abstract

The syntheses and photophysical characterization of ZP9, 2-{2-chloro-6-hydroxy-3-oxo-5-[(2-{[pyridin-2-ylmethyl-(1H-pyrrol-2-ylmethyl)amino]methyl}phenylamino)methyl]-3H-xanthen-9-yl}benzoic acid, and ZP10, 2-{2-chloro-6-hydroxy-5-[(2-{[(1-methyl-1H-pyrrol-2-ylmethyl)pyridin-2-ylmethylamino]methyl}phenylamino)methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid, two asymmetrically derivatized fluorescein-based dyes, are described. These sensors each contain an aniline-based ligand moiety functionalized with a pyridyl-amine-pyrrole group and have dissociation constants for Zn(II) in the sub-micromolar (ZP9) and low-micromolar (ZP10) range, which we define as "midrange". They give approximately 12- (ZP9) and approximately 7-fold (ZP10) fluorescence turn-on immediately following Zn(II) addition at neutral pH and exhibit improved selectivity for Zn(II) compared to the di-(2-picolyl)amine-based Zinpyr (ZP) sensors. Confocal microscopy studies indicate that such asymmetrical fluorescein-based probes are cell permeable and Zn(II) responsive in vivo.

Publication types

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

MeSH terms

  • Aniline Compounds / analysis
  • Aniline Compounds / chemistry
  • Animals
  • Biosensing Techniques / methods*
  • Cells, Cultured
  • Chemistry, Inorganic / methods*
  • Female
  • Fluorescence
  • Hippocampus / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • In Vitro Techniques
  • Kinetics
  • Molecular Biology / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Fluorescence
  • Thermodynamics
  • Zinc / analysis
  • Zinc / metabolism*

Substances

  • Aniline Compounds
  • Zinc
  • aniline