A turn-on fluorescent iron complex and its cellular uptake

Inorg Chem. 2011 Sep 19;50(18):9178-83. doi: 10.1021/ic201495r. Epub 2011 Aug 3.

Abstract

In the treatment of chronic iron overload disorders, ligands capable of complexing so-called "labile" (nonprotein bound) Fe are required to enter iron-loaded cells, sequester excess Fe, and then exit the cell (and the body) as an intact Fe complex. Despite the emergence of several ligand families that show high activity in mobilizing intracellular Fe, the mechanism and the locations of these subcellular labile Fe pools are still poorly understood. Our previous studies have unearthed a class of heterocyclic hydrazine-based chelators (e.g., benzoyl picolinoyl hydrazine, H(2)BPH) that show excellent activity at mobilizing Fe from Fe-loaded cells. Herein, we have grafted a fluorescent tag (rhodamine B) onto H(2)BPH to generate a ligand (L(1)) that is nonfluorescent in its uncomplexed form but becomes strongly fluorescent in complex with Fe(III). The free ligand and its 1:2 Fe complex [Fe(III)(L(1))(2)](3+) have both been fully characterized spectroscopically and with X-ray crystallography. Confocal fluorescent microscopy of HeLa cells incubated with [Fe(III)(L(1))(2)](3+) shows that the complex rapidly enters HeLa cells and localizes within endosomes/lysosomes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane Permeability
  • Crystallography, X-Ray
  • Endosomes / metabolism
  • Fluorescent Dyes / chemistry*
  • Fluorescent Dyes / metabolism
  • HeLa Cells
  • Humans
  • Hydrazines / chemistry*
  • Hydrazines / metabolism
  • Iron Chelating Agents / chemistry*
  • Iron Chelating Agents / metabolism
  • Ligands
  • Lysosomes / metabolism
  • Models, Molecular
  • Rhodamines / chemistry*
  • Rhodamines / metabolism

Substances

  • Fluorescent Dyes
  • Hydrazines
  • Iron Chelating Agents
  • Ligands
  • Rhodamines
  • rhodamine B