A turn-on fluorescent iron complex and its cellular uptake.

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 f...

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Main Authors: Chartres, J, Busby, M, Riley, M, Davis, J, Bernhardt, P
Format: Journal article
Language:English
Published: 2011
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author Chartres, J
Busby, M
Riley, M
Davis, J
Bernhardt, P
author_facet Chartres, J
Busby, M
Riley, M
Davis, J
Bernhardt, P
author_sort Chartres, J
collection OXFORD
description 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.
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spelling oxford-uuid:3ba70569-646d-451c-ab39-edcc10684ed72022-03-26T14:08:55ZA turn-on fluorescent iron complex and its cellular uptake.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3ba70569-646d-451c-ab39-edcc10684ed7EnglishSymplectic Elements at Oxford2011Chartres, JBusby, MRiley, MDavis, JBernhardt, PIn 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.
spellingShingle Chartres, J
Busby, M
Riley, M
Davis, J
Bernhardt, P
A turn-on fluorescent iron complex and its cellular uptake.
title A turn-on fluorescent iron complex and its cellular uptake.
title_full A turn-on fluorescent iron complex and its cellular uptake.
title_fullStr A turn-on fluorescent iron complex and its cellular uptake.
title_full_unstemmed A turn-on fluorescent iron complex and its cellular uptake.
title_short A turn-on fluorescent iron complex and its cellular uptake.
title_sort turn on fluorescent iron complex and its cellular uptake
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