Targeting the Lysosome: Fluorescent Iron(III) Chelators To Selectively Monitor Endosomal/Lysosomal Labile Iron Pools

Abstract

Iron-sensitive fluorescent chemosensors in combination with digital fluorescence spectroscopy have led to the identification of a distinct subcellular compartmentation of intracellular redox-active "labile" iron. To investigate the distribution of labile iron, our research has been focused on the development of fluorescent iron sensors targeting the endosomal/lysosomal system. Following the recent introduction of a series of 3-hydroxypyridin-4-one (HPO) based fluorescent probes we present here two novel HPO sensors capable of accumulating and monitoring iron exclusively in endosomal/lysosomal compartments. Flow cytometric and confocal microscopy studies in murine macrophages revealed endosomal/lysosomal sequestration of the probes and high responsiveness toward alterations of vesicular labile iron concentrations. This allowed assessment of cellular iron status with high sensitivity in response to the clinically applied medications desferrioxamine, deferiprone, and deferasirox. The probes represent a powerful class of sensors for quantitative iron detection and clinical real-time monitoring of subcellular labile iron levels in health and disease.

A New Ratiometric Fluorescent Probe for Detection of Fe2+ with High Sensitivity and Its Intracellular Imaging Applications

“…The solid was purified on silica gel chromatography eluted with ethyl methylene chloride/methanol/ethyl acetate (2:2:1, v/v). 1 …”

“…As the most abundant transition metal in cellular systems, [1] iron plays an indispensable role in many biological processes because it exists widely in the structures of numerous enzymes, proteins, [2,3] and transcriptional events. [4][5][6] Either its deficiency or excess can disturb cellular homeostasis and metabolism.…”

“…The damages to cells may further result in many kinds of diseases, such as hepatitis, cancer, neurodegeneration Alzheimers disease, and Parkinsons disease. [1,7,8] In living organisms, iron readily engages in one-electron oxidation-reduction reactions between its ferric (Fe 3 + ) and ferrous (Fe 2 + ) states. [9] In particular, ferrous iron (Fe 2 + ) may facilitate the generation of highly reactive oxygen species, especially the hydroxyl radical.…”

Atom-Economic Synthesis of 4-Pyrones from Diynones and Water

“…4-Pyrones are heterocycles with multiple biological activities [48][49][50], which are widely found in biologically active natural products and functional chemicals [51][52][53][54][55][56][57][58][59]. Particularly, phenoxans, funicones and rapicones possess potent anti-HIV actitivity ( Figure 1) [60][61][62].…”

Nickel(II) and Cobalt(II) 3‐Hydroxy‐4‐pyridinone Complexes: Synthesis, Characterization and Speciation Studies in Aqueous Solution

“…Both classes of ligands and respective complexes have been extensively studied due to their broad field of application namely in therapeutics and diagnosis, solvent extraction and chemical analysis. [1][2][3][4][5][6] 3-Hydroxy-4-pyridinones are heterocyclic compounds that include a nitrogen atom in the ring and hydroxylic and ketonic oxygen atoms in positions 3 and 4, respectively (Figure 1) which confer the strong chelating properties exhibited by the ligands towards M II /M III metal ions. The ligands are synthetically versatile allowing the introduction of different substituents in several positions of the heterocyclic ring without producing a significant change in complexation ability and acid-base properties.…”