Molecular Imaging of Labile Iron(II) Pools in Living Cells with a Turn-On Fluorescent Probe

Iron is an essential
metal for living organisms, but misregulation
of its homeostasis at the cellular level can trigger detrimental oxidative
and/or nitrosative stress and damage events. Motivated to help study
the physiological and pathological consequences of biological iron
regulation, we now report a reaction-based strategy for monitoring
labile Fe2+ pools in aqueous solution and living cells.
Iron Probe 1 (IP1) exploits a bioinspired, iron-mediated oxidative
C–O bond cleavage reaction to achieve a selective turn-on response
to Fe2+ over a range of cellular metal ions in their bioavailable
forms. We show that this first-generation chemical tool for fluorescence
Fe2+ detection can visualize changes in exchangeable iron
stores in living cells upon iron supplementation or depletion, including
labile iron pools at endogenous, basal levels. Moreover, IP1 can be
used to identify reversible expansion of labile iron pools by stimulation
with vitamin C or the iron regulatory hormone hepcidin, providing
a starting point for further investigations of iron signaling and
stress events in living systems as well as future probe development.