Reaction-Based "Off-On" Fluorescent Probe Enabling Detection of Endogenous Labile Fe(2+) and Imaging of Zn(2+)-induced Fe(2+) Flux in Living Cells and Elevated Fe(2+) in Ischemic Stroke

• Published in: Bioconjugate chemistry 2016-02, Vol.27 (2), p.302-308
• Main Authors: Xuan, Weimin, Pan, Rong, Wei, Yongyi, Cao, Yanting, Li, Huanqiu, Liang, Fu-Sen, Liu, Ke-Jian, Wang, Wei
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; Brain - pathology; Fluorescence; Fluorescent Dyes - chemistry; Fluorescent Dyes - metabolism; Iron - analysis; Iron - metabolism; Male; Naphthalimides - chemistry; Naphthalimides - metabolism; Optical Imaging - methods; Rats; Rats, Sprague-Dawley; Stroke - metabolism; Stroke - pathology; Zinc - analysis; Zinc - metabolism
• ISSN: 1520-4812
• DOI: 10.1021/acs.bioconjchem.5b00259

Fluorogenic sensors capable of spatiotemporally detecting Fe(2+) in biological systems are highly valuable in the study of iron biology. Toward this end, a new "off-on" Fe(2+)-selective fluorescent probe has been developed by incorporating an Fe(2+)-induced N-O cleavage of acylated hydroxylamine moiety into the naphthalimide fluorophore. The probe displays facile response (within 15 min) and good selectivity toward Fe(2+) with >27-fold enhancement of fluorescence intensity and high sensitivity of as low as 0.5 μM with a noticeable 3-fold fluorescence enhancement. These features of the probe have been transformed into in the convenient detection of endogenous, basal level of labile Fe(2+) pools in living cells. Furthermore, we have demonstrated the capacity of the probe for the studies of important Fe(2+) related biological functions. It can respond to the Zn(2+)-induced Fe(2+) flux, an important event observed in stroke, and facilely detect the elevated level of Fe(2+) in the brain tissue of a rat undergoing ischemic stroke at the ischemic site.