Bright fluorescent chemosensor platforms for imaging endogenous pools of neuronal zinc.

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作者：

CJ Chang，EM Nolan，J Jaworski，SC Burdette，M Sheng，SJ Lippard

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摘要：

A series of new fluorescent Zinpyr (ZP) chemosensors based on the fluorescein platform have been prepared and evaluated for imaging neuronal Zn. A systematic synthetic survey of electronegative substitution patterns on a homologous ZP scaffold provides a basis for tuning the fluorescence responses of "off-on" photoinduced electron transfer (PET) probes by controlling fluorophore p values and attendant proton-induced interfering fluorescence of the metal-free (apo) probes at physiological pH. We further establish the value of these improved optical tools for interrogating the metalloneurochemistry of Zn; the novel ZP3 fluorophore images endogenous stores of Zn in live hippocampal neurons and slices, including the first fluorescence detection of Zn in isolated dentate gyrus cultures. Our findings reveal that careful control of fluorophore p can minimize proton-induced fluorescence of the apo probes and that electronegative substitution offers a general strategy for tuning PET chemosensors for cellular studies. In addition to providing improved optical tools for Zn in the neurosciences, these results afford a rational starting point for creating superior fluorescent probes for biological applications.

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关键词：

Hippocampus Neurons Zinc Fluorescent Dyes Spectrometry, Fluorescence Biosensing Techniques Hydrogen-Ion Concentration Thermodynamics