High-Affinity Ratiometric Fluorescence Probe Based on 6-Amino-2,2'-Bipyridine Scaffold for Endogenous Zn²⁺ and Its...

Area of Science:

• Chemical Biology
• Biochemistry
• Analytical Chemistry

Background:

• Zinc is an essential trace element with incompletely understood biological roles.
• Endogenous labile Zn²⁺ plays a critical part in various cellular processes.
• Developing tools to study Zn²⁺ is crucial for biological research.

Purpose of the Study:

• To develop a novel ratiometric fluorescence probe for detecting endogenous labile Zn²⁺.
• To characterize the probe's performance under physiological conditions.
• To demonstrate the probe's utility in live-cell imaging.

Main Methods:

• Synthesis of a novel ratiometric fluorescence probe, 6-(4-methoxyphenyl)-4-(methylsulfanyl)-[2,2′-bipyridin]-6-amine (rBpyZ), based on the 6-amino-2,2′-bipyridine scaffold.
• Characterization of the probe's photophysical properties, including its response to Zn²⁺.
• Evaluation of the probe's performance, including dissociation constant, Stokes shift, and detection limit.
• Application of the probe in fluorescence imaging of Zn²⁺ in A549 human lung adenocarcinoma cells.

Main Results:

• The probe rBpyZ exhibits a ratiometric fluorescence response upon Zn²⁺ binding, with emission shifts at 438 nm and 465 nm.
• rBpyZ demonstrates high sensitivity with a nanomolar dissociation constant (Kd = 0.77 nM) and a low detection limit (0.10 nM).
• Fluorescence imaging reveals good cell membrane permeability and clear visualization of endogenous labile Zn²⁺ in A549 cells.

Conclusions:

• The ratiometric fluorescence probe rBpyZ is a sensitive and effective tool for detecting labile Zn²⁺.
• rBpyZ enables visualization of endogenous Zn²⁺ in living cells, aiding in understanding its biological roles.
• This probe holds significant potential for advancing research in biological systems involving zinc.