A fluorogenic probe based on chelation-hydrolysis-enhancement mechanism for visualizing Zn²⁺ in Parkinson's disease models

Developing efficient methods for the real-time detection of Zn²⁺ levels in biological systems is highly relevant to improving our understanding of the role of Zn²⁺ in the progression of Parkinson's disease (PD). In this work, a novel Schiff base based Zn²⁺ fluorescent probe (ZP) was designed, synthesized and systematically investigated. A significant turn-on effect on ZP upon the addition of Zn²⁺ was observed, accompanied by a blue-shift of the fluorescence spectra. ZP is sensitive to Zn²⁺ and has excellent selectivity against various biologically relevant cations, anions and amino acids. The sensing mechanism of ZP was studied by ¹H NMR, MS, single crystal X-ray diffraction and theoretical calculations. The results showed that the response of ZP to Zn²⁺ was based on the chelation-hydrolysis-enhancement process. Upon bonding, Zn²⁺ hydrolyzes the Schiff base to an aldehyde precursor, the resulting aldehyde further coordinates to Zn²⁺ to form a more stable heterobimetallic complex leading to the emission enhancement and blue-shift. ZP was applied to imaging exogenous/endogenous Zn²⁺ in live HeLa cells. Furthermore, we successfully measured the Zn²⁺ levels using in vitro PD models, which provided a visualization method to better understand the relationship between Zn²⁺ levels and PD development.