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A Bright Spiropyran-Based Zinc Sensor for Live-Cell Imaging.

Annika M Pick1, Kristin Weber1, Marisa F Jakobs1

  • 1Department of Chemistry, RPTU Kaiserslautern-Landau, Erwin-Schroedinger-Str. 54, Kaiserslautern 67663, Germany.

ACS Omega
|August 11, 2025
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Summary

A new zinc sensor, SpiroZin2-COOH, offers enhanced brightness and a significant red-shift for improved imaging of labile zinc pools in cells. This tool aids in understanding neurodegenerative diseases linked to zinc dysregulation.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Neuroscience
  • Chemical Biology

Background:

  • Labile bound zinc ions are crucial for cellular signal transduction, particularly in the central nervous system.
  • Dysregulation of zinc homeostasis is implicated in various neurodegenerative diseases.
  • Zinc fluorescence sensors are vital tools for investigating zinc's molecular mechanisms.

Purpose of the Study:

  • To introduce and characterize SpiroZin2-COOH, a novel spiropyran-based fluorescent sensor for zinc.
  • To evaluate its performance in detecting intracellular zinc pools in live cells.

Main Methods:

  • SpiroZin2-COOH was synthesized in a 5-step process.
  • Zinc-sensing properties were assessed using cuvette studies and live-cell imaging.
  • Lysotracker costaining was employed to determine sensor localization.

Main Results:

  • SpiroZin2-COOH exhibits a ~7-fold higher quantum yield and ~6-fold greater brightness compared to its parent sensor.
  • A 30 nm red-shift in emission and a turn-on ratio of 30 were observed in cuvette studies.
  • Live-cell studies showed a turn-on ratio of 14.6, the highest in the SpiroZin family, with lysosomal localization.

Conclusions:

  • SpiroZin2-COOH is a superior fluorescent sensor for imaging intracellular zinc pools.
  • Its enhanced properties facilitate a deeper understanding of zinc's role in cellular processes and neurodegeneration.