Fluorogenic Probe Using a Mislow-Evans Rearrangement for Real-Time Imaging of Hydrogen Peroxide

Area of Science:

• Biochemistry
• Chemical Biology
• Cell Biology

Background:

• Hydrogen peroxide (H₂ O₂ ) is a key signaling molecule in biological processes like wound healing and inflammation.
• Existing small-molecule probes for H₂ O₂ imaging are slow, requiring minutes for detection.
• Protein-based probes offer rapid H₂ O₂ imaging but have limitations.

Purpose of the Study:

• To develop a novel, fast-acting fluorogenic probe for selective detection of hydrogen peroxide.
• To enable real-time imaging of endogenous H₂ O₂ in biological systems.
• To overcome the kinetic limitations of existing small-molecule H₂ O₂ probes.

Main Methods:

• A new fluorogenic probe was designed to undergo a [2,3]-sigmatropic rearrangement (seleno-Mislow-Evans rearrangement) with H₂ O₂.
• The probe acts as a nucleophile, reacting rapidly with H₂ O₂ followed by acetal hydrolysis.
• Real-time imaging was performed in endothelial cells and a zebrafish wound healing model.

Main Results:

• The probe produces a green fluorescent signal within seconds of reacting with H₂ O₂.
• Real-time imaging of H₂ O₂ in endothelial cells was achieved in as little as 8 seconds.
• The probe successfully visualized H₂ O₂ dynamics during zebrafish wound healing.

Conclusions:

• A novel nucleophilic fluorogenic probe enables unprecedented real-time imaging of H₂ O₂.
• This probe overcomes the slow kinetics of previous small-molecule probes.
• The developed probe offers a promising platform for endogenous H₂ O₂ detection in various biological contexts.