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A Novel Technique for Generating and Observing Chemiluminescence in a Biological Setting
08:57

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Published on: March 9, 2017

Burst-Mode Near-Infrared Chemiluminescent Probes for In Vivo Imaging.

Jingsheng Huang1, Youshi Lin1, Donghao Li1

  • 1School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore 637457, Singapore.

Journal of the American Chemical Society
|June 9, 2026
PubMed
Summary

Researchers developed new near-infrared chemiluminophores with high brightness for imaging. These burst-mode compounds offer enhanced signal intensity and stability, enabling sensitive molecular imaging in living systems.

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Area of Science:

  • Organic Chemistry
  • Biomedical Imaging
  • Chemical Biology

Background:

  • Chemiluminescence (CL) is attractive for diagnostics due to its excitation-free optical readout and low background.
  • Existing 1,2-dioxetane-based chemiluminophores often have low instantaneous intensity, limiting their use in imaging applications.

Purpose of the Study:

  • To develop novel burst-mode near-infrared (NIR) chemiluminophores with high instantaneous brightness.
  • To create activatable probes for sensitive molecular imaging in live systems.

Main Methods:

  • Substituent-driven electronic tuning of 1,2-dioxetane chemiluminophores.
  • Synthesis and characterization of dicyanomethylene-phenoxy-dioxetane (DPD) analogues.
  • Construction of an activatable probe (DPD4g) for β-galactosidase (β-gal) detection.

Main Results:

  • A trifluoroethyloxy-modified analogue (DPD4) showed a 3-fold lower activation energy barrier and a 15.0-fold increase in chemiexcitation rate compared to DPD1.
  • DPD4 exhibited a ~79,978-fold intensity enhancement with a short CL half-life (10 s) but high chemical stability (6.8 days).
  • The DPD4g probe selectively detected β-gal in live cells and distinguished β-gal-overexpressing tumors in vivo with a 15.2-fold signal enhancement.

Conclusions:

  • Trifluoroethyl substitution is an effective strategy for creating burst-mode chemiluminophores with high brightness.
  • The developed probes enable sensitive and selective chemiluminescence molecular imaging in living systems.
  • This approach holds promise for advancing diagnostic and imaging technologies.