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Updated: Aug 6, 2026

A Novel Technique for Generating and Observing Chemiluminescence in a Biological Setting
Published on: March 9, 2017
Oxygen-Driven [2 + 2] Photocycloaddition for In Vivo Chemiluminescence
Yutao Zhang1, Juan Li1, Ruihua Pu2
1Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, State Key Laboratory of Bioreactor Engineering, State Key Laboratory of Green Chemical Engineering and Industrial Catalysis, Center of Photosensitive Chemicals Engineering, East China University of Science and Technology, Shanghai 200237, China.
Abstract:
Chemiluminescence, the direct conversion of chemical energy into light, offers an exceptionally sensitive platform for molecular imaging. However, its in vivo application is practically hindered by the lack of a biocompatible strategy for generating highly strained cyclic peroxides─the energetic cores of light emission. Herein, we present an in vivo [2 + 2] intermolecular photocycloaddition that harnesses molecular oxygen as a direct reactant to in situ generate high-energy 1,2-dioxetanes within living systems. Rationally designed electron donor-substituted olefins provide oxygen-specific addition sites and exhibit prolonged intermediate lifetimes (25-fold) via bioconfined catalysis, as demonstrated by femtosecond transient absorption spectroscopy. Our de novo designed chemiluminophores, termed as Rubines, emit bright red in vivo luminescence, greatly surpassing conventional luminescent substrates. Rubines enable direct visualization in Biomphalaria snails and living mice, and particularly function as nonradioactive "chemiluminescent nuclides" probes to monitor progressive degradation and self-repair of the blood-brain barrier (BBB) integrity in real time. This work establishes a next-generation, high-brightness in vivo chemiluminescence platform suited for ultrasensitive, noninvasive molecular imaging and diagnostics.
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