Recent Advances and Challenges in Luminescent Imaging: Bright Outlook for Chemiluminescence of Dioxetanes in Water

Abstract

Chemiluminescence is gradually being recognized as a powerful tool for sensing and imaging. Most known light-emitting compounds undergo chemiexcitation through spontaneous decomposition of cyclic peroxide moieties. A ground-breaking milestone in the chemistry of such compounds was achieved 30 years ago with the discovery of triggerable dioxetanes by Schaap’s group. Our group has recently developed a distinct methodology to significantly improve the light emission efficiency of such phenoxy-dioxetane luminophores under physiological conditions. Introduction of an electron-withdrawing substituent at the ortho position of the phenoxy-dioxetane resulted in an approximately 3000-fold increase of the chemiluminescence quantum yield in aqueous media. Furthermore, we discovered that the emission wavelength and the kinetics of the chemiexcitation could be determined by the electronic nature of the substituent incorporated on the dioxetane luminophore. This recent development has provided scientists with new powerful chemiluminophores that can act as single-component probes for in vivo and in vitro detection and imaging of various analytes and enzymes. This outlook describes the recent progress toward applications of synthetic chemiluminescence luminophores suitable for sensing and imaging in aqueous environments.

A programmable chemical switch based on triggerable Michael acceptors

“…35 The ability to incorporate various releasable functionalities with this approach has great potential in the design of cleavable traceless linkers for antibody drug conjugates, neuromodulator delivery strategies, triggered catalysis and bioimaging. [35][36][37][38][39][40] Thiol/amine associated reactions that concurrently capture the key advantageous features of trigger-torelease and trigger-to-reverse processes are not well-studied. Combining these features offers the opportunity to bring about new functions in areas that are independently represented by both these strategies.…”

Smart Chemiluminescence Probes and Dual-Amplification of Signal for Detection of Amyloid Beta Species in Alzheimer’s Disease Model

“…Recently, great progression has been achieved for developing new chemiluminescence probes and their application. Most of chemiluminescence probes are dependent on ROS reactions and most of the probes have been used to detect ROS in solutions, cells, and in vivo [11][12][13][14][15][16][17][18] . Surprisingly, we found that ADLumin-1 was much more sensitive to O2 (27-fold change), and the responses were very quick (within seconds).…”

“…chemiluminescence, including dioxetane 12,[59][60][61] , luminol 62 , imidazo[1,2-a]pyrazin-3(7H)-one 63 , oxalate [15][16] , lucigenin 62 , 9,10-dimethyl-anthracene 18 , and 10-methyl-9-(phenoxycarbonyl) acridinium 64 . All of these scaffolds have short emission wavelengths (< 500 nm) and are not ideal for in vivo imaging, particularly for deep locations such as brains.…”

“…However, compared to fluorescence imaging, chemiluminescence imaging is being applied far less in biological studies, primarily due to its low sensitivity and irreversibility of the probes. Another drawback of chemiluminescence is the need of a chemical reaction to produce the emission light [11][12][13][14][15][16][17][18] . In most cases the reaction is dependent on stimulation from reactive oxygen (nitrogen) species (ROS).…”

Activatable molecular agents for cancer theranostics

“…Chemiluminescence, a phenomenon of light radiation accompanied by chemical reactions, has been increasingly recognized as a powerful tool for disease diagnosis and biological analysis. [100][101][102] Compared to traditional uorescence imaging, CLI has the advantages of high sensitivity, low phototoxicity, and high signal-to-noise ratio due to the removal of the external excitation source. Peroxalate derivatives working as lightemitting functionalities have been widely explored for chemiluminescence.…”