ortho-Chlorination of phenoxy 1,2-dioxetane yields superior chemiluminescent probes forin vitroandin vivoimaging

Abstract

A recent methodology, developed by our group, has enabled a dramatic improvement in the emissive nature of the excited species, formed during the chemiexcitation of dioxetanes under physiological conditions. This approach has resulted in the discovery of distinct phenoxy-dioxetane luminophores that produce a chemiluminescence signal via a direct-mode of emission. Here, we show a significant pK effect of our new phenoxy-dioxetanes on their chemiexcitation and on their ability to serve as chemiluminescent turn-ON probes for biological applications. Using an appropriate phenoxy-dioxetane probe with a direct-mode of emission, we were able to image β-galactosidase activity, in cancer cells and in tumor-bearing mice. To the best of our knowledge, this is the first example to demonstrate in vitro and in vivo endogenous enzymatic chemiluminescence images obtained by a single-component phenoxy-dioxetane probe. We anticipate that our strategy, for the design and synthesis of such distinct luminophores, will assist in providing new effective turn-ON probes for non-invasive intravital chemiluminescence imaging techniques.

Chemiluminescent Carbapenem‐Based Molecular Probe for Detection of Carbapenemase Activity in Live Bacteria

“…[35][36][37][38][39][40][41][42][43] In addition, the intense light emitted from the probe can be used to effectively image transfected and native enzymatic activity in live cells. [30,44] Another important milestone was achieved with the developmento f chemiluminescent probesf or ultrasensitive detection of the two deadliest food-borne pathogenic bacteria, Salmonella and Listeria monocytogenes. [45] Our continued interest in the use of small molecular chemiluminescent probes to identify as pecific target has now motivated us to design and evaluate an ovel chemiluminescent probe for carbapenem.…”

Ultrasensitive Detection of Salmonella and Listeria monocytogenes by Small‐Molecule Chemiluminescence Probes

“…Presumptive colonies have to be confirmed after the initial isolation. [25][26][27][28][29][30][31][32][33][34] Ar emarkable enhancement of light emission was obtained by simply improving the emissive nature of the excited species,f ormed during the chemiexcitation of Schaapsdioxetanes. Positive results are available after 96-144 h(4-6 days), depending on the growth of the bacteria.…”

Ultrasensitive Detection of Salmonella and Listeria monocytogenes by Small‐Molecule Chemiluminescence Probes

“…Chemiluminogenic assays for enzymatic detection have been shown to be orders of magnitude more sensitive than equivalent fluorescence detection assays . Recently, our group has explored new approaches for amplifying chemiluminescence light intensity under physiological conditions . A remarkable enhancement of light emission was obtained by simply improving the emissive nature of the excited species, formed during the chemiexcitation of Schaap's dioxetanes .…”