Chemiluminescent probes for imaging H₂S in living animals

Abstract

Responsive 1,2-dioxetane chemiluminescent probes have been developed that display instantaneous, sensitive, and selective responses to H2S and are capable of imaging H2S in living mice.

In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation

“…22,23 Our strategy for designing these reaction-based chemiluminescent probes relies on tethering a para -nitrobenzyl moiety to a 1,2-dioxetane chemiluminescent scaffold via carbonate or ether linkage (Scheme 1). The nitrobenzene group is sensitive to nitroreductase enzymes and has been frequently used in prodrugs and hypoxia detection.…”

“…The nitrobenzene group is sensitive to nitroreductase enzymes and has been frequently used in prodrugs and hypoxia detection. The synthesis of HyCL-1 proceeds from the previously reported phenol 1 23 by dimethylaminopyridine-catalyzed coupling with the mixed N -hydroxysuccinimidyl carbonate 2 to form the enol ether precursor 3 (Scheme 2) . For HyCL-2 , the ether linkage of the precursor was prepared by a Mitsunobu reaction 31 between the phenol 1 and para -nitrobenzyl alcohol 4 to form the enol ether precursor 5 (Scheme 2).…”

“…22,23 Chemiluminescence results from the formation of an excited state product during an exothermic chemical reaction 24 and is emerging as a useful preclinical in vivo imaging modality. 25 Triggered chemiluminescence emission of spiroadamantane 1,2-dioxetanes has been extensively used for clinical assays 26,27 and analyte sensing 28 and has been recently demonstrated as an effective in vivo imaging modality for β -galactosidase 22 and H 2 S. 23 The high-energy 4-membered dioxetane ring can be sterically stabilized by synthetically appending spiroadamantane, 26,28 fenchyl, 29 or other frameworks, allowing for purification, synthetic manipulation, and long term storage. These systems can be designed such that a chosen chemical trigger will initiate an electron transfer cascade that leads to dioxetane ring cleavage.…”

Solvent viscosity influence on the chemiexcitation efficiency of inter and intramolecular chemiluminescence systems

“…11,12 However, more recently it has been shown that the quantum yields obtained in the catalyzed decomposition of diphenoyl peroxide and 1,2-dioxetanones are much lower than that initially reported, 13 therefore these model CIEEL systems proved to be inefficient CL transformations. 18,19 The decomposition mechanism for these 1,2-dioxetane derivatives, which have found widespread utilization, most prominently as a detection system in immunoassays, [20][21][22][23][24] has been formulated as the intramolecular version of the CIEEL mechanism; 1, [16][17][18][19] however only quite recently, direct experimental evidence on the occurrence of an initial intramolecular electron transfer from a phenolate unit to the 1,2dioxetane ring has been reported. 18,19 The decomposition mechanism for these 1,2-dioxetane derivatives, which have found widespread utilization, most prominently as a detection system in immunoassays, [20][21][22][23][24] has been formulated as the intramolecular version of the CIEEL mechanism; 1, [16][17][18][19] however only quite recently, direct experimental evidence on the occurrence of an initial intramolecular electron transfer from a phenolate unit to the 1,2dioxetane ring has been reported.…”

Direct Real‐Time Monitoring of Prodrug Activation by Chemiluminescence

“…[4][5][6] Subsequently,n umerous examples of theranostic prodrugs,p redominantly based on fluorescence,h ave reported. [17][18][19][20][21][22] We have recently developed an ew class of chemiluminescent probes with remarkable light-emission efficiency under physiological conditions. [15,16] Monitoring of drug release through analysis of ac hemiluminescence modality offers attractive advantages over fluorescence,m ainly due to the higher signal-to-noise ratio and the fact that an external light source is unnecessary with chemiluminescent agents.…”