Chemiluminescent Probes for Activity‐Based Sensing of Formaldehyde Released from Folate Degradation in Living Mice

Abstract

Formaldehyde (FA) is a common environmental toxin that is also produced naturally in the body through a wide range of metabolic and epigenetic processes, motivating the development of new technologies to monitor this reactive carbonyl species (RCS) in living systems. Herein, we report a pair of first‐generation chemiluminescent probes for selective formaldehyde detection. Caging phenoxy‐dioxetane scaffolds bearing different electron‐withdrawing groups with a general 2‐aza‐Cope reactive formaldehyde trigger provides chemiluminescent formaldehyde probes 540 and 700 (CFAP540 and CFAP700) for visible and near‐IR detection of FA in living cells and mice, respectively. In particular, CFAP700 is capable of visualizing FA release derived from endogenous folate metabolism, providing a starting point for the use of CFAPs and related chemical tools to probe FA physiology and pathology, as well as for the development of a broader palette of chemiluminescent activity‐based sensing (ABS) probes that can be employed from in vitro biochemical to cell to animal models.

Development of organic semiconducting materials for deep-tissue optical imaging, phototherapy and photoactivation

“…Chemiluminescent small molecular probes using a 2-aza-Cope reactive trigger as the PG were developed for activatable detection of formaldehyde (FA) in living animals. 105 Specific reaction between FA and the 2-aza-Cope reactive trigger within probes resulted in an immolation of the two-carbon linker, generating free phenoxydioxetane that subsequently decomposed to produce chemiexcitation. Two different EWGs were conjugated to the dioxetane scaffolds to allow the visible (CFAP540 probe) and NIR (CFAP700 probe) emission, respectively (Fig.…”

Activity‐Based Fluorescent Probes for Sensing and Imaging of Reactive Carbonyl Species (RCSs)

“…In 2018, Bruemmer et al . from Prof. Chang's group of UC Berkeley reported the first generation chemiluminescent probe ( CFAP 540 and CFAP 700 ) for FA sensing as one of the most significant developments (Figure 5E) [71] . It was applied for FA imaging in HEK293T cell line and FVB‐luc+ mice models.…”

ALP-Activated Chemiluminescence PDT Nano-Platform for Liver Cancer-Specific Theranostics

“…Profiting from the specific activity, a CL substrate of ALP, 3-[(2-spiroadamatane)-4-methoxy-4-(3-phosphoryloxy]-phenyl-1,2-dioxetane]­dioxetane (AMPPD), − is successfully presented. Utilizing AMPPD, we constructed CL-excited PDT nanoparticles MSN@H 6 L@β-CD@AMPPD for high-specific diagnosis and treatment of liver cancer.…”