A highly selective two-photon fluorogenic probe for formaldehyde and its bioimaging application in cells and zebrafish

Fluorescent probes for imaging formaldehyde in biological systems

“…These first-generation probes are highly selective for FA and exhibit good ratiometric responses, but are limited by relatively slow reaction kinetics, taking hours to display a statistically significant turn-on signal to millimolar levels of exogenously added FA and thus limiting their applicability to image endogenous FA pathways. The first examples of two-photon FA probes FATP-1 [53] and TPNF [54] were applied to image FA in tissue and zebrafish, respectively. Both FATP-1 and TPNF report a 3 h incubation in cells to show a statistically significant turn-on response but illustrate the compatibility of the 2-aza-Cope reaction for tissue and whole organism settings.…”

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

“…The small and transient nature of FA has motivated growing interest in developing new activity‐based sensing (ABS) methods for selective FA detection, including aza‐Cope, aminal, and formimine reaction‐based approaches. Indeed, recent progress in developing fluorescent probes for FA detection in cells has elucidated more sophisticated biological roles for FA as both an exogenous toxin and an endogenous signaling molecule.…”

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

“…The small and transient nature of FA has motivated growing interest in developing new activity-based sensing (ABS) methods [11–14] for selective FA detection, [15,16] including aza-Cope, [17–24] aminal, [25,26] and formimine [27–32] reaction-based triggers. Indeed, recent progress in developing fluorescent probes for FA detection in cells has elucidated more sophisticated biological roles for FA as both an exogenous toxin and an endogenous signaling molecule.…”

“…[1,2] This major onecarbon unit lies at the nexus of metabolism and epigenetics, participating in the synthesis of key biological molecules, including purines,a mino acids,a nd neurotransmitters, [3][4][5] as well as in the methylation status of av ariety of nucleic acid, protein, and small-molecule metabolites. [6][7][8][9][10] Thes mall and transient nature of FA has motivated growing interest in developing new activity-based sensing (ABS) methods [11][12][13][14] for selective FA detection, [15,16] including aza-Cope, [17][18][19][20][21][22][23][24] aminal, [25,26] and formimine [27][28][29][30][31][32] reactionbased approaches.I ndeed, recent progress in developing fluorescent probes for FA detection in cells has elucidated more sophisticated biological roles for FA as both an exogenous toxin and an endogenous signaling molecule. Included is the discovery that FA is endogenously produced in the folate cycle through specific intermediates like tetrahydrofolate and 5,10-methylenetetrahydrofolate,b ut not others like 5-methyltetrahydrofolate, [8] opening new doors to investigate the intriguing yet complex relationships between FA,m ethylation status,a nd carcinogenesis.D espite these advances in fluorescent FA detection, FA imaging in living mammals is limited to an aza-Cope-based PET tracer, [19] which requires specialized equipment to implement.…”