A Fluorogenic Probe for Ultrafast and Reversible Detection of Formaldehyde in Neurovascular Tissues

Formaldehyde (FA) is endogenously produced in live systems and has been implicated in a diverse array of pathophysiological processes. To disentangle the detailed molecular mechanisms of FA biology, a reliable method for monitoring FA changes in live cells would be indispensable. Although there have been several fluorescent probes reported to detect FA, most are limited by the slow detection kinetics and the intrinsic disadvantage of detecting FA in an irreversible manner which may disturb endogenous FA homeostasis. Herein we developed a coumarin-hydrazonate based fluorogenic probe (PFM) based on a finely-tailored stereoelectronic effect. PFM could respond to FA swiftly and reversibly. This, together with its desirable specificity and sensitivity, endows us to track endogenous FA in live neurovascular cells with excellent temporal and spatial resolution. Further study in the brain tissue imaging showed the first direct observation of aberrant FA accumulation in cortex and hippocampus of Alzheimer's mouse model, indicating the potential of PFM as a diagnostic tool.