Development of an Acetaldehyde-Specific Fluorescent Probe: Strategy and Applications.

Acetaldehyde (AA), the principal metabolite of ethanol, is a highly reactive species capable of forming covalent adducts with DNA and proteins, contributing to the pathogenesis and progression of multiple diseases. Conventional methods for detecting endogenous AA are commonly invasive and lack specificity against other aldehydes, hampering in-depth investigation of its in vivo mechanisms and biological functions. To overcome these limitations, we developed a fluorescent probe, TZ11008, for the selective and noninvasive detection of AA in living systems. The sensing strategy employs 2-aminobenzaldehyde as an AA-specific "capture"-type recognition unit, which undergoes a chemoselective quinoline cyclization reaction with AA. This reaction quenches the photoinduced electron transfer (PET) effect, resulting in a turn-on fluorescence response that effectively discriminates AA from formaldehyde and other aldehydes. TZ11008 was successfully applied for visual monitoring of AA in live mammalian cells, C. elegans and zebrafish. Furthermore, utilizing TZ11008, we established an analysis method to monitor dynamic changes in AA levels during ethanol metabolism and evaluated the modulatory effects of aldehyde dehydrogenase 2 (ALDH2) activator and inhibitor. This work provides a "capture"-based strategy for the specific identification of AA in biological systems and demonstrates its utility for preclinical evaluation of interventions targeting alcohol metabolism.