A reaction-based fluorescence probe for selective detection of formaldehyde in food samples and its imaging application in living cells†

Formaldehyde (FA) is a toxic pollutant that threatens both environmental and human health. Effective methods to detect FA in real-world samples and biological systems are urgently needed. Herein, we report the rational design and synthesis of NAPh-Lyso, a new lysosome-targetable reaction-based fluorescent probe for rapid and selective FA detection. NAPh-Lyso integrates three functional components, namely, a 1,8-naphthalimide fluorophore as the signaling unit, a hydrazine group as the specific FA-reactive site, and a morpholine moiety for subcellular localization. NAPh-Lyso operates through a distinctive Schiff base formation-coupled photoinduced electron transfer (PET) modulation mechanism, exhibiting a remarkable “turn-on” fluorescence response to FA in aqueous media with exceptional selectivity, rapid response kinetics (<2 min), and high sensitivity (LOD = 0.21 μM). It enables precise FA quantification in food (cabbage and mushrooms) and water samples (pond water and tap water), and lysosomal FA imaging in live cells. This work presents an advanced analytical platform for FA monitoring, while simultaneously offering valuable insights for the structural design of FA probes with broad applications in both analytical chemistry and biomedical research.