Visualization of endogenous formaldehyde in the nucleus via a robust activatable fluorescent probe

As one of the most basic substances in the live system, the improper regulation of nucleic acid behavior may cause cell dysfunction and induce serious diseases. As the main storage location of nucleic acids, the nucleus is also an important site for the production and transfer of endogenous formaldehyde (FA) in live cells. However, the disorder of FA metabolism could affect the methylation and demethylation of nucleic acids, leading to cognitive impairment and even could cause Alzheimer's disease, sarcosinemia and dwarfism, etc. Therefore, the design of FA fluorescent probes that can precisely target the nucleus is of great significance for the detection of nuclear FA. Herein, the first nucleus-targeting FA specific fluorescent probe (Nu-FA) was rationally designed and demonstrated. Encouraged by the advantageous affinity to DNA and RNA in molecular docking calculations and titration experiments, and the excellent specific response to FA in spectroscopy experiments, Nu-FA has been successfully employed for the first time to visualize endogenous FA in the nucleus and monitored the removal of endogenous FA from the nucleus by exogenous drug. This effective probe would provide an unprecedented approach to enable exploring FA in the nucleus and greatly promote basic research on related diseases caused by FA.