An Activatable and Switchable Nanoaggregate Probe for Detecting H2S and Its Application in Mice Brains

Employing a sequentially activated probe design method, an activatable, switchable and dual‐mode probe was designed. This nanoprobe, HSDPP, could be effectively activated by H2S to form H‐type aggregates with green emission; subsequently, the aggregates could bind to mtDNA to form monomers and the emIssion color switched from green to deep‐red. We exploited HSDPP to image exogenous and endogenous H2S in living cells. Of note, for the first time, this novel nanoprobe with an optimal partition coefficient value (LogP=1.269) was successfully applied for tracking the endogenous H2S upregulation stimulated by cystathionase activator S‐adenosyl‐L‐methionine (SAM) in mice brains. Finally, our work provides an invaluable chemical tool for probing endogenous H2S upregulation in vitro/vivo and, importantly, affords a prospective design strategy for developing switchable chemosensors to unveil the relationship between biomolecules and DNA in mitochondria in many promising areas. An activatable and switchable nanoaggregate probe for detecting H2S in mice brains was developed. It could be effectively activated by H2S to form H‐type aggregates with green emission; subsequently, the aggregates could bind to mtDNA to form monomers and the emission color switched from green to deep‐red.