Molecular Engineering to Access Fluorescent Trackers of Organelles by Cyclization: Chemical Environment of Nitrogen Atom‐Modulated Targets

In the application of new fluorescent bioimaging reagents, typically, one synthetic method yields one type of organelle tracker. Herein, a molecular engineering approach to access fluorescent trackers of multiple organelles via a powerful synthetic toolbox is described. Starting from easily available acridone and analogues, a one-pot strategy is set up for the synthesis of structurally diversified heteroatom-doped polycyclic aromatic hydrocarbons (PAHs, types I-V) through the rhodium-catalyzed oxidative [4 + 2] cyclization of C = X (X = N, O, S) bonds with alkynes, which assembles both ionic and neutral fluorescent frameworks. The tetracyclic acridine-type luminogens (I-IV) are capable of targeting multiple organelles, including lysosome, endoplasmic reticulum, mitochondria, and mitochondria-nucleus, in which the chemical environments of the nitrogen atom modulate the targeting regions. The fluorescent organelle trackers developed herein possess unique features. The formally protonated type I molecules are suitable for the long-term detection of the lysosomes (>24 h). The type IV molecules exhibit the photo-induced transfer from mitochondria to nucleus targeting, which indicates that IV can be used as an effective tool for real-time research on physiological processes related to cell trafficking.