Activatable self-reporting cyclization reaction for in-cell synthesis of cyclocyanines

Generally, fluorescence "turn-on" click reactions require special activation triggers and heavily rely on preformed fluorophores. Herein, we reported an activatable self-reporting click-like reaction for one-pot synthesis of cyclic cyanines (CCClick) by clicking formaldehyde (FA) into dimeric Fischer bases, using biocompatible metal ions or complexes (<i>e.g.</i>, copper, iron, and hemin) as an activator. CCClick involves FA-specific dehydration cyclization and metal-catalyzing oxidative dehydrogenation. Hemin-activated CCClick is flexible with Fischer base structures, satisfies the strict requirements for in-cell synthesis of bioimaging molecules and provides a convenient chemical tool for disease diagnosis.