Conventional "Click Chemistry" requires the presence of a Cu(I) catalyst that is toxic to most organisms and thus, prevents its use in many biological systems.
The novel Copper-free Click Chemistry is based on the reaction of a diarylcyclooctyne (DBCO) moiety with an azide-labeled reaction partner, known as strain-promoted alkyne azide cycloaddition (SPAAC). This new "Click Chemistry" is very fast at room temperature and does not require a cytotoxic Cu(I) catalyst. Diarylcyclooctynes are thermostable with very narrow and specific reactivity toward azides, resulting in almost quantitative yields of stable triazoles.
Bertozzi and coworkers used this reaction for in vivo applications,,,.
Cu(I)-free ligation reaction scheme: Diarylcyclooctyne-activated biomolecule A reacts with azide-activated biomolecule B without Cu(I) in aqueous conditions to form a stable triazole