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

Area of Science:

• Organic Chemistry
• Bioconjugation Chemistry
• Chemical Biology

Background:

• Traditional "turn-on" fluorescence click reactions often need specific triggers and pre-made fluorophores.
• Developing efficient and versatile methods for synthesizing fluorescent molecules is crucial for bioimaging and diagnostics.

Purpose of the Study:

• To report a novel activatable, self-reporting click-like reaction for one-pot synthesis of cyclic cyanines (CCClick).
• To utilize formaldehyde (FA) and biocompatible metal activators for this synthesis.
• To explore the application of CCClick in in-cell synthesis and disease diagnosis.

Main Methods:

• Developed a one-pot reaction involving formaldehyde (FA) and dimeric Fischer bases.
• Employed biocompatible metal ions or complexes (copper, iron, hemin) as activators.
• Investigated the reaction mechanism involving FA-specific dehydration cyclization and metal-catalyzed oxidative dehydrogenation.

Main Results:

• Successfully synthesized cyclic cyanines (CCClick) using the novel reaction.
• Demonstrated that hemin-activated CCClick is compatible with various Fischer base structures.
• Showcased the reaction's suitability for in-cell synthesis of bioimaging molecules.

Conclusions:

• The CCClick reaction offers a new, efficient pathway for synthesizing cyclic cyanines.
• Hemin-activated CCClick provides a flexible and convenient tool for in-cell bioimaging and disease diagnosis.
• This method overcomes limitations of traditional fluorescence "turn-on" reactions.