Reversible Click Reactions in Water: A Robust and Customizable Synthetic Tool

Area of Science:

• Organic Chemistry
• Chemical Biology

Background:

• Reversible click chemistry enables controllable bond formation and cleavage, crucial for dynamic molecular systems.
• Traditional click reactions lack efficient and controllable decoupling mechanisms due to high reaction energy.
• Developing reversible click reactions compatible with biological conditions remains a significant challenge.

Purpose of the Study:

• To report a novel reversible click reaction between sulfur-bridged N-aryl quinolinium derivatives and thiols.
• To demonstrate controllable coupling and decoupling using acid and base triggers.
• To achieve reversible protein modification in aqueous conditions.

Main Methods:

• Utilized antagonistic nucleophilic addition toward aromatization for the reversible reaction.
• Employed base and acid to control the click and declick processes, respectively.
• Investigated reaction efficiency, dynamics, selectivity, and robustness in aqueous media.

Main Results:

• Achieved near-unity efficiency and fast dynamics for both click and declick reactions.
• Demonstrated stoichiometric dependence and excellent selectivity and robustness.
• Successfully performed reversible protein modification in pure aqueous solution for the first time.

Conclusions:

• Developed a novel, efficient, and robust reversible click chemistry methodology.
• The reaction is controllable, highly selective, and operates effectively in aqueous conditions.
• This work offers a new platform for green synthesis and erasable biochemical modifications.