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

Beyond the context of click chemistry, reversible click chemistry refers to a class of coupling reactions that satisfy all the characters of click reaction, besides offering well access for controllable decoupling process. Endowing click reaction with reversibility is extremely challenging due to the strong energy gain, which inhibits the path of disassociation. Herein, we report the reversible click reactions between highly customizable sulfur-bridged N-aryl quinolinium derivatives and thiols in a closed-loop approach, enabled by antagonistic nucleophilic addition toward aromatization. The click and declick process can be manipulated by employing base and acid, respectively, both featured with near-unity efficiency, fast dynamics and stoichiometric dependence. Owing to excellent selectivity and robustness, this reversible click reaction can be well conducted in pure aqueous condition for the first time and achieve reversible protein modification. We anticipate that this work provides a novel methodology for green synthesis with high atom economy and biochemical modification in an erasable manner.