A dynamic nucleophilic aromatic substitution of tetrazines (SNTz) is presented herein. It combines all the advantages of dynamic covalent chemistry with the versatility of the tetrazine moiety. Indeed, libraries of compounds or sophisticated molecular structures can be easily obtained, which are susceptible to post‐functionalization by inverse electron demand Diels–Alder (IEDDA) reaction, which also locks the exchange. Additionally, the structures obtained can be disassembled upon the application of the right stimulus, either UV irradiation or a suitable chemical reagent. Moreover, SNTz is compatible with the imine chemistry of anilines. The high potential of this methodology has been proved by building two responsive supramolecular systems: A macrocycle that displays a light‐induced release of acetylcholine; and a truncated [4+6] tetrahedral shape‐persistent fluorescent cage, which is disassembled by thiols unless it is post‐stabilized by IEDDA.

Dynamic Covalent Chemistry (DCvC) has gained increasing importance in supramolecular chemistry and materials science. Herein we prove the dynamic nature of the exchange between phenols and vinyl ethers. Exchange is fast at room temperature and under mild conditions. The equilibrium constants and the electronic effect of the phenol substituents were calculated. This novel incorporation to the DCvC toolbox could be quite useful, and as a proof it was used for the synthesis of a responsive molecular cage.

Dynamic nucleophilic aromatic substitution of tetrazines (SNTz) has been employed to build theranostic prodrugs which are activated by hydrogen sulfide. H2S is typically found in high concentration in some kind...

A dynamic nucleophilic aromatic substitution of tetrazines (SNTz) is presented herein. It combines all the advantages of dynamic covalent chemistry with the versatility of the tetrazine moiety. Indeed, libraries of compounds or sophisticated molecular structures can be easily obtained, which are susceptible to post‐functionalization by inverse electron demand Diels–Alder (IEDDA) reaction, which also locks the exchange. Additionally, the structures obtained can be disassembled upon the application of the right stimulus, either UV irradiation or a suitable chemical reagent. Moreover, SNTz is compatible with the imine chemistry of anilines. The high potential of this methodology has been proved by building two responsive supramolecular systems: A macrocycle that displays a light‐induced release of acetylcholine; and a truncated [4+6] tetrahedral shape‐persistent fluorescent cage, which is disassembled by thiols unless it is post‐stabilized by IEDDA.