Organic chemistry

Covalent bond

Combinatorial chemistry

Reagent

Dynamic covalent chemistry

Nucleophilic aromatic substitution

Catalysis

Nucleophilic substitution

Nucleophile

Aromaticity

Chemistry

Moiety

Imine

Tetrazine

Molecule

Supramolecular chemistry

Click chemistry

Bioorthogonal chemistry

Angewandte Chemie International Edition

A dynamic nucleophilic aromatic substitution of tetrazines (SN Tz) 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, SN Tz 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 Nucleophilic Aromatic Substitution of Tetrazines