Dynamic Nucleophilic Aromatic Substitution of Tetrazines

Abstract

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.

Advanced Multifunctional Hydrogels for Enhanced Wound Healing through Ultra‐Fast Selenol‐SNAr Chemistry

“…It is well established that dichlorotetrazine can undergo reactions with various nucleophiles, including alcohols, amines, thiols, and others. [ 20 ] However, there are a lack of reports in the literature regarding the nucleophilic substitution of selenols for dichlorotetrazine (DT), and we present here the first use of the aryl nucleophilic reaction of selenol to synthesize tetrazinyl selenide. The nucleophilicity of selenol is exceptionally high, leading to an ultrafast reaction rate.…”

“…According to the properties of tetrazines, [ 20,23 ] the structure of tetrazinyl selenide exhibits potential photoresponsive degradation performance (Figure S3a, Supporting Information). The photoresponse properties of the small molecule tetrazine selenide were investigated under green light (520 nm) irradiation.…”

“…NMR, gas chromatography‐time of fight‐mass spectrometry (GCT‐TOF‐MS) and fourier transform infrared spectroscopy (FT‐IR) analysis of the reaction solution (Figure S3c–e, Supporting Information) revealed that the decomposition product corresponded to a selenocyanide compound, consistent with the photolysis mechanism of tetrazinyl sulfide. [ 17a,20b ] Upon light excitation, a single tetrazine molecule decomposes to yield one nitrogen molecule and two selenocyanate (SeCN) molecules, and these compounds have been experimentally proved to have significant biological activities., such as antioxidant and antibacterial effects. [ 25 ]…”

Sulfur in Dynamic Covalent Chemistry

“…Recently, the Carrillo group reported the nucleophilic aromatic substitution of tetrazines with alkyl thiols. The exposure of the tetrazine 51 to dodecanethiol in the presence of a base led to the two exchange tetrazine products 52 and 53 along with benzylmercaptan (Scheme 6a) [115] . The reaction is fast and can be halted by acidification of the medium or by post‐functionalization through an inverse‐electron‐demand Diels–Alder reaction of the tetrazine compounds.…”