Additive-free clicking for polymer functionalization and coupling by tetrazine-norbornene chemistry.

Herein we report the use of a tetrazine-norbornene inverse electron demand Diels-Alder conjugation applied to polymer end-functionalization and polymer-polymer coupling. The reaction was found to be applicable to polymer-polymer coupling, as judged by SEC, DOSY NMR, and LCxSEC analyses, giving diblock copolymers by merely mixing the constituent homopolymers together under ambient conditions, using no catalyst, additive, or external stimulus.

Tetrazine-norbornene click reactions to functionalize degradable polymers derived from lactide.

Post-polymerization modification of polymers derived from sustainable resources using the click reaction between tetrazines and norbornenes is shown to provide a mild and efficient route for the synthesis of functional degradable polymers. Norbornene chain-end functional poly(lactide) was synthesized using organocatalytic methods and functionalized by the addition of 3,6-di-2-pyridyl-1,2,4,5-tetrazine without degradation of the polymer backbone. The versatility of this reaction was demonstrated by the application of analogues bearing amine and poly(ethylene oxide) groups to realize amine-functional polymers and block copolymers. Poly(spiro[6-methyl-1,4-dioxane-2,5-dione-3,2'-bicyclo[2.2.1]hept[5]ene]) was prepared from lactide. The pendant norbornene group on the backbone of the resultant polymer was modified in a similar manner to produce functional degradable polymers and graft co-polymers.

Exploiting the tetrazine-norbornene reaction for single polymer chain collapse.

Single chain polymer nanoparticles (SCNPs) have been formed using polystyrenes decorated with pendent norbornenes and a bifunctional tetrazine crosslinker. Characterisation by size exclusion chromatography and (1)H NMR gives evidence for the formation of SCNPs by the tetrazine-norbornene reaction, whilst light scattering, neutron scattering, transmission electron microscopy and atomic force microscopy show that discrete well-defined nanoparticles are formed and their size in solution calculated.

A "Mix-and-Click" Approach to Double Core-Shell Micelle Functionalization.

A micellar scaffold formed by self-assembly of a reversible addition-fragmentation chain transfer (RAFT)-synthesized amphiphilic diblock copolymer has been prepared to contain two orthogonal click-compatible functionalities in the core and shell. These functionalities (norbornenes in the core and terminal alkynes in the shell) have been used as handles to modify the micellar assembly in the core using tetrazine-norbornene chemistry or the shell using the copper-catalyzed azide-alkyne reaction. Additionally, both core and shell modifications were carried out in a tandem, one-pot process using the orthogonal chemistries mentioned above. In all cases the reactions were found to be highly efficient, requiring little excess of the modifying small molecule and very simple to perform under ambient conditions.