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.