Thermal Azide-Alkyne Cycloaddition (TAAC) as Efficient Clicked Chemistry Tool for the Functionalization of Dendrimers and Polymers

Abstract

With the aim of exploring new methodologies for the functionalization of GATG dendrimers while taking advantage of their of decoration with terminal azides, we have focused on the thermal azide-alkyne cycloaddition (TAAC). Using internal alkynes activated with carbamates, reliable TAAC conditions were optimized with a model system mimicking the GATG periphery. Simultaneously, a scaling up of the synthesis of GATG dendrimers (2G-3G families) was achieved that allowed preparation of G4 dendrimers in gram scale. With these two pieces in hand, internal alkynes functionalized with several ligands of biomedical interest (anionic and cationic, biotin, carbohydrates, alcohols, catechol, fluorophores, and chelating agents) were efficiently synthesized and used for the TAAC functionalization of several generations of GATG dendrimers. The resulting functionalized dendrimers were reproducibly obtained in very high yields after easy purification by ultrafiltration. These dendrimers are envisaged as promising tools for biomedical applications, including drug delivery, multivalent recognition and cell internalization.