Perfluoroaryl azides (PFAAs) constitute a special class of azides. The ease of introducing additional functional groups on PFAAs makes them ideal candidates as multifunctional coupling agents. The PFAA-mediated conjugation reactions can be accomplished by using the azide as the nitrene precursor through the CH insertion reaction, or as an electrophile through the reaction with a dipolarophile or a nucleophile. Perfluorination on the aryl ring increases the lifetime of the singlet nitrene, leading to significantly enhanced CH insertion reaction efficiency. Perfluorination also lowers the LUMO and increases the electrophilicity of the PFAAs, leading to unique reactivities towards nucleophiles, electron-rich or strained dipolarophiles, in some cases, new transformations that do not require any catalysts, or products that are impossible to obtain from the non-electrophilic azides. Additionally, PFAAs are thermally stable, and are compatible with biological conditions. This talk will present methods for the synthesis of glycopolymers and glyconanoparticles via the PFAA-mediated photoclick reaction, and catalyst-free click reactions with enamines and phosphines. The PFAA-enamine reaction can be carried out in a one-pot fashion using readily available starting materials of aldehyde and amine, making the reaction especially attractive for the synthesis of glyconanoparticles. Examples comparing glyconanoparticles synthesized by this method vs. the classic CuAAC reaction showed similar reactivity, and slightly higher ligand density and binding affinity with lectin. In the PPAA-mediated Staudinger reaction, fast kinetics was observed at a rate of 10<sup>4</sup> times higher than the Staudinger ligation, giving stable phosphoimines in high yields. The reaction was applied to synthesize maltoheptaose-grafted poly(lactic acid) (PLA) and trehalose-grafted poly(2-hydroxyethyl methacrylate) (pHEMA). The reactions proceeded at room temperature within one hour without the need of any catalyst. Interactions of the synthesized glycopolymers and glyconanoparticles with lectins and cells will be presented, as well as the application of the trehalose-glycopolymers in capturing mycobacteria.

Perfluoroaryl azide-mediated conjugation reactions for the syntheses of glycopolymers and glyconanoparticles

ACS Fall 2020 Virtual Meeting

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