Amphiphilic polymeric nanoparticles enable homogenous rhodium-catalysed NH insertion reactions in living cells.

Abstract

Rh-catalysed NH carbene insertion reactions were exported to living cells with help of amphiphilic polymeric nanoparticles. Hereto, hydrophobic dirhodium carboxylate catalysts were efficiently encapsulated in amphiphilic polymeric nanoparticles comprising dodecyl and Jeffamine as side grafts. The developed catalytic nanoparticles promoted NH carbene insertions between α-keto diazocarbenes and 2,3-diaminonaphthalene, followed by intramolecular cyclisation to form fluorescent or biologically active benzoquinoxalines. These reactions were studied in reaction media of varying complexity. The best-performing catalyst was exported to HeLa cells, where fluorescent and cytotoxic benzoquinoxalines were synthesized in situ at low catalyst loading within a short time. Most of the developed bioorthogonal transition metal catalysts reported to date are easily deactivated by the reactive biomolecules in living cells, limiting their applications. The high catalytic efficiency of the Rh-based polymeric nanoparticles reported here opens the door to expanding the repertoire of bioorthogonal reactions and is therefore promising for biomedical applications.