A Ligand System for the Flexible Functionalization of Quantum Dots via Click Chemistry

We present a novel ligand, 5-norbornene-2-nonanoicacid, which can be directly added during established quantumdot (QD) syntheses in organic solvents to generate “clickable”QDs at a few hundred nmol scale. This ligand has a carboxylgroup at one terminus to bind to the surface of QDs anda norbornene group at the opposite end that enables straight-forward phase transfer of QDs into aqueous solutions viaefficient norbornene/tetrazine click chemistry. Our ligandsystem removes the traditional ligand-exchange step and canproduce water-soluble QDs with a high quantum yield anda small hydrodynamic diameter of approximately 12 nm at anorder of magnitude higher scale than previous methods. Wedemonstrate the effectiveness of our approach by incubatingazido-functionalized CdSe/CdS QDs with 4T1 cancer cells thatare metabolically labeled with a dibenzocyclooctyne-bearingunnatural sugar. The QDs exhibit high targeting efficiency andminimal nonspecific binding.