skip to main content


This content will become publicly available on April 2, 2019

Title: Azide–Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination

Functionalization of nanocrystals is essential for their practical application, but synthesis on nanocrystal surfaces is limited by incompatibilities with certain key reagents. The copper-catalyzed azide-alkyne cycloaddition is among the most useful methods for ligating molecules to surfaces, but has been largely useless for semiconductor quantum dots (QDs) because Cu+ions quickly and irreversibly quench QD fluorescence. To discover nonquenching synthetic conditions for Cu-catalyzed click reactions on QD surfaces, we developed a combinatorial fluorescence assay to screen >2000 reaction conditions to maximize cycloaddition efficiency while minimizing QD quenching. We identify conditions for complete coupling without significant quenching, which are compatible with common QD polymer surfaces and various azide/alkyne pairs. Based on insight from the combinatorial screen and mechanistic studies of Cu coordination and quenching, we find that superstoichiometric concentrations of Cu can promote full coupling if accompanied by ligands that selectively compete with the Cu from the QD surface but allow it to remain catalytically active. Applied to the conjugation of a K + channel-specific peptidyl toxin to CdSe/ZnS QDs, we synthesize unquenched QD conjugates and image their specific and voltage-dependent affinity for K + channels in live cells.
 [1] ;  [1] ;  [2] ; ORCiD logo [3] ; ORCiD logo [1]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). The Molecular Foundry
  2. Univ. of California, Davis, CA (United States). Dept. of Physiology and Membrane Biology
  3. Univ. of California, Davis, CA (United States). Dept. of Physiology and Membrane Biology
Publication Date:
Grant/Contract Number:
Accepted Manuscript
Journal Name:
ACS Nano
Additional Journal Information:
Journal Volume: 12; Journal Issue: 5; Journal ID: ISSN 1936-0851
American Chemical Society (ACS)
Research Org:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Institutes of Health (NIH)
Country of Publication:
United States
77 NANOSCIENCE AND NANOTECHNOLOGY; quantum dot; CuAAC; quenching; copper; synthesis; combinatorial nanoscience; bioconjugation; high-throughput screen
OSTI Identifier: