Azide-Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination

Victor R. Mann, Alexander S. Powers, Drew C. Tilley, Jon T Sack, Bruce E. Cohen

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)4469-4477
Number of pages9
JournalACS Nano
Volume12
Issue number5
DOIs
StatePublished - May 22 2018

Fingerprint

Alkynes
Azides
alkynes
conjugation
Semiconductor quantum dots
Copper
quantum dots
copper
Quenching
Cycloaddition
quenching
cycloaddition
Nanocrystals
nanocrystals
Fluorescence
fluorescence
incompatibility
reagents
affinity
Assays

Keywords

  • bioconjugation
  • combinatorial nanoscience
  • copper
  • CuAAC
  • high-throughput screen
  • quantum dot
  • quenching
  • synthesis

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Azide-Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination. / Mann, Victor R.; Powers, Alexander S.; Tilley, Drew C.; Sack, Jon T; Cohen, Bruce E.

In: ACS Nano, Vol. 12, No. 5, 22.05.2018, p. 4469-4477.

Research output: Contribution to journalArticle

Mann, Victor R. ; Powers, Alexander S. ; Tilley, Drew C. ; Sack, Jon T ; Cohen, Bruce E. / Azide-Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination. In: ACS Nano. 2018 ; Vol. 12, No. 5. pp. 4469-4477.
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