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.

doi:10.1021/acsnano.8b00575

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

Journal Article · Mon Apr 02 00:00:00 EDT 2018 · ACS Nano

DOI:https://doi.org/10.1021/acsnano.8b00575· OSTI ID:1460332

Mann, Victor R. ^[1]; Powers, Alexander S. ^[1]; Tilley, Drew C. ^[2]; ^[3]; ^[1]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). The Molecular Foundry
Univ. of California, Davis, CA (United States). Dept. of Physiology and Membrane Biology
Univ. of California, Davis, CA (United States). Dept. of Physiology and Membrane Biology

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); National Inst. of Health (NIH)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1460332

Journal Information:: ACS Nano, Journal Name: ACS Nano Journal Issue: 5 Vol. 12; ISSN 1936-0851

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: English

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

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