Accessible Requires Authentication Published by Oldenbourg Wissenschaftsverlag October 26, 2018

Copper-catalyzed click reactions: quantification of retained copper using 64Cu-spiked Cu(I), exemplified for CuAAC reactions on liposomes

Karolin Wagener, Dennis Renisch, Meike Schinnerer, Matthias Worm, Yvonne Jakob, Klaus Eberhardt and Frank Rösch
From the journal Radiochimica Acta


The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a powerful, highly reliable and selective reaction which allows for a rapid synthesis in high yields and under mild conditions (pH, temperature). However, the cytotoxicity of copper requires its complete removal prior to an application in vivo. This is an issue especially when it comes to CuAAC reactions on macromolecular structures or drug delivery systems, as copper might be retained by these systems. Thus, a quantification of the final copper content of these systems is inevitable, which we exemplified for a CuAAC reaction on liposomes using 64Cu-spiked Cu(I). In this respect, a Cu(II) nitrate solution was irradiated at the TRIGA Mark II research reactor Mainz to obtain c.a. [64Cu]Cu(II). The irradiated solution was directly used for a CuAAC on liposomes. After purification, their copper content was calculated utilizing γ-ray spectrometry. Only 0.018% of the added 64Cu-activity was still present in the liposome containing fractions after purification. This refers to a total amount of copper of 0.17 ng. The amount of retained copper is so low, that an in vivo application of the liposomes is absolutely reasonable. Besides this particular study, the experimental methodology may be applied to study many other CuAAC reactions, used for the synthesis of radiolabeled or non-radioactive species, which are intended for human applications.

Corresponding author: Prof. Dr. Frank Rösch, Institute of Nuclear Chemistry, Johannes Gutenberg University, Fritz-Strassmann-Weg 2, 55128 Mainz, Germany, Tel.: +49 6131 39 25302, Fax: +49 6131 39 25253


The authors are very grateful to the Max-Planck Graduate Center (MPGC, K. Wagener) as well as to the DFG in the context of the SFB 1066 for financial support. K. Wagener and M. Schinnerer and M. Worm are members of the Graduate School of the SFB 1066.


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Supplementary Material

The online version of this article offers supplementary material (

Received: 2018-06-06
Accepted: 2018-09-25
Published Online: 2018-10-26
Published in Print: 2019-07-26

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