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Carbon labeling with light

Researchers from the CEA-Joliot Institute (Carbon 14 Marking Laboratory), in collaboration with a team from AstraZeneca, have developed a labeling method, based on the exchange of carbon dioxide, simply using visible blue light and a photocatalyst. Ideal for organic molecules of therapeutic interest, the method is described in the journal ACS Catalysis

Published on 24 February 2021

SCBM chemists are continuing their efforts to explore ways of labeling organic molecules to make them simpler, faster and more environmentally friendly.

In the beginning, a bioinspired approach...

In collaboration with  NIMBE (CEA-IRAMIS), they discovered a new labeling strategy involving carbon isotope exchange (JACS 2019, read the news " Du CO2 et du cuivre pour marquer des produits pharmaceutiques au carbone" published in January 2019).This innovative approach was inspired by an enzyme capable of reversibly removing a carbon dioxide molecule from its substrate. The method allows, in the same reaction, the rupture of a C-12C bond and the formation of a new C-14C bond (14C = radioactive carbon isotope) while keeping the original structure of the drug. This first proof of concept required the use of a copper catalyst and high temperatures. 

... then heating...

In 2020, a new method was developed by the SCBM[1], allowing an exchange of 12CO2 by 14CO2 by simple heating, without a catalyst (Angewandte Chemie, see the news « Marquage au carbone 14 d’anti-inflammatoires avec du CO2 » published in May 2020). This method was adapted to a family of carboxylic acids, phenyl acetic acids, present in non-steroidal anti-inflammatory drugs such as ibuprofen and ketoprofen. This second method always required high temperatures in the order of 150 to 190°C.

... replaced by light

With the aim of making this process gentler and more practical, SCBM researchers explored the use of photochemistry in 2021: an organic catalyst (i.e. one that does not carry metals) activated by light should enable them to carry out the same exchange of CO2, at much lower temperatures. And indeed, they show in ACS catalysis that, thanks to this new technology, ibuprofen can be labelled with carbon-14 in 3 hours at just 40°C using the 4CzIPN[2] photocatalyst activated by blue light (wavelength 450 nm), which greatly increases the compatibility of these reaction conditions with the most complex structures.

These increasingly gentle carbon isotope labeling methods should help pharmaceutical laboratories interested in labeling molecules of the phenyl acetic acid family either for their pharmaceutical potential (carbon 14 labeling for pre-market clinical studies) or for their development as a medical imaging tracer (carbon 11 labeling).

European fundings
This work was funded under the ERC Consolidator Grant (ERC-COG-2019)FASTLabEX, the FET-OPEN FLIX and the ITN ISOTOPICS, coordinated by the CEA.

[1] In collaboration with NIMBE (CEA-IRAMIS, UMR CEA/CNRS), Astra Zeneca and Karolinska Instituet
[2] 4CzIPN is the short name for 2,4,5,6-Tetrakis(9H-carbzole-9-yl) isophthalonitrile, photocatalyst that has given the best results for this study.   

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