SCBM chemists continue to explore ways to label organic molecules, to make them faster and less polluting, in order to facilitate their use, for example in pharmacological studies. During the preclinical and clinical testing phases, drugs are "labelled" to track their absorption, distribution, metabolism and excretion in a living organism (animal or human). 

A team from SCBM (LMC) are interested in the carbon-14 (¹⁴C) labelling of therapeutic molecules. In 2019, in collaboration with NIMBE (CEA-IRAMIS), they discovered a new labelling strategy involving isotopic carbon exchange. This involves, in the same reaction, the breaking of a C-C bond and the formation of a new C-¹⁴C bond while keeping the original structure of the drug. They found favourable experimental conditions for the catalysis of an exchange of an unlabelled CO₂ molecule against a labelled molecule in molecules of therapeutic interest containing a carboxylic group. This method, which is suitable for aromatic carboxylic acids, was catalysed by copper (JACS 2019, read the news " CO₂ and copper to label carbon-based pharmaceuticals " published in January 2019).

In the article published in Angewandte Chemie, researchers from the SCBM and NIMBE, in collaboration with Astra Zeneca and the Karolinska Institutet, describe a new method that allows an exchange of ¹²CO₂ by ¹⁴CO₂ in the absence of catalysis, simply by thermal heating. This method is particularly suitable for a family of carboxylic acids, phenyl acetic acids, present in non-steroidal anti-inflammatory drugs such as ibuprofen, naproxen, ketoprofen and many others.

Radiolabeled molecules obtained with the new CO2 isotopic exchange method. © D. Audisio

Gianluca Destro developed this project as part of his thesis, funded by the European ISOTOPICS project (https://www.isotopics-project.eu/). After finding the optimal conditions, he was able to apply this new method to the labelling of 15 drugs at AstraZenenca. Finally, at the Karolinska Institute (Stockholm, Sweden), he succeeded in adapting the method to carbon-11, the other carbon radioisotope, for the very first time.