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Launch of FLIX, a European project for the isotopic labeling of molecules with high added values

​In June 2019, the SCBM obtained a European FET-Open funding for the FLIX project (FLow chemistry for Isotopic eXchange), a radically innovative concept of isotopic labeling of molecules with high added values. This 4-year project, coordinated by CEA/SCBM, with an overall budget of 3.5 million euros started on January 1, 2020 and consists of seven European academic or industrial partners in five countries.

Published on 19 February 2020
FLIX FLow chemistry for Isotopic eXchange 

The kick-off meeting of FLIX project in Paris, on January 30, at CEA's headquarters

Isotopes are variants of the same chemical element having the same number of protons but a different number of neutrons (and atomic weight or molecular mass). Uncommon isotopes can be substituted for standard ones in molecules of interest. The equal protons (and electrons) make them almost the same chemically. Then, molecules containing the substituted isotopes can be detected with analytical methods like mass spectroscopy and nuclear magnetic resonance (NMR).
FLIX is making the creation of isotope-labelled molecules easier, faster, and more effective with new generations of catalysts for isotope exchange along with flow chemistry. Success will have tremendous impact on fields from synthetic chemistry to biomedical diagnostics to materials research.

FLIX is a radically new concept for the ultimate-stage chemical isotopic labeling of high added-value molecules (drugs, biologics, smart materials) with stable isotopes (D, 13C and 15N). It utilizes the unique properties of new generations of catalysts, which specifically and selectively exchange predetermined atoms and chemical motifs of end-use organic compounds. The ultimate outcome of the project is to devise and build a modular and adaptable flow chemistry system for the straightforward and combinable isotopic labeling of complex chemicals and biologics.

The 'FLIX machinery' will use a combination of specialized reactor modules operating under continuous flow conditions, either in closedloop or open systems for the on-line H/D, C-12/C-13, N-14/N-15 and methoxy group direct isotopic exchanges with an unprecedented efficacy and without any chemical alteration of the molecules.

The project's objectives are to:
1) develop new generations of organometallic catalysts for isotopic exchange reactions;
2) screen catalysts for the isotopic exchange on a relevant portfolio of organic molecules in batch and flow chemistries and assess catalyst robustness;
3) devise and validate the 'combinable isotope labeling' concept;
4) design and build an adaptable multi-module machinery for combinable chemical exchange labeling.

FLIX synergistically associates the expertise and innovation potential of a mixed academic/industrial multidisciplinary consortium. The project is expected to have a multi-billion Euro positive impact on all sectors using stable isotopes in particular:
1) drug innovation, by accelerating preclinical studies, de-risking clinical trials and fostering the development of novel deuterated 'heavy drugs';
2) design of new tracers for diagnostic imaging with improved biological properties;
3) streamlining the production of multi-labeled complex molecules for NMR studies;
4) the development of novel isotopically-enriched materials.

Contact : Sophie Feuillastre, project coordinator

CEA staff involved in the project (SCBM) :
Sophie Feuillastre, researcher, FLIX coordinator
Christophe Dugave, researcher, assistant coordinator
Grégory Pieters, team leader Marquage par les isotopes de l'hydrogène (deutérium, tritium) & Matériaux
Davide Audisio, head of the 14Carbone-labeling laboratory, holder of an ERC Consolidator Grant
Antoine Sallustrau, researcher
Frédéric Taran, head of SCBM

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