Hydrogen isotope exchange catalyzed by Ru nanocatalysts: labelling of complex molecules containing N-heterocycles and reaction mechanism insights

Viktor Pfeifer (1, 2) , Marie Certiat (3) , Donia Bouzouita (3) , Alberto Palazzolo (1, 2) , Sébastien Garcia-Argote (1, 2) , Elodie Marcon (1, 2) , David-Alexandre Buisson (1, 2) , Philippe Lesot (4) , Laurent Maron (3) , Bruno Chaudret (3) , Simon Tricard (3) , Iker Del rosal (3) , Romuald Poteau (3) , Sophie Feuillastre (1, 2, 5) , Grégory Pieters (1, 2)

1 SCBM - Service de Chimie Bio-Organique et de Marquage
2 LMT2 - LMT équipe 2
3 Optoélectronique Quantique (LPCNO)
4 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay
5 MTS - Médicaments et Technologies pour la Santé

Ruthenium nanocatalysis can provide effective deuteration and tritiation of oxazole, imidazole, triazole and carbazole substructures in complex molecules using D$_2$ or T$_2$ gas as isotopic sources. Depending on the substructure considered, this approach does not only represent a significant step forward in practice, with notably higher isotope uptakes, a broader substrate scope and a higher solvent applicability compared to existing procedures, but also the unique way to label important heterocycles using hydrogen isotope exchange. In terms of applications, the high incorporation of deuterium atoms, allows the synthesis of internal standards for LC-MS quantification. Moreover, the efficacy of the catalyst permits, even under subatmospheric pressure of T$_2$ gas, the preparation of complex radiolabeled drugs owning high molar activities. From a fundamental point of view, a detailed DFT-based mechanistic study identifying undisclosed key intermediates, allowed a deeper understanding of C-H (and N-H) activation processes occurring at the surface of metallic nanoclusters.

Mots clés: Isotopic exchange; Heterogeneous catalysis; Deuteration; C-H activation; N-heterocyclic carbenes; Tritium

Domaines: Chimie; Catalyse; Chimie organique; Radiochimie; Chimie thérapeutique

Viktor Pfeifer, Marie Certiat, Donia Bouzouita, Alberto Palazzolo, Sébastien Garcia-Argote, et al.. Hydrogen isotope exchange catalyzed by Ru nanocatalysts: labelling of complex molecules containing N-heterocycles and reaction mechanism insights. Chemistry - A European Journal, 2020, 26, pp.4988-4996. ⟨10.1002/chem.201905651⟩. ⟨cea-02487414⟩