Hydrogen Isotope Exchange Catalyzed by Ru Nanocatalysts: Labelling of Complex Molecules Containing N-Heterocycles and Reaction Mechanism Insights

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

1 SCBM - Service de Chimie Bio-Organique et de Marquage
2 LPCNO - Laboratoire de physique et chimie des nano-objets
3 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay

Ruthenium nanocatalysis can provide effective deuteration and tritiation of oxazole, imidazole, triazole and carbazole substructures in complex molecules using D2 or T2 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 T2 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.

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

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry; Chemical Sciences; Radiochemistry; Chemical Sciences; Catalysis; Chemical Sciences; Medicinal Chemistry

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⟩