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

Abstract

Rutheniumn anocatalysisc an provide effective deuteration and tritiation of oxazole, imidazole, triazole and carbazole substructuresi nc omplex molecules using D 2 or T 2 gas as isotopic sources. Depending on the substructure considered,t his approach does not only represent as ignificant step forwardi np ractice, with notably higher isotope uptakes, abroader substrate scope and ahighersolventapplicability compared to existing procedures, buta lso the unique way to label importanth eterocyclesu sing hydrogen isotope exchange. In terms of applications,t he high incorporation of deuterium atoms, allows the synthesis of internal standards for LC-MS quantification. Moreover,t he efficacy of the catalyst permits, even under subatmospheric pressure of T 2 gas, the preparation of complex radiolabeled drugs owning high molara ctivities.F rom af undamental pointo fv iew,adetailed DFT-based mechanistics tudy identifyingu ndisclosed key intermediates, allowed ad eeperu nderstanding of CÀH (and NÀH) activation processes occurring at the surfaceo f metallicnanoclusters.Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.org/10.

Chemoselective H/D exchange catalyzed by nickel nanoparticles stabilized by N-heterocyclic carbene ligands

“…A somewhat similar effect has been observed in hydrogenation reactions involving Ru NPs stabilized long chain NHCs bearing mesityl substituents. 54 The catalytic mechanism is likely to involve oxidative addition in a variety of approaches: (i) a fourmembered ring for the deuteration of position A as proposed for Ru(0) NPs 29 for NPs 1 and 2 or (ii) a five-or six-membered ring depending on the number of Ni atoms implied, 55 for the deuteration of position B using NPs 2 (Scheme 2 shows the six-membered metallacycle); and (iii) after π-coordination of the pyridyl ring, a more complex mechanism can act, which has not been elucidated here. It is interesting to note that the other positions of the phenyl ring are not deuterated which probably emphasizes the importance of the coordination through nitrogen atom for the C-H activation to proceed.…”

Nanocatalyzed Hydrogen Isotope Exchange

“…We obtained molar activities up to 24.7 Ci.mmol -1 , in accordance with the prerequisites for ADME studies (see Figure XX). 19 Following our NP engineering studies, organo-soluble RuNP@NHC-ICy was used to achieve the tritiation of Didanosine (an antiretroviral agent) and Idelalisib (used for the treatment of blood cancer) which were obtained with good specific activities (> 23 Ci.mmol -1 ). 23 Pergolide, a sulphur-containing compound, was also tritiated with a molar activity of 15 Ci.mmol -1 in similar conditions using ruthenium on carbon, again making it compatible with ADME requirements.…”

Recent Advances in the Synthesis of Deuterium‐Labeled Compounds

“…A series of common antibody–drug conjugate linker side chains with more than 99% deuterium incorporation were obtained with high yields and regioselectivity. Pfeifer et al [106] . demonstrated highly effective deuteration of oxazole and imidazole molecules using Ru‐based catalysts and D 2 as the isotope source.…”