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With this work, we report the synthesis and full characterization of nickel nanoparticles (NPs) stabilized by N-heterocyclic carbene (NHC) ligands, namely 1,3-bis(cyclohexyl)-1,3-dihydro-2H-imidazol-2-ylidene (ICy) and 1,3-bis(2,4,6-trimethylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene (IMes). Although the resulting NPs have the same size, they display different magnetic properties and different reactivities, which result from ligand effects. In the context of H/D exchange on pharmaceutically relevant heterocycles, Ni@NHC shows a high chemoselectivity, avoiding the formation of undesired reduced side-products and enabling a variety of H/D exchange on nitrogen-containing aromatic compounds. Using 2-phenylpyridine as a model substrate, it was observed that deuteration occurred preferably at the α position of the nitrogen atom, which is the most accessible position for the C-H activation. In addition, Ni@IMes NPs are also able to fully deuterate the ortho positions of the phenyl substituents.

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., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

The preparation of N-heterocyclic carbene-stabilized iridium nanoparticles and their application in hydrogen isotope exchange reactions is reported. These air-stable and easy-to-handle iridium nanoparticles showed a unique catalytic activity, allowing selective and efficient hydrogen isotope incorporation on anilines using D 2 or T 2 as isotopic source. The usefulness of this transformation has been demonstrated by the deuterium and tritium labeling of diverse complex pharmaceuticals., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Activation of H-H, Si-H, and C-H bonds through σ-bond coordination has grown in the past 30 years from a scientific curiosity to an important tool in the functionalization of hydrocarbons. Several mechanisms were discovered via which the initially σ-bonded substrate could be converted: oxidative addition, heterolytic cleavage, σ-bond metathesis, electrophilic attack, etc. The use of metal nanoparticles (NPs) in this area is a more recent development, but obviously nanoparticles offer a much richer basis than classical homogeneous and heterogeneous catalysts for tuning reactivity for such a demanding process as C-H functionalization. Here, we will review the surface chemistry of nanoparticles and catalytic reactions occurring in the liquid phase, catalyzed by either colloidal or supported metal NPs. We consider nanoparticles prepared in solution, which are stabilized and tuned by polymers, ligands, and supports. The question we have addressed concerns the differences and similarities between molecular complexes and metal NPs in their reactivity toward σ-bond activation and functionalization.

Bimetallic ruthenium-platinum nanoparticles (RuPt NPs) of different surface distributions and stabilized by using a sulfonated N-heterocyclic carbene ligand (1-(2,6-diisopropylphenyl)-3-(3-potassium sulfonatopropyl)-imidazol-2-ylidene) were prepared from Ru(COD)(COT) (COD = cyclooctadiene and COT = cyclooctatriene), and platinum precursors having various decomposition rates (Pt(NBE) 3 , NBE = norbornene, Pt(CH 3 ) 2 (COD) and Pt 2 (DBA) 3 , DBA = dibenzylideneacetone). Structural and surface studies by FT-IR and solid-state MAS NMR, using carbon monoxide as a probe molecule, revealed the presence of different structures and surface compositions for different nanoparticles of similar sizes, which principally depend on the decomposition rate of the organometallic precursors used during the synthesis. Specifically, the slower the decomposition rate of the platinum precursor, the higher the number of Pt atoms at the NP surface. The different bimetallic RuPt NPs, as well as their monometallic equivalents (Pt and Ru NPs), were used in isotopic H/D exchange through C-H activation on l-lysine. Interestingly, the activity and selectivity of the direct C-H deuteration were dependent on the NP surface composition at the α position but not on that at the ε position. Chemical shift perturbation (CSP) experiments revealed that the difference in reactivity at the α position is due to a Pt-carboxylate interaction, which hinders the H/D exchange.

A general approach for the efficient hydrogen-isotope exchange of nucleobase derivatives is described. Catalyzed by ruthenium nanoparticles, using mild reaction conditions, and involving either D 2 or T 2 as isotopic sources, this reaction possesses a wide substrate scope and a high solvent tolerability. This novel method facilitates the access to essential diagnostic tools in drug discovery and development: tritiated pharmaceuticals with high specific activities and deuterated oligonucleotides suitable for use as internal standards during LC-MS quantification., (© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)