Sylvain Roland

N‐heterocyclic carbene‐capped cyclodextrin (ICyD) ligands, α‐ICyD and β‐ICyD derived from α‐ and β‐cyclodextrin, respectively give opposite regioselectivities in a copper‐catalyzed hydroboration. The site‐selectivity results from two different mechanisms: the conventional parallel one and a new orthogonal mechanism. The shape of the cavity was shown not only to induce a regioselectivity switch but also a mechanistic switch. The scope of interest of the encapsulation of a reactive center is therefore broadened by this study.

N‐heterocyclic carbene‐capped cyclodextrin (ICyD) ligands, α‐ICyD and β‐ICyD derived from α‐ and β‐cyclodextrin, respectively give opposite regioselectivities in a copper‐catalyzed hydroboration. The site‐selectivity results from two different mechanisms: the conventional parallel one and a new orthogonal mechanism. The shape of the cavity was shown not only to induce a regioselectivity switch but also a mechanistic switch. The scope of interest of the encapsulation of a reactive center is therefore broadened by this study.

N-Heterocyclic carbenes (NHCs) have emerged as a new class of ligands for materials chemistry that appears particularly relevant for metal nanocrystals stabilization and functionalization. The particular properties and high synthetic flexibility of NHCs make them highly attractive tools for the development of new (nano)materials and the fundamental study of their properties. The relationships between the NHC structure and nanocrystal (NC) structure/properties, including physical, biological or self-assembling properties, remain largely unknown. In the last decade, many efforts have been made to gain more fundamental understanding in this area. In this feature article, we present our contribution in this field focusing on the formation of NHC-based Au NCs, their stability, and their ability to self-assemble in 3D crystalline structures called supracrystals. First, the formation of stabilized NHC-based Au NCs is discussed by comparing different NHC structures, NHC-based Au precursors, and synthetic methods. This study shows the major role of the NHC structure to obtain both stable NHC-coated Au NCs and narrow size distributions. In a second part, a comparative study of the oxygen resistance of NHC- and thiol-based NCs is presented, demonstrating the enhanced stability of NHC-coated Au NCs to oxygen-based treatments. Finally, the self-assembly of NHC-coated Au NCs into 3D Au superlattices is presented. The formation of large organized domains of several micrometers is described from the design of NHCs tailored with long alkyl chains. In these different contexts, efforts have been made to get more in-depth understanding of the behavior of NHC ligands at the surface of nanocrystals. These results show that the NHC-based approach to nanomaterials has many assets to open a new research area in the supracrystal world.

The stability of Au nanocrystals (NCs) coated with different N-heterocyclic carbenes (NHCs) or dodecanethiol (DDT) to oxygen-based treatments was investigated. A dominant effect of the ligand type was observed with a significantly greater oxygen resistance of NHC-coated Au NCs compared to that of the thiol-based analogues. NHC-coated Au NCs are stable to 10 W oxygen plasma etching for up to 180 s whereas the integrity of DDT-coated Au NCs is strongly affected by the same treatment from 60–80 s. In the latter case, the average size of the NCs (from 2.6 to 6.3 nm) and the method of synthesis have no effect on the stability. NHC-coated Au NCs were found to generate of a smaller quantity of ligand-derived species under molecular oxygen treatment, which could account for the increased stability.

A set of molecules including a majority of metal‐N‐heterocyclic carbene (NHC) complexes (metal=Ag, Cu, and Au) and azolium salts were evaluated by high‐throughput screening of their activity against biofilm formation associated with pathogenic bacteria. The anti‐planktonic effects were compared in parallel. Representative biofilm‐forming strains of various genera were selected (Listeria,Pseudomonas,Staphylococcus, andEscherichia). All the compounds were tested at 1 mg L⁻¹by using the BioFilm Ring Test. An information score (IS, sum of the activities) and an activity score (AS, difference between anti‐biofilm and anti‐planktonic activity) were determined from normalized experimental values to classify the most active molecules against the panel of bacterial strains. With this method we identified lipophilic Ag^Iand Cu^Icomplexes possessing aromatic groups on the NHC ligand as the most efficient at inhibiting biofilm formation.

Synthesizing stable Au and Ag nanocrystals of narrow size distribution from metal–N-heterocyclic carbene (NHC) complexes remains a challenge, particularly in the case of Ag and when NHC ligands with no surfactant-like properties are used. The formation of nanocrystals by one-phase reduction of metal–NHCs (metal = Au, Ag) bearing common NHC ligands, namely 1,3-diethylbenzimidazol-2-ylidene (L¹), 1,3-bis(mesityl)imidazol-2-ylidene (L²), and 1,3-bis(2,6-ⁱPr₂C₆H₃)imidazol-2-ylidene (L³), is presented herein. We show that both Au and Ag nanocrystals displaying narrow size distribution can be formed by reduction with amine–boranes. The efficiency of the process and the average size and size distribution of the nanocrystals markedly depend on the nature of the metal and NHC ligand, on the sequence in the reactant addition (i.e., presence or absence of thiol during the reduction step), and on the presence or absence of oxygen. Dodecanethiol was introduced to produce stable nanocrystals associated with narrow size distributions. A specific reaction is observed with Ag–NHCs in the presence of thiols whereas Au–NHCs remain unchanged. Therefore, different organometallic species are involved in the reduction step to produce the seeds. This can be correlated to the lack of effect of NHCs on Ag nanocrystal size. In contrast, alteration of Au nanocrystal average size can be achieved with a NHC ligand of great steric bulk (L³). This demonstrates that a well-defined route for a given metal cannot be extended to another metal.

Fourteen silver(I) complexes bearingN‐heterocyclic carbene (NHC) ligands were prepared and evaluated for anticancer activity. Some of these were found to exhibit potent antiproliferative activity toward several types of human cancer cell lines, including drug‐resistant cell lines, with IC₅₀values in the nanomolar range. An initial investigation into the mechanism of cell death induced by this family of silver(I) complexes was carried out. Cell death was shown to result from the activation of apoptosis without involvement of primary necrosis. In HL60 cells, silver–NHCs induce depolarization of the mitochondrial membrane potential (ΔΨ_m) and likely allow the release of mitochondrial proteins to elicit early apoptosis. This effect is not related to the overproduction of reactive oxygen species (ROS). In addition, apoptosis is not associated with the activation of caspase‐3, but is triggered by the translocation of apoptosis‐inducing factor (AIF) and caspase‐12 from mitochondria and the endoplasmic reticulum, respectively, into the nucleus to promote DNA fragmentation and ultimately cell death. No modification in cell‐cycle distribution was observed, indicating that silver–NHCs are not genotoxic. Finally, the use of a fluorescent complex showed that silver–NHCs target mitochondria. Altogether, these results demonstrate that silver–NHCs induce cancer cell death independent of the caspase cascade via the mitochondrial AIF pathway.