Search Results (131)

We report the synthesis and biological characterization of N-heterocyclic carbene (NHC) complexes with gold(I), silver(I), copper(I), and palladium(II) metal centers, and 3-(2,6-diisopropyl-phenyl) imidazolinium- and imidazolium-based ligands, including their biscarbene complexes, along with metal complexes of 4-(S)-tert-butyl-imidazolinium-derived carbenes carrying various substituents in position 1. Compared to the imidazolium complexes, the corresponding imidazolinium complexes displayed superior cytotoxicity against the Mes-Sa uterine sarcoma cell line, while the biscarbene complexes exhibited greatly enhanced cytotoxicity with nanomolar activity. The ABCB1-overexpressing multidrug-resistant sublines of Mes-Sa demonstrated only marginal resistance to monocarbene imidazolinium complexes lacking a 4-(S)-tert-butyl group, whereas significant resistance was observed for all other complexes, with its extent further influenced by the nature of the metal center. Probing a subset of the complexes confirmed their strong cytotoxicity against the CST murine breast cancer cell line and its cisplatin-resistant variant, with little or no cross-resistance observed. Within a defined subset, compounds triggered apoptosis, and intracellular ROS production was consistently induced by the copper complexes. Collectively, these results indicate that imidazolinium-based metal NHCs are promising anticancer drug candidates, with copper and silver centers standing out for their potent cytotoxicity and evasion of both ABCB1-mediated and cisplatin resistance. Full article

Transition metal complexes bearing protic N-heterocyclic carbene (pNHC) ligands are promising precatalysts for organic reactions due to their capacity for unique hydrogen-bonding interactions. Herein, we report the synthesis and structural characterization of the first Pd(II) complex featuring a pNHC derived from 1,2,4-triazole—a heterocyclic system previously unexplored for the preparation of metal/pNHC complexes. The complex was synthesized via oxidative addition of 3-bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole to Pd(PPh₃)₄ in the presence of NH₄BF₄. Its molecular structure was characterized by NMR spectroscopy and X-ray diffraction analysis. Full article

In this review, we focused on advances made over the last two decades in the field of catalysis using N-heterocyclic carbenes (NHCs), which can be used for metallic or non-metallic catalysis. We listed the advantages of these NHCs and their modes of action in various couplings. With regard to metal catalysis, we have focused here on palladium and nickel catalysis, and then we looked at their use without transition metals. The work mentioned, in this review, only concerns research carried out under sustainable conditions, both in terms of the types of reactions and reaction conditions used (solvents, quantities, accessibility, and easy purification). Full article

This review updates the field of enantioselective copper-catalysed domino reactions promoted by chiral green copper catalysts, covering the literature since 2017. These complexes are derived from a diversity of chiral ligands, including mostly bisoxazolines and biphosphines along with monophosphines, N-heterocyclic carbenes, proline derivatives, phosphoric acids, phosphoramidates, and different types of N,N-ligands. The review shows that asymmetric copper catalysis, that suits the growing demand for greener processes, offers a real opportunity to replace toxic and expensive metals in the near future. Full article

N-heterocyclic carbenes (NHCs) have demonstrated their versatility as catalysts for new activations and synthetic transformations of aldehydes. NHCs were originally applied in benzoin condensation and the Stetter reaction, while the development of new protocols under oxidative conditions has further expanded the potential of this methodology for the formation of carbon−carbon and carbon−heteroatom bonds. Among these reactions, NHCs are recognized as promising organocatalysts for the aerobic oxidation of aldehydes to carboxylic acids. However, to our knowledge, a comparison with other metal-free protocols has never been conducted. This review is intended to provide a perspective on aldehyde oxidation into the corresponding carboxylic acid catalyzed by NHCs, from its first practical description in 2009 until the beginning of 2025, and to compare it with other metal-free methods. Full article

Neurodegenerative diseases (NDDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD), are characterized by progressive neuronal dysfunction and loss and represent a significant global health challenge. Oxidative stress, neuroinflammation, and neurotransmitter dysregulation, particularly affecting acetylcholine (ACh) and monoamines, are key hallmarks of these conditions. The current therapeutic strategies targeting cholinergic and monoaminergic systems have some limitations, highlighting the need for novel approaches. Metallodrugs, especially ruthenium and platinum complexes, are gaining attention for their therapeutic use. Among metal complexes, gold(I) and silver(I) N-heterocyclic carbene (NHC) complexes exhibit several biological activities, but their application in NDDs, particularly as monoamine oxidase (MAO) inhibitors, remains largely unexplored. To advance the understanding of this field, we designed, synthesized, and evaluated the biological activity of a new series of Au(I) and Ag(I) complexes stabilized by NHC ligands and bearing a carboxylate salt of tert-butyloxycarbonyl (Boc)-N-protected proline as an anionic ligand. Through in silico and in vitro studies, we assessed their potential as acetylcholinesterase (AChE) and MAO inhibitors, as well as their antioxidant and anti-inflammatory properties, aiming to contribute to the development of potential novel therapeutic agents for NDD management. Full article

N-heterocyclic carbenes (NHCs) were first isolated as stable species by Arduengo in 1991. Since then, they have expanded the boundaries of carbene chemistry and sparked extensive research. Utilizing NHCs to modify the electronic properties of transition metal complexes represents a significant advancement in the field. Pincer-type NHCs, which occupy half or more of the vacant sites on metal centers, typically result in structurally well-defined molecular platforms with specific active sites for a variety of applications. This review provides an overview of late transition metal complexes based on pincer-type NHCs, discussing their synthetic strategies, reactivities, and electronic properties, as well as their applications. Additionally, some perspectives will be presented to highlight future directions in this rapidly growing field. Full article

Liquid crystals exhibit unique properties that can be tailored in response to external stimuli. Significant research is directed toward the development of luminescent materials exhibiting liquid crystallinity for various applications. The present work reports Au(I) complexes featuring N-heterocyclic carbene and phenyl acetylide ligands. Metal complexes enable the utilization of the triplet excitons through their inherent spin–orbit coupling, promoting intersystem crossing from singlet (S_n) to triplet (T_n) states to observe room-temperature phosphorescence (RTP). The strong bonds between carbene and Au enhance the thermal stability, and the substituted benzimidazole ring alters the thermodynamic and photophysical properties of the complexes. Incorporating the acetylide ligands with long alkoxy chains led to the formation of liquid crystalline (LC) phases, which exhibited stability over a wide temperature range. Additionally, the luminescence behavior was affected by the ethynyl ligands, and high quantum yields of RTP were observed. This study establishes the development of LC Au(I) complexes with a thermodynamically stable LC mesophase over a wide temperature range for applications in the field of light-emitting functional materials. Full article

The reactions of N-heterocyclic carbenes (IMesNHC and IPrNHC) with transition metal carbonyls of group VI (Cr(CO)₆, Mo(CO)₆, and W(CO)₆) were carried out in acetonitrile in simple one-pot syntheses and led to the formation of the coordination compounds IMesNHC–Cr(CO)₅ (1a), IMesNHC–Mo(CO)₅ (2a), IMesNHC–W(CO)₅ (3a), IPrNHC–Cr(CO)₅ (1b), IPrNHC–Mo(CO)₅ (2b), and IPrNHC–W(CO)₅ (3b). With the exception of 1b, the coordination compounds were formed selectively and in high yields. The method represents an effective and easy-to-perform alternative to the previously described methods for NHC–M(CO)₅ (M = Cr, Mo, W). All prepared compounds were characterized by NMR and Raman spectroscopy. Compounds 1a, 2a, 3a, and 2b were also crystallized and structurally characterized by X-ray structure analysis. Finally, the structural features of all compounds were compared with DFT calculations of structurally optimized coordination compounds. Full article

Approaches capable of simultaneously treating cancer and protecting susceptible patients from lethal infections are highly desirable, although they prove challenging. Taking inspiration from the well-known anticancer platinum complexes, successive studies about the complexation of organic compounds with other late transition metals, such as silver, gold, palladium, rhodium, ruthenium, iridium, and osmium, have led to remarkable anticancer activities. Among the numerous chemical moieties studied, N-heterocyclic carbenes (NHCs) have revealed very attractive activities due to their favorable chemical properties. Specifically, gold–NHC complexes emerged as some of the most active complexes acting as antitumor agents. On the other hand, some recent studies have highlighted the involvement of these complexes in antiviral research as well. The well-known gold-based, orally available complex auranofin approved by the Food and Drug Administration (FDA) for the treatment of rheumatoid arthritis has been suggested as a repositioned drug for both cancer and viral infections. In the era of the COVID-19 pandemic, the most interesting goal could be the discovery of gold–NHC complexes as dual antiviral and anticancer agents. In this review, the most recent studies regarding the anticancer and antiviral activities of gold(I)–NHC complexes will be analyzed and discussed, offering an interesting insight into the research in this field. Full article

The strict connections/interactions between microbial infections and cancer are nowadays widely accepted. Hence, the dual (or multiple) targeting of microbial infections and cancer is an essential issue to be addressed. In this context, metal complexes have gained considerable importance and effectiveness in medicinal chemistry. Particularly, N-heterocyclic carbene (NHC) complexes with transition metals have emerged as very promising compounds. Among the myriad of NHC–metal complexes, those bearing silver will be the subject of this review. Numerous Ag(I)-NHC complexes have revealed high antibacterial and/or anticancer properties, even higher than those of reference drugs. Herein, we summarize the most recent studies while also discussing the proposed mechanism of action and offering an interesting remark about the research in this field. Literature databases (PubMed/MEDLINE, Scopus, and Google Scholar) were used as sources to search the literature, referring to the last five years. Full article

Background/Objectives: Infectious diseases represent a serious threat due to rising antimicrobial resistance, particularly among multidrug-resistant bacteria and influenza viruses. Metal-based complexes, such as N-heterocyclic carbene–gold (NHC–gold) complexes, show promising therapeutic potential due to their ability to inhibit various pathogens. Methods: Eight NHC–gold complexes were synthesized and tested for antibacterial activity against Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and for anti-influenza activity in lung and bronchial epithelial cells infected with influenza virus A/H1N1. Antibacterial activity was assessed through the determination of the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC), while the viral load was quantified using qRT-PCR. Results: Complexes 3, 4, and 6 showed significant antibacterial activity at concentrations of 10–20 µg/mL. Additionally, these complexes significantly reduced viral load, with complexes 3 and 4 markedly inhibiting replication. Conclusions: These findings support the potential use of NHC–gold complexes in combined antimicrobial and antiviral therapies, representing an attractive option for fighting resistant infections. Full article

N-heterocyclic carbene (NHC)–gold and –silver complexes have attracted the interest of the scientific community because of their multiple applications and their versatility in being chemically modified in order to improve their biological properties. However, most of these complexes contain one or more chiral centers, and have been obtained and studied as racemic mixture. In particular, concerning the interesting biological and medicinal properties, many questions about how the chirality may influence these properties still remain unanswered. Aiming at a better understanding, herein a series of enantiopure NHC–gold and –silver complexes was synthesized, characterized and biologically evaluated in different in vitro systems. The individuated complexes exerted different properties based on the complexed metal and the specific configuration, with the (R)-gold–NHC complexes being the most active, particularly as anti-inflammatory molecules. Docking simulations indicated a different binding mode for each enantiomer. Moreover, anticancer and antibacterial activities were also evaluated for the considered enantiomers. Overall, the reported data may contribute to a better understanding of the different biological properties exerted by the enantiopure gold and silver complexes. Full article

Carbon–carbon bond formation represents a key reaction in organic synthesis, resulting in paramount importance for constructing the carbon backbone of organic molecules. However, traditional metal-based catalysis, despite its advantages, often struggles with issues related to efficiency, selectivity, and sustainability. On the other hand, while biocatalysis offers superior selectivity due to an extraordinary recognition process of the substrate, the scope of its applicable reactions remains somewhat limited. In this context, Artificial Metalloenzymes (ArMs) and Metallo Peptides (MPs) offer a promising and not fully explored solution, merging the two fields of transition metal catalysis and biotransformations, by inserting a catalytically active metal cofactor into a customizable protein scaffold or coordinating the metal ion directly to a short and tunable amino acid (Aa) sequence, respectively. As a result, these hybrid catalysts have gained attention as valuable tools for challenging catalytic transformations, providing systems with new-to-nature properties in organic synthesis. This review offers an overview of recent advances in the development of ArMs and MPs, focusing on their application in the asymmetric carbon–carbon bond-forming reactions, such as carbene insertion, Michael additions, Friedel–Crafts and cross-coupling reactions, and cyclopropanation, underscoring the versatility of these systems in synthesizing biologically relevant compounds. Full article

This study investigates the antibacterial N-heterocyclic carbene (NHC)–silver complexes using the SwissADME platform, a web-based tool developed by the Swiss Institute of Bioinformatics (SIB). NHCs, particularly their silver complexes, have gained significant interest in medicinal chemistry for their potential as antibacterial and anticancer agents. The effectiveness of these complexes is closely linked to their structure, including factors like lipophilicity, which enhance their ability to penetrate bacterial cells and sustain the release of active silver ions. SwissADME provides computational estimates of pharmacokinetic properties, including absorption, distribution, metabolism, and excretion (ADME) characteristics, as well as drug-likeness and toxicity assessments. By evaluating parameters like molecular weight, topological polar surface area, lipophilicity (LogP), and water solubility, SwissADME offers insights into the drug-like potential of compounds. This study is inspired by a comprehensive review of antibacterial NHC–silver complexes published from 2006 to 2023, which identified superior structures with notable biological activity. The primary aim is to determine whether these active complexes exhibit distinct SwissADME parameters compared to others, providing a deeper understanding of the factors that influence their biological efficacy and aiding in the identification of promising drug candidates. Finally, experimental stabilities of exemplary complexes were confronted with absolute LUMO values derived from DFT calculations. Full article