Metal N-heterocyclic Carbene Complexes Research Articles

Nickel and palladium N-heterocyclic carbene complexes. Synthesis and application in cross-coupling reactions

N-Heterocyclic carbenes (NHCs) are widely used as ligands in catalysis by transition metal complexes. The catalytic activity of transition metal NHC complexes is much higher than that of the transition metal complexes bearing the phosphine and nitrogen-containing ligands. They show excellent catalytic performance in different transformations of the organic compounds, especially in the carbon—carbon and carbon—element bond forming reactions. Palladium NHC complexes are very efficient catalysts for the cross-coupling reactions. On the other hand, nickel is less expensive and regarded as a promising alternative to palladium and, therefore, it attracts increasing attention from the researches. The present review is focused on the recent advances in the synthesis of N-heterocyclic carbene complexes of nickel and palladium and their application in catalysis of cross-coupling reactions of organic, organoelement and organometallic compounds with organic halides.

N-Heterocyclic Carbene Coinage Metal Complexes Containing Naphthalimide Chromophore: Design, Structure, and Photophysical Properties

A series of novel N-heterocyclic carbene coinage metal complexes containing a naphthalimide (NI) chromophore has been prepared and fully characterized. Two types of molecules are described those where the NI unit is directly attached to the carbene unit with the general formulae [(L1)–M–X], M = Cu, X = Cl (1a); M = Ag, X = I (1b) and M = Au, X = Cl, (1c). While in the second family, a π-extended carbene ligand precursor L2–H+I− (3) was prepared where the NI unit is distant from the imidazole unit via a phenyl-alkyne bridge. Only two N-heterocyclic carbene metal complexes were prepared [(L2)–M–Cl], M = Cu (2a) and M = Au (2c). The related silver carbene compound could not be isolated. The molecular structure of the carbene complex 1c was determined and confirmed the formation of the target compound. Interestingly, the structure shows the presence of an aurophilic interaction Au···Au at 3.407 Å between two individual molecules. The photophysical properties of the compounds were investigated in solution at room temperature. Preliminary results suggested that all compounds are luminescent and act as blue emitters (420–451 nm). These transition emissions can be attributed to the intraligand origin of the NI chromphore. Moreover, the carbene complexes featuring L2 ligand with π-extended system were found to be more luminescent.

Synthesis, Structure and Antitumoural Activity of Triazole‐Functionalised NHC–Metal Complexes

Silver(I), gold(I), copper(I) and ruthenium(II) N‐heterocyclic carbene (NHC) complexes have been synthesised and their cytotoxic activities towards various cancer cell lines have been evaluated. The N‐heterocyclic carbene ligand has been functionalised with a 1,2,3‐triazole moiety tethered in the backbone of the ligand. The molecular structure of the silver(I) and gold(I) complexes has been solved by X‐ray diffraction analysis. The AgI, AuI and RuII complexes display good stability in aqueous conditions and show cytotoxic activities comparable or slightly superior to those of similar unfunctionalised complexes.

Synthesis and investigation of new cyclic haloamidinium salts

AbstractThe presented work describes the synthesis of new six- and seven-membered haloamidinium salts and their reaction with different metals. The isolated metal complexes were tested in a catalytic reaction. Two different synthetic routes were applied to prepare five different salts. Chloroamidinium salts were very water-sensitive in comparison to their corresponding bromoamidinium salts. Hence, the preparation of the less sensitive bromoamidinium salts was higher prioritized. The formed salts were converted with metal sources to N-heterocyclic carbene (NHC) metal complexes through an oxidative insertion into the C–X bond. This type of formation is less examined for the synthesis of extended NHC metal complexes. Pd(PPh3)4and cobalt powder were applied as metal sources, whereby two palladium complexes were isolated, characterized, and their crystal and molecular structures determined. The palladium complexes were investigated in the Suzuki-Miyaura reaction and showed promising catalytic activity.

Recent Progress of Supported N-Heterocyclic Carbene Catalyst in Organic Reactions

The supported N-heterocyclic carbene (NHC) catalysts have been extensively applied in the catalysis of different organic reactions due to its unique characteristic such as high reactivity, easy separation, purification and recyclability. In this paper, the recent progresses in synthesis and application of supported N-heterocyclic carbene metal complexes based on various types of supports, such as polymer, magnetic nanoparticles, carbon and silica material have been reviewed.

Mechanism of the sequential activation of two C–H bonds of a NHC N-methyl group on a triruthenium carbonyl cluster

Recent experimental studies on metal complexes of N-heterocyclic carbenes (NHCs) showed a few examples of the unique sequential activation of two C–H bonds of NHC N-methyl group on triruthenium carbonyl clusters. However, the corresponding theoretical calculations showed that the reactions are highly endergonic (>40 kcal/mol) and involve very high barriers (up to ~80 kcal/mol), failing to rationalize the experimental observations that the reactions were carried out under mild conditions (<100 °C). The present work re-examines a representative example of the sequential activation of the two C–H bonds with the aid of density functional theory calculations. From the present results, the reaction is predicted to be endergonic by only 14.7 kcal/mol with an overall barrier of 35.1 kcal/mol, which is in good agreement with the experimental observations that the reaction smoothly proceeds under thermal reaction conditions and that the reversed transformation from the product to reactant occurs when carbon monoxide was gently bubbled into the reaction system at room temperature.

Biological Screening of Newly Synthesized BIAN N-Heterocyclic Gold Carbene Complexes in Zebrafish Embryos.

N-Heterocyclic carbene (NHC) metal complexes possess diverse biological activities but have yet to be extensively explored as potential chemotherapeutic agents. We have previously reported the synthesis of a new class of NHC metal complexes N-heterocyclic with acetate [IPr(BIAN)AuOAc] and chloride [IPr(BIAN)AuCl] ligands. In the experiments reported herein, the zebrafish embryos were exposed to serial dilutions of each of these complexes for 10–12 h. One hundred percent mortality was observed at concentrations ≥50 µM. At sub-lethal concentrations (10–30 µM), both compounds influenced zebrafish embryonic development. However, quite diverse categories of abnormalities were found in exposed embryos with each compound. Severe brain deformation and notochord degeneration were evident in the case of [IPr(BIAN)AuOAc]. The zebrafish embryos treated with [IPr(BIAN)AuCl] exhibited stunted growth and consequently had smaller body sizes. A depletion of 30%–40% glutathione was detected in the treated embryos, which could account for one of the possible mechanism of neurotoxicity. The fact that these compounds are capable of both affecting the growth and also compromising antioxidant systems by elevating intracellular ROS production implies that they could play an important role as a new breed of therapeutic molecules.

N-heterocyclic carbene metal complexes as bio-organometallic antimicrobial and anticancer drugs.

Late transition metal complexes that bear N-heterocyclic carbene (NHC) ligands have seen a speedy growth in their use as both, metal-based drug candidates and potentially active homogeneous catalysts in a plethora of C-C and C-N bond forming reactions. This review article focuses on the recent developments and advances in preparation and characterization of NHC-metal complexes (metal: silver, gold, copper, palladium, nickel and ruthenium) and their biomedical applications. Their design, syntheses and characterization have been reviewed and correlated to their antimicrobial and anticancer efficacies. All these initial discoveries help validate the great potential of NHC-metal derivatives as a class of effective antimicrobial and anticancer agents.

ChemInform Abstract: Post‐Functionalization of Metal‐NHC Complexes: A Useful Toolbox for Bioorganometallic Chemistry (And Beyond)?

AbstractReview: 109 refs.

Crystal Structure Studies towards the Synthesis and Applications of N-heterocyclic Carbene–Metal Complexes Derived from [2.2]Paracyclophane

The crystal structures of six planar chiral N-heterocyclic carbene (NHC) precursors and one NHC–Rh complex derived from [2.2]paracyclophane were described. The NHC–metal complexes were prepared to examine their catalytic activities toward the Rh-catalyzed asymmetric addition of phenylboronic acid to 1-naphthaldehyde. The results were correlated to the single-crystal crystallographic studies. The novel NHC precursor 5 can achieve high catalytic activity in the asymmetric addition of phenylboronic acid to 1-naphthaldehyde.

N-heterocyclic carbene metal complexes: photoluminescence and applications

This review covers the advances made in the synthesis of luminescent transition metal complexes containing N-heterocyclic carbene (NHC) ligands. The presence of a high field strength ligand such as an NHC in the complexes gives rise to high energy emissions, and consequently, to the desired blue colour needed for OLED applications. Furthermore, the great versatility of NHC ligands for structural modifications, together with the use of other ancillary ligands in the complex, provides numerous possibilities for the synthesis of phosphorescent materials, with emission colours over the entire visible spectra and potential future applications in fields such as photochemical water-splitting, chemosensors, dye-sensitised solar cells, oxygen sensors, and medicine.

ChemInform Abstract: Metal N‐Heterocyclic Carbene Complexes as Potential Antitumor Metallodrugs

AbstractReview: 214 refs.

Group XII Metal–N-Heterocyclic Carbene Complexes: Synthesis, Structural Diversity, Intramolecular Interactions, and Applications

This review covers the different methods for the synthesis of group XII metal–NHC complexes with five- and six-membered NHC systems that have different N-heterocyclic cores: viz., imidazole, triazole, tetrazole, pyridine-fused imidazole, ruthenocene-fused imidazole, pyrimidine, and benzimidazole. Moreover, this review focuses on the structural divergence of group XII metals toward NHCs and their interesting intramolecular interactions as well as their suitable applications in the field of catalysis and carbene transfer. Several Zn–NHC complexes were used as catalysts in lactide polymerization because of their stability and suitable stereochemically diverse topologies. The structural diversity of both single- and double-site chelates of group XII metals, which bear NHC ligands, was reviewed. In particular, we aim to evaluate the widely adopted Et2Zn, ZnCl2, Me2Cd, and Hg(II) acetate techniques for the preparation of group XII metal(II)–NHC complexes and their subsequent catalysis (Zn–NHCs) as well as carbe...

Isolation of N-Heterocyclic Alkyl Intermediates en Route to Transition Metal N-Heterocyclic Carbene Complexes: Insight into a C–H Activation Mechanism

An imidazolinium cation has been incorporated into an arene-linked diphosphine pincer ligand, [2]+, and the metalation of this ligand has been investigated via direct imidazolinium C–H activation to Pd0 and Pt0. The expected NHC-ligated metal-hydride species [5]PF6 (M = Pt) and 6 (M = Pd) are obtained if the halide-free imidazolinium salt [2]PF6 is used. In contrast, treatment of the imidazolinium chloride salt [2]Cl with M(PPh3)4 leads to isolation of N-heterocyclic alkyl MII species 3 (M = Pd) and 4 (M = Pt), in which the imidazolinium C–H bond remains intact. Interestingly, there are no apparent agostic interactions between the imidazolinium protons and the metal centers in 3 and 4, indicating that these species represent an unusual type of arrested C–H activation intermediate. While Pd complex 3 is thermally stable, Pt complex 4 undergoes C–H activation to afford the corresponding NHC-PtII-hydride species [5]Cl upon heating. Additionally, both complexes 3 and 4 undergo rapid C–H activation upon abstraction of the metal-bound halide to form 6 and [5]PF6, respectively. The nature of the bonding in the unusual N-heterocyclic alkyl species is investigated computationally.

Metal N-heterocyclic carbene complexes as potential antitumor metallodrugs

The discovery of cisplatin's antitumor activity in 1969 prompted the search for novel metal-containing complexes as potential anticancer drugs. Among these novel complexes, metal N-heterocyclic carbene (NHC) complexes have recently gained considerable attention because they perfectly fit prerequisites for efficient drug design and fast optimization. Moreover, most of them have shown higher cytotoxicity than cisplatin. This review describes the advances that have been achieved in using transition metal (Ag, Au, Pt, Pd, Cu, Ni, and Ru) complexes containing NHC ligands as antitumor agents. Their modes of action at the cellular lever are further discussed. All these initial achievements clearly demonstrate the great potential of metal-NHC complexes as antitumor agents.

N-Heterocyclic carbene metal complexes in medicinal chemistry

Metal complexes with N-heterocyclic carbene (NHC) ligands are widely used in chemistry due to their catalytic properties and applied for olefin metathesis among other reactions. The enhanced application of this type of organometallics has over the last few years also triggered a steadily increasing number of studies in the fields of medicinal chemistry, which take advantage of the fascinating chemical properties of these complexes. In fact it has been demonstrated that metal NHC complexes can be used to develop highly efficient metal based drugs with possible applications in the treatment of cancer or infectious diseases. Complexes of silver and gold have been biologically evaluated most frequently but also platinum or other transition metals have demonstrated promising biological properties.

Group 7 transition metal complexes with N-heterocyclic carbenes

This tutorial review summarizes all works and highlights recent advances published in the growing field of group 7 N-heterocyclic carbene (NHC) complexes. It provides a valuable source for all scientists that are interested in conducting research with new compounds bearing these metals. The article provides an overview of all manganese NHC complexes that are known to date. There are a lot of examples where manganese NHC complexes show unpredicted behaviour during synthesis, very different from other transition metal NHC complexes and their higher homologues rhenium and technetium. These differences are depicted and discussed. Furthermore, the chemistry of technetium NHC compounds and their chemical behaviour are discussed. To date published work on technetium NHC chemistry has been restricted to the oxidation state +v. It was found that such compounds are very reactive but show great stability in dry air. Their radioactivity makes such compounds interesting candidates for radiochemical applications. Since most group 7 NHC chemistry was conducted on rhenium NHC complexes, this tutorial review highlights the chemical behaviour of such compounds. Rhenium(i) complexes reveal luminescent properties, making them interesting candidates for applications ranging from biological markers to organic light-emitting diodes (OLEDs). Another interesting feature is the radioactivity of some compounds, which makes them excellent candidates for radiopharmaceutical research; hence their synthesis and reactivity are discussed.

Imidazol(in)ium-2-Carboxylates as Efficient Precursors to N-Heterocyclic Carbene Complexes of Copper and Silver

Copper and silver N-heterocyclic carbene (NHC) complexes were prepared through a simple, base-free protocol involving the decomposition of corresponding imidazol(in)ium-2-carboxylates under thermolytic conditions and a subsequent reaction of the in situ generated carbenes with copper(I) or silver(I) chloride, respectively. The desired NHC metal complexes were isolated with good yields after simple crystallization.

Synthesis and Biological Activity of Ester- and Amide-Functionalized Imidazolium Salts and Related Water-Soluble Coinage Metal N-Heterocyclic Carbene Complexes

N-Heterocyclic carbene (NHC) ligand precursors, namely, HIm(A)Cl [1,3-bis(2-ethoxy-2-oxoethyl)-1H-imidazol-3-ium chloride] and HIm(B)Cl {1,3-bis[2-(diethylamino)-2-oxoethyl]-1H-imidazol-3-ium chloride}, functionalized with hydrophilic groups on the imidazole rings have been synthesized and were used in the synthesis of corresponding carbene complexes of silver(I) and copper(I), {[Im(A)]AgCl}, {[Im(A)]CuCl}, and {[Im(B)](2)Ag}Cl. Related Au(I)NHC complexes {[Im(A)]AuCl} and {[Im(B)]AuCl} have been obtained by transmetalation using the silver carbene precursor. These compounds were characterized by several spectroscopic techniques including NMR and mass spectroscopy. HIm(B)Cl and the gold(I) complexes {[Im(A)]AuCl} and {[Im(B)]AuCl} were also characterized by X-ray crystallography. The cytotoxic properties of the NHC complexes have been assessed in various human cancer cell lines, including cisplatin-sensitive and -resistant cells. The silver(I) complex {[Im(B)](2)Ag}Cl was found to be the most active, with IC(50) values about 2-fold lower than those achieved with cisplatin in C13*-resistant cells. Growth-inhibitory effects evaluated in human nontransformed cells revealed a preferential cytotoxicity of {[Im(B)](2)Ag}Cl versus neoplastic cells. Gold(I) and silver(I) carbene complexes were also evaluated for their ability to in vitro inhibit the enzyme thioredoxin reductase (TrxR). The results of this investigation showing that TrxR appeared markedly inhibited by both gold(I) and silver(I) derivatives at nanomolar concentrations clearly point out this selenoenzyme as a protein target for silver(I) in addition to gold(I) complexes.

Carbene Transfer Reactivities of Nickel(II)–N-Heterocyclic Carbene Complexes and Their Applications in the Synthesis of Metal–NHC Complexes

We describe a new synthetic procedure for transition-metal N-heterocyclic carbene complexes (NHCs). A number of Pd(II), Pt(II), Co(III), and Ru(II) complexes containing functionalized NHCs have been obtained in good to excellent yields using NiII–NHC complexes as carbene transfer reagents. NiII–NHC complexes are easily prepared from the direct reactions of the corresponding imidazolium salts with commercially available Raney nickel powder. The byproduct of transmetalation reactions, NiCl2, can be easily removed by simple filtration. This study offers a new, economical, and practical synthetic method for metal–NHC complexes.