Silver Carbene Research Articles

Silver-Catalyzed Asymmetric Insertion into Phenolic O-H Bonds using Aryl Diazoacetates and Theoretical Mechanistic Studies.

An enantioselective insertion reaction of silver carbenes generated from donor-acceptor-substituted diazo compounds into the O-H bond of phenols was developed. A homobinuclear silver complex with a chiral phosphorous ligand was created in situ from AgNTf2 and (S)-XylylBINAP (in a 2:1 mole ratio). Detailed mechanistic studies using combined experimental and computational techniques revealed that one silver atom center of the catalyst forms a silver carbene and another one works as a Lewis acid for the nucleophilic addition of a phenol. Two counter-anions, two water molecules, and two silver atoms cooperatively mediate the subsequent protonation event to lower the activation energy and control enantioselectivity, affording an array of valuable α-aryl-α-aryloxy esters.

Synthesis, characterization, crystal structure and antibacterial properties of N– and O–functionalized (benz)imidazolium salts and their N–heterocyclic carbene silver(I) complexes

Here, two series of structurally and electronically varied benzonitrile and coumarin substituted imidazolium (2–5) and benzimidazolium (7–10) hexafluorophosphate salts and corresponding NHC silver(I) complexes (11–18) are reported. Substituents on the coumarin ring are varied with an intention of bringing appropriate electronic changes in the complex, which facilitates the targeted activity. Additionally, the structure of two azolium salts (2 and 7) has been established by SCXRD technique. Extended structure of these salts witnessed a series of hydrogen bonds between the azolium cations and the hexafluorophosphate anions along with moderate π–π stacking interactions operating between the adjacent heterocyclic and/or aromatic rings such as coumarin, (benz)imidazole and benzonitrile phenyl systems. Further, a preliminary antibacterial study of the representative salts and silver complexes against a Gram positive (S. aureus, ATCC 29213) and a Gram negative (E. coli, ATCC 25922) bacteria has been carried out. Both the series of silver complexes demonstrated potent antibacterial activity with a MIC of 8/16 μg/mL against E. coli, while there activity against S. aureus found moderate with a MIC in the range 32–128 μg/mL. Furthermore, the salts evidenced no activity in the working concentration range against tested bacteria, indicating that the activity of the complexes is due to the metal center.

Macrometallocycle binuclear NHC silver(I) complex with bridging azobenzene: Synthesis, structure and recognition for hydrogen sulfate

One bis-imidazolium salt 2,2′-di[2’’-(N-methyl-imidazoliumyl)ethoxyl]azobenzene hexafluorophosphate (LH2·(PF6)2) and its macrometallocycle binuclear N-heterocyclic carbene silver(I) complex [(LAg)2](PF6)2 were prepared and characterized. The structure of [(LAg)2](PF6)2 was determined by X-ray single crystal diffraction, 1H NMR and 13C NMR spectroscopy. In complex [(LAg)2](PF6)2, one 34-membered macrometallocycle was formed by two biscarbene ligand L and two silver(I) ions. Additionally, the selective recognition of hydrogen sulfate using [(LAg)2](PF6)2 as a chemosensor was investigated on the basis of fluorescence titrations, ultraviolet titrations, 1H NMR titrations, HRMS and IR spectra. Complex [(LAg)2](PF6)2 was demonstrated to be an effective chemosensor for hydrogen sulfate.

Synthesis and Characterization of Ag(I) Complexes Derived from New N-Heterocyclic Carbenes

Two new unsymmetrical imidazolium salts viz., [1-(4-ethylphenyl)-3-propyl-1H-imidazole-3-ium bromide] (3) and [1-(2,6-dimethylphenyl)-3-propyl-1H-imidazole-3-ium bromide] (4) have been synthesized via the reaction of propyl bromide with imidazole derivatives, [1-(4-ethylphenyl)-1Himidazole] (1) and [1-(2,6-dimethylphenyl)-1H-imidazole] (2) in absence of solvent. Then two new N-heterocyclic carbene silver complexes (5 and 6) were prepared through the reaction of imidazoluim salts (3 and 4) as a source of N-heterocyclic carbene with Ag2O by in situ method. These complexes can be used in the future as a transfer agent for preparing other transitional metal carbine complexes (NHCs) via transmetallation method. The formation of these compounds was confirmed by spectral analysis.

Amine-fnctionalized silver and gold N-heterocyclic carbene complexes: Synthesis, characterization and antitumor properties

Diisopropilamine-tethered benzimidazolium salts have been prepared as precursors for Ag(I)NHC and Au(I)NHC complexes. These NHC ligands were metallated with Ag2O on moderate conditions to give novel silver-NHC complexes. Gold-NHC complexes have been obtained by transmetalation using the silver-NHC precursor. The structures of all compounds were characterized by 1H NMR, 13C NMR, IR and elemental analysis techniques. The cytotoxic properties of the silver(I) and gold(I) complexes have been assessed in various human cancer lines, including cisplatin-sensitive and resistant cell. IC50 values of these four complexes were determined by the MTS based assay on three human cancer cell lines (SHSY5Y, HTC116 and HEP3B) and human healthy cell line (HF). These silver and gold N-heterocyclic carbene complexes have been highlighted metal-based cancer therapeutic agent with unique structures and functions. These strategies provide exciting opportunities for discovering new type metalodrug.

A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis, Characterization, and Biological Studies.

The silver(I) N-heterocyclic carbene (NHC) complex bis(1-(anthracen-9-ylmethyl)-3-ethylimidazol-2-ylidene) silver chloride ([Ag(EIA)2 ]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)2 ]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH-SY5Y neuroblastoma cells. The interactions of [Ag(EIA)2 ]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)2 ]Cl does not react with a few model proteins, but is capable of binding the C-terminal dodecapeptide of thioredoxin reductase hTrxR(488-499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C-terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)2 complexes.

Novel N-heterocyclic carbene silver(I) complexes: Synthesis, structural characterization, and anticancer activity

In this study, we synthesized four novel unsymmetrically substituted NHC ligands (1a-d) and their Ag(I) complexes (2a-d). All new compounds were characterized using elemental analysis, FT-IR, 1H NMR, and 13C NMR spectroscopy and X-ray crystallography. The molecular structure of complex 2d was elucidated through single crystal X-ray diffraction analyses. Single crystal structural studies for complex 2d show that the benzene rings (C9–C14) and the central benzimidazole ring system make dihedral angles of 85.65(11)°. The Ag–Cl and Ag–C single bond lengths are 2.3553(7) and 2.096(2) Å, respectively. The C–Ag–Cl bond angle is 168.27(7)°. Both salts and complexes were tested for their anti-cancer potential against three human cancer cell lines (DU-145, MCF-7, and MDA-MB-231) and non-cancer cells adipose from mouse (L-929) for 24 h, 48 h and 72 h using the MTT assays. However, the Ag(I)–NHC complexes (2a-d) showed a dose and time-dependent cytotoxic activity against all cell lines. MDA-MB-231 human breast carcinoma cells were the most sensitive to the Ag(I)–NHC complex displaying IC50 lower than 1 μM all time points. Further, the IC50s for Ag(I)–NHC were higher in non-cancer cells, suggesting that complexes possessed noteworthy selectivity for human cancer cells.

Dinuclear N-heterocyclic carbene silver complexes: Synthesis, luminescence and catalytic studies

A new dibenzimidazole compound (1) and three dibenzimidazolium salts (2a-2c) were prepared. Reactions of these salts with silver(I) oxide in methanol led to dinuclear N-heterocyclic carbene silver complexes (3a-3c). All of the compounds were characterized by 1H NMR, 13C NMR and elemental analyses. Molecular weights of the silver complexes were confirmed by MALDI-TOF mass spectrometry. Preliminary catalytic studies using all the silver complexes were performed on three-component coupling reaction of p-formaldehyde, piperidine and phenylacetylene. Complexes 3a and 3c exhibited good catalytic activities under neat conditions. The silver complexes showed luminescence properties in CH3CN at room temperature.

Silver carbene complexes: An emerging class of anticancer agents.

Cancer is a major global health problem with large therapeutic challenges. Although substantial progress has been made in cancer therapy, there still remains a need to develop novel and effective treatment strategies to treat several relapsed and refractory cancers. Recently, there has been growing demand for considering organometallics as antineoplastic agents. This review is focused on a group of organometallics, silver N-heterocyclic carbene complexes (SCCs) and their anticancer efficacy in targeting multiple pathways in various in vitro cancer model systems. However, the precise molecular mechanism of SCCs anticancer properties remains unclear. Here, we discuss the SCCs chemistry, potential molecular targets, possible molecular mechanism of action, and their application in cancer therapies.

Synthesis, characterization and anticancer activity of allyl substituted N-Heterocyclic carbene silver(I) complexes

Metal N-heterocyclic carbene (NHC) complexes have attracted considerable attention in biological fields for their potential applications in cancer and antimicrobial therapies. In this study, four new benzimidazole-based N-heterocyclic carbene salts (1a-d) and their silver (I) complexes (2a-d) were synthesized. All new compounds were characterized by elemental analysis, FT-IR, 1H NMR and, 13C NMR spectroscopy. Additionally, single crystal structural studies for complex 2d show that the benzene rings (C9C14) and the central benzimidazole ring system make dihedral angles of 83.58(13)°. The AgCl and AgC single bond lengths are 2.3267(8) and 2.087(3) Å, respectively. The CAgCl bond angle is 175.20(7)°. The prop-1-ene moiety attached at the second N-atom of benzimidazole is disordered at two set of sites with an occupancy ratio of 0.592(6): 0.408(6). There is one intramolecular hydrogen bond interaction between C22A-H22A … N2. The salts and Ag-complexes were further evaluated for their in vitro anticancer activities against DU-145 human prostate cancer cells, MCF-7, MDA-MB-231 human breast cancer cells and L-929 non-cancer cell for 24 h, 48 h and 72 h using the MTT assay. The Ag(I)NHC complexes (2a-d) showed a dose and time-dependent cytotoxic activity against all cell lines. The IC50s for all Ag(I)NHC complexes lower than 1 μM for 72 h time points on cancer cells. The results showed that complex 2d exhibited the highest activity against all cancer cell lines studied. Further, the complexes had relatively higher cytotoxicity to cancer cells than to non-cancer cell lines.

Mononuclear Silver Complexes for Efficient Solution and Vacuum‐Processed OLEDs

AbstractCarbene metal amides are a new class of highly efficient light‐emitting molecules based on a linear donor–metal–acceptor geometry. Here the synthesis, structure, and photo‐ and electroluminescence of carbene silver carbazolato complexes, (AdL)Ag(Cz) [AdL = adamantyl‐substituted cyclic (alkyl)(amino)carbene; Cz = carbazolate (1) and 3,6‐tBu2Cz (2)], are reported. They display green emission with photoluminescence quantum yields of up to 74%. Efficient mixing of triplet and singlet excited states is observed, with sub‐microsecond thermally activated radiative triplet lifetimes. These complexes provide prototype organic light‐emitting diodes based exclusively on silver emitters, with external quantum efficiencies of up to 14%.

Phosphorescent Cyclometalated Platinum(II) aNHC Complexes.

The synthesis and characterization of the first bidentate C^C* cyclometalated platinum(II) complexes based on abnormal N-heterocyclic carbenes (aNHC) is presented. The aNHC ligand precursors are prepared from benzonitriles and anilines to form 1,2,3-trisubstituted imidazolium salts. The title compounds were synthesized by in situ generation of the silver carbene complex, followed by transmetalation to platinum and subsequent introduction of the β-diketonate ligand. Structural characterization by 2D NMR experiments, as well as solid-state structures unequivocally prove the abnormal binding mode of the aNHC ligands. Additionally, the photophysical properties of the platinum(II) complexes were examined and studied in detail by DFT calculations and cyclic voltammetry experiments. The title compounds proved to be strongly emissive at room temperature in the green to orange region of the visible spectrum, with emission efficiencies of up to 69 %.

Investigation of structural and biological properties of N-heterocyclic carbene silver(I) and palladium(II) complexes

abstractComputational investigations were done on bis(1-allyl-3-benzyl-2,3-dihydro-1H-benzo[d]imidazol-2-yl)silver(I), bis(1-benzyl-3-butyl-2,3-dihydro-1H-benzo[d]imidazol-2-yl)silver(I), bis(1-allyl-3-benzyl-2,3-dihydro-1H-benzo[d]imidazol-2-yl)dibromidepalladium(II), and bis(1-benzyl-3-butyl-2,3-dihydro-1H-benzo[d]imidazol-2-yl)dibromidepalladium(II) complexes. Related complexes were optimized at different six calculation levels which are HF/6-31G(LANL2DZ), HF/6-31G(d,p)(LANL2DZ), B3LYP/6-31G(LANL2DZ), B3LYP/6-31G(d,p)(LANL2DZ), M062X/6-31G(LANL2DZ) and M062X/6-31G(d,p)(LANL2DZ) levels in vacuo. IR and NMR spectrum are calculated and examined in detail. Energy diagram of molecular orbitals, contour diagram of frontier molecular orbitals, molecular electrostatic potential maps and the harmonic surface of related molecules are examined in detail. Finally, interactions between mentioned complexes and related proteins (1BNA, 1JNX, and 2ING) are investigated in detail. As a result, it is found that biological and anti-cancer properties of silver N-heterocyclic carbene complexes are higher than those of palladium complexes.

Measuring the Relative Reactivity of the Carbon-Hydrogen Bonds of Alkanes as Nucleophiles.

We report quantitative measurements of the relative reactivities of a series of C-H bonds of gaseous or liquid Cn H2n+2 alkanes (n=1-8, 29 different C-H bonds) towards in situ generated electrophiles (copper, silver, and rhodium carbenes), with methane as the reference. This strategy surpasses the drawback of previous model reactions of alkanes with strong electrophiles suffering from C-C cleavage processes, which precluded direct comparison of the relative reactivities of alkane C-H bonds.

Mono- and dinuclear palladium(II) complexes incorporating 1,2,3-triazole-derived mesoionic carbenes: syntheses, solid-state structures and catalytic applications

Two 1,2,3-triazole-derived monocationic salts 3 and 4 bearing N-aryl wingtips were prepared using copper-catalyzed “click” reactions followed by alkylations with iodomethane. Employing a silver–carbene transfer method, two dinuclear palladium(II) complexes of triazolin-5-ylidenes (5/6) were obtained, the former of which has been reported previously. Bridge-cleavage reaction of 5 as a representative with PPh3 yielded cis-configured mesoionic carbene/phosphine hybrid complex cis-7 and homoleptic bis(phosphine) complex 8, suggesting the presence of a ligand exchange process. In contrast, bridge breakages of 5/6 with pyridine cleanly afforded PEPPSI-type complexes 9 and 10 in near quantitative yields. Finally, all complexes were exploited to catalyze Mizoroki–Heck coupling reactions with aryl bromides as the substrates, and PEPPSI-type complex 9 was found to be the best performer generally giving good to excellent yields.

Benzotriazole functionalized N-heterocyclic carbene–silver(I) complexes: Synthesis, cytotoxicity, antimicrobial, DNA binding, and molecular docking studies

In this study, six [Ag(NHC)2]+[AgCl2]− type silver complexes were synthesized by the reaction of corresponding carbene precursor and Ag2O. One [Ag(NHC)2]+NO3− type complex was synthesized by the anion exchange reaction of corresponding silver–NHC and NaNO3. The synthesized complexes were characterized by 1H NMR, 13C NMR and IR spectroscopic methods, and elemental analysis. X-ray crystal structure of 5a was also reported. Cytotoxicities of all compounds were evaluated against human breast (MCF-7) and colorectal (Caco-2) cancer cell lines and non-cancer mouse fibroblast (L-929) cell lines. All complexes performed stronger activity against both cancer cell lines than standard compound cisplatin while complex 3b performed nearly equal cytotoxicity to cisplatin against non-cancer L-929. Antimicrobial effects of all compounds were evaluated against Escherichia coli, Bacillus subtilis and Candida albicans and good activities were observed. The docking results indicated that complex 3b might be classified as druggable molecule in drug design. DNA binding study also demonstrates that 3b complex has an interaction ability to DNA. Combination of experimental and molecular docking results revealed that reported complexes are promising structures and deserve further research as anticancer drugs.

Two Amphoteric Silver Carbene Clusters.

Two highly labile silver carbene cluster complexes are described, which are unique in that they mark the transition point at which the carbene center transmutes from a fairly common NHC-like nucleophilic behavior to an electrophilic character befitting reactive silver carbene intermediates of relevance in various catalytic transformations. This amphoteric character is the distinguishing attribute of a μ-bridged donor/donor carbene entity that connects two silver atoms of triangular or tetrahedral metallic core units.

Two Amphoteric Silver Carbene Clusters

AbstractTwo highly labile silver carbene cluster complexes are described, which are unique in that they mark the transition point at which the carbene center transmutes from a fairly common NHC‐like nucleophilic behavior to an electrophilic character befitting reactive silver carbene intermediates of relevance in various catalytic transformations. This amphoteric character is the distinguishing attribute of a μ‐bridged donor/donor carbene entity that connects two silver atoms of triangular or tetrahedral metallic core units.

Benzoxazole and dioxolane substituted benzimidazole–based N–heterocyclic carbene–silver(I) complexes: Synthesis, structural characterization and in vitro antimicrobial activity

A novel series of 1,3–benzoxazole and 1,3–dioxolane substituted benzimidazole–based N–heterocyclic carbene (NHC) precursors (6a–b and 11a–b) and their corresponding NHC–silver(I) acetate (12a–b and 14a–b) and bis–NHC–silver(I) hexafluorophosphate complexes (13a–b and 15a–b) were synthesized and characterized by 1H NMR, 13C NMR, ATR-IR spectroscopic methods and elemental analysis techniques. Also, the molecular structure of benzimidazolium salt (6a) and bis–NHC–silver(I) hexafluorophosphate complex (13b) were unambiguously established by single crystal X–ray diffraction analysis. Fascinatingly, bis–NHC–silver(I) hexafluorophosphate complex (13b) was revealed to be dinuclear in nature. All the azolium salts (6a–b and 11a–b) as well as the corresponding silver(I) complexes (12a–b, 13a–b, 14a–b and 15a–b) were evaluated for their antimicrobial potential against Gram positive (Staphylococcus aureus), and a set of Gram negative (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) bacterial strains and two fungi, Candida albicans and Cryptococcus neoformans. Antimicrobial studies revealed the comparable activities of benzimidazolium salts (6a–b and 11a–b) and the silver(I) complexes (12a–b, 13a–b and 15a–b). Whereas, the 1,3–dioxolane substituted benzimidazole–based silver(I) acetate complexes (14a–b) demonstrated excellent potentials with both bacterial and fungal growth inhibition above 95%.

Novel derivatives of the antibiotic NHC–Ag(I) drug candidate SBC3: Synthesis, biological evaluation and 109Ag NMR studies

The synthesis of six novel N-heterocyclic carbene silver(I) acetate complexes, three symmetrical and three non-symmetrical, were achieved using 4,5-diphenylimidazole to produce intermediate imidazolium salts and then obtain the corresponding silver(I) complexes through complexation with silver acetate via the Youngs’ method. In vitro biological testing, using the Kirby–Bauer disk diffusion method, was conducted against Methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli, with a NHC–silver(I) acetate compound, SBC3, and Tetracycline as standards. Silver(I) acetate complex 7 resulted in a 4 mm clearance against MRSA, showing the highest antibiotic activity of the novel derivatives. Crystallographic data revealed similar bond lengths and angles to previously reported NHC–silver(I) acetate complexes, with complex 8 showing interesting η2-coordination between the silver atom and acetate oxygens. 109Ag NMR studies were conducted, highlighting the effects of the substituents of the imidazole ring on the silver atom shown by the corresponding shifts in the 109Ag NMR spectra. The incorporation of isopropyl groups to several of the novel complexes resulted in larger upfield 109Ag NMR shift values compared to all other substituents.