Silver N-heterocyclic Carbene Research Articles

Enantioselectivity switch in copper-catalyzed conjugate addition reactions under the influence of a chiral N-heterocyclic carbene–silver complex

The reversal of enantioselectivity using the same catalytic system was achieved simply by changing the order of the addition of substrates.

Synthesis, characterization and antimicrobial activities of novel silver(I) complexes with coumarin substituted N-heterocyclic carbene ligands

Eight new coumarin substituted silver(I) N-heterocyclic carbene (NHC) complexes were synthesized by the interaction of the corresponding imidazolium or benzimidazolium chlorides and Ag2O in dichloromethane at room temperature. Structures of these complexes were established on the basis of elemental analysis, 1H NMR, 13C NMR, IR and mass spectroscopic techniques. The antimicrobial activities of carbene precursors and silver NHC complexes were tested against standard strains: Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and the fungi Candida albicans and Candida tropicalis. Results showed that all the compounds inhibited the growth of the all bacteria and fungi strains and some complexes performed good activities against different microorganisms. Among all the compounds, the most lipophilic complex bis[1-(4-methylene-6,8-dimethyl-2H-chromen-2-one)-3-(naphthalene-2-ylmethyl)benzimidazol-2-ylidene]silver(I) dichloro argentate (5e) was found out as the most active one.

Erratum to: N-Propylphthalimide-Substituted Silver(I) N-Heterocyclic Carbene Complexes and Ruthenium(II) N-Heterocyclic Carbene Complexes: Synthesis and Transfer Hydrogenation of Ketones

This study deals with the synthesis of N-propylphthalimide substituted Ag(I)–N-heterocyclic carbene (NHC) complexes and N-propylphthalimide substituted Ru(II)–NHC complexes in the transfer hydrogenation of ketones. The Ag(I)–NHC complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II)–NHC complexes have been prepared from Ag(I)–NHC complexes using transmetallation method. The six N-propylphthalimide substituted Ag(I)–NHC complexes and six N-propylphthalimide substituted Ru(II)–NHC complexes have been characterized by spectroscopic techniques and elemental analyses. N-propylphthalimide substituted Ru(II)–NHC complexes have been analyzed as catalysts for the transfer hydrogenation of ketones and exhibit activity in this reaction. This study deals with the synthesis of N-propylphthalimide substituted Ag(I)-N-heterocyclic carbene (NHC) complexes and N-propylphthalimide substituted Ru(II)–NHC complexes in the transfer hydrogenation of ketones. The Ag(I)–NHC complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II)–NHC complexes have been prepared from Ag(I)–NHC complexes using transmetallation method. The six N-propylphthalimide substituted Ag(I)–NHC complexes and six N-propylphthalimide substituted Ru(II)–NHC complexeshavebeencharacterizedbyspectroscopictechniquesandelementalanalyses. N-propylphthalimide substituted Ru(II)–NHC complexes have been analyzed as catalysts for the transfer hydrogenation of ketones and exhibit activity in this reaction.

Novel ruthenium(II)–N-heterocyclic carbene complexes; synthesis, characterization and catalytic application

The synthesis of highly active ruthenium(II) catalyst based on N-heterocyclic carbene (NHC) bearing alkyl and aryl groups is reported. The complexes are easily handled in very good yields via synthesis of silver–NHC complexes and subsequent reaction with [RuCl2(p-cymene)]2 in dichloromethane (DCM) under N2 condition. All new compounds were characterized by LC-MSMS, elemental analysis, NMR spectroscopy and X-ray diffraction. With the development of a more efficient catalytic system for transfer hydrogenation of aryl ketones and aldehydes in mind, the catalytic performance of the Ru–NHC complexes for transfer hydrogenation was investigated.

Synthesis, crystal structures, characterization and biological studies of nitrile-functionalized silver(I) N-heterocyclic carbene complexes

The synthesis of a series of silver(I) complexes (3a–d), [1-(2′/3′-methylbenzyl)-3-(2″/3″-benzonitrile)benzimidazol-2-ylidenesilver(I)]PF6, of nitrile-functionalized N-heterocyclic carbenes (NHCs) based on benzimidazole core and their characterization and biological evaluations have been reported. The NHC precursors (1a–d and 2a–d) have been synthesized from successive N-alkylation of benzimidazole with appropriate substituted benzyl halides. Their corresponding bis-NHC silver(I) complexes, 3a–d, have been prepared from the reaction of the nitrile-functionalized benzimidazolium salts with silver(I) oxide in methanol/acetonitrile at mild reaction conditions in good yield (65–73%). Both, salts and complexes, were characterized by 1H and 13C NMR, FT-IR spectroscopic and elemental analysis techniques. The molecular structures of the silver(I)–NHC complexes, 3a and 3c, were elucidated by X-ray diffraction technique. Both the complexes displayed weak π–π stacking interactions between benzimidazole and benzyl benzene rings. All four silver(I) complexes exhibited potent antimicrobial activity against a Gram negative (Escherichia coli) and Gram positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Also the IC50 values of both, salts (2a–d) and complexes (3a–d) have been determined by an MTT-based assay method against the human colon cancer cell line, HCT 116. Complexes 3a–d displayed three- to fivefold increase in the anticancer activity with the IC50 values 18.8±1.3, 20.6±1.5, 19.2±1.0, 14.9±0.8μM compared to the anticancer potential of salts 2a–d (64.3±2.5, 58.3±4.5, 83.9±1.5, 72.4±1.0μM), respectively.

Highly selective carboxylative cyclization of allenylmethylamines with carbon dioxide using N-heterocyclic carbene-silver(I) catalysts.

Silver(I) carboxylate complexes promote the carboxylative cyclization of allenylmethylamines to afford 5-alkenyl-1,3-oxazolidin-2-ones in 2-propanol. The use of an N-heterocyclic carbene ligand (IPr) under pressurized CO2 is effective in suppressing the intramolecular hydroamination that leads to 2,5-dihydropyrroles. The mechanism involving a nucleophilic attack of the carbamate of the allene moiety and a subsequent protonation was realized on the basis of experimental and theoretical results involving a model intermediate, the alkenylgold(I) complex, which was synthesized from Au(OH)(IPr) and 1-methylamino-2,3-butadiene.

In vitro antimicrobial studies of naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene complexes

Seven novel naphthalen-1-ylmethyl substituted silver N-heterocyclic carbene (Ag–NHC) complexes (1–7) were synthesized by the interaction of benzimidazolium salts with silver carbonate in dry dichloromethane at room temperature and characterized by means of spectroscopic methods and elemental analysis techniques. The Ag–NHC compounds were tested for their in vitro antibacterial and antifungal activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Candida albicans and Candida tropicalis and showed high antimicrobial activities. The synthesized complexes, in particular, demonstrated better results against both fungi and gram-positive bacteria.

Macrophage and colon tumor cells as targets for a binuclear silver(I) N-heterocyclic carbene complex, an anti-inflammatory and apoptosis mediator

Chronic inflammation intensifies the risk for malignant neoplasm, indicating that curbing inflammation could be a valid strategy to prevent or cure cancer. Cancer and inflammation are inter-related diseases and many anti-inflammatory agents are also used in chemotherapy. Earlier, we have reported a series of novel ligands and respective binuclear Ag(I)–NHC complexes (NHC=N-heterocyclic carbene) with potential anticancer activity. In the present study, a newly synthesized salt (II) and respective Ag(I)–NHC complex (III) of comparable molecular framework were prepared for a further detailed study. Preliminarily, II and III were screened against HCT-116 and PC-3 cells, wherein III showed better results than II. Both the compounds showed negligible toxicity against normal CCD-18Co cells. In FAM-FLICA caspase assay, III remarkably induced caspase-3/7 in HCT-116 cells most probably by tumor necrosis factor-alpha (TNF-α) independent intrinsic pathway and significantly inhibited in vitro synthesis of cytokines, interleukin-1 (IL-1) and TNF-α in human macrophages (U937 cells). In a cell-free system, both the compounds inhibited cyclooxygenase (COX) activities, with III being more selective towards COX-2. The results revealed that III has strong antiproliferative property selectively against colorectal tumor cells which could be attributed to its pro-apoptotic and anti-inflammatory abilities.

N-heterocyclic carbene gold(I) and silver(I) complexes bearing functional groups for bio-conjugation.

This work describes several synthetic approaches to append organic functional groups to gold and silver N-heterocyclic carbene (NHC) complexes suitable for applications in biomolecule conjugation. Carboxylate appended NHC ligands (3) lead to unstable Au(I) complexes that convert into bis-NHC species (4). A benzyl protected carboxylate NHC-Au(I) complex 2 was synthesized but deprotection to produce the carboxylic acid functionality could not be achieved. A small library of new alkyne functionalized NHC proligands were synthesized and used for subsequent silver and gold metalation reactions. The alkyne appended NHC gold complex 13 readily reacts with benzyl azide in a copper catalyzed azide-alkyne cycloaddition reaction to form the triazole appended NHC gold complex 14. Cell cytotoxicity studies were performed on DLD-1 (colorectal adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MCF-7 (breast adenocarcinoma), CCRF-CEM (human T-Cell leukemia), and HEK (human embryonic kidney). Complete spectroscopic characterization of the ligands and complexes was achieved using (1)H and (13)C NMR, gHMBC, ESI-MS, and combustion analysis.

Structure and bonding of [(SIPr)AgX] (X = Cl, Br, I and OTf).

A series of iso-structural complexes [(SIPr)AgX] (X = Cl, Br, I, OTf; SIPr = 1,3-bis(2,6-diisopropylphenyl)imidazolidene) were synthesised, including the first example of a N-heterocyclic carbene silver(I) complex containing an O-bound triflate. Bond Energy Dissociation and Natural Orbitals for Chemical Valence bond analyses (BEDA & ETS-NOCV) revealing a significant NHC → M σ-back-donation, which influences the stability and sigma-donicity of these complexes.

Synthesis and anticancer activity of silver(i)–N-heterocyclic carbene complexes derived from the natural xanthine products caffeine, theophylline and theobromine

A new library of silver(I)-N-heterocyclic carbene complexes prepared from the natural products caffeine, theophylline and theobromine is reported. The complexes have been fully characterised using a combination of NMR spectroscopy, mass spectrometry, elemental analysis and X-ray diffraction analysis. Furthermore, the hydrophobicity of the complexes has been measured. The silver(I)-N-heterocyclic carbenes have been evaluated for their antiproliferative properties against a range of cancer cell lines of different histological types, and compared to cisplatin. The data shows different profiles of response when compared to cisplatin in the same panel of cells, indicating a different mechanism of action. Furthermore, it appears that the steric effect of the ligand and the hydrophobicity of the complex both play a role in the chemosensitivity of these compounds, with greater steric bulk and greater hydrophilicity delivering higher cytotoxicity.

Antimicrobial Studies of N-Heterocyclic Carbene Silver Complexes Containing Benzimidazol-2-ylidene Ligand

Seven novel 4-vinylbenzyl substituted N-heterocyclic carbene (NHC) silver complexes were synthesized from different benzimidazolium salts and silver (I) oxide in dichloromethane at room temperature. These new 4-vinylbenzyl substituted NHC silver complexes were characterized by spectroscopic (NMR, IR) and elemental analysis techniques. Using the agar dilution procedure, the antimicrobial activities of these synthesized new compounds were investigated against Gram (+)/(−) bacterial and fungal strains. These NHC silver complexes showed effective activities against Escherichia coli, Pseudomonas aeruginosa (Gram-negative bacterial strains), Enterococcus faecalis, Staphylococcus aureus (Gram-positive bacterial strains), and Candida tropicalis and Candida albicans (fungal strains).

4-Vinylbenzyl-substituted silver(I) N-heterocyclic carbene complexes and ruthenium(II) N-heterocyclic carbene complexes: synthesis and transfer hydrogenation of ketones

4-Vinylbenzyl-substituted Ag(I) N-heterocyclic carbene (NHC) complexes and Ru(II) NHC complexes have been synthesized. The Ag(I) complexes were synthesized from the imidazolium salts and Ag2O in dichloromethane at room temperature. The Ru(II) complexes were prepared from Ag(I) NHC complexes by transmetallation. The six 4-Vinylbenzyl-substituted Ag(I) NHC complexes and six 4-Vinylbenzyl-substituted Ru(II) NHC complexes have been characterized by spectroscopic techniques and elemental analyses. The Ru(II) NHC complexes show catalytic activity for the transfer hydrogenation of ketones.

Synthesis and crystal structures of sterically tuned ether functionalized NHC–silver(I) complexes: antibacterial and nucleic acid interaction studies

A series of new imidazolium salts (1–4) as N-heterocyclic carbene (NHC) precursors have been synthesized by successive N-alkylation method. Reactions of these salts with Ag2O by varying the metal to salt ratio forms a series of new Ag(I)–NHC complexes (5–8). All compounds were characterized by physico-chemical and spectroscopic techniques. The molecular structures of 1 and 5 were characterized by single-crystal X-ray diffraction analysis. A comparative investigation of the bacterial growth inhibition potential of the salts and respective complexes indicates that 5–8 displayed good antibacterial activities on Staphylococcus aureus (ATCC 12600) and Escherichia coli (ATCC 11303) compared with the salts. Furthermore, it was observed that with increase in chain length at N-positions, the antibacterial activities also increased. Nuclease activity of the reported salts and Ag(I)–NHC complexes with nucleic acids (DNA and RNA) were also studied using agarose gel electrophoresis; the results show that the compounds do not have any apparent interaction with nucleic acids in the absence of hydrogen peroxide (H2O2). However, 5 and 8 were efficient in promoting the cleavage of nucleic acids in the presence of H2O2.

NHC–Silver(I) Complexes as Chemical Nucleases; Synthesis, Crystal Structures, and Antibacterial Studies

ABSTRACTA series ofN‐heterocyclic carbene (NHC) precursors, 1‐methoxylethyl‐3‐allylimidazolium hexafluorophosphate (1), 1‐ethyl‐3‐allylimidazolium hexafluorophosphate (2), and 1‐pentyl‐3‐allylimidazolium hexafluorophosphate (3) were synthesized. These salts were treated with Ag2O to afford their corresponding mononuclear Ag(I)‐NHC complexes, namely 1‐methoxylethyl‐3‐allylimidazolium silver(I) hexafluorophosphate (4), 1‐ethyl‐3‐allylimidazolium silver(I) hexafluorophosphate (5), and 1‐pentyl‐3‐allylimidazolium silver(I) hexafluorophosphate (6), respectively. These compounds were characterized by physicochemical and spectroscopy techniques. Compounds4and5were structurally characterized by single crystal X‐ray diffraction, and their stability in solution was investigated and found to be acceptable for the antibacterial studies. These new NHC precursors and their respective Ag–NHC complexes were screened for their antibacterial activities againstStaphylococcus aureus(ATCC 12600) andEscherichia coli(ATCC 25922). Compounds1–3showed no inhibition, whereas4–6inhibited the growth of these bacteria. The nuclease activities of the reported compounds against plasmid DNA and RNA were assessed by gel electrophoresis, and the results indicate that complexes5and6can degrade both DNA and RNA in the absence of an oxidant.

Palladium(II)‐N‐heterocyclic carbene complexes: synthesis, characterization and catalytic application

N‐Heterocyclic carbenes (NHCs) are of great importance and are powerful ligands for transition metals. A new series of sterically hindered benzimidazole‐based NHC ligands (LHX) (2a, 2b, 2c, 2d, 2e, 2f), silver–NHC complexes (3a, 3b, 3c, 3d, 3e, 3f) and palladium–NHC complexes (4a, 4b, 4c, 4d, 4e, 4f) have been synthesized and characterized using appropriate spectroscopic techniques. Studies have focused on the development of a more efficient catalytic system for the Suzuki coupling reaction of aryl chlorides. Catalytic performance of Pd–NHC complexes and in situ prepared Pd(OAc)2/LHX catalysts has been investigated for the Suzuki cross‐coupling reaction under mild reaction conditions in aqueous N,N‐dimethylformamide (DMF). These complexes smoothly catalyzed the Suzuki–Miyaura reactions of electron‐rich and electron‐poor aryl chlorides. Copyright © 2014 John Wiley & Sons, Ltd.

Structure of Silver–N-Heterocyclic Carbenes in Solution: Evidence of Equilibration in DMSO at Very Different Time Scales by 1H NMR Experiments

Ag–N-heterocyclic carbene (NHC) complexes can occur as neutral [(NHC)AgX] and/or ionic [(NHC)2Ag][AgX2] species in solution. Herein, the behavior of four complexes bearing common bulky N,N′-diaryl NHCs was examined in DMSO. 1H NMR experiments performed systematically in CDCl3 and in DMSO-d6 were used to detect DMSO or chloride ion induced equilibration between the neutral and ionic forms at very different time scales. We observed that solubilization of IMesAgCl and SIMesAgCl in DMSO at 300 K led in less than a few minutes to a complete equilibration. Here, magnetization exchange rate constants were determined from EXSY experiments. In contrast, IPrAgCl and SIPrAgCl, which possess more bulky NHCs, were found to exhibit much lower exchange rates (or no exchange) at 300 K. IPrAgCl was shown to slowly generate an increasing amount of homoleptic cationic complex in DMSO for several hours before reaching equilibrium. In this case, the initial rate of formation of the cationic complex was determined.

Oxirane synthesis from diazocarbonyl compounds via NHC-Ag+ catalysis

A new method was developed to synthesize oxirane products from the reaction of diazocarbonyl substrates with aryl aldehydes by using Ag(I) N-heterocyclic carbene complex as the catalyst. A combination of N-heterocyclic carbene silver complex (IPrAgCl) with another silver salt (AgOTf) generated the catalytic active IPr-Ag+ intermediate, which then catalyzed the epoxidation reaction.

N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis, characterization and antimicrobial activities

A series of unsymmetrically substituted N‐heterocyclic carbene (NHC) precursors (1a, 1b, 1c, 1d, 1e) were synthesized from the reaction of N‐phenylbenzimidazole with various alkyl halides. These compounds were used to synthesize NHC–silver(I) complexes (2a, 2b, 2c, 2d, 2e). The five new 1‐phenyl‐3‐alkylbenzimidazolium salts (1a, 1b, 1c, 1d, 1e) and their NHC–silver complexes (2a, 2b, 2c, 2d, 2e) were characterized by the 1H NMR, 13C NMR and FT‐IR spectroscopic methods and elemental analysis techniques. Also, the two NHC–silver complexes 2b and 2c were characterized by single‐crystal X‐ray crystallography, which confirmed the linear C―Ag―Cl arrangements. The antibacterial activities of the NHC precursor and NHC–silver complexes were tested against three Gram‐positive bacterial strains (Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus) and three Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) using the microdilution broth method. The NHC–silver complexes showed higher antibacterial activity than the NHC precursors. In addition, silver complexes 2a, 2b, 2c, 2d showed high antibacterial activity against the Gram‐positive bacteria L. monocytogenes and S. aureus compared to the standard, tetracycline. Copyright © 2014 John Wiley & Sons, Ltd.

N-Heterocyclic carbene silver complexes: synthesis, characterization andin vitroantimicrobial studies

Six new 2-morpholinoethyl and 2-diethylaminoethyl substituted N-heterocyclic carbene (NHC) silver complexes (2a-f) were synthesized from the reaction 1-(2-morpholinoethyl)-3-napthalenomethlbenzimidazolium chloride (1a), 1-(2-morpholinoethyl)-3-(2-methylbenzyl)benzimidazolium chloride (1b), 1-(2-morpholinoethyl)-3-(2,3,5,6-tetramethylbenzyl)benzimidazolium chloride (1c), [1-(2-diethylaminoethyl)-3-(3-methylbenzyl)benzimidazolium chloride (1d), [1-(2-diethylaminoethyl)-3-(2,3,5,6-tetramethylbenzyl)benzimidazolium chloride (1e), [1-(N,N-diethylethane)-3-(2,3,4,5,6-pentamethylbenzyl)benzimidazolium chloride (1f) with silver oxide (Ag2O) in dichloromethane at room temperature. These silver complexes were characterized by means of 1H NMR, 13C NMR, FT-IR spectroscopy and elemental analysis techniques. Also, [1-(N,N-diethylethane)-3-(2,3,4,5,6-pentamethylbenzyl)benzimidazol-2-ylidene]chlorosilver(I) complex (2f) was characterized by means of LC-MS and Maldi-MS methods. All silver complexes (2a-f) were screened fo...