Silver Carbene Research Articles

Photoluminescence of Tetra(benzimidazole)phenylethene Derivatives and Their Carbene Metallacycles in Aggregates and Langmuir-Blodgett Films.

Molecular structure, external stimuli, and environmental factors all have a strong effect on the internal molecular rotation and vibration of aggregate-induced emission (AIE) luminogens. Here, we report the AIE effect for several newly synthesized amphiphilic tetra(benzimidazole)phenylethene (TBiPE) derivatives and their binuclear N-heterocyclic carbene silver (NHC-Ag) metallacycles in solutions, aggregates, and Langmuir-Blodgett (LB) films. Monolayer behaviors and microscopic images indicate that introducing alkyl chains and binuclear NHC-Ag metallacycles can facilitate the formation of a well-defined insoluble monomolecular layer at the air-water interface. Absorption and luminescence spectral features suggest that both the TBiPEs' cyclization structure and binuclear NHC-Ag metallacycles can provide additional driving forces to restrict the internal molecular motion of the tetraphenylethene (TPE) unit, thus enhancing the AIE effects. Further, external stimuli and environmental factors such as poor solvent addition and LB film deposition also play important roles in the photoluminescent intensity, maximum wavelength, and lifetime. These internal and external factors can result in around 30-40 nm blue-shift for the maximum luminescence wavelength and 2-3 times shorter for the luminescent lifetime. These phenomena can be attributed to the reason that the nonradiative energy transfer efficiency is weakened because of the enhanced hydrophobic interaction and metal-carbene coordination as well as the closely packed arrangement of AIEgens in the LB films; consequently, the radiation energy transfer efficiency increased.

Catalytic Behavior of NHC–Silver Complexes in the Carboxylation of Terminal Alkynes with CO2

A number of N-heterocyclic carbene–silver compounds (NHCs)AgX were tested in the direct carboxylation of terminal alkynes using carbon dioxide as the C1 carbon feedstock. The reactions proceed at a pressure of 1 atm of CO2 at room temperature, in the presence of Cs2CO3, and using silver–NHC complexes as catalysts. Thus, phenylacetylene and several alkynes are converted to the corresponding propiolic acids in good to high conversions. The activity of the catalysts is strongly influenced by the substituents on the NHC backbone and the nature of the counterion. Specifically, the most active compound exhibits iodide as the counterion and is stabilized by a benzimidazole derivative. After 24 h of reaction, a quantitative conversion is obtained utilizing DMF as the solvent and phenylacetylene as the substrate.

Anticancer, Antihaemolytic and Anticoagulant Studies of Coumarin‐Substituted Sterically Tuned N‐Heterocyclic Carbene Silver(I) Complexes

Anticancer, Antihaemolytic and Anticoagulant Studies of Coumarin‐Substituted Sterically Tuned <i>N</i>‐Heterocyclic Carbene Silver(I) Complexes

Fluorinated N-Heterocyclic Carbene Silver(I) Complexes with High Cancer Cell Selectivity.

This work presents the synthesis of five new functionalized (benz)imidazolium N-heterocyclic (NHC) ligands (L) and four new (benz)imidazole silver(I) NHC (Ag(I)-NHC) complexes of mononuclear [Ag(L)2](PF6) or binuclear [Ag2(L)2](PF6)2 type. The complexes have been fully characterized, including single crystal X-ray diffraction of three new structures. The complexes and their corresponding free NHC ligands have been screened against breast cancer and noncancerous cell lines, showing the mononuclear benzimidazole complex has the highest activity, while the binuclear benzimidazole complex has the highest cancer cell selectivity. The silver uptake was measured by ICP-MS and highlights a strong link between cytotoxicity and cellular uptake. DNA interaction studies, molecular docking, and evaluation of reactive oxygen species (ROS) have been conducted for the most promising complexes to identify modes of action. Overall, the binuclear benzimidazole complex is the most selective and promising candidate against the MDA-MD-231 (breast cancer) cell line and has potential to be developed for treatment of late-stage breast cancers.

Design of efficient benzimidazole-derived N-heterocyclic carbene Ag(I) catalysts for aldehyde–amine–alkyne coupling

A mild catalytic protocol for aldehyde, amine, and alkyne coupling (A3-coupling) allows for the selective synthesis of propargyl amines using 5,6-dimethylbenzimidazole-derived N-heterocyclic carbene (BNHC) silver(I) catalysts. A series of BNHC Ag(Ⅰ) halide complexes were synthesized and their structures have been elucidated through the use of multinuclear NMR and FT-IR spectroscopy. Furthermore, the pseudo-linear geometry of two different compounds was substantiated by single-crystal X-ray diffraction. Silver-based A3-coupling was achieved for both acyclic and cyclic secondary amines using a diverse set of alkynes to afford propargyl amines with yields of up to 95 %. The present approach is environmentally benign and water is generated as the sole byproduct.

In Vitro Efficacy of Silver Carbene Complexes, SCC1 and SCC22, Against Some Enteric Animal Pathogens

Silver carbene complexes (SCCs), a group of novel silver-based compounds capable of gradually ‎releasing ‎silver ions, have shown significant antimicrobial activity against a wide range of ‎bacterial pathogens mainly ‎isolated from human cases. The antimicrobial activity against ‎animal isolated pathogens has yet been done. ‎The in vitro efficacy of two SCCs with different ‎carrier molecules (SCC1 with a methylated caffeine backbone ‎and SCC22 with a ‎dichloroimidazolium backbone) was investigated against three important animal and ‎human ‎pathogen species. SCC1 and SCC22 exhibited bacteriostatic and bactericidal effects against ‎multidrug ‎resistant Salmonella Typhimurium (poultry isolate), E. coli 843 and E. coli 1568 ‎‎(swine isolates), and the ‎poultry field isolates Salmonella Heidelberg, Salmonella Enteritidis, and ‎Salmonella Montevideo with MICs ‎and MBCs ranged from 16-21 µM (6-8 µg/mL) and 16-32 µM ‎‎(6-12 µg/mL), respectively. Clostridium ‎perfringens type A was sensitive to both SCC1 and ‎SCC22 with the MICs being 11 (4 µg/mL) and 21 µM ‎‎(8 µg/mL), respectively. These values were ‎comparable to the MICs and MBCs for silver acetate. The MBCs ‎against C. ‎perfringens was &gt;85 µM for ‎SCCs and &gt;192 µM for silver acetate (&gt;32 µg/mL for all compounds). Ten hours incubation ‎of C. ‎perfringens with ‎‎40 µg/mL of all three products showed down regulation of virulence genes plc and netB, ‎‎suggesting viable cells and silver can modulate the virulence. Treating the C. ‎perfringens with higher ‎concentration (100 ‎‎µg/mL) of each SCC for 10 hours inhibited more bacteria compared to the ‎untreated bacterial cells, however, no ‎differences in the ultrastructure of lysed bacteria were seen ‎and this concentration might not induce viable ‎but non-culturable (VBNC) state as suggested by ‎transmission electron microscopy findings. SCCs showed a ‎broad antimicrobial activity against ‎all bacterial species tested including multidrug resistant pathogens. Both ‎SCCs demonstrated ‎inhibitory effect against the Gram-positive anaerobic C. perfringens type A ‎which ‎could have a high accumulation capacity for silver ion. These data suggest that SCCs may ‎represent a ‎novel class of broad-spectrum antimicrobial agents, which may be used to reduce the ‎burden of pathogenic ‎bacteria in the gastrointestinal tract of poultry‎‎‎.

In vitro and in silico anticancer potential of binuclear silver (I) N-heterocyclic carbene (NHCs) complexes: Investigation of interaction with surfactants

N-heterocyclic carbene (NHCs) silver complexes are getting tremendous attention for appealing biological potentials. The present study is planned to synthesize silver-NHC complexes to investigate their anticancer potential against breast, colon and ovarian cancer cell lines. The synthesized benzimidazolium salts (C1-C2) and their binuclear silver complexes (C3-C4) were assured through spectroscopy (UV–visible, FTIR, NMR and FLR), HPLC-DAD (high performance liquid chromatography), elemental analysis as well as mass spectrometry. Molecular docking studies indicated that compound C4 has lower binding energy values of −4.49, −1.95 and −2.95 kcal/mol for Bruton’s tyrosine kinase, Human topoisomerase II alpha and Aromatase cytochrome P450 protein targets respectively. The In Vitro cytotoxicity assay confirmed the C4 is better cytotoxic agent from other studied compounds of present study having lower IC50 values of 0.996 ± 0.04, 0.97 5 ± 0.04, 0.872 ± 0.05 and 0.987 ± 0.05 µg/mL against MCF-7, A-549, A-2780 and HCT-116 cell lines. Stability of compounds in solution form studied through spectroscopy and all compounds were found stable for studied course of time. Interactions of C3-C4 with surfactants (SDS, tween-20, tween-80) have confirmed the substantial interaction to improve aqueous solubility. Interaction of C3-C4 with surfactants indicates that there is potential affinity among test compounds and surfactants for complex formation spontaneously, having strongest binding affinity for SDS (sodium dodecyl sulfate) as compared to Tween-20 and Tween-80.

Synthesis, characterization, crystal structure and anticancer study of symmetrical binuclear bis-N-heterocyclic carbene silver(I) complexes

The synthesis of binuclear silver(I)-NHC complexes from bis-benzimidazolium salts and silver(I) ions has been carried out via an in-situ deprotonation (NHC = N-heterocyclic carbene). The reaction between 1,3-dibromopropane and two moles of N-substituted alkyl benzimidazole (R = methyl, hexyl, heptyl, octyl, and 4-methyl-benzyl) resulted in the formation of bis-benzimidazolium salts, H2L‧2Br- (1–5). Subsequent reactions of the respective salts with excess Ag2O yielded the formation of bis-NHC binuclear silver(I) complexes with the formula of [Ag2L2]·2PF6 (Ag1-Ag5). All compounds were characterized by 1H and 13C NMR, FTIR, elemental analysis, molar conductivity measurement, melting point analysis, and solubility tests. Single crystal X-ray crystallography data reveals that Ag2 exists as a dinuclear complex with no significant intramolecular argentophilic interactions. Anticancer studies of salts 1-5 and complexes Ag1-Ag5 were carried out by employing breast cancer cell lines (MCF-7). None of the salts showed antiproliferative activity, while all the complexes possessed significant anticancer properties in a dose-dependent manner. The complexes indicate better activity than a positive control except for Ag4.

Investigating the Catalytic Efficiency of Supported NHC‐Ag(I) Complexes in the Borono‐Minisci Reaction

AbstractA series of supported N‐heterocyclic carbene silver complexes (NHC‐Ag(I)) were prepared and characterized as catalysts for the borono‐Minisci reaction. After characterization, the synthesized catalysts were evaluated in batch mode to determine the reaction performance and kinetics. Interestingly, cyclic voltammetric analysis showed that the structure of both the complex and the ligand significantly influences the Ag(I)/Ag(II) redox potential and, in turn, the catalytic efficiency. Among the tested catalysts, the Si‐supported NHC‐Ag(I) 6 afforded the desired products in good to excellent yields in only 15 min, providing a complementary tactic to standard homogeneous approaches.

Synthesis and catalytic activity of silver N-heterocyclic carbene complexes based on bis(3,5-dimethylpyrazol-1-yl)methyl-substituted pyridylimidazole

A series of N-heterocyclic carbene (NHC) silver complexes derived from 6-[bis(3,5-dimethylpyrazol-1-yl)methyl]-2-pyridylimidazole have been synthesized and characterized by physico-chemical and spectroscopic methods, and the structures of four complexes have been confirmed by X-ray structural analyses. The functionalized NHC is a monodentate ligand in (NHC)AgCl through the carbene carbon atom, and a bridging [C,N,N] tridentate ligand in (NHC)2Ag2(BF4)2 and (NHC)2Ag2(PF6)2 through two pyrazolyl nitrogens and the carbene carbon to form a metallomacrocycle, in which a head (carbene)– to tail (nitrogen) coordination mode to two silver atoms is observed. Preliminary catalytic tests show that these newly synthesized Ag–NHC complexes exhibit excellent catalytic activity at a low catalyst loading (0.1–1 mol%) in the aldehyde–amine–alkyne coupling reaction.

Silver and Gold Complexes with NHC-Ligands Derived from Caffeine: Catalytic and Pharmacological Activity.

N-heterocyclic carbene (NHC) silver(I) and gold(I) complexes have found different applications in various research fields, as in medicinal chemistry for their antiproliferative, anticancer, and antibacterial activity, and in chemistry as innovative and effective catalysts. The possibility of modulating the physicochemical properties, by acting on their ligands and substituents, makes them versatile tools for the development of novel metal-based compounds, mostly as anticancer compounds. As it is known, chemotherapy is commonly adopted for the clinical treatment of different cancers, even though its efficacy is hampered by several factors. Thus, the development of more effective and less toxic drugs is still an urgent need. Herein, we reported the synthesis and characterization of new silver(I) and gold(I) complexes stabilized by caffeine-derived NHC ligands, together with their biological and catalytic activities. Our data highlight the interesting properties of this series as effective catalysts in A3-coupling and hydroamination reactions and as promising anticancer, anti-inflammatory, and antioxidant agents. The ability of these complexes in regulating different pathological aspects, and often co-promoting causes, of cancer makes them ideal leads to be further structurally functionalized and investigated.

Silver-Catalyzed Dearomative Skeletal Editing of Indazoles by Donor Carbene Insertion.

Given the prevalence of heterocyclic scaffolds in drug-related molecules, converting these highly modular heterocyclic scaffolds into structural diversified and dearomatized analogs is an ideal strategy for improving their physicochemical and pharmacokinetic properties. Here, we described an efficient method for silver carbene-mediated dearomative N-N bond cleavage leading to skeletal hopping between indazole and 1,2-dihydroquinazoline via a highly selective single-carbon insertion procedure. Using this methodology, a series of dihydroquinazoline analogues with diarylmethylene-substituted quaternary carbon centers were constructed with excellent yields and good functional group compatibility, which was further illustrated by the late-stage diversification of important pharmaceutically active ingredients. DFT calculations indicated that the silver catalyst not only induces the formation of the silver carbene, but also activates the diazahexatriene intermediate, which plays a crucial role in the formation of the C-N bond.

The Fluoride Method: Access to Silver(III) NHC Complexes.

We have synthesized the first silver(III) carbene complexes, (CF3 )3 Ag(NHC), by direct reaction of the silver(III) fluoride precursor complex [PPh4 ][(CF3 )3 AgF] with different imidazolium salts. This novel methodology circumvents the use of free NHC molecules. The silver(III) carbene complexes thus prepared are unprecedented and show remarkable thermal stabilities. They display square-planar or square-pyramidal geometry. Following our calculations, the electronic structure of a model representative complex exhibits Inverse Ligand Field (ILF). The compounds reported herein are synthetic analogues of the elusive difluorocarbene and carbonyl species proposed as intermediates in the acidic decomposition of [Ag(CF3 )4 ]- . The synthetic procedure reported is envisaged to enable access to carbene complexes of other late transition-metals in high oxidation states.

Air stable N-heterocyclic carbene silver complexes: synthesis, characterization, and antibacterial activity

A new benzimidazolium salt containing a 2,5-dimethylbenzyl substituent and six N-heterocyclic carbene (NHC) silver complexes were prepared. The complexes were characterized by NMR, FTIR, and LC-MS spectroscopic methods and elemental analyses. They are stable in solution for a week. The antibacterial properties of the Ag(I) complexes against two Gram-positive and two Gram-negative bacteria were investigated. Inhibition zone and minimum inhibitory concentration (MIC) data establish that these NHC-Ag(I) complexes possess antibacterial activities; 2b showed the highest antibacterial activity overall against Gram-positive and Gram-negative bacteria.

Theoretical and experimental investigation of N-alkyl substituted bis-imidazolium salts and their binuclear N-heterocyclic carbene silver acetate complexes

Our research centers on structural, biological, and electronic properties of N-heterocyclic carbene salts and their silver acetate-based complexes. After theoretical calculations, compounds were synthesized. In the DFT studies, functional of B3LYP was used with the basis set of 6-31++G and LanL2DZ for salts and complexes, respectively. The most stable structures were calculated and non-covalent interactions evaluated. Electronic parameters were checked while calculating their HOMO and LUMO energies so that their biological potential can be evaluated. Density of states were studied to check the electronic densities. Among all compounds, 3 was considered the best with energy gap of 0.121 eV. As all eight compounds have very reasonable HOMO-LUMO energy gaps they were considered feasible to synthesize and have strong biological potentials. Compounds were characterized by FT-IR and NMR spectroscopy.

Silver(I)-Catalyzed Tandem Reaction of Enynones and 4-Alkenyl Isoxazoles: Synthesis of 2-(Furan-2-yl)-1,2-dihydropyridines.

Silver(I)-catalyzed tandem reaction of enynones with 4-alkenyl isoxazoles provides access to 2-(furan-2-yl)-1,2-dihydropyridines. No competitive cyclopropanation of alkenes and O-H insertion via (2-furyl)carbene complexes were observed. The cascade reaction proceeds via the formation of (2-furyl)metal carbene intermediate, the N-O bond cleavage of 4-alkenyl isoxazoles/rearrangement, subsequent 6π electrocyclic reaction, and [1,5] H-shift. The successive construction of both 1,2-dihydropyridine skeleton and furan frame has been achieved in the one-pot reaction. A broad range of readily available enynones and 4-alkenyl isoxazoles are suitable to this protocol; however, when R3 is the alkyl group such as n-Bu and Me, a complicated mixture was generated without the desired products. In addition, in the case of R4 = bulky group such as R3'SiOCH2, the reaction gave an in situ oxo-product of (2-furyl)silver carbene. An atom-economic strategy for the synthesis of 2-(furan-2-yl)-1,2-dihydropyridines has been established.

Synthesis, structural characterization, and antibacterial activity of alkenyl functionalized imidazolium N-heterocyclic silver(I) and gold(I) carbene complexes

Synthetic, structural, and antibacterial studies of a series of functionalized monocarbene NHC of silver(I) and gold(I) complexes are reported. Silver NHC compounds of general formula [AgCl{NHC}] 1a–e have been obtained in excellent yields by the traditional synthetic method using Ag2O, as starting material, and the corresponding 3-substituted 1-(2-methylallyl)imidazolium chloride salts L1–L5. NHC–Ag(I) compounds 1a–e were used as transmetalation agents to synthesize monocarbenes NHC–Au(I) complexes [AuCl{NHC}] 2a–e in good yields by using [AuCl(SMe2)] as a source of gold (I). All compounds were characterized by spectroscopic and analytic techniques. The molecular structures of seven compounds L3, 1a, 1d, 2a, 2a′, 2c and 2d were confirmed by a single-crystal X-ray diffraction method. Elemental analysis and powder X-ray diffraction (PXRD) experimental studies were also carried out. In addition, in vitro antibacterial assays, of the series NHC–Ag(I) 1a–e and NHC–Au(I) 2a–e were tested against three Gram positives: Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis, and three Gram negatives: Pseudomonas aeruginosa, Escherichia coli and Salmonella typhi bacterial strains by Kirby–Bauer’s disk diffusion method. Silver compounds 1a, 1d, and all gold compounds showed excellent activity against S. aureus and S. typhi, though both types of complexes showed antibacterial activity, gold complexes were found to be the most active antibacterials. Good activity was shown by complexes 1a and 1d against P. aerouginosa, E. coli, S. typhi, S. aureus and E. feacalis and compounds 2b and 2e against E. faecalis. An excellent activity was shown by compound 2a against S. aureus with the highest inhibitory zone of 26 ± 0 mm.

Stereoselective Synthesis of trans-Stilbenes through Silver-Catalyzed Self-Coupling of N-Triftosylhydrazones: An Experimental and Theoretical Study.

A silver-mediated homocoupling of N-triftosylhydrazones for the construction of trans-stilbenes has been presented. This protocol is characterized by its suitability for both inter- and intramolecular reactions, operational simplicity, high efficiency with excellent stereoselectivity, broad substrate scope, and good functional group tolerance. A plausible mechanism involving nucleophilic attack of in situ generated sulfonium ylides on silver carbene was proposed on the basis of experimental results and DFT calculations, which further indicates that π-π stacking interactions play a dominant role in stereoselectivity control.

Insights into the Three-Component Coupling Reactions of Aldehydes, Alkynes, and Amines Catalyzed by N-heterocyclic Carbene Silver: A DFT Study

Density functional theory (DFT) was used to investigate the three-component coupling reactions of aldehydes, alkynes, and amines (A3 coupling) using N-heterocyclic carbene silver as the catalyst. This study reveals that the addition reaction between the catalyst N-heterocyclic carbene silver and phenylacetylene (PAE) forms Ag_PAE. Subsequently, one hydrogen atom of the Ag_PAE migrates to the nitrogen atom of the Amine. Thereafter, the amine aldehyde condensation reaction generates a molecule of water and an imine ion with (Path one) or without (Path two) another amine catalyst. Path one has a lower reaction barrier than Path two. Subsequently, the imine ion reacts with silver phenylacetylide to generate the A3 coupling reaction product propargylamine (PPA). Furthermore, the triple bond and −N3 group in PPA undergo a cycloaddition reaction and generate the final product (PR). The entire reaction is strongly exothermic, and, therefore, the reaction is easy to conduct. Moreover, conceptual density functional theory calculations confirm the reaction mechanism. Investigating the mechanism of these reactions will be helpful for understanding and developing new synthesis strategies for similar functional compounds.

Synthesis of Propargyl Boranes via Silver Catalyzed Insertion of Alkynyl Carbene into B‐H Bond

AbstractA silver‐catalyzed insertion reaction of alkynyl carbenes derived in situ by decomposition of alkynyl N‐nosylhydrazones, into a B−H bond is reported. This protocol emerges as a straightforward synthesis of various propargylic boron compounds with up to 95 % yield. The operationally simple method exhibits high functional group tolerance and produces a variety of propargyl boranes which are synthetically useful building blocks. Deuterium labelling experiment and DFT studies show that the reaction proceeds via insertion of alkynyl Ag‐carbene into the B−H bond and generation of silver carbene occurs in the rate‐determining step.