Silver NHC Research Articles

An NHC silver(i) macrometallocycle: synthesis, structure and selective recognition of iodide anions

An NHC silver(i) crown ether 1 has been synthesized, and the recognition of I− using 1 as a receptor was studied.

Cytotoxicity and biodistribution studies of luminescent Au(i) and Ag(i) N-heterocyclic carbenes. Searching for new biological targets.

A range of fluorescent and biologically compatible gold(i)-N-heterocyclic carbenes bearing acridine as a wingtip group and either a 2-mercaptopyridine or a tetra-O-acetyl-1-thio-β-d-glucopyranoside as an ancillary ligand has been synthesised. Their luminescence, cytotoxicity and biodistribution have been investigated together with those of analogous gold(i) and silver(i) chloride- and bis-NHC complexes. All complexes displayed emissions based on IL transitions centred on the acridine moiety. The cytotoxic activity measured in lung, A549, and pancreatic, MiaPaca2, carcinoma cell lines revealed a general cytotoxicity pattern (thiolate > biscarbene > chloride derivatives) and flow cytometry assays pointed towards apoptosis as the cell death mechanism. Moreover, fluorescence cell microscopy disclosed an unusual biodistribution behavior, being mainly localised in lysosomes and to a lesser extent in the nucleus. Preliminary DNA interaction experiments suggested the metal fragment and not the acridine moiety as responsible for such biodistribution, which widen the scope for new biological targets.

Synthesis and Characterization of Axially Chiral Imidazoisoquinolin-2-ylidene Silver and Gold Complexes

The selective Suzuki cross-coupling of 1,3-dichloroisoquinoline with 2-substituted 1-naphthylboronic acids/esters followed by construction of the imidazo[1,5-b]isoquinoline ring and alkylation constitutes a straightforward route to imidazolium salts fused into an axially chiral biaryl skeleton. Metalation of these azolium salts afforded the corresponding NHC silver complexes, which were used as carbene transfer agents for the synthesis of Au(I) derivatives.

ChemInform Abstract: Silver(I) NHC Mediated C—C Bond Activation of Alkyl Nitriles and Catalytic Efficiency in Oxazoline Synthesis.

AbstractThe reaction of Ag2O in refluxing MeCN with triazolium iodide leads to the formation of Ag‐NHC complexes via selective C—C bond cleavage and from C—CN bond activation.

From Simple Ligands to Complex Structures: Structural Diversity of Silver(I) Complexes Bearing Tetradentate (alkylenebimpy) NHC Ligands

The synthesis of five new silver(I) NHC complexes, bearing alkylenebimpy ligands with bridge lengths ranging from ethylene to hexylene is described. Their solid-state structures exhibit an unforeseen variety, including infinite strands of Ag3 units within a helically wound ligand environment. The very first infinite chain of almost linear Ag3 units within a cage of helically wound ligand molecules is described. All complexes are spectroscopically characterized and emit polychromatic blue light (420 nm ≤ λ ≤ 510 nm) after laser excitation at λ = 337 nm. This latter behavior might lead to applications in the field of organic light-emitting diodes.

Silver(I) NHC mediated C-C bond activation of alkyl nitriles and catalytic efficiency in oxazoline synthesis.

Preparation of silver triazolylidene (trz) species from triazolium salts and Ag2O in refluxing MeCN leads to a selective C-C bond cleavage and the formation of complexes of general formula [(trz)Ag(CN)] from Calkyl-CN bond activation. Moreover, these silver carbene complexes are precursors of highly active catalysts for oxazoline formation via aldol condensation.

Structural diversity of late transition metal complexes with flexible tetra-NHC ligands.

The synthesis of copper, gold, nickel, palladium, platinum, and iron complexes with open chain tetra-N-heterocyclic carbene (NHC) ligands via transmetalation using silver NHC complexes is presented. The obtained complexes show differing coordination geometries depending on both ligand structure and metal. While the complexes of the coinage metals form di- or tetranuclear structures, the group 10 metal complexes exhibit a distorted square planar coordination geometry at the metal centers. In the case of iron an enhanced flexibility of the ligand - caused by a longer alkyl bridge - leads to octahedral complexes with a sawhorse-type coordination by the tetracarbene ligand and two cis acetonitrile ligands. To the best of our knowledge, this is the first known example of a tetracarbene ligand in sawhorse-type coordination within an octahedral coordination sphere. The remaining cis-labile sites are prone to exchange reactions as shown by addition of trimethylphosphine.

Selective aerobic oxidation of alcohols to aldehydes, carboxylic acids, and imines catalyzed by a Ag-NHC complex.

Silver NHC catalysts have been developed for the selective oxidation of alcohols to aldehydes or carboxylic acids in the presence of BnMe3NOH or KOH under dry air. The aerobic oxidation conditions are mild, and the yield is excellent. Further tandem catalysis enables the one-pot synthesis of imines in excellent yield. Only 0.1 mol % of the catalyst is required.

Synthesis and characterization of oxygen-functionalised-NHC silver(i) complexes and NHC transmetallation to nickel(ii)

The new alcohol- and ether-functionalised-NHC silver(I) complexes bis(1-(2,6-diisopropylphenyl)-3-(2-hydroxyethyl)-1H-imidazol-2(3H)-ylidene)silver(I) chloride, [Ag{ImDiPP(C2OH)}2]Cl (4), bis(1-(2-hydroxyethyl)-3-mesityl-1H-imidazol-2(3H)-ylidene)silver(I) chloride, [Ag{ImMes(C2OH)}2]Cl (5), bis(1-(2-hydroxyethyl)-3-methyl-1H-imidazol-2(3H)-ylidene)silver(I) chloride, [Ag{ImMe(C2OH)}2]Cl (6), bis(1-(2,6-diisopropylphenyl)-3-(2-hydroxyethyl)-1H-imidazol-2(3H)-ylidene)silver(I) tetrafluoroborate, [Ag{ImDiPP(C2OH)}2]BF4 (9), and bis(1-(2,6-diisopropylphenyl)-3-(2-methoxyethyl)-1H-imidazol-2(3H)-ylidene)silver(I) chloride, [Ag{ImDiPP(C2OMe)}2]Cl (13), were synthesized and fully characterized by NMR spectroscopy and single crystal X-ray diffraction. For some complexes, an uncommon heteronuclear coupling (4)J((107/109)Ag-H) was unveiled. Their ability to transfer the NHC ligand to Ni(II) was assessed in the presence of different nickel(II) sources; the bis-NHC Ni(II) complex bis(1-(2,6-diisopropylphenyl)-3-(2-methoxyethyl)-1H-imidazol-2(3H)-ylidene)nickel(II) chloride, [NiCl2{ImDiPP(C2OMe)}2] (15), was obtained from 13 and shown by X-ray diffraction study to have a trans-arrangement of the two NHC ligands. However, in contrast to other Ag(I) NHC complexes the transmetallation reaction failed with the hydroxyl-functionalised silver complexes, possibly due to the acidity of the alcohol OH function, leading overall to reprotonation of the C(NHC) and isolation of the corresponding imidazolium salts.

Sterically driven synthesis of ruthenium and ruthenium-silver N-heterocyclic carbene complexes.

A straightforward and efficient synthetic route to novel Ru N-heterocyclic carbene (NHC) complexes by transmetallation of non-bulky silver NHC to ruthenium dicarbonyl tetraarylcyclopentadienone is described. The same procedure with sterically demanding NHC leads to unprecedented heterobimetallic Ru-Ag(NHC) complexes.

Synthesis, cytotoxic and antibacterial studies of p-benzyl-substituted NHC–silver(I) acetate compounds derived from 4,5-di-p-diisopropylphenyl- or 4,5-di-p-chlorophenyl-1H-imidazole

4,5-Di(p-isopropylphenyl)-1H-imidazole (2a) and 4,5-di(p-chlorophenyl)-1H-imidazole (2b) were prepared from the appropriately substituted benzoin precursors and then reacted with five p-substituted benzyl halide derivatives through N-dibenzylation to the symmetrically (3a–j) or through N-monobenzylation followed by N-methylation to the un-symmetrically substituted (5b) imidazolium halides. These halides were further used for the synthesis of the corresponding N-heterocyclic carbene–silver(I) (NHC–silver) acetate complexes 4a–j and 5c. The silver(I) compounds 4b, 4e and 4g were characterised by single crystal X-ray diffraction.Semiquantitative antibacterial studies against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus, using the Kirby–Bauer disc diffusion method, were carried out on the imidazolium halides 3a–j and NHC–silver(I) acetate complexes 4a–g and 4i–j. Imidazolium halide precursors 3a–j showed bacterial growth inhibition in the range of 1–5 mm (weak) while their NHC–silver(I) acetate derivatives 4a–g and 4i–j were found to inhibit bacterial growth in range 2–6 mm (weak to medium).The NHC–silver(I) acetate complexes 4a–g and 4i–j were found to be cytotoxic by producing IC50 values of 4.7 (±0.5), 2.1 (±0.8), 3.4 (±0.6), 15 (±2), 25 (±7), 24 (±3), 14 (±3), 21 (±5) and 50 (±2) μM against the breast cancer cell line MCF-7, respectively. The same NHC–silver(I) complexes 4a–g and 4i–j exhibited IC50 values of 8.7 (±1.5), 4.6 (±0.6), 5.5 (±0.6), 34 (±1), 42 (±4), 44 (±3), 29 (±1), 100 (±2) and 140 (±10) μM against the renal cancer cell-line Caki-1, respectively. The un-symmetrically substituted compound 5c has IC50 values of 24 (±3) μM against MCF-7 and 44 (±3) μM against Caki-1.

Biologically Relevant Silver(I)–N‐Heterocyclic Carbene Complexes: Synthesis, Structure, Intramolecular Interactions, and Applications

AbstractN‐Heterocyclic carbenes (NHCs) complexed with silver represent new, broad‐spectrum antimicrobial and anticancer agents, normally with low toxicity profiles, and they provide a range of versatile structures for targeted biological applications. Most of these complexes have shown higher cytotoxicity than cisplatin, a potent anticancer drug. This study reviews the design, synthesis, structural characterization, and biological applications of silver complexes derived from both functionalized and nonfunctionalized NHC ligands. Specifically, silver complexes of functionalized and nonfunctionalized imidazole‐ and benzimidazole‐based NHC systems employed in antimicrobial and anticancer applications are reviewed. Advancements achieved in the use of silver(I)–NHC complexes of miscellaneous azolium ligands, such as 1,2,4‐triazole and the heterocycle‐fused imidazolium derivative xanthene are also reviewed. Encapsulation of a series of silver–NHC complexes in a polymer‐based carrier material represents a promising method for the targeted delivery of silver ions to the infected sites. The advances achieved in this particular area are systematically reviewed in this paper. In general, these preliminary achievements reveal the potential of silver(I)–NHC complexes as efficient antimicrobial and anticancer candidates.

Sulfonated Water-Soluble N-Heterocyclic Carbene Silver(I) Complexes: Behavior in Aqueous Medium and as NHC-Transfer Agents to Platinum(II)

This report describes the synthesis of water-soluble silver(I) and platinum(II) complexes bearing sulfonated mono- or dianionic N-heterocyclic carbene ligands. Thus, treatment of the corresponding zwitterionic imidazolium derivative with silver(I) oxide in water afforded the light-sensitive bis(carbene) complexes Ag[Ag(NHC)2] (2Ag+), which were transformed into the stable salts Na[Ag(NHC)2] (2) by addition of sodium chloride. In contrast, the same reaction in dmso afforded mono(carbenes) of general formula Na[AgCl(NHC)] (3). The solvent-dependence of the reaction product can be rationalized on the basis of the equilibrium [AgCl2]− ↔ AgCl + Cl–. The precipitation of silver chloride is more favored in protic solvents than in aprotic solvents such as dmso, thus explaining the formation of bis(carbenes) in water. The formation of silver chloride may also promote the hydrolysis of silver NHC complexes under some conditions. The water-soluble platinum(II) complexes Na[PtCl2(dmso)(NHC)] were synthesized by using...

Silver(I), palladium(II) and mercury(II) NHC complexes based on bis-benzimidazole salts with mesitylene linker: Synthesis, structural studies and catalytic activity

The diimidazolium salts bis[1-R-imidazoliumylmethyl]mesitylene·2X (1: R = PhCH2, X = Br− and 2: R = Et, X = PF6−) and the dibenzimidazolium salts bis[1-R-benzimidazoliumylmethyl]mesitylene·2X (3: R = nPr, X = I−; 4: R = PhCH2, X = I−), as well as their four NHC silver(I), palladium(II) and mercury(II) complexes, {[mesitylene(CH2imyPhCH2)2]2Ag2·Ag2Br4}n (6), {mesitylene[(CH2imyPhCH2)PdCl2(CH3CN)]2} (7), {mesitylene[(CH2imyEt)2Hg2(CHCN)][HgI4]} (8) and {[mesitylene(CH2bimynPr)2HgI][HgI4]0.5} (9), as well as one anionic complex {[1,3-bis(1-benzylbenzimidazolemethyl)mesitylene][HgI4]} (5) (imy = imidazol-2-ylidene and bimy = benzimidazol-2-ylidene), have been prepared and characterized. In the complex 6, the macrometallocycles formed by two precursor 1 and two silver(I) atoms are connected together via Ag2Br4 unit to form a 1D polymeric chain. Complex 7 adopted an open structure formed by one precursor 1 and two Pd(II) atoms. In complex 8, a bidentate dicarbene from precursor 2 and a doubly deprotonated acetonitrile coordinate with two Hg(II) atoms to afford a funnel-like structure. The 10-membered macrometallocycle of 9 was formed by one precursor 3 and one Hg(II) atom. In the crystal packings of these compounds, 1D supramolecular chains, 2D supramolecular layers or 3D architectures are formed via intermolecular weak interactions, including π–π interactions, hydrogen bonds, C–H···π contacts and weak Hg···N and Hg···I bonds. Additionally, the catalytic activity of the NHC palladium(II) complex 7 in Suzuki–Miyaura cross-coupling reaction was studied.

Synthesis and antimicrobial activity of novel gold(I) N-heterocyclic carbene complexes

Benzimidazolium salts and six anionic gold–NHC complexes (NHC = N,N’-dialkylbenzimidazol-2-ylidene) were prepared and characterized. Novel [Au(NHC)2]AuCl2-type complexes were prepared in good yields from silver–NHC complexes by treatment with [AuCl(PPh3)], following the commonly used silver carbene transfer route. All compounds were characterized using 1H and 13C NMR spectroscopy, elemental analysis, and IR. The gold complexes showed antimicrobial activity against Gram-positive/negative and fungal strains.

A hexahydro-s-indacene based NHC ligand for olefin metathesis catalysts

The reaction of amino hexahydro-s-indacene with glyoxal, reduction of the diimine to the diamine and cyclization with HC(OEt)3 yields the new 1,3-bis(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-4,5-dihydro-1H-imidazol-3-ium chloride 3· HCl with conformationally restricted alkyl groups ortho to the heterocyclic substituent. Reaction of 3· HCl with Ag2O gave the respective silver NHC complex (yield 78%), which was used to synthesize the respective (3)IrCl(cod) (yield 86%), whose reaction with CO gave (3)IrCl(CO)26 (yield 98%). The Grubbs II type complex [(3)RuCl2(PCy3)(3-phenyl-indenylid-1-ene)] was synthesized (yield 68%) and converted into [(3)RuCl2(py)(3-phenyl-indenylid-1-ene)] (yield 78%) in pyridine solvent. With this complex the respective Grubbs–Hoveyda species (yield 68%) and two bisNHC complexes [(3)(NHCewg)RuCl2(3-phenyl-indenylid-1-ene)] (yield 87%, 89%) were obtained. The stereoelectronic properties of the new NHC ligand were determined employing IR spectroscopy, cyclic voltammetry and buried-volume analysis based on the crystal structure of complex 6. The activity of the ruthenium complexes in RCM reactions of sterically hindered substrates was tested.

Synthesis and antimicrobial studies of 1-methyl-2-dimethylaminoethyl-substituted benzimidazolium salts and N-heterocyclic carbene–silver complexes

The synthesis and antimicrobial studies of 1-methyl-2-dimethylaminoethyl-substituted carbene precursors and silver complexes are reported. The carbene precursors (1a–d) have been prepared from 1-methyl-2-dimethylaminoethyl-substituted benzimidazole and various alkyl halides. The silver–NHC complexes (2a–d) were synthesized from the benzimidazolium salts and Ag2O in dichloromethane at room temperature. The new compounds were characterized by 1H NMR, 13C NMR, FT-IR, and elemental analyses. The new carbene precursors and Ag-complexes were tested for their in vitro antimicrobial activity against a variety of Gram-positive and Gram-negative bacteria, as well as for their antifungal activities against Candida albicans and Candida tropicalis.

Syntheses, spectral and structural characterization of η5- and η6-cyclic π-perimeter hydrocarbon platinum group metal complexes containing pyridazine–NHC analogues

A family of platinum group metal complexes containing bidentate pyridazine–NHC ligands (L1=3,6-bis(N-n-methylimidazolyl)pyridazine dichloride, L2=3,6-bis(N-n-butylimidazolyl)pyridazine dichloride) have been synthesized. The typical mechanism of the reactions for these syntheses involved an in situ carbene transfer reactions. Reaction of L1/L2 with silver oxide in absence of light yielded silver–NHC complexes (1) and (2). When, the respective metal precursors were added to the silver–NHC complexes, transmetallation occurred with the possible isolation of the following cationic complexes: [(η6-C6H6)Ru(L)Cl]2+ {L=L1 (3), L2 (5)}, [(η6-p-iPrC6H4Me)Ru(L)Cl]2+ {L=L1 (4), L2 (6)}, [Cp∗Rh(L)Cl]2+ {L=L1 (7), L2 (9)} and [Cp∗Ir(L)Cl]2+ {L=L1 (8), L2 (10)}. All these complexes were stable in ambient atmosphere, and could be obtained in good yield. All these complexes were characterized by spectroscopic analyses. The molecular structure of the complex 9 was determined by single crystal X-ray diffraction studies.

Novel platinum group metal complexes bearing bidentate chelating pyrimidyl-NHC and pyrimidyl imidazolyl-thione ligands: Syntheses, spectral and structural characterization

A family of novel platinum group metal complexes containing bidentate chelating 1-pyrimidyl-3-methylimidazolyl bromide (HL1·Br) and 1-pyrimidyl-3-methylimidazolyl-2-thione (L2) ligands has been synthesized. The synthetic protocol for the formation of these complexes differs from one ligand to the other. Treatment of ligand (HL1·Br) with the metal precursors led to the formation of complexes via in situ carbene transfer reactions. The silver–NHC complex (1) was formed by the reaction of HL1·Br with silver oxide under light-free conditions. Subsequent addition of appropriate metal precursors to the silver–NHC complex yielded [(η6-arene)Ru(L1)Cl]PF6 complexes {arene=C6H6 (2), p-iPrC6H4Me (3), C6Me6 (4)} on stirring at room temperature, whereas the complexes [CpRu(L1)(PPh3)]PF6 {Cp=C5H5 (5), C9H7 (6)} were obtained under reflux conditions. In the case of ligand L2, stirring of equimolar quantities of metal precursors and the ligand at room temperature yielded [(η6-arene)Ru(L2)Cl]PF6 {arene=C6H6 (7), p-iPrC6H4Me (8), C6Me6 (9)}, and [Cp∗M(L2)Cl]PF6 {Cp∗=C5Me5, M=Rh (10), Ir (11)}. All these complexes were characterized by CHN analysis, IR, NMR and mass spectrometry besides confirmation by single crystal X-ray diffraction studies for some representative complexes as their hexafluorophosphate salts [3]PF6, [5]PF6, [8]PF6 and [10]PF6.

Silver(I), mercury(II) and palladium(II) complexes of functionalized N-heterocyclic carbenes: Synthesis, structural studies and catalytic activity

A series of NHC silver(I), mercury(II) and palladium(II) complexes, [(1,3-diethylbimy)6Ag4I3]I (2), [(1-benzyl-3-picolylbimy)Ag2Br2]n (3), [(1-benzyl-3-picolylbimy)HgI(CH2CN)]2 (4), {[(1-picolyl-3-npropylbimy)2Hg][Hg2I6]}n (5) and [(1,3-dipicolylbimy)PdCl]Cl (6), as well as one anionic complex [1,3-diethylbimidazolium]2[HgI4] (1) (bimy=benzimidazol-2-ylidene), have been prepared and characterized. Interestingly, a wind wheel-like Ag4I3 arrangement in 2 is formed, 1D polymeric chain containing 12-membered macrometallocycles and quadrangle Ag2Br2 units in 3 is generated, and the α-carbon atom of deprotonated acetonitrile ([CH2CN]−) in 4 participates in coordination with mercury(II) atom. In the crystal packings of complexes 1–6, 2D supramolecular layers or 3D supramolecular architectures are formed via intermolecular weak interactions, including π–π interactions, hydrogen bonds, C–H···π contacts, weak Hg···I bonds and I···I bonds. Additionally, the catalytic activity of the NHC palladium(II) complex 6 in Suzuki–Miyaura cross-coupling reaction was studied.