NHC Complexes Research Articles

Synthesis, characterization, crystal structure and bioactivity properties of the benzimidazole-functionalized PEPPSI type of Pd(II)NHC complexes

Herein, six new benzimidazole-functionalized Pd-based complexes bearing N-propylphthalimide group were synthesized. These new PEPPSI type of Pd(II)NHC complexes (PEPPSI: Pyridine Enhanced Precatalyst Preparation, Stabilization and Initiation) were prepared from the N-propylphthalimide substituted benzimidazolium salts, palladium chloride (PdCl2) and 3-chloropyridine. The structures of all (NHC)PdX2(3-chloropyridine) complexes have been clearly characterized by using NMR (1H and 13C), FTIR spectroscopic method, and elemental analysis techniques. Also, the structures of three of the (NHC)PdX2(3-chloropyridine) complexes were confirmed by single-crystal X-ray diffraction. Also, novel N-propylphthalimide-substituted (NHC)PdX2(3-chloropyridine) complexes effectively inhibited acetylcholinesterase (AChE), with Ki values in the range of 0.54 ± 0.10 to 3.01 ± 0.63 µM. For butyrylcholinesterase (BChE) was obtained with Ki values in the range of 0.82 ± 0.11 to 5.03 ± 0.86 µM. For α-glycosidase (α-Gly) the most effective Ki values of 1c, 1d, and 1b were with Ki values of 23.83 ± 5.98, 26.04 ± 7.11, and 30.61 ± 3.85 µM, respectively. All novel N-propylphthalimide-substituted PEPPSI complexes and control compounds had almost similar inhibition profiles.

Synthesis, characterization and catalytic activity of PEPPSI-type palladium–NHC complexes

Eight benzimidazolium salts (2a–h) with two nitrogen atoms substituted by various alkyl groups have been synthesized in high yields. The benzimidazolium salts were readily converted into the corresponding PEPPSI-type palladium–NHC complexes (PEPPSI = pyridine-enhanced precatalyst preparation, stabilization, and initiation) (3a–h). The structures of all compounds were characterized by 1H NMR, 13C NMR, and IR spectroscopy as well as by elemental analysis techniques, which support the proposed structures. The catalytic activity of the PEPPSI-type palladium–NHC complexes was evaluated with respect to the direct C5-arylation of 2-substituted heteroaryl derivatives (thiophene, furan and thiazole) with various aryl bromides. This arylation occurs efficiently and selectively at the C5-position of the 2-substituted thiophene, furan and thiazole derivatives.

Donor-Stabilized Monocarba-Bridged Bis(cyclopentadienyl)alanes.

Five monocarba‐bridged bis(cyclopentadienyl)aluminum halide NHC and thione complexes and one monocarba‐bridged bis(cyclopentadienyl)phosphanylalane NHC complex are reported. The former were synthesized by transmetalation of a C[1]magnesocenophane with the corresponding aluminum(III) chloride and aluminum(III) bromide donor adducts. The phosphanylalane complex was obtained by a subsequent functionalization of the corresponding bromoalane with lithium diphenylphosphide. All complexes were characterized in solution by multinuclear NMR spectroscopy and in the solid state by single crystal X‐ray diffraction. Bonding energies of the NHC and thione ligands to the aluminum centres were estimated by DFT calculations.

Direct (Hetero)arylation of Heteroarenes Catalyzed by Unsymmetrical Pd-PEPPSI-NHC Complexes under Mild Conditions

With the aim of developing a facile and efficient method to access structurally intriguing and valuable functionalized (hetero)aryls, two unsymmetrical Pd-PEPPSI-type NHC complexes (PEPPSI, pyridin...

Synthesis and Reactivity of Remarkably Stable and Nucleophilic Hydroxide-Bridged Dimetallic Nickel NHC Complexes

The novel class of dicationic homodimetallic nickel(II) NHC complexes [(NHC)2Ni(μ-OH)2Ni(NHC)2]2+ was synthesized starting from nickel acetate as the metal precursor. Symmetrically substituted N-al...

Naphthyl-Derived Orthometalated RuII-NHC Complexes: Effect of the NHC Donors and/or Substitution Pattern on Their Synthesis and Catalytic Activity

Naphthyl-derived orthometalated RuII-NHC complexes have been developed for catalytic applications considering the stereoelectronic profiles of the NHC ligands, which can be modified easily via alte...

Bis‐NHC Aluminium and Gallium Dihydride Cations [(NHC)2EH2]+ (E = Al, Ga)

The NHC alane and gallane adducts (NHC)·AlH2I (NHC = Me2ImMe 7, iPr2Im 8, iPr2ImMe 9) and (NHC)·GaH2I (NHC = Me2ImMe 10, iPr2ImMe 11, Dipp2Im 12; R2Im = 1,3‐di‐organyl‐imidazolin‐2‐ylidene; Dipp = 2,6‐diisopropylphenyl; iPr = isopropyl; Me2ImMe = 1,3,4,5‐tetra‐methyl‐imidazolin‐2‐ylidene) were prepared either by the simple yet efficient reaction of the NHC adduct (NHC)·AlH3 with elemental iodine or by the treatment of (NHC)·GaH3 with an excess of methyl iodide at room temperature. The reaction of one equivalent of the group 13 NHC complexes with an additional equivalent of the corresponding NHC afforded cationic aluminium and gallium hydrides [(NHC)2·AlH2]+I− (NHC = Me2ImMe 13, iPr2Im 14, iPr2ImMe 15) and [(NHC)2·GaH2]+I− (NHC = Me2ImMe 16, iPr2ImMe 17) and the normal and abnormal NHC coordinated compound [(Dipp2Im)·GaH2(aDipp2Im)]+I− 18. Compounds 7–18 were isolated and characterized by means of elemental analysis, IR and multinuclear NMR spectroscopy and by X‐ray diffraction of the compounds 7, 9, 10, 15, 16 and 18.

Formation of a nona-nuclear copper(II) cluster with 3,5-di-methyl-pyrazolate starting from an NHC complex of copper(I) chloride.

The complete nona-nuclear cluster in bis-[1,3-bis-(2,6-di-methyl-phen-yl)imid-azol-ium] di-μ-chlorido-tetra-chlorido-octa-kis-(μ-3,5-di-methyl-pyrazolato)hexa-μ3-hydroxido-nona-copper(II) chloro-form disolvate, [HIXy]2[Cu9(μ-pz*)8(μ3-OH)6(μ2-Cl)2Cl4]·2CHCl3 or (C19H21N2)2[Cu9(C5H7N2)8Cl6(OH)6]·2CHCl3, where pz* is the 3,5-di-methyl-pyrazolyl anion, C5H7N2 -, and HIXy is the 1,3-bis-(2,6-di-methyl-phen-yl)imidazolium cation, C19H21N2 +, is generated by a crystallographic centre of symmetry with a square-planar CuII ion bound to four μ3-OH ions lying on the inversion centre. Of the four remaining unique CuII atoms, three adopt CuN2O2Cl square-pyramidal coordination geometries with the chloride ion in the apical position and one has a distorted CuN2OCl tetra-hedral geometry. The dianionic nona-nuclear core can be described as a 24-membered [CuNN]8 ring that contains a Cu9O6Cl6 core. The cluster features three intra-molecular O-H⋯Cl hydrogen bonds. In the crystal, weak C-H⋯N and C-H⋯Cl inter-actions link the components. Polynuclear paramagnetic clusters of this type are of considerable inter-est due to their relevance to both the bioinorganic and single-mol-ecule magnets research fields.

Killing effects of Candida albicans through alteration of cellular morphology and growth metabolism using Tris-NHC ligand coordinated to AgI and CuI

Benzimidazolium-based novel compounds containing ethyl group as a substituent were prepared and their silver and copper complexes were synthesized to evaluate the antifungal properties. In the present study, we have designed trisbenzimidazolydine benzene and silver and copper complexes. The trisbenzimidazolium salt L2 reacts with 1.5 equiv of Ag2O to yield the trinuclear AgI hexacarbene complex Ag(I)-NHC, which is transmetalation of Ag-NHC with 3 equiv of CuI yields the trinuclear CuI hexacarbene complex Cu(I)-NHC, respectively, where there their formation is influenced by the polarity of solvent as evidenced by FT-IR, FT-Raman, NMR and Mass Spectrometry (Electrospray Ionization/High Resolution) data distinguished by examining the antimicrobial activity, MIC determination and SEM analysis against antimicrobial growth. The inhibitory effects of tested compounds were investigated against Candida albicans and several other medicinally important pathogens. The most potent Ag(I)-NHC and Cu(I)-NHC complexes showing a higher degree of activity against C. albicans among the other tested strains. A significant level of growth in C. albicans was clearly observed through Minimum Inhibitory Concentration (MIC), here the least inhibitory concentration of Ag(I)-NHC (0.165 mg/mL) was several times lesser than L1, L2 and Cu(I)-NHC but higher than the positive control Amphotericin B (0.065 mg/mL). The impacts of ligands and metal complexes on cell wall integrity of C. albicans were investigated by scanning electron microscope (SEM) showed wrinkled and distinguished morphological features by higher accumulation of Propidium Iodide (PI). Further, the mode of action was found the cell death medicated due to severe loss of membrane integrity.

Halo and Pseudohalo Gold(I)-NHC Complexes Derived from 4,5-Diarylimidazoles with Excellent In Vitro and In Vivo Anticancer Activities Against HCC.

A series of halo and pseudohalo gold(I)-NHC complexes (NHC-Au-X) (X = Cl, Br, I, NCO, and OAc) derived from 4,5-diarylimidazoles were synthesized, structurally characterized, and analyzed for their biological activities. The most active complex was iodo(1,3-diethyl-4,5-bis(4-methoxyphenyl)imidazol-2-ylidene)gold(I) (6), which was at least 2-fold more cytotoxic than cisplatin and auranofin against hepatocellular carcinoma (HCC) cells. In vivo studies indicated that complex 6 exhibited a considerably higher anticancer efficacy (IRT = 75.7%) than cisplatin (IRT = 44.4%) in a HepG2 xenograft mouse model and ameliorated liver injury caused by CCl4 in chronic HCC. Further studies revealed that complex 6 can inhibit the expression of the thioredoxin reductase (TrxR) both in vitro and in vivo, block the HepG2 cells in the G2/M phase, induce reactive oxygen species (ROS) production, damage mitochondrial membrane potential (MMP), and promote HepG2 cell apoptosis.

Dinuclear gold(I)‐N‐heterocyclic carbene complexes: Synthesis, characterization, and catalytic application for hydrohydrazidation of terminal alkynes

Dinuclear gold(I)‐N‐heterocyclic carbene complexes were developed for the hydrohydrazidation of terminal alkynes. The gold(I)‐N‐heterocyclic carbene complexes 2a‐2b were synthesized in good yields from silver complexes synthesized in situ, which in turn were obtained from the corresponding imidazolium salts with Ag2O in dichloromethane as a solvent. The new air‐stable gold(I)‐NHC complexes, 2a‐2b, were characterized using NMR spectroscopy, elemental analysis, infrared, and mass spectroscopy studies. The gold(I) complex 2a was characterized using X‐ray crystallography. Bis‐N‐heterocyclic carbene–based gold(I) complexes 2a‐2b exhibited excellent catalytic activities for hydrohydrazidation of terminal alkynes yielding acylhydrazone derivatives. The working catalytic system can be used in gram‐scale synthesis. In addition, the catalytic reaction mechanism of the hydrohydrazidation of terminal alkynes by gold(I)‐NHC complex was studied in detail using density functional theory.

Mechanisms underlying the cytotoxic activity of syn/anti-isomers of dinuclear Au(I) NHC complexes

The syn- and anti-isomers of dinuclear Au(I) complexes of the type Au2(RLOH)(PF6)2 (R = isopropyl or mesityl) bearing 2-hydroxyethane-1,1-diyl-bridged bisimidazolylidene ligands were separated by reversed phase high performance liquid chromatography (HPLC) and characterized by NMR spectroscopy, elemental analysis, ESI mass spectrometry as well as single crystal X-ray diffraction analysis. Evaluation of the antiproliferative activity of the isolated isomers has shown very small difference in their cytotoxic behavior in various cancer cell lines. Additional counter-anion exchange (hexafluorophosphate to chloride) allows to increase the water solubility of synAu2(MesLOH)(PF6)2 and leads to higher antiproliferative activity when compared to the hexafluorophosphate-complex. Both isomers were treated with l-cysteine as nucleophilic thiol source and only the anti-isomer shows dissociation of one bisimidazolylidene ligand after 24 h. In the case of the syn-isomer, density functional theory calculations indicate a lower reactivity due to the higher steric hindrance of the N-substituents and additional hydrogen bond interaction, which prevents a nucleophilic attack. When the N-substituent is replaced by the bulkier mesityl group, both conformations remain unreactive and result to be the most cytotoxic complexes in the above-mentioned cancer cell lines. Interestingly, synAu2(MesLOH)(PF6)2 exhibits a high selectivity in the MCF-7 cell line with a selectivity index (SI) of 19, which is superior to auranofin (SI < 1), making this compound an ideal candidate for further studies. Preliminary mechanistic studies reveal that the cytotoxic complexes possess mitochondrial-TrxR inhibition properties in the nanomolar range. Additionally, the cellular distribution studies by ICP-MS and nuclear microscopy have shown that the compound accumulates in the membranes. These results suggest that the mitochondrial membrane is the main target for this type of dinuclear complexes, causing oxidative stress by inhibiting mitochondrial thioredoxin reductase.

Coumarin substituted 4–aryl–1,2,4–triazolium salts and their silver(I) N–heterocyclic carbene complexes: Effects of counterions on the antioxidant and antihaemolytic properties

Although numerous silver complexes have been found to target human derived leukemia cells, the nature and reactivity of such species with normal human red blood cells and targeting oxidants remain unexplored. In this contribution, we report the synthesis and characterization of three series of structurally varied silver complexes derived from biologically active coumarin substituted 1,2,4–triazol–5–ylidine ligands. 1,2,4–Triazolium salts (6–13) that serve as NHC precursors have been prepared by treating 4–(2,6–dimethylphenyl) triazole with substituted 4–bromomethylcoumarin derivatives, and corresponding silver NHC complexes (14–25) by in situ deprotonation method using appropriate silver sources. Complexes 14, 15 and 18 have been studied for their structure following single crystal X–ray diffraction technique, which adjudicates the presence of silver atom in an almost linear coordination geometry. Complexes 21 and 22 displayed promising antioxidant potential with the IC50 (a concentration of test sample required to neutralize DPPH radicals by 50%) value of 7.49 ± 0.702, 7.42 ± 0.125 μM, respectively; while the triazolium salt displayed no activity in the working concentration range (10–250 μM). Likewise, at a concentration of 100 μM the silver complexes showed significantly less percentage lysis of human red blood cells in the range 2.36 ± 0.59 to 8.49 ± 0.27% (except 18, 24 and 25).

Synthesis of N-Aryl- and N-alkyl-Substituted Imidazolium Silver Complexes: Cytotoxic Screening by Using Human Cell Lines Modelling Acute Myeloid Leukaemia.

A series of N-aryl- and N-alkyl substituted imidazoles has been synthesised and complexed with Ag+ to obtain silver-NHC complexes of the form [Ag(NHC)2 ]X. These silver-NHC complexes were tested in vitro against the human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). A substantial difference in cytotoxicity was revealed varying in the range 13-4 μM and 22-9 μM for HL-60 and MOLM-13, respectively. Furthermore, this study revealed that when an alkyl group is installed on the imidazole scaffold, its position substantially influences the cytotoxicity of the corresponding silver NHC complex.

Rhodium(I)-NHC Complexes Bearing Bidentate Bis-Heteroatomic Acidato Ligands as gem-Selective Catalysts for Alkyne Dimerization.

A series of Rh(κ2 -BHetA)(η2 -coe)(IPr) complexes bearing 1,3-bis-hetereoatomic acidato ligands (BHetA) including carboxylato (O,O), thioacetato (O,S), amidato (O,N), thioamidato (N,S), and amidinato (N,N), have been prepared by reaction of the dinuclear precursor [Rh(μ-Cl)(IPr)(η2 -coe)]2 with the corresponding anionic BHetA species. The RhI -NHC-BHetA compounds catalyze the dimerization of aryl alkynes, showing excellent selectivity for the head-to-tail enynes. Among them, the acetanilidato-based catalyst has shown an outstanding catalytic performance reaching unprecedented TOF levels of 2500 h-1 with complete selectivity for the gem-isomer. Investigation of the reaction mechanism supports a non-oxidative pathway in which the BHetA ligand behaves as proton shuttle through intermediate κ1 -HBHetA species. However, in the presence of pyridine as additive, the identification of the common RhIII H(C≡CPh)2 (IPr)(py)2 intermediate gives support for an alternative oxidative route.

Synthesis, antimicrobial properties, and theoretical analysis of benzimidazole-2-ylidene silver(I) complexes

A series of symmetrical and nonsymmetrical N,N-disubstituted benzimidazolium salts were synthesized as N-heterocyclic carbene precursors. These salts were treated with Ag2O to afford their corresponding mononuclear Ag(I)-NHC complexes. These compounds were characterized by spectroscopy techniques and analyzed by DFT/TDDFT and docking methods. Also, the structures of 2a and 2e were determined by single-crystal X-ray crystallography. These new Ag–NHC complexes were screened for their antibacterial activities against Gram-positive, Gram-negative bacteria, fungi, and nosocomial agents.

Piano-Stool Iron Complexes as Precatalysts for gem-Specific Dimerization of Terminal Alkynes

A series of piano-stool Fe–NHC complexes have been prepared and characterized. The NHC ligands used herein possess a benzyl and a mesityl wingtip groups and have different electronic structures wit...

Dinuclear Gold(I) Complexes Bearing N,N'-Allyl-Bridged Bisimidazolylidene Ligands.

A novel N,N’‐allyl‐bridged bisimidazolium salt and a novel dinuclear Ag(I) and a Au(I) NHC complex are reported. Both metallacyclic complexes have a twisted structural shape due to the rigid allylic system and form two different isomers relating to the position of the double bonds. The allyl‐group shows photoisomerisation, but no reactivity towards bases for the additional coordination of Pd(II).

Ligand‐Facilitated Reductive Coupling of Benzyl Chlorides with Aryl Chlorides Catalyzed by Well‐Defined Heteroleptic Ni (II)‐NHC Complexes

Novel heteroleptic Ni (II) complexes bearing a highly hindered yet flexible IPr* ligand, Ni (IPr*)(PPh3)Br2 (1) and Ni (IPr*)(PCy3)Br2 (2) (IPr* = 1,3‐bis(2,6‐bis (diphenylmethyl)‐4‐methylphenyl)imidazol‐2‐ylidene), were easily prepared in 78% and 89% yield, respectively. Both were characterized by elemental analysis and NMR spectroscopy, and 1 was subjected to X‐ray crystallography. Compared with 2 and its analogue bearing a less sterically demanding IPr ligand (IPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene), complex 1 exhibited superior catalytic activity in the magnesium‐mediated reductive coupling of benzyl chlorides with aryl chlorides, featuring outstanding tolerance of both coupling partners with steric demand. This study discloses a ligand‐facilitated reductive coupling of benzyl chlorides with aryl chlorides, which provides a new and practical synthetic tool for the synthesis of diarylmethanes.

Influence of graphene sheet properties as supports of iridium-based N-heterocyclic carbene hybrid materials for water oxidation electrocatalysis

The effect of the structural properties of graphene materials on the local structure of –OH anchored Ir(I)–NHC complexes is herein investigated. For that, two partially reduced graphene oxides exhibiting different sheet properties due to an adequate selection of the crystalline characteristics of their parent graphite were used. The main differences among them were the size of Csp2 domains within their graphenic layers and the distribution of functional groups at the basal planes and edges. Anchoring of N-methylimidazolium moieties through the graphene –OH functional groups and subsequent formation of the Ir(I)–NHC complexes resulted in graphene-based hybrid materials. The structural differences of the support have an influence in the interaction of the supported iridium compounds with the graphene sheet. The oxygenated functional groups in the material with a smaller graphene sheet are closer leaving larger Csp2 domains in the graphene layer, favoring their interaction with the supported iridium atoms therefore displacing the chlorido ligand from the first coordination shell. In contrast, the hybrid material in which the distribution of the oxygenated functional groups within the basal planes of the graphenic layer is more homogeneous shows partial chlorido displacement. This fact has an influence on the electrocatalytic performance of the iridium-based hybrid materials as water oxidation catalysts (WOCs), exhibiting improved catalytic activity the catalyst having coordinated chlorido ligands.