NHC Precursors Research Articles

Engineering the Coordination Environment in the Silver(I)- and Ruthenium(II)-N-Heterocyclic Carbene Complexes in Instigating the Electrocatalytic Hydrogen Evolution Reaction.

The quest for cost-efficient and high-performance electrocatalysts towards electrocatalytic water splitting is a key and an interdisciplinary area of study. Considerable progress is being driven by developments in the field of energy research. In a fundamental study, we have synthesized NHC precursors (6 and 7) and corresponding metal-NHC complexes of silver(I)- (8 and 9) and ruthenium(II)- (10 and 11) of a N-heterocyclic carbene-based ligand type incorporating coumarins. These NHC precursors and metal-NHC complexes were characterized through various analytical and spectral techniques. The silver(I)-NHC complexes 8 and 9 displayed a linear coordination geometry with a center of inversion, which is evidenced by the single-crystal X-ray diffraction technique. Both the series of complexes were assessed for their efficacies in the hydrogen evolution reaction (HER). The results demonstrated that attributed to its peculiar coordination geometry, high electrical conductivity the silver(I)- and ruthenium(II)-NHC complexes exhibited exemplary electrocatalytic activity. Activities of the hydrogen evolution reaction on two differently modified electrode substrates with metal-NHC complexes have been studied. To attain the benchmark HER current density of 10 mA cm-2, in 1.0 M KOH, an overpotential of -375 to -527 mV vs RHE was required for the metal-NHC complexes. Based on the analysis of the Tafel slope values, the rate-determining step was the adsorption of hydrogen as investigated in the potential window. The molecular electrocatalyst 10 presented a superior stability and maintained the electrocatalytic activity for a duration of 18 h with complex 8 and 24 h with respect to complex 10 in 1.0 M KOH. Apace with these studies, hydrogen oxidation studies were examined in 0.5 M H2SO4 by a substantial current density at the platinum ring electrode. This research offers feasible guidance for developing organometallic-based molecular electrocatalysts with good electrocatalytic performance.

A convenient bottom up route to covalently anchor Pd(II)-PEPPSI on layered zirconium(IV) phosphonate: Efficient catalyst for Suzuki-Miyaura cross coupling of aryl chlorides

A rational and bottom-up route for assembling layered Zr(IV) phosphonate framework decorated with covalently anchored N-heterocyclic carbene NHC-Pd(II) fragment has been developed. Reaction of phosphonic acid functionalized Pd(II)-NHC precursor complex with ZrOCl2·8H2O provides easy access to a layered material with covalently anchored catalytically active Pd(II)-NHC sites. The Pd(II)-NHC functionalized Zr(IV) phosphonate showed enhanced catalytic activity in Suzuki-Miyaura cross coupling reaction of both aryl bromides and chlorides with aryl boronic acid, as compared to their homogeneous counterparts. The Zr(IV) phosphonate framework imparts remarkable robustness to the Pd(II)-NHC catalyst and allowed recycling of the catalyst up to nine catalytic cycles without any major loss of catalytic activity.

Highly Efficient N‐Heterocyclic Carbene Precursor from Sterically Hindered Benzimidazolium Salt for Benzoin Condensation

AbstractA diverse array of simple benzoin compounds featuring aryl and heteroaryl substituents were prepared from corresponding aldehydes, achieving moderate to excellent yields. To achieve this, a library of NHC precursors was designed and synthesized from imidazole and benzimidazole. Our custom‐designed NHC precursors (L1–L10) varied in size and structure. Built on imidazolinium and benzimidazolinium salts, these catalysts sported substituents at the N1 and N3 positions ranging from compact groups like butyl or benzyl to the much bulkier anthracenyl group. Treatment with a base transforms these salts into highly effective NHC precursors. After being activated, these NHCs become highly effective catalysts for the benzoin condensation reaction. We tested all the NHC precursors we made and found that L10, the one containing the large and bulky anthracenyl group attached to a benzimidazolium ring, worked the best for making benzoin derivatives.

Atropisomeric N‐Heterocyclic Carbene‐Palladium(II) Complexes: Influence of the Backbone Substitution

AbstractIn order to facilitate the synthesis of NHC precursors as well as to incorporate new moieties, the influence of the NHC backbone substitution was investigated within the concept of atropisomeric NHC‐metal complexes. A series of NHC precursors was prepared from new anilines and used to synthesize the corresponding Pd(allyl)Cl(NHC) complexes, most of the time as a mixture of diastereomers (meso and chiral). Chiral HPLC at preparative scale enabled to obtain enantiopure complexes in low to excellent yields. These complexes displayed good activity in the intramolecular α‐arylation of amides and, as a function of the structure of the chiral catalyst, excellent enantioselectivities were reached (up to 96 % ee).

Chiral imidazolium and triazolium salts as NHC and aNHC ligand precursors: A promising framework for asymmetric epoxidation catalysis

Two chiral imidazolium salts and one chiral triazolium salt were synthesized containing a chiral cyclohexane bridge based on the salen ligand framework of the Jacobsen-Katsuki epoxidation catalysts. They are promising NHC and aNHC ligand precursors for asymmetric epoxidation or C–H oxidation catalyzed by organometallic compounds. The ligand framework offers plenty of opportunities for modification.

Chan−Evans−Lam coupling for the synthesis of N–aryl derivatives catalyzed by copper(I) chloride and sterically varied imidazolium salts at mild reaction conditions

First-row transition–metal–catalyzed organic transformations have received colossal interest in the modern synthetic organic chemistry due to their step– and atom–economic approaches. As a consequence, direct arylation of azoles through C–H or N–H activations acquired a broad spectrum of applications for accessing valuable small organic molecules that are of pharmaceutical interest. In this connection, sterically varied coumarin–functionalized imidazolium salts bearing bromide (5–7) and hexafluorophosphate anions (8–10) have been prepared and used as NHC precursors. The salts have been characterized by both, spectroscopic and analytical techniques. A hexafluorophosphate salt 9 was also studied for its structure using the single-crystal XRD technique. The salts that indeed, generate carbene that trap Cu(I) to form Cu(I)–NHC complexes in situ for the Chan−Evans−Lam C–N coupling of 1H–azoles/anilines and phenyl/thiopheneboronic acids, resulting in the formation of N–aryl derivatives in moderate to excellent yields. The structure-activity relationship studies revealed that the steric bulk around the metal center would help increase the catalytic Chan−Evans−Lam C–N coupling potential of the catalysts.

New sugar-incorporated N-heterocyclic carbene precursors and their Ag(I) and Pd(II) complexes: Synthesis, characterization, and cytotoxicity studies

In the present work, a new series of sugar-incorporated N-heterocyclic carbene precursors namely 1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7a), 4-methyl-1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7b), 4,5-diphenyl-1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]imidazolium bromide (7c), and 1-(3,4,5-trimethoxybenzyl)-3-[2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl]benzimidazolium bromide (8) were synthesized by the direct reaction of the N-alkylated benzimidazoles with 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-ethyl bromide. Ag(I)–NHC complexes (9a-c, 10) of the abovementioned precursors were synthesized by in-situ reaction with Ag2O in light-excluded conditions. The transmetallation reaction technique was used to synthesize Pd(II)–NHC complexes (11a-c, 12) by the reaction of [PdCl2(MeCN)2] with corresponding Ag(I)–NHC complexes. All NHC precursors and their corresponding Ag(I) and Pd(II) complexes were spectrally characterized using 1H &13C NMR, and mass spectrometry. Further, Pd(II) complexes were evaluated for their anticancer activity against eight diverse cancer cell lines, namely; Pancreatic Adenocarcinoma (Capan-1), Colorectal Carcinoma (HCT-116), Glioblastoma (LN229), Lung Carcinoma (NCI-H1975), Acute Lymphoblastic Leukemia (DND-41), Acute Myeloid Leukemia (HL-60), Chronic Myeloid Leukemia (K562), and non-Hodgkin Lymphoma (Z138). Standard antineoplastic drugs docetaxel and etoposide were included as reference compounds. Among the tested complexes, complex 11c displayed broad activity against all tested cancer types, albeit at higher concentrations when compared to the reference drugs.

Interaction analysis of a new NHC precursor and its Ag-NHC complex with bovine serum albumin by spectrophotometric and molecular docking methods

Potential bioactive molecules must reach the target tissue safely and serum albumin, which is a well-known major component in human blood, is an efficient transporter. Therefore, the interactions of possible bioactive species with serum albumin must be determined. In the current study, an N-heterocyclic carbene precursor and its silver complex were synthesized, characterized, and analyzed for interactions with bovine serum albumin. Stern-Volmer constant was recorded as 4.50 × 105 for Ag-NHC with a 1.255 binding number at 298 K. Also, the molecules have spontaneously interacted with bovine serum albumin with a negative ΔG value (−32.93 kJ mol−1) for the complex at 298 K. Additionally, the effects of Ca2+, Mg2+, and Zn2+ on binding properties were evaluated by fluorescence spectroscopy. The binding constant of the complex was recorded as 6.76 × 103 in the presence of Zn2+ and 5.93 × 105 without the metals. The molecules were optimized by DFT-based calculations and the details of the bindings were investigated by molecular docking methods. Ag-NHC has interacted with the IIA subdomain region of bovine serum albumin with −8.46 kcal/mol.

Rhodium and iridium NHC complexes from chiral NHC precursors: Synthesis, structure, transfer hydrogenation catalysis and method validation

Heteroleptic [RhIIICp*(NHC)] and [IrIIICp*(NHC)] complexes bearing a N-amino acid functionality derived from imidazolium salts were synthesized and characterized by NMR, IR, HR-MS, and single-crystal X-ray diffraction. A discussion of the structure of the [RhCp*{κ2(C,O)–NHC}Cl] complex 3f as a pair of diastereomers is presented. Catalysts were assessed for the transfer hydrogenation (TH) of ketones in basic propan-2-ol, obtaining good yields for the reduction products. A chromatographic method applied for measurements of compounds in TH as analytes was validated. The Rh and Ir complexes described here offer an original approach in the development of catalysts based in classic NHC precursors.

New PEPPSI-Pd-NHC complexes bearing 4-hydroxyphenylethyl group: Synthesis, characterization, molecular docking, and bioactivity properties.

Five 4-hydroxyphenylethyl substituted pyridine enhanced, precatalyst, preparation, stabilization, and initiation-Pd-N-heterocyclic carbene(PEPPSI-Pd-NHC) complexes are synthesized in a straightforward way. All PEPPSI-Pd-NHC complexes were prepared by mixing 4-hydroxyphenylethyl substituted NHC precursors, palladium chloride, potassium carbonate, and potassium bromide in pyridine. All complexes were screened for human carbonic anhydrase I (hCA I)and hCA II, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glucosidase (α-Glu) inhibitory activities. The ChE inhibitory activities of the new PEPPSI-Pd-NHC complexes bearing the 4-hydroxyphenylethyl group (1a-e) against α-Glu, AChE, and BChE were determined by the Tao and Ellman methods. The results indicated that all the synthetic complexes exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. The Ki values of the new PEPPSI-Pd-NHC complexes 1a-e for hCA I, hCA II, AChE, BChE, and α-Glu were obtained in the ranges of 18.98-32.65, 22.95-38.13, 3.67-11.65, 4.09-9.36, 186.92-287.45 µM, respectively. Among the synthesized complexes, the most potent complexes were 1c toward hCA I and II with Ki values 18.98 and 22.95 µM, and 1d toward AChE and BChE with Ki = 3.67 and 4.09 µM, respectively.

Direct Synthesis of Vinylene Carbonates from Aromatic Aldehydes**

AbstractSubstituted vinylene carbonates were directly prepared from aromatic aldehydes following a one‐pot Benzoin condensation/transcarbonation sequence under solvent‐free conditions. The combination of a N‐phenyl substituted triazolium salt NHC precursor and 4‐dimethylaminopyridine (DMAP) was found essential to reach high yield and selectivity. The reaction scope was investigated with a range of aromatic aldehydes and the corresponding vinylene carbonates were obtained with 32–86 % isolated yields (14 examples).

Synthesis and Vibrational Circular Dichroism Analysis of N-Heterocyclic Carbene Precursors Containing Remote Chirality Centers.

VCD analysis of 16 diastereomeric pairs of NHC precursors containing two isolated chirality centers and different substitution patterns identified VCD transitions characteristic of the chirality center in the imidazolium ring or in the side chain, which, in contrast to ECD and OR, could be utilized to assign the two chirality centers separately by simple comparison, regardless of the type and position of achiral aromatic substituents. While the ECD and OR data showed great dependence on the position of an achiral substituent such as a methoxy group, characteristic experimental VCD transitions remained consistent and they could be used to determine the absolute configuration of all the regio- and stereoisomers and substituted analogues. VCD, ECD and OR approaches were evaluated, and several carbene precursors were found, for which only the VCD method could distinguish the four stereoisomers. With t-butyl, phenyl or 2-naphthyl substituents at the C-1′ chirality center, the ECD spectra of the C-1′ epimers were near-identical, and hence it was only the VCD approach that showed distinct differences suitable for the configurational assignment. The chiroptical characterization of our diastereomeric pairs of NHC precursors enables the future application of related derivatives having different substitution patterns in stereoselective transformations.

Picolyl and benzyl functionalized biphenyl NHC carbenes and their silver complexes: Sigma donating and antimicrobial properties

Picolyl and benzyl linked biphenyl NHC ligands L1H2Br2to L4H2Br2(L1-L4) and their silver-N-heterocyclic carbene complexes [AgL2]PF6(1), [AgL3]PF6(2), and [AgL4]PF6(3) were synthesized and characterized. Sigma donating properties of the NHC ligands were calculated by proton-coupled 13C-NMR spectroscopy. Silver-N-heterocyclic carbene complexes were synthesized via in situ deprotonation of azolium salts with silver(I) oxide under the light exclusion. One of the silver complexes, [AgL3]PF6(2), was confirmed by a single crystal XRD. All the ligands and silver-N-heterocyclic carbene complexes were investigated for antimicrobial activity against the bacterial strains grown from human clinical isolates. The NHC ligands and Ag-NHC complexes showed better antimicrobial activity than the reported phenyl-substituted NHC precursors and their Silver-NHC complexes against Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacterial strains.

New Ag(I) and Pd(II) complexes derived from symmetrical and asymmetrical NHC precursors: Synthesis, Characterization, Antibacterial activity, and Theoretical calculations

• New N-heterocyclic carbene precursors derived from the reaction of 2-chloro-N-(2,5-dimethylphenyl)-acetamide with imidazoles. • Ag(I) and Pd(II) complexes of the NHCs were synthesized. • The synthesized compounds have a good antibacterial activity against E. coli and S. aureus. • The estimated anticancer activity of the compounds was determined using docking calculation. New symmetric and asymmetric imidazolium salts namely 1-methyl-3-(2,5-dimethylphenyl)-acetamideimidazolium chloride ( 2 ), 1-benzyl-3-(2,5-dimethylphenyl)-acetamideimidazolium chloride ( 3 ) and 1,3-bis-(2,5-dimethylphenyl)-acetamideimidazolium chloride ( 4 ) were synthesized. In situ deprotonation technique was employed to synthesize Ag(I)-NHC complexes ( 5 - 7 ) from the reaction of Ag 2 O with the abovementioned ligand precursors. Subsequent reactions of Ag(I)-NHC complexes with [PdCl 2 (MeCN) 2 ] resulted the Pd(II)-NHC complexes ( 8 - 10 ) via transmetallation method. All the synthesized compounds were characterized using various techniques such as 1 H and 13 C NMR, FTIR and CHN analysis. The antibacterial activity of all the compounds was evaluated against bacterial strains E. coli as gram-negative and S. aureus as gram-positive bacteria using azithromycin as a standard antibiotic. The density functional theory (DFT) method was used to optimize the structures of the synthesized compounds using Gaussian 09 and Molecular Graphic Laboratory (MGL). Electronic energy, HOMO, LUMO, and dipole moment were calculated as well. Further, the estimated anticancer activity of the compounds was determined using docking calculations.

Low oxidation potential electrochemiluminescence from novel Iridium(III) complexes comprising N-heterocyclic carbene main ligands containing dibenzothiophene motif

Dibenzothiophene and derivatives-substituted imidazolium salts as NHC precursors have been designed as novel C^C*NHC bidentate main ligands to construct two novel heteroleptic iridium(III) complexes containing two NHC-based main ligands with dibenzothiophene motif in this work. The emission peaks of these two novel NHC-based iridium(III) luminophores are centered at ca. 530 nm and the quantum efficiency of IrNHC-S is up to 79.8%. Beside excellent photophysical properties, CV results revealed that these two novel NHC-based iridium(III) complexes comprising dibenzothiophene motif exhibited very low oxidation potential (<0.5 V vs Fc/Fc+). At last, ECL performance under various conditions are comprehensively investigated in this work. Though ECL efficiencies under current experimental conditions are still lower than the benchmark of Ru(bpy)32+ due to lack of suitable co-reactants, the novel kinds of NHC-based iridium(III) complexes revealed in this study would indeed provide some new avenues to design ECL luminophores with low oxidation potential and emission colors different from Ru(bpy)32+ in the future.

Synthesis of NHC Complexes with an N‐(2‐Oxopropyl) Group

AbstractThe unsymmetrically N,N’‐substituted NHC precursor N‐(2‐oxopropyl),N’‐picolylbenzimidazolium chloride (H‐1)Cl, featuring an N‐protecting group has been prepared. Reaction of (H‐1)Cl with Ag2O followed by transmetallation of the NHC to [MCl2(Cp*)]2 (M=Rh, Ir) yielded complexes [MCl(Cp*)(κ2‐1)]Cl (M=Rh, [2]Cl; M=Ir, [3]Cl) with a chelating coordinated CNHC Npyridine ligand. Anion exchange gave complexes [2]BF4 (M=Rh) and [3]BF4 (M=Ir). Transmetallation of the NHC ligand from silver(I) to gold(I) gave the mononuclear complex [AuCl(1)] [4] bearing a monodentate, N‐picoly funtionalized NHC ligand. Complex [4] reacts with AgBF4 to yield the dinuclear complex [5](BF4)2 featuring two bridging μ2‐CNHC Npyridine ligands. The molecular structures of [2]BF4 ⋅ CH2Cl2 and [3]BF4 ⋅ CH2Cl2 have been determined by X‐ray diffraction studies.

Synthesis, characterization, antimicrobial and antibiofilm activity, and molecular docking analysis of NHC precursors and their Ag-NHC complexes.

Microorganisms attach to surfaces and interfaces and form biofilms which create a sheltered area for host cell response. Therefore, biofilms provide troubles in fields such as medicine, food, and pharmaceuticals. Inhibition of formation of biofilms through hindering of quorum sensing could be a method for the production of new generation antibiotics. In this study, four new benzimidazole type NHC precursors (1-allyl-3-benzyl-5,6-dimethylbenzimidazolium chloride, 1-allyl-3-(2,4,6-trimethylbenzyl)-5,6-dimethylbenzimidazolium chloride, 1-allyl-3-(2,3,5,6-tetramethylbenzyl)-5,6-dimethylbenzimidazolium chloride, and 1-allyl-3-(2,3,4,5,6-pentamethylbenzyl)-5,6-dimethylbenzimidazolium chloride and Ag-NHC complexes of these molecules were synthesized and characterized by elemental analysis, FT-IR spectroscopy, 1H, and 13C{1H} NMR spectroscopy, LC-MS, and single crystal crystallography. Antimicrobial and biofilm formation inhibition activities of the molecules were evaluated. In addition, the activities of the molecules were examined in detail by molecular docking analysis. According to the results obtained, higher activity was achieved with the complex molecules when compared with the benzimidazole derivative ligands.

Dehydrogenative amide synthesis from alcohols and amines utilizing N-heterocyclic carbene-based ruthenium complexes as efficient catalysts: The influence of catalyst loadings, ancillary and added ligands

The metal-catalyzed dehydrogenative coupling of alcohols and amines to access amides has been recognized as an atom-economic and environmental-friendly process. Apart from the formation of the amide products, three other kinds of compounds (esters, imines and amines) may also be produced. Therefore, it is of vital importance to investigate product distribution in this transformation. Herein, N-heterocyclic carbene-based Ru (NHC/Ru) complexes [Ru-1]-[Ru-5] with different ancillary ligands were prepared and characterized. Based on these complexes, we selected condition A (without an added NHC precursor) and condition B (with an added NHC precursor) to comprehensively explore the selectivity and yield of the desired amides. After careful evaluation of various parameters, the Ru loadings, added NHC precursors and the electronic/steric properties of ancillary NHC ligands were found to have considerable influence on this catalytic process.

Modular Synthesis of Chiral NHC Precursors and Their Silver and Gold Complexes

The stereoselective synthesis of chiral heterocyclic carbene precursors and the structural features of their silver and gold complexes were investigated. The prepared compounds are all based on the...

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).