In this study, a series of amine-functionalized benzimidazolium salts and their PEPPSI-type N-heterocyclic carbene (NHC) palladium(II) complexes 3a-e were synthesized and characterized by FT-IR, 1H NMR and 13C NMR spectroscopy, elemental analysis, and mass spectrometry. The molecular and crystal structure of 3c and 3d was confirmed by the single-crystal X-ray diffraction (SC-XRD) method. Structural analysis reveals that the geometries of the PdII centers of the complexes adopt slightly distorted square planar environment. The new palladium complexes were tested as catalysts in the direct C5 arylation of 2-acetylfuran and 2-acetylthiophene with aryl bromides at 120 degrees C in N,N-dimethylacetamide. The arylation reactions proceeded selectively at the C5 position of the heteroaromatic compounds, and the corresponding coupling products were obtained in moderate to good yields by using 1 mol% of the palladium complex. Also, solid computational validation of the experimental results was achieved by geometric optimizations, frontier molecular orbital and molecular electrostatic potential studies, as well as natural bonding orbital analysis utilizing density functional theory.

The ruthenium, palladium, and silver complexes with N-heterocyclic carbene (NHC) ligands have been widely studied for promising anticancer activities, and they have been found to exhibit strong cytotoxic activity toward a range of cancer cells. However, the ruthenium and palladium NHC complexes have been less studied compared to silver and gold NHC complexes as antimicrobial agents. Herein, Ag, Ru, and Pd complexes of a benzimidazol-2-ylidene ligand bearing p-nitrobenzyl and diisopropylaminoethyl groups were synthesized and characterized by FT-IR, H-1 NMR and C-13 NMR spectroscopy, elemental analysis and mass spectrometry. The molecular and crystal structures of 2 and 4 were confirmed by the single-crystal X-ray diffraction (SC-XRD) method. All compounds were tested for antibacterial and antifungal activities and the minimum inhibitory concentrations were determined. The results indicates that some compounds exert effective antibacterial activity against Gram-negative and four Gram-positive bacterial strains and two yeast strains. Ag complex 2 had great antibacterial activity against Staphylococcus aureus at MIC value of 12.5 mu g/mL. However, the presence of ruthenium in the structure of the compounds increased overall antibacterial and antifungal activity.

Although the ruthenium N-heterocyclic carbene (NHC) complexes have been widely used in catalysis, they have only recently been evaluated for medicinal applications. Herein, a series of new ruthenium(II) p-cymene complexes with benzimidazole-based NHC ligands were synthesized by the transmetalation reaction from silver(I)- NHC complexes. These complexes were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy, elemental analysis, and mass spectrometry. Also, the molecular and crystal structures of 3f has been determined by the single-crystal X-ray diffraction method. Acetylcholinesterase (AChE) plays an important role in neurotransmission by hydrolyzing the neurotransmitter acetylcholine. On the other hand, carbonic anhydrase (CA) has a crucial role in living organisms for the maintenance of some obligatory metabolic functions. All the ruthenium(II) complexes were tested against the enzymes including AChE, hCAs I and II, which associated with epilepsy, glaucoma, and Alzheimer's disease (AD), respectively. These complexes 3a-f were recognized as highly potent inhibition effects towards hCA I isoenzyme (Kis: 2.80 f 0.05-35.46 f 9.07 mu M) and hCA II isoenzyme (Kis: 4.52 f 0.24-20.20 f 2.28 mu M) and AChE enzyme (Kis: 0.39 f 0.21-1.31 f 0.03 mu M). Besides these, molecular docking simulations and the ADMET process, which are computational methods, were used to elucidate and verify the results obtained from the above-mentioned studies at the molecular level.

In this study, a series of PEPPSI-type N-heterocyclic carbene palladium(II) complexes 3a-e were synthesized using amine functionalized benzimidazolium salts 2a-e as N-heterocyclic carbene precursors. These complexes were characterized by FT-IR, 1H NMR and 13C NMR spectroscopy, elemental analysis and mass spectrometry. Also, the molecular and crystal structure of 3b has been determined by the single-crystal X-ray diffraction method. According to the structural analysis, the geometry of the palladium center of the complex adopts a slightly distorted square planar environment. The benzimidazolium salts 2a-e and their palladium(II) complexes 3a-e were screened for human carbonic anhydrase I, II (hCAs I and II), and alpha-glycosidase inhibitory activities. Results indicated that all the synthetic compounds exhibited potent inhibitory activities against all targets as compared to the standard inhibitors, revealed by IC50 values. Ki values of 2a-e and 3a-e for hCA I, hCA II, and alpha-glycosidase enzymes were obtained in the ranges 1.17 +/- 0.11-65.50 +/- 8.20 mu M, 1.02 +/- 0.08-57.60 +/- 6.41 mu M, and 118.86 +/- 11.92-509.21 +/- 26.61 nM, respectively. Besides these, molecular docking calculations of potent compounds 2b, 2d, 2e, 3a, 3b, 3c and 3e towards human carbonic anhydrase I (hCA I), human carbonic anhydrase II (hCA II), and alpha-glycosidase (alpha-Gly) were presented using AutoDock 4. Among the compounds discussed, compounds 3c, 3a, 2e and 2b have the best binding affinity for alpha-Gly (-9.87,-9.77,-9.04 and-8.63 kcal/mol); compounds 3e, 3b, 2d and 2e turn out to have the second-best binding affinity (-8.80,-8.74,-8.39 and-7.57 kcal/mol) against hCA II. Lastly, compounds showing the lowest binding affinity for hCA I enzyme are 3e, 3b, 2d and 2e, respectively. These findings show that especially NHC-palladium(II) complexes 3a-e are more active for all three enzyme structures than their N-heterocyclic carbene precursors 2a-e and may be potential candidates for the discovery and development of effective inhibitors for the related enzymes in the future.

In this study, a series of new salts containing quinoxaline and imidazole moieties were synthesized in good yield by the reaction of 2,3 -bis(bromomethyl)quinoxalines and 1-alkylimidazoles in N,N-dimethylformamide. These salts were characterized by elemental analysis, IR, H-1 NMR and C-13 NMR spectroscopy, which support the proposed structures. Furthermore, the enzyme inhibition activities of these compounds were investigated. They showed highly potent inhibition effect on acetylcholinesterase (AChE) and carbonic anhydrases (hCAs) (Ki values are in the range of 44.80 +/- 14.87 to 288.64 +/- 42.68 nM, 21.50 +/- 4.76 to 187.30 +/- 22.43 nM, and 5.81 +/- 0.71 to 164.52 +/- 26.0 nM for AChE, hCA I, and hCA II, respectively). Compound 3 showed the best inhibition effect for hCA I and compound 4 showed the best inhibition effect for hCA II and AChE.

A series of new silyl-substituted benzimidazolium salts were synthesized in good yield by the reaction of 1-(dimethylvinylsilyl)methylbenzimidazole and various alkyl halides. These salts were characterized by spectroscopic techniques. Also, crystal structure of 2c has been determined by the single-crystal X-ray diffraction method. Newly synthesized compounds were tested for antibacterial and antifungal activities and the minimum inhibitory concentrations were determined. The results indicates that some of compounds exert effective antibacterial activity against four Gram (-) bacterial and four Gram (+) bacterial strains and two yeast strains.

A series of new imidazolium salts were prepared in good yield by the reaction between 1-alkylimidazole and a variety of alkyl halides. The structures of the compounds were identified by FT-IR, 1 H NMR, and 13 C NMR spectroscopy, elemental analysis, and mass spectrometry. The crystal structure of 1b was determined by the single-crystal X-ray diffraction method. The phthalimide-tethered imidazolium salts exhibited inhibition abilities toward acetylcholinesterase (AChE) and human carbonic anhydrases (hCAs) I and II, with Ki values in the range of 24.63 ± 3.45 to 305.51 ± 35.98 nM for AChE, 33.56 ± 3.71 to 218.01 ± 25.21 nM for hCA I and 17.75 ± 0.96 to 308.67 ± 13.73 nM for hCA II. The results showed that the new imidazolium salts can play a key role in the treatment of Alzheimer's disease, epilepsy, glaucoma, and leukemia, which is related to their inhibition abilities of hCA I, hCA II, and AChE. Molecular docking and in silico absorption, distribution, metabolism, excretion and toxicity studies were used to look into how the imidazolium salts interacted with the specific protein targets. To better visualize and understand the binding positions and the influence of the imidazolium salts on hCA I, hCA II, and AChE conformations, each one was subjected to molecular docking simulations.

A series of chiral and achiral cyclic seleno-and thiourea compounds bearing benzyl groups on N-atoms were prepared from enetetramines and appropriate Group VI elements in good yields. All the synthesized compounds were characterized by elemental analysis, FT-IR, H-1 NMR and C-13 NMR spectroscopy, and the molecular and crystal structures of (R,R)-4b and (R,R)-5b were confirmed by the single-crystal X-ray diffraction method. These assayed for their activities against metabolic enzymes acetylcholinesterase, butyrylcholinesterase, and alpha-glycosidase. These selenourea and thiourea derivatives of chiral and achiral enetetramines effectively inhibit AChE and BChE with IC50 values in the range of 3.32-11.36 and 1.47-9.73 mu M, respectively. Also, these compounds inhibited alpha-glycosidase enzyme with IC50 values varying between 1.37 and 8.53 mu M. The results indicated that all the synthesized compounds exhibited excellent inhibitory activities against mentioned enzymes as compared with standard inhibitors. Representatively, the most potent compound against alpha-glycosidase enzyme, (S,S)-5b, was 12-times more potent than standard inhibitor acarbose; 7b and 8a as most potent compounds against cholinesterase enzymes, were around 5 and 13-times more potent than standard inhibitor tacrine against achethylcholinesterase (AChE) and butyrylcholinesterase (BChE), respectively.

The benzimidazolium salts were prepared by quaternazition of 1-(2-diisopropylaminoethyl)benzimidazoles in N,N-dimethylformamide with alkyl halides. The salts were characterized spectroscopically and their crystal structures were determined by the single-crystal X-ray diffraction method. The 1H NMR and 13C NMR and FT-IR features were also characterized by using Density Functional Theory at B3LYP level with 6–31G* basis set and were compared to the experimental ones. Detailed vibrational assignments of the wavenumbers were performed based on the potential energy distribution (PED) analysis. Quantum chemistry calculations of geometries, electronic properties (FMOs) and reactivity features of the compounds were investigated using the same level of the DFT theory. Natural bond orbital (NBO) analysis was used to analyze the stability of the molecules arising from hyperconjugative interactions and charge delocalization. Global reactivity descriptors were calculated to understand the biological activity behaviors. Additionally, the 3D Hirshfeld surfaces and the associated 2D fingerprint plots were carried out to obtain an insight into the behavior of the interactions in the compounds. A predictive study for the biological activities of the compounds was done using PASS online software and compared to the DFT results.

New ruthenium chelate and ruthenate complexes were synthesized through the reaction of benzimidazolium salts and [RuCl2(p-cymene)](2) in toluene and characterized by elemental analysis, H-1 NMR and C-13 NMR spectroscopy. These ruthenium complexes were tested as catalysts in the intermolecular hydroamination reactions between styrene with aromatic amines in ionic liquid. All of these complexes tested here showed good catalytic activity in these reactions. The hydroamination reactions regioselectively produced anti-Markovnikov addition products in moderate to good yields by using 1 mol% of the ruthenium complex.

A series of new rhodium(I) complexes with benzimidazole based N-heterocyclic carbene (NHC) ligand were synthesized by reactions of benzimidazolium salts with [Rh(OMe)COD](2). The characterization of rhodium(I) complexes with the general formula [RhCl(NHC)(eta(4)-1,5-cyclooctadiene)] was done by physicochemical and spectroscopic methods. All the synthesized complexes were tested as catalysts in the intermolecular hydroamination reactions between styrene with aromatic amines in ionic liquid. All of these complexes tested here are catalytically active for the intermolecular hydroamination of styrene with aromatic amines in ionic liquid. The anti-Markovnikov addition products were obtained selectively by using 1 mol% of the rhodium complex.

A series of new ruthenium(II) complexes bearing N-heterocyclic carbene ligands with benzylic groups were prepared by transmetallation reactions between silver(I) N-heterocyclic carbene complexes and [RuCl2(P-cymene)](2). All of the obtained complexes were characterized by FT-IR, H-1 NMR and C-13 NMR spectroscopy, and the molecular structure of compound 3c was also determined by X-ray crystallography. These ruthenium complexes were tested for the alkylation of aromatic amines with a wide range of primary alcohols under solvent-free conditions using the hydrogen borrowing strategy. All of the compounds tested here showed excellent catalytic activity for these reactions and N-monoalkylated products were obtained selectively using 2.5 mol% of the ruthenium complexes. (C) 2019 Elsevier Ltd. All rights reserved.

A series of amine-tethered benzimidazolium salts were synthesized by the reactions between 1-(1-methyl-2-dimethylaminoethyl)benzimidazole and various alkyl halides. The characterization of the newly synthesized salts was done by spectroscopic methods. Also, 2e, 2f, and 2h have been docked into the catalytic active site hCA I, hCA II, AChE, BChE, and alpha-glycosidase enzymes. We have identified high binding affinity and explained inhibition mechanism of the compounds against the enzymes. These novel amine-functionalized benzimidazolium salts derivatives were good inhibitor compounds of the aglycosidase, hCA I and II isoforms, and both cholinesterase enzymes with K-i values in the range of 0.63 +/- 0.05-3.63 +/- 0.83 nM for a-glycosidase, 8.42 +/- 1.03-27.04 +/- 3.74 nM for hCA I, 7.94 +/- 0.74 - 21.82 +/- 5.81 nM for hCA II, 136.38 +/- 19.55-247.34 +/- 34.06 nM for BChE, and 124.24 +/- 13.94 - 283.55 +/- 54.06 nM for AChE, respectively. Among the inhibitors, 2e, 2e, 2f, 2f, and 2h were obtained to be the excellent inhibitors with Ki values of 8.42 +/- 1.03, 7.94 +/- 0.74,124.24 +/- 13.94,136.38 +/- 19.55, and 0.63 +/- 0.05 nM for hCA I, hCA II, AChE, BChE, alpha-glycosidase enzymes, respectively. The ability to model some metabolic enzymes receptors and theirs inhibitors in silico are important because they can save valuable resources and help to rationalize the mode of binding, and to design better inhibitors. (C) 2020 Elsevier B.V. All rights reserved.

New ruthenium(II) complexes with N-heterocyclic carbene ligand were synthesized by transmetalation reactions between silver(I) N-heterocyclic carbene complexes and [RuCl2(p-cymene)]2. The complexes were characterized by physicochemical and spectroscopic methods. These ruthenium complexes were applied to the N-monoalkylation of aromatic amines with a wide range of primary alcohols under solvent-free conditions using the hydrogen borrowing strategy. The catalytic reactions using all ruthenium complexes resulted in N-monoalkylated products with high selectivities using furfuryl alcohol as the alkylating agent.

Both in situ prepared Pd-NHC and NHC-Pd-PEPPSI complexes were tested as catalysts in the intermolecular hydroamination reactions between styrene with various anilines in ionic liquid. All of the compounds tested here are catalytically active for the intermolecular hydroamination of styrene with aromatic amines. The anti-Markovnikov addition products were obtained selectively by using 1 mol% of the palladium complex.

A series of symmetrical imidazolinium chloride salts bearing secondary N-alkyl substituents were synthesized in good yield by the reaction of N,N'-dialkylethane-1,2-diamines and HC(OEt)(3) in the presence of NH4Cl. These salts were characterized by spectroscopic methods. All compounds were tested as enzyme inhibitory agents. These novel symmetrical imidazolinium chloride salts derivatives (3a-h) effectively inhibited the cytosolic hCA I and hCA II, BChE, alpha-glycosidase and AChE with K-i values in the range of 18.41-121.73 nM for hCA I, 12.50-63.12 nM for hCA II, 3.72-34.58 nM for AChE, 5.50-32.36 nM for BChE, and 94.72-364.51 nM for alpha-glycosidase, respectively. CA isoenzymes play a crucial roles including acid-base balance homeostasis by excreting and secreting protons (H+) due to the CO2 hydration, HCO3- reabsorption mechanisms, and renal NH4+ output. Also, the molecular modeling is an implementation for estimation of the binding proximity of symmetrical imidazolinium chloride salts bearing secondary wingtip groups and their inhibition mechanisms and kinetics in atomic levels at the catalytic domains. (C) 2018 Elsevier B.V. All rights reserved.

The molecular structure of the benzimidazol-2-ylidene-PdCl2-pyridine-type PEPPSI (pyridine-enhanced precatalyst, preparation, stabilization and initiation) complex {1,3-bis[2-(diisopropylamino)ethyl]benzimidazol-2-ylidene-κC2}dichlorido(pyridine-κN)palladium(II), [PdCl2(C5H5N)(C23H40N4)], has been characterized by elemental analysis, IR and NMR spectroscopy, and natural bond orbital (NBO) and charge decomposition analysis (CDA). Cambridge Structural Database (CSD) searches were used to understand the structural characteristics of the PEPPSI complexes in comparison with the usual N-heterocyclic carbene (NHC) complexes. The presence of weak C-H...Cl-type hydrogen-bond and π-π stacking interactions between benzene rings were verified using NCI plots and Hirshfeld surface analysis. The preferred method in the CDA of PEPPSI complexes is to separate their geometries into only two fragments, i.e. the bulky NHC ligand and the remaining fragment. In this study, the geometry of the PEPPSI complex is separated into five fragments, namely benzimidazol-2-ylidene (Bimy), two chlorides, pyridine (Py) and the PdII ion. Thus, the individual roles of the Pd atom and the Py ligand in the donation and back-donation mechanisms have been clearly revealed. The NHC ligand in the PEPPSI complex in this study acts as a strong σ-donor with a considerable amount of π-back-donation from Pd to Ccarbene. The electron-poor character of PdII is supported by π-back-donation from the Pd centre and the weakness of the Pd-N(Py) bond. According to CSD searches, Bimy ligands in PEPPSI complexes have a stronger σ-donating ability than imidazol-2-ylidene ligands in PEPPSI complexes.

The new imidazolinium, tetrahydropyrimidinium and tetrahydrodiazepinium salts were synthesized in good yield by the reaction of the corresponding N,N'-dialkylalkanediamine with triethyl orthoformate in the presence of ammonium chloride. All of the compounds were obtained, and spectroscopically characterized. The crystal structure for the 1,3-bis(4-benzyloxy-3-methoxybenzyl)-3,4,5,6-tetrahydropyrimidinium chloride (5g) was determined by single-crystal X-ray diffraction. The biological properties of all novel compounds were tested and the influence of ring size and benzylic N-substituents on the biological activities were examined. Also, they were found as effective inhibitors against cytosolic carbonic anhydrase I and II isoforms (hCA I and II), and acetylcholinesterase (AChE) enzyme. Among these compounds, 1,3-bis(4-(1-piperidinyl)benzyl)-3,4,5,6-tetrahydropyrimidinium chloride (5f) demonstrated the the best inhibition effects against hCA I, 1,3-bis(4-benzyloxy-3-methoxybenzyl)-3,4,5,6-tetrahydropyrimidinium chloride (5g) demonstrated the the best inhibition effects against cytosolic hCA II isoenzyme. On the other hand, 1,3-Bis(4-methylthiobenzyl)-3,4,5,6-tetrahydropyrimidinium chloride, (5e) demonstrated the the best inhibition effects against AChE enzyme.

Six palladium(II) complexes with benzimidazole-based N-heterocyclic carbene ligands were synthesized by transmetallation reactions between silver(I) N-heterocyclic carbene complexes and PdCl2(PhCN)(2). The complexes were characterized by physicochemical and spectroscopic methods. The palladium complexes were tested as catalysts for intermolecular hydroamination reactions of styrene with various anilines in ionic liquids under both conventional and microwave heating. All of these complexes proved to be catalytically active in these reactions. The anti-Markovnikov addition products were selectively obtained by using 1 mol% of the palladium complex.