Vitamin B1-based thiazol-2-ylidene-Ru(II) complexes: recyclable transfer hydrogenation catalysts in water.

The [(p-cymene)RuCl(κ2C,N-{CNHC-NH})]+X- (CNHC = thiazol-2-ylidene) complexes with a bidentate ligand (2: X = Cl and 3: X = PF6) were prepared by a one-pot reaction of vitamin B1 (VB1, 1), Ag2O and [(p-cymene)RuCl2]2. In the complexes, VB1 coordinates through C2 and the exocyclic N in the imino form with the κ2-(C,N) coordination mode. The complexes 2 and 3 are stable in the solid state, but slowly release p-cymene in solution. Furthermore, upon heating in polar solvents, 2 or 3 can be converted by ligand exchange reactions to produce [(L)3RuCl(κ2C,N-{CNHC-NH})]+PF6- (4: L = py).Robustness was improved remarkably for 4. The complex 4 is stable in the solid state and in solution. The complexes 2-4 have been identified by 1H and 13C{1H} 2D NMR spectroscopy and 2 and 4 were studied by X-ray crystallography. In an effort to develop a recyclable catalyst in water, 2-4 were evaluated for TH of ketones and aldehydes with an azeotropic mixture of HCOOH/Et3N in water. The complexes 3 and 4 exhibited very good catalytic activity and 4 could be reused nine times without significant loss of activity, giving a high turnover frequency (TOF50%(h-1) = 1286).

Novel Benzotriazole-ß-lactam Derivatives as Antimalarial Agents: Design, Synthesis, Biological Evaluation and Molecular Docking Studies.

Many people around the world suffer from malaria, especially in tropical or subtropical regions. While malaria medications have shown success in treating malaria, there is still a problem with resistance to these drugs. Herein, we designed and synthesized some structurally novel benzotriazole-ß-lactams using 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid as a key intermediate. To synthesize the target molecules, the ketene-imine cycloaddition reaction was employed. First, The reaction of 1H-benzo[d][1,2,3]triazole with 2-bromoacetic acid in aqueous sodium hydroxide yielded 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid. Then, the treatment of 2-(1H-benzo[d][1,2,3]triazol-1-yl)acetic acid with tosyl chloride, triethyl amine, and Schiff base provided new ß-lactams in good to moderate yields.The formation of all cycloadducts was confirmed by elemental analysis, FT-IR, NMR and mass spectral data. Moreover, X-ray crystallography was used to determine the relative stereochemistry of 4a compound. The in vitro antimalarial activity test was conducted for each compound against P. falciparum K1. The IC50 values ranged from 5.56 to 25.65 µM. A cytotoxicity profile of the compounds at 200 µM final concentration revealed suitable selectivity of the compounds for malaria treatment. Furthermore, the docking study was carried out for each compound into the P. falciparum dihydrofolate reductase enzyme (PfDHFR) binding site to analyze their possible binding orientation in the active site.

Benzimidazol-2-ylidene ruthenium complexes for C-N bond formation through alcohol dehydrogenation.

A low temperature hydrogen borrowing approach to generate secondary amines using benzimidazole-based N-heterocyclic carbene (BNHC) ruthenium complexes is reported. A series of the piano-stool complexes of the type [(η6-p-cymene)(BNHC)RuCl2] (1a-g) were synthesized via one-pot reaction of the NHC salt precursor, Ag2O, and [RuCl2(p-cymene)]2 and characterized using conventional spectroscopic techniques. The geometry of two precursors, [(η6-p-cymene)(Me4BnMe2BNHCCH2OxMe)RuCl2] (1f) and [(η6-p-cymene)(Me5BnMe2BNHCCH2OxMe)RuCl2] (1g), was studied by single crystal X-ray diffraction. These catalysts were found to dehydrogenate alcohols efficiently at temperatures as low as 50 °C to allow Schiff-base condensation and subsequent imine hydrogenation to afford secondary amines. Notably, this ruthenium-based procedure enables the N-alkylation of aromatic and heteroaromatic primary amines with a wide range of primary alcohols in excellent yields of up to 98%. The present methodology is green and water is liberated as the sole byproduct.

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.

Water-soluble silver(i) complexes with N-donor benzimidazole ligands containing an imidazolium core: stability and preliminary biological studies.

Herein, we report the synthesis, characterisation and preliminary biological evaluation of two novel silver(i) complexes of type [AgL2](NO3)3 (3 and 4) with ionic N-donor benzimidazoles. The complexes have been synthesized by the reaction of 1.5 equivalents of silver nitrate and N-donor benzimidazoles containing an imidazolium core at the 2-position (1 and 2) in ethanol. The X-ray analysis of 4 shows that it has two free imidazolium cores and the charge is balanced with three nitrate anions. A study by the combination of NMR, IR, LC-MS and elemental analysis techniques also suggests that the complexes have this structure both in the solid-state and solution. The complexes are highly soluble and stable in water. Cytotoxicity evaluation against four cancerous human cells and one non-cancerous human cell revealed that the complexes have no significant anti-growth effect. However, the complexes showed a remarkable antimicrobial effect at normalized minimum inhibitory concentrations (normalized MICs) in the range of 33-268 µM against a panel of microorganisms consisting of Gram-negative and Gram-positive bacteria, and fungi.

Crystal structure and DFT computational studies of (E)-2,4-di-tert-butyl-6-{[3-(tri-fluoro-meth-yl)benz-yl]imino-meth-yl}phenol.

The title compound, C23H28F3NO, is an ortho-hy-droxy Schiff base compound, which adopts the enol-imine tautomeric form in the solid state. The mol-ecular structure is not planar and the dihedral angle between the planes of the aromatic rings is 85.52 (10)°. The tri-fluoro-methyl group shows rotational disorder over two sites, with occupancies of 0.798 (6) and 0.202 (6). An intra-molecular O-H⋯N hydrogen bonding generates an S(6) ring motif. The crystal structure is consolidated by C-H⋯π inter-actions. The mol-ecular structure was optimized via density functional theory (DFT) methods with the B3LYP functional and LanL2DZ basis set. The theoretical structure is in good agreement with the experimental data. The frontier orbitals and mol-ecular electrostatic potential map were also examined by DFT computations.

Synthesis, structural, cytotoxic and pharmacokinetic evaluation of some thiosemicarbazone derivatives.

Iron(III) and nickel(II) complexes bearing a thiosemicarbazone framework were synthesized by a one-pot synthesis method. The structures were characterized by elemental analysis, IR, 1 H NMR, APCI Mass, conductivity, magnetic moment measurements. Molecular and crystal structures of the iron(III) complex were obtained from single-crystal X-ray diffraction. The findings showed that the metal atom adopts a slightly distorted square-pyramidal coordination, with the four donor atoms of the thiosemicarbazone ligand defining the basal plane and a chloride atom occupying the apical position. In the crystal lattice, the structure is stabilized by intermolecular O─H···O and C─H···O interactions. The cytotoxic activity was studied by MTT assay, the expression levels of cytochrome P450 (CYP) enzymes by Western blot, and the lipophilicity (LogP) by using the shake-flask method, another pharmacokinetic parameter. The findings showed that the IC50 values decreased with the decrease of the LogP values of the substances. Cytochrome P450 expression levels were found specific for each compound and each cell line. As a result, the pharmacokinetic properties of the newly synthesized thiosemicarbazone compounds are crucial for oral administration and provide us with clues for prospective in vivo studies.

Investigations of antiproliferative and antioxidant activity of ß-lactam morpholino-1,3,5-triazine hybrids.

This article reports for the first time the synthesis of some novel ß-lactam morpholino-1,3,5-triazine hybrids by a [2+2]-cycloaddition reaction of imines 7a-c, 9a-c and 11 with ketenes derived from substituted acetic acids. The reaction was totally diastereoselective, leading exclusively to the formation of cis-ß-lactams 8a-l, 10a-f and 12a-c. The synthesized compounds were tested for activity towards SW1116, MCF-7 and HepG2 cancer cell lines and non-cancerous HEK-293 cell line by MTT assay. None of the compounds exert an observable effect on HepG2, MCF-7 and HEK-293 cells, but compounds 7b, 8f, 8g, 8l, 10c, and 10e exhibited excellent growth inhibitory activity (IC50 < 5 µM) against SW 1116 cells, comparable to that of doxorubicin (IC50 = 6.9 µM). An evaluation of the antioxidant potential of each of the compounds, performed by diphenylpicrylhydrazyl (DPPH) assay, indicated that 7b, 9a, 9b and 9c have strong free radical scavenging activity. UV absorption titration studies reveal that 7b, 8l, 8g and 8f interact strongly with calf-thymus DNA (CT-DNA) in the order of 8l > 7b > 8f > 8g. Collectively, the in vitro capabilities of some of these morpholino-triazine imines and ß-lactams suggest possible applications to development of new antioxidants and DNA binding therapeutics.

Crystal structure and Hirshfeld surface analysis of 4-[4-(1H-benzo[d]imidazol-2-yl)phen-oxy]phthalo-nitrile dimethyl sulfoxide monosolvate.

This work presents the synthesis and structural characterization of [4-(1H-benzo[d]imidazol-2-yl)phen-oxy]phthalo-nitrile, a phthalo-nitrile derivative carrying a benzimidazole moiety. The compound crystallizes as its dimethyl sulfoxide monosolvate, C21H12N4O·(CH3)2SO. The dihedral angle between the two fused rings in the heterocyclic ring system is 2.11 (1)°, while the phenyl ring attached to the imidazole moiety is inclined by 20.7 (1)° to the latter. In the crystal structure, adjacent mol-ecules are connected by pairs of weak inter-molecular C-H⋯N hydrogen bonds into inversion dimers. N-H⋯O and C-H⋯O hydrogen bonds with R 2 1(7) graph-set motifs are also formed between the organic mol-ecule and the disordered dimethyl sulfoxide solvent [occupancy ratio of 0.623 (5):0.377 (5) for the two sites of the sulfur atom]. Hirshfeld surface analysis and fingerprint plots were used to investigate the inter-molecular inter-actions in the crystalline state.

Microwave-assisted synthesis of 1-substituted-1H-benzimidazolium salts: Non-competitive inhibition of human carbonic anhydrase I and II.

A series of 1-substituted-1H-benzimidazolium p-toluenesulfonate salts were synthesized in good yields by the reaction of 1-substituted benzimidazole derivatives and p-toluenesulfonic acid under microwave irradiation. Two iodide salts were synthesized by the anion exchange reaction of the corresponding p-toluenesulfonate salt and NaI. All compounds were characterized by 1 H NMR, 13 C NMR, IR, LC-MS spectroscopic methods, and elemental analyses. The crystal structure of 1-methoxyethyl-1H-benzimidazolium p-toluenesulfonate 2d showed that cation and anion are interconnected by N-H···O and C-H···O hydrogen bonds. All compounds were examined as inhibitor of human carbonic anhydrase (hCA) I and II, and all of them inhibited hCA I and hCA II. Kinetic investigation results revealed that these compounds inhibit hCA I and hCA II in a non-competitive manner. The iodide salts had higher inhibitory activity than their corresponding p-toluenesulfonate salts.

Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis, characterization and molecular docking studies.

Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a-5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 µM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 µM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results.

Crystal structure of 2-{[(5-nitro-thio-phen-2-yl)methyl-idene]amino}-phenol.

The title compound, C11H8N2O3S, is roughly planar; the di-hedral angle between the planes of the thio-phene and benzene rings is 8.38 (10)°. An intra-molecular O-H⋯N hydrogen bond generates an S(5) ring motif. In the crystal, mol-ecules are linked into centrosymmetric dimers by pairs of O-H⋯O hydrogen bonds with an R 2 (2)(22) graph-set motif. Aromatic π-π stacking inter-actions [centroid-centroid sep-ar-ations = 3.653 (3) and 3.852 (3) Å] link the dimers into a three-dimensional network.

Experimental and theoretical studies of (E)-2-(2-hydroxystyryl)-6-(4-methoxybenzoyl)-5-(4-methoxyphenyl)-1,2,4-triazin-3(2H)-one.

Crystal structure of the title compound, C26H21N3O5, has been synthesized and characterized by FT-IR, (1)H NMR, (13)C NMR and X-ray single crystal determination. The molecular geometry was also calculated by using Gaussian 03 software and structure was optimized by using HF and DFT/B3LYP method with the 6-31G(d) basis sets in ground state. The comparison of the theoretical and experimental geometries of the title compound indicated that the X-ray parameters agree with the theoretically obtained values. It was seen that R(2) value changes from 0.015 to 0.021 Å for bond length and angle. The calculated vibrational frequencies are also in good agreement with the experimental results. The (1)H and (13)C NMR chemical shifts values of (E)-2-(2-hydroxystyryl)-6-(4-methoxybenzoyl)-5-(4-methoxyphenyl)-1,2,4-triazin-3(2H)-one molecule have been calculated by the GIAO method. Besides, molecular electrostatic potential maps (MEP), Mulliken charges and Nonlinear Optical effects (NLO) analysis of the compound have been calculated by the HF and B3LYP/6-31G(d) methods.

Direct and solvent-assisted keto-enol tautomerism and hydrogen-bonding interactions in 4-(m-chlorobenzylamino)-3-phenyl-4,5-dihydro-1H-1,2,4-triazol-5-one: a quantum-chemical study.

The tautomeric equilibrium of the title triazole compound was computationally analyzed at the B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory. The solvent effect was considered for three solvents (chloroform, methanol, and water). Two distinct mechanisms were applied: a direct intramolecular transfer using the polarizable continuum model (PCM) and a solvent-assisted mechanism. The calculations indicated that the keto form is more stable in all cases. It was found that the barrier heights for the tautomerization reaction are very high, indicating a relatively disfavored process. Although the barrier heights for solvent-assisted reactions are significantly lower than those for the unassisted tautomerization reaction, implying the importance of the superior catalytic effect of the solvents, monosolvation was not found to be sufficient for the reaction to occur. Finally, the two intermolecular hydrogen-bonding interactions in the crystal structure were investigated in the gas phase; according to the calculated energies and structural parameters, the order of stability is N3-H3···O1 > N1-H1···O1.

Structural and spectroscopic characterization of a thiosemicarbazidatodioxouranium(VI) complex: a combined experimental and DFT study.

The title thiosemicarbazidatodioxouranium(VI) compound was synthesized and characterized by FT-IR, NMR and UV-vis spectroscopies. Solid-state structure of the compound was confirmed by X-ray crystallography. Besides, the molecular geometry, vibrational frequencies and gauge-independent atomic orbital (GIAO) (1)H and (13)C NMR chemical shift values of the compound in the ground state have been calculated using the density functional theory (DFT/B3LYP) method with the 6-311++G(d,p) basis set for the C, H, Cl, N, O, S atoms and SDD pseudo-potential for the U atom, and compared with the experimental data. Using the TD-DFT method, electronic absorption spectra of the compound have been predicted at same level. As a result, a good agreement is obtained between the experimental and theoretical ones.

A novel one-pot synthesis of heterocyclic compound (4-benzoyl-5-phenyl-2-(pyridin-2-yl)-3,3a-dihydropyrazolo[1,5-c]pyrimidin-7(6H)-one): structural (X-ray and DFT) and spectroscopic (FT-IR, NMR, UV-Vis and Mass) characterization studies.

In this study, the title compound named as 4-benzoyl-5-phenyl-2-(pyridin-2-yl)-3,3a-dihydropyrazolo[1,5-c]pyrimidin-7(6H)-one (C24H18N4O2) was both experimentally and theoretically investigated. The compound was synthesized and characterized by FT-IR, NMR ((1)H NMR, (13)C NMR and HETCOR-NMR), Mass spectroscopies and single-crystal X-ray diffraction methods. The compound crystallizes in the monoclinic space group P2(1)/n with a=6.1402 (3) Å, b=21.4470 (15) Å, c=15.0049 (8) Å and ß=97.407 (4)°. The molecular geometry was obtained from the X-ray structure determination optimized using density functional theory (DFT/B3LYP) method with the 6-31+G(d, p) basis set in ground state. From the optimized structure, geometric parameters, vibrational wavenumbers and chemical shifts of molecule were obtained. Experimental measurements were compared with its corresponding the calculated data. An excellent harmony between the two data was ascertained. Besides, molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs) and non-linear optical (NLO) properties of the title molecule were investigated by theoretical calculations at the B3LYP/6-31+G(d, p) level.

1-[3-(Morpholin-4-yl)prop-yl]-3-[(naph-tha-len-2-yl)oxy]-4-(3-nitro-phen-yl)azeti-din-2-one.

In the title compound, C26H27N3O5, the ß-lactam (azetidin-2-one) ring is nearly planar [maximum deviation = 0.011 (3) Å]. The mean plane formed by the four C atoms of the morpholine ring, which adopts a chair conformation, the benzene ring and the naphthalene ring system form dihedral angles of 72.85 (17), 87.46 (15) and 65.96 (11)°, respectively, with the ß-lactam ring. In the crystal, molecules are linked via C-H⋯O hydrogen bonds, forming inversion dimers with R 2 (2)(8).

3-(2,4-Di-chloro-phen-oxy)-1-(4-meth-oxy-benz-yl)-4-(4-nitro-phen-yl)azetidin-2-one.

The ß-lactam ring of the title compound, C23H18Cl2N2O5, is nearly planar [maximum deviation = 0.019 (2) Šfor the N atom] and its mean plane makes dihedral angles of 56.86 (15), 68.83 (15) and 83.75 (15)° with the di-chloro-, nitro- and meth-oxy-substituted benzene rings, respectively. In the crystal, mol-ecules are linked by pairs of C-H⋯O hydrogen bonds, forming inversion dimers with R 2 (2)(10) loops. The dimers are linked by further C-H⋯O hydrogen bonds, forming sheets lying parallel to (001). The mol-ecular packing is further stabilized by C-H⋯π inter-actions.

1-(Morpholin-4-yl)-4-(2-nitro-phen-yl)spiro-[azetidine-3,9'-xanthen]-2-one.

In the title compound, C22H21N3O5, the ß-lactam (azetidin-2-one) ring is nearly planar [maximum deviation = 0.010 (1) Å] and makes dihedral angles of 69.22 (5), 55.32 (5) and 89.42 (4)° with the least-squares planes formed by the four C atoms of the morpholine ring, which adopts a chair conformation, the benzene ring and the xanthene ring system, respectively. In the crystal, C-H⋯O hydrogen-bond contacts connect neighbouring mol-ecules into infinite zigzag chains running parallel to the b axis.

(E)-4-{[(Morpholin-4-yl)imino]-meth-yl}benzo-nitrile.

In the title compound, C12H13N3O, the morpholine ring adopts a chair conformation and its mean plane is inclined to that of the benzene ring by 16.78 (12)°. The N-N=C-C bridge, which has an E conformation, has a torsion angle of 173.80 (19)°. In the crystal, mol-ecules stack along the a axis but there are no significant inter-molecular inter-actions present.