Influence of Initial pH Value on the Adsorption of Reactive Black 5 Dye on Powdered Activated Carbon: Kinetics, Mechanisms, and Thermodynamics.

The aim of this work was to investigate the influence of initial pH value (pH0) on the isothermal adsorption of Reactive Black 5 (RB5) dye on commercial powdered activated carbon. Four initial pH values were chosen for this experiment: pH0 = 2.00, 4.00, 8.00, and 10.00. In order to investigate the mechanism of adsorption kinetic, studies have been performed using pseudo-first-order and pseudo-second-order kinetic models as well as an intraparticle diffusion model. In addition, thermodynamic parameters of adsorption were determined for pH0 = 4.00. Results of this research showed that the initial pH value significantly influences the adsorption of RB5 dye onto activated carbon. The highest adsorption capacities (qe) and efficiencies of decolouration were observed for initial pH values of pH0 = 2.00 (qe = 246.0 mg g-1) and 10.00 (qe = 239.1 mg g-1) due to strong electrostatic interactions and attractive π···π interactions, respectively. It was also shown that the adsorption of RB5 dye on activated carbon at all initial pH values is kinetically controlled, assuming a pseudo-second-order model, and that intraparticle diffusion is not the only process that influences on the adsorption rate.

Amidino substituted 2-aminophenols: biologically important building blocks for the amidino-functionalization of 2-substituted benzoxazoles.

Unlike the closely related and widely investigated amidino-substituted benzimidazoles and benzothiazoles with a range of demonstrated biological activities, the matching benzoxazole analogues still remain a largely understudied and not systematically evaluated class of compounds. To address this challenge, we utilized the Pinner reaction to convert isomeric cyano-substituted 2-aminophenols into their amidine derivatives, which were isolated as hydrochlorides and/or zwitterions, and whose structure was confirmed by single crystal X-ray diffraction. The key step during the Pinner synthesis of the crucial carboximidate intermediates was characterized through mechanistic DFT calculations, with the obtained kinetic and thermodynamic parameters indicating full agreement with the experimental observations. The obtained amidines were subjected to a condensation reaction with aryl carboxylic acids that allowed the synthesis of a new library of 5- and 6-amidino substituted 2-arylbenzoxazoles. Their antiproliferative features against four human tumour cell lines (SW620, HepG2, CFPAC-1, HeLa) revealed sub-micromolar activities on SW620 for several cyclic amidino 2-naphthyl benzoxazoles, thus demonstrating the usefulness of the proposed synthetic strategy and promoting amidino substituted 2-aminophenols as important building blocks towards biologically active systems.

Thienochromene derivatives inhibit pSTAT1 and pSTAT5 signaling induced by cytokines.

Furanocoumarins, particularly furo[3,2-c]coumarins, are found in many natural products. However, coumarins annulated to a thiophene ring have received scarce attention to date in the literature. Therefore, we synthesized 4-oxo-4H-thieno[3,2-c]chromene derivatives and tested in vitro their anti-inflammatory activity. Anti-inflammatory potential of the synthesized compounds (1, 2, 6-8, 9a-e and 10a-c) has been evaluated by measuring various pSTAT (signal transducer and activator of transcription) inhibition within the JAK (Janus-activated family kinase)/STAT signaling pathway. Ethyl 7-hydroxy-4-oxo-4H-thieno[3,2-c]chromene-2-carboxylate (7) showed best inhibition properties on pSTAT5 in GM-CSF (Granulocyte-macrophage colony-stimulating factor)-triggered PBMC assay, with IC50 value of 5.0 µM.

Magnetostructural Characterization of Oxalamide Dihalo-Bridged Copper Dimers: Intra- and Interdimer Interactions Studied by Single-Crystal Electron Spin Resonance Spectroscopy.

Detailed single-crystal electron spin resonance (ESR) analysis of oxalamide complexes with halogen-bridged copper dimers, supported by X-ray, magnetic susceptibility, and powder ESR studies, is reported. Four complexes with two different ligands are synthesized: [CuLA (µ-X)]2 and [CuLV (µ-X)]2 , for which LA =N-(l-alanine methyl ester)-N'-[(2-pyridine-2-yl)methyl]oxalamide and LV =N-(l-valine methyl ester)-N'-[(2-pyridine-2-yl)methyl]oxalamide, for which X=Cl or Br. X-ray analysis shows that the geometry at each copper(II) ion is square pyramidal, whereas two pyramids share one base-to-apex edge with parallel basal planes. The complexes are linked by hydrogen bonds into infinite chains and are further linked into a 3D network. Susceptibility measurements show that the copper centers in the dimers are weakly antiferromagnetically coupled (|J|≈1-2 cm-1 ). From powder ESR spectroscopy, the g values and dx2-y2 orbital as the ground state of the unpaired electron are determined. The complexes show unusual anisotropic splitting and merging of the ESR lines if their single crystals rotate in a magnetic field. The observation of this partially resolved intradimer dipolar splitting enables estimation of the weak interdimer exchange interaction parameter |J'|≈0.001 cm-1 .

Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases.

A series of mono-pyrrolo[2,3-d]pyrimidines 4a-4k, unsymmetrical bis-purine isosteres 5a-5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolyl)phenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa) cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1) cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9)/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma) and p38 MAP (mitogen-activated protein) kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole.

Copper-catalyzed mechanochemical click reactions using Cu(II), Cu(I) and Cu(0) catalysts have been successfully implemented to provide novel 6-phenyl-2-(trifluoromethyl)quinolines with a phenyl-1,2,3-triazole moiety at O-4 of the quinoline core. Milling procedures proved to be significantly more efficient than the corresponding solution reactions, with up to a 15-fold gain in yield. Efficiency of both solution and milling procedures depended on the p-substituent in the azide reactant, resulting in H < Cl < Br < I reactivity bias. Solid-state catalysis using Cu(II) and Cu(I) catalysts entailed the direct involvement of the copper species in the reaction and generation of highly luminescent compounds which hindered in situ monitoring by Raman spectroscopy. However, in situ monitoring of the milling processes was enabled by using Cu(0) catalysts in the form of brass milling media which offered a direct insight into the reaction pathway of mechanochemical CuAAC reactions, indicating that the catalysis is most likely conducted on the surface of milling balls. Electron spin resonance spectroscopy was used to determine the oxidation and spin states of the respective copper catalysts in bulk products obtained by milling procedures.

1,2,3-Triazole pharmacophore-based benzofused nitrogen/sulfur heterocycles with potential anti-Moraxella catarrhalis activity.

Versatile 1,2,3-triazole pharmacophore-based benzofused heterocycles containing halogen-substituted aromatic (9-17 and 25-28), 7-substituted coumarin (18-23 and 29-30) or penciclovir-like subunit (31a,b-38a) were designed and synthesized to evaluate their antibacterial activities against selected Gram-positive and Gram-negative bacteria. Hybridization approach using environmentally friendly Cu(I)-catalyzed click reaction under microwave irradiation was adopted in the synthesis of regioselective 1,4-disubstituted 1,2,3-triazole tethered heterocycles (9-23 and 25-30), while post-N-alkylation of NH-1,2,3-triazoles afforded both 2,4- (31a-38a) and 1,4-disubstituted (31b-33b, 35b-37b) 1,2,3-triazole regioisomers. The compounds 18-23 and 25-30 revealed fluorescence in the violet region of the visible spectrum with a strong influence of phenyl spacer in 25-30 on both wavelength and emission intensity. Fusion of selected subunits led to new hybrid architecture, benzothiazole-1,2,3-triazole-coumarin 29 that demonstrated extremely narrow spectrum activity towards fastidious Gram-negative bacteria Moraxella catarrhalis. Selected hybrid showed the potency against Moraxella catarrhalis (MIC⩽0.25µg/mL) comparable to that of reference antibiotic azithromycin, which suggested that further investigations are necessary to optimize this potential hit compound as a new anti-Moraxella catarrhalis agent.

Enantiomerically pure trinuclear helicates via diastereoselective self-assembly and characterization of their redox chemistry.

A tris(bipyridine) ligand 1 with two BINOL (BINOL = 2,2'-dihydroxy-1,1'-binaphthyl) groups has been prepared in two enantiomerically pure forms. This ligand undergoes completely diastereoselective self-assembly into D2-symmeteric double-stranded trinuclear helicates upon coordination to copper(I) and silver(I) ions and to D3-symmetric triple-stranded trinuclear helicates upon coordination to copper(II), zinc(II), and iron(II) ions as demonstrated by mass spectrometry, NMR and CD spectroscopy in combination with quantum chemical calculations and X-ray diffraction analysis. According to the calculations, the single diastereomers that are formed during the self-assembly process are strongly preferred compared to the next stable diastereomers. Due to this strong preference, the self-assembly of the helicates from racemic 1 proceeds in a completely narcissistic self-sorting manner with an extraordinary high degree of self-sorting that proves the power and reliability of this approach to achieve high-fidelity diastereoselective self-assembly via chiral self-sorting to get access to stereochemically well-defined nanoscaled objects. Furthermore, mass spectrometric methods including electron capture dissociation MS(n) experiments could be used to elucidate the redox behavior of the copper helicates.

Recognition of N-alkyl and N-aryl acetamides by N-alkyl ammonium resorcinarene chlorides.

N-alkyl ammonium resorcinarene chlorides are stabilized by an intricate array of intra- and intermolecular hydrogen bonds that leads to cavitand-like structures. Depending on the upper-rim substituents, self-inclusion was observed in solution and in the solid state. The self-inclusion can be disrupted at higher temperatures, whereas in the presence of small guests the self-included dimers spontaneously reorganize to 1:1 host-guest complexes. These host compounds show an interesting ability to bind a series of N-alkyl acetamide guests through intermolecular hydrogen bonds involving the carbonyl oxygen (C=O) atoms and the amide (NH) groups of the guests, the chloride anions (Cl(-)) and ammonium (NH2(+)) cations of the hosts, and also through CH⋅⋅⋅π interactions between the hosts and guests. The self-included and host-guest complexes were studied by single-crystal X-ray diffraction, NMR titration, and mass spectrometry.

An efficient synthesis of pyridoxal oxime derivatives under microwave irradiation.

Quaternary salts of pyridoxal oxime have been synthesized by the quaternization of pyridoxal oxime with substituted phenacyl bromides using microwave heating. Microwave-assisted rapid synthesis was done both in solvent (acetone) and under solvent-free conditions. Good to excellent yields (58%-94%) were obtained in acetone in very short reaction times (3-5 min) as well as in the solvent-free procedure (42%-78%) in very short reaction times (7-10 min) too. Effective metodologies for the preparation of pyridoxal oxime quaternary salts, having the advantagies of being eco-friendly, easy to handle, and performed in shorter reactions time are presented. The structure of compound 7, in which a 4-fluorophenacyl moiety is bonded to the pyridinium ring nitrogen atom, was unequivocally confirmed by the single-crystal X-ray diffraction method.

A mononuclear iron(III) complex with unusual changes of color and magneto-structural properties with temperature: synthesis, structure, magnetization, multi-frequency ESR and DFT study.

From the reaction of 2-hydroxy-6-methylpyridine (L) with iron(II) tetrafluoroborate, a new mononuclear iron(III) octahedral complex [FeL6](BF4)3 has been isolated. The color of the complex reversibly changed from red at room temperature to yellow-orange at the liquid nitrogen temperature. Magnetization measurements indicate that iron(III) in [FeL6](BF4)3 is in a high-spin state S = 5/2, from room temperature to 1.8 K. The high-spin ground state of iron(III) is also confirmed by DFT calculations. Although the spin-crossover of the complex is not observed, X-band and multifrequency high-field/high-frequency electron spin resonance (ESR) spectroscopy shows rather uncommon iron(III) spectra at room temperature and an unusual change with cooling. Spectral simulations reveal that the S = 5/2 ground state multiplet of the complex can be characterized by the temperature independent axial zero-field splitting parameter of |D| = +2 GHz (0.067 cm-1) while the value of the rhombic parameter E of the order of some tenths MHz increases on lowering the temperature. Single crystal X-ray diffraction (SCXRD) shows that the iron(III) coordination geometry does not change with temperature while supramolecular interactions are temperature dependent, influencing the iron(III) rhombicity. Additionally, the DFT calculations show temperature variation of the HOMO-LUMO gap, in agreement with the changes of color and ESR-spectra of the iron(III) complex with temperature.

Synthesis of [5]rotaxanes containing bi- and tridentate coordination sites in the axis.

A new example of a linear [5]rotaxane has been synthesized by using the traditional "gathering-and-threading" approach but based on an unusual axle incorporating a symmetrical bis(bidentate) chelating fragment built on a 4,7-phenanthroline core. The stoppering reaction is particularly noteworthy since, instead of using a trivial bulky stopper as precursor to the blocking group, two semistoppered copper-complexed [2]pseudorotaxanes (namely [2]semirotaxanes) are used, which leads to the desired [5]rotaxane in good yield. The efficiency of the method relies on the use of "click" chemistry, with its very mild conditions, and on the protection by a transition-metal (copper(I)) of the various coordinating groups present in the fragments to be interconnected (terpy and bidentate chelating groups), thus inhibiting potential detrimental side reactions during the copper-catalyzed stoppering reaction. Since the external fragments and the central core of the system contain tri- and bidentate chelating units, respectively, the axle of the final [5]rotaxane incorporates two types of coordinating units: two external terpy groups (terpy: 2,2':6',2''-terpyridine) and two central bidentate ligands. Such a situation enables the system to tidy two different metals centers, and to localize them in a priori well-defined positions. This is what was observed when mixing the free ligand with a mixture of Zn(2+) and Li(+) : the zinc(II) ions were unambiguously shown to occupy the external sites, whereas the Li(+) cations were found in the central part of the [5]rotaxane. An X-ray diffraction study carried out on a [3]pseudorotaxane, the axis of which is similar to the central part of the [5]rotaxane axle, demonstrates that Zn(2+) is clearly five-coordinate, the fifth ligand being a counterion, even when the coordination site of the pseudorotaxane is designed for four-coordinate metals, which is in marked contrast with copper(I) or Li(+) .

Benzylidene-bis-(4-hydroxycoumarin) and benzopyrano-coumarin derivatives: synthesis, ¹H/¹³C-NMR conformational and X-ray crystal structure studies and in vitro antiviral activity evaluations.

We report on the synthesis of 4-hydroxycoumarin dimers 1-15 bearing an aryl substituent on the central linker and fused benzopyranocoumarin derivatives 16-20 and on their in vitro broad anti-DNA and RNA virus activity evaluations. The chemical identities and structure of compounds 1-20 were deduced from their homo- and heteronuclear NMR measurements whereas the conformational properties of 5, 14 and 20 were assessed by the use of 1D difference NOE enhancements. Unequivocal proof of the stereostructure of compounds 7, 9, 16 and 18 was obtained by single crystal X-ray diffraction method. The X-ray crystal structure analysis revealed that two 4-hydroxycoumarin moieties in the 4-trifluoromethylphenyl- and 2-nitrophenyl derivatives (compounds 7 and 9, respectively) are intramolecularly hydrogen-bonded between hydroxyl and carbonyl oxygen atoms. Consequently, the compounds 7 and 9 adopt conformations in which two 4-hydroxy-coumarin moieties are anti-disposed. Antiviral activity evaluation results indicated that the 4-bromobenzylidene derivative of bis-(4-hydroxycoumarin) (compound 3) possesses inhibitory activity against HSV-1 (KOS), HSV-2 (G), vaccinia virus and HSV-1 TK⁻ KOS (ACVr) at a concentration of 9-12 µM and at a minimum cytotoxic concentration (MCC) greater than 20 µM. Compounds 4-6, 8, and 20 were active against feline herpes virus (50% effective concentration, EC50 = 5-8.1 µM), that is at a 4-7-fold lower concentration than the MCC.

N,N-Dibenzoyl-ferrocenecarboxamide.

In the title compound, [Fe(C(5)H(5))(C(20)H(14)NO(3))], the cyclo-penta-dienyl rings deviate by 9.3 (2)° from an eclipsed conformation, defined by C-Cg(1)-Cg(2)-C pseudo-torsion angles ranging from 8.8 (1) to 9.85 (1)°. The coordination at the N atom is slightly pyramidal, as indicated by the angular sum around it of 352.6°. The amide group is inclined at 17.86 (9) and 27.27 (11)° with respect to the aromatic rings. In the crystal, mol-ecules are linked by one C-H⋯O hydrogen bond and one C-H⋯π inter-action into a two-dimensional framework parallel to the b axis.

The unsaturated acyclic nucleoside analogues bearing a sterically constrained (Z)-4'-benzamido-2'-butenyl moiety: Synthesis, X-ray crystal structure study, cytostatic and antiviral activity evaluations.

A series of the novel acyclic unsaturated pyrimidine (1-12) and adenine (13) nucleoside analogues bearing conformationally restricted (Z)-2'-butenyl moiety were synthesized and evaluated for their antiviral and cytostatic activity potency against malignant tumor cell lines and normal human fibroblast (WI38). The N-1 and/or N-3 acyclic side chain substitution in pyrimidine ring in N-3 substituted 5-trifluoromethyluracil derivative (11), N-1, N-3 disubstituted 5-fluorouracil derivative (12) and adenine derivative (13) was deduced from their (1)H and (13)C NMR spectra and confirmed by single crystal X-ray structure analysis. The X-ray crystal structure analysis 11-13 revealed also supramolecular self-assemblies, in which infinite chains or dimers built two- and three-dimensional networks. The results of the in vitro cytostatic activity evaluations of 1-13 indicate that the majority of the compounds tested exhibited a non-specific and moderate antiproliferative effect at the highest concentration (100 microM). Of all evaluated compounds on the cell lines tested only the N-1 4''-fluoro-substituted-benzamide uracil derivative (7) showed rather marked and selective inhibitory activity against the growth of MCF-7 cells at a concentration of 2.7 microM and no cytotoxic effect on normal fibroblasts WI38. This compound can be therefore considered as a potential antitumor lead compound for further synthetic structure modification.

Synthesis, X-ray crystal structure study and antitumoral evaluations of 5,6-disubstituted pyrimidine derivatives.

5,6-Disubstituted pyrimidine derivatives (3-20) were prepared by intramolecular cyclization reaction of alpha-(1-carbamyliminomethylene)-gamma-butyrolactone (2) with sodium ethoxide and subsequent chemical transformation of 2-hydroxy group in C-5 side chain as well as lithiation reaction for introduction of acyclic side chain at C-6. All compounds were characterized by (1)H NMR, (13)C NMR and mass spectra. Structures of compounds 4, 7 and 14 were unambiguously confirmed by X-ray crystal structural analysis. Supramolecular structures of these three compounds differ significantly. Two N-H...O and one C-H...O hydrogen bonds in 4 form three-dimensional network. One O-H...N hydrogen bond and one pi...pi interaction self-assemble the molecules of 7 into sheets. In supramolecular aggregation of 14, only pi...pi stacking interactions participate, so forming chains. The compounds were evaluated for their cytostatic activities against human malignant cell lines. Of all tested compounds, 2,4-dimethoxy-5-methoxytritylethylpyrimidine (9) and 2,4-dichloro-5-chloroethylpyrimidine (14) exhibited the most prominent inhibitory effects. Furthermore, compound 14 showed marked activity against human colon carcinoma (IC(50)=0.4microM).

[2,6-Bis(di-tert-butyl-phosphinometh-yl)phenyl-κP,C,P'](trifluoro-acetato)palladium(II).

The Pd(II) atom in the title compound, [Pd(C(2)F(3)O(2))(C(24)H(43)P(2))], adopts a distorted square-planar geometry with the P atoms in a trans arrangement, forming two five-membered chelate rings. Four intra-molecular C-H⋯O hydrogen bonds occur. The crystal packing reveals one weak inter-molecular C-H⋯O hydrogen bond, which self-assembles the mol-ecules into infinite chains parallel to the b axis.

Synthesis and structural characterization of the 5-(2-haloethyl)pyrimidines--hydrogen-bonded chains in alpha-(1-carbamyliminomethylene)-gamma-butyrolactone.

Three novel 5-(2-haloethyl)pyrimidine derivatives were synthesized and characterized by 1H-NMR, 13C-NMR, MS, IR spectra and elemental analysis. Iodine and chlorine atoms in the C-5 side chain were introduced by reaction of 5-(2-hydroxyethyl)pyrimidine with hydroiodic acid and phosphoryl chloride, respectively. The structure of the intermediate alpha-(1-carbamyliminomethylene)-gamma-butyrolactone was determined by X-ray crystal structure analysis. The molecule deviates very slightly from planarity. Three N-H...O hydrogen bonds link the molecules into one-dimensional chains of edge-fused rings.

Self-Complementary Dimers of Oxalamide-Functionalized Resorcinarene Tetrabenzoxazines.

Self-complementarity is a useful concept in supramolecular chemistry, molecular biology and polymeric systems. Two resorcinarene tetrabenzoxazines decorated with four oxalamide groups were synthesized and characterized. The oxalamide groups possessed self-complementary hydrogen bonding sites between the carbonyls and amide groups. The self-complementary nature of the oxalamide groups resulted in self-included dimeric assemblies. The hydrogen bonding interactions within the tetrabenzoxazines gave rise to the formation of dimers, which were confirmed by single-crystal X-ray diffractions analysis and supported by NMR spectroscopy and mass spectrometry. The self-included dimers were connected by numerous and strong intermolecular N-H⋅⋅⋅O and C-H⋅⋅⋅O hydrogen bonds supplemented with C-H⋅⋅⋅π interactions, forming one-dimensional polymers, which were then further linked into three-dimensional networks.

Novel pyrimidine-2,4-dione-1,2,3-triazole and furo[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids as potential anti-cancer agents: Synthesis, computational and X-ray analysis and biological evaluation.

Regioselective 1,4-disubstituted 1,2,3-triazole tethered pyrimidine-2,4-dione derivatives (5-23) were successfully prepared by the copper(I)-catalyzed click chemistry. While known palladium/copper-cocatalyzed method based on Sonogashira cross-coupling followed by the intramolecular 5-endo-dig ring closure generated novel 6-alkylfuro[2,3-d]pyrimidine-2-one-1,2,3-triazole hybrids (24b-37b), a small library of their 5-alkylethynyl analogs (24a-37a) was synthesized and described for the first time by tandem terminal alkyne dimerization and subsequent 5-endo-trig cyclization, which was additionally corroborated with computational and X-ray crystal structure analyses. The nature of substituents on alkynes and thereof homocoupled 1,3-diynes predominantly influenced the ratio of the formed products in both pathways. In vitro antiproliferative activity of prepared compounds evaluated on five human cancer cell lines revealed that N,N-1,3-bis-(1,2,3-triazole)-5-bromouracil (5-7) and 5,6-disubstituted furo[2,3-d]pyrimidine-2-one-1,2,3-triazole 34a hybrids exhibited the most pronounced cytostatic acitivities against hepatocellular carcinoma (HepG2) and cervical carcinoma (HeLa) cells with higher potencies than the reference drug 5-fluorouracil. Cytostatic effect of pyrimidine-2,4-dione-1,2,3-triazole hybrid 7 in HepG2 cells could be attributed to the Wee-1 kinase inhibition and abolishment of sphingolipid signaling mediated by acid ceramidase and sphingosine kinase 1. Importantly, this compound proved to be a non-mitochondrial toxicant, which makes it a promising candidate for further lead optimization and development of a new and more efficient agent for the treatment of hepatocellular carcinoma.