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We present a series of pyrazolato-bridged copper complexes with interesting structures that can be considered prototypic patterns for tri-, hexa- and hepta- nuclear systems. The trinuclear shows an almost regular triangle with a μ3-OH central group. The hexanuclear has identical monomer units, the Cu6 system forming a regular hexagon. The heptanuclear can be described as two trinuclear moieties sandwiching a central copper ion via carboxylate bridges. In the heptanuclear system, the pyrazolate bridges are consolidating the triangular faces, which are sketching an elongated trigonal antiprism. The magnetic properties of these systems, dominated by the strong antiferromagnetism along the pyrazolate bridges, were described transparently, outlining the energy levels formulas in terms of Heisenberg exchange parameters J, within the specific topologies. We succeeded in finding a simple Kambe-type resolution of the Heisenberg spin Hamiltonian for the rather complex case of the heptanuclear. In a similar manner, the weak intermolecular coupling of two trimer units (aside from the strong exchange inside triangles) was resolved by closed energy formulas. The hexanuclear can be legitimately proposed as a case of coordination-based aromaticity, since the phenomenology of the six-spins problem resembles the bonding in benzene. The Broken-Symmetry Density Functional Theory (BS-DFT) calculations are non-trivial results, being intrinsically difficult at high nuclearities.

Two new mixed ligand copper complexes with 1,10-phenanthroline and monodentate pyrazoles (3,5-dimethyl-4-R-pyrazole, where R = nitro or iodo), stand as case-studies for a revisited view on Ligand-Field (LF) qualitative and semi-quantitative issues, brought in conjunction with the rich information offered by the state-of-the art computational methods. The combined analysis of the first TD-DFT energies and density difference maps enables a scheme of the LF split in the complexes with a specific variety of square-pyramidal coordination geometry, namely the case when the π-type anisotropy due to the two types of aromatic amine ligands shows different orientation with respect of the averaged basal plane. The density difference maps were used as ancillary tools for checking the coordination process and observing the nephelauxetic effect. Clear correlations are drawn between computed and experimental UV–Vis and EPR spectra, rationalizing the Lande factors in terms of Ligand Field states.

Hederagenin, a saponin known for its therapeutic effect was isolated from leaves of Hedera helix. Hederagenin was obtained by repeated maceration of ground plant material in 95% (v/v) ethanol. The ethanolic extract was subjected to acid hydrolysis and purification with acetonitrile. Isolated hederagenin (IHe) was analyzed by HPLC-MS/MS and compared to standard hederagenin. In vitro cytotoxicity of IHe was tested in a culture of fibroblast cells from NCTC clone L929 cell line by MTT assay, using dioscin as positive control. For the determination of IHe antitumor effect, in vitro tests were performed in a culture of human cervix carcinoma Hep-2 cells cultivated in the presence of different concentrations of sample for 48 h. IHe was biocompatible in the range of concentrations 2-200 mg/mL, in NCTC cell culture. The compound showed cell cytotoxicity in the concentration range of 100-400 mg/mL, in Hep-2 cell culture, revealing its antitumor activity. These results demonstrated the possible use of hederagenin isolated from H. helix extract as an antitumor agent.

Cancer is a terrible disease that is spread around the world. [...]

A new series of substituted N,N-bis-[(1H-pyrazol-1-yl)methyl]-aminohexadecane Mannich bases were synthesized, characterized by IR, 1 H NMR 13 C NMR, UV–Vis, MS and elemental analysis, and tested for their biological activity. All the synthesized compounds were tested for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using erythromycin and clotrimazole as standards. Most of the synthesized compounds demonstrated very good activity at minimum inhibitory concentrations (MICs). Compound 3b with an halogen atom into the pharmacophore structure exhibited the most significant activity against Bacillus subtilis (MIC = 0.007 μgmLL −1 ) versus erythromycin as standard. In vitro cytotoxicity of the new compounds was studied using MTT assay. The analysis of the test cells showed that the newly synthesized alkylaminopyrazoles derivatives were biocompatible until a concentration of 5 μgmL −1 ; two compounds presented a high degree of biocompatibility on the studied concentration range.

We revisit, in the key of structural chemistry, one of the most known and important drugs: the aspirin. Although apparently simple, the factors determining the molecular structure and supramolecular association in crystals are not trivial. We addressed the problem from experimental and theoretical sides, considering issues from X-ray measurements and results of first-principle reconstruction of molecule and lattices by ab initio calculations. Some puzzling problems can give headaches to specialists and intrigue the general public. Thus, the reported polymorphism of aspirin is disputed, a so-called form II being alleged as a result of misinterpretation. At the same time, were presented evidences that the structure of common form I can be disrupted by domains where the regular packing is changed to the pattern of form II. The problems appear even at the level of independent molecule: the most stable conformation computed by various techniques of electronic structure differs from those encountered in crystals. Because the energy difference between the related conformational isomers (computed as most stable vs. the experimental structure) is small, about 1 kcal/mol, comprised in the error bars of used methods, the unresting question is whether the modelling is imprecise, or the supramolecular factors are mutating the conformational preferences. By a detective following of the issue, the intermolecular effects were made responsible for the conformation of the molecule in crystal. The presented problems were gathered from literature results, debates, glued with modelling and analysis redone by ourselves, in order to secure the unitary view of the considered prototypic topic.

The aim of this research was to investigate the chemical composition of Coreopsis tinctoria Nutt. fruits extract, to highlight the potential of ultrasound assisted extraction in the fast preparation of extracts rich in polyphenols using different solvents (55%, 78% and 96% hydrous ethanol) and to evaluate the antioxidant potential of formulated extracts. LC-MS/MS was used to characterize the ethanolic extract from Coreopsis tinctoria Nutt. dried fruits. The extract contains different flavonoids (marein, flavanomarein, quercetagetin-7-O-glucoside, okanin aurone, leptosidin, luteolin, apigenin) and phenolic acids (chlorogenic acid, caffeic acid). Several parameters that could affect extraction efficiency were evaluated. Finally, this study focused on determination of plant extracts total phenolic content and their antioxidant capacity. The experimental results allowed the selection of the optimum operating parameters leading to the highest total polyphenolic content, expressed as gallic acid equivalents, and avoiding the degradation of phenolic compounds (ethanol 55%; extraction temperature 323.15 K, extraction time 30 min, liquid/solid ratio 20/1). A good relationship between total phenolic content and antioxidant capacity was obtained.

In this study, three of the saponins present in leaves of Hedera helix L., &alpha, hederin, hederagenin, and hederacoside C were studied for their antiproliferative activity. The three saponins were analyzed in different concentrations by in vitro tests on normal fibroblasts cells and cervix ephitelial tumor cells. Determination of cytotoxicity and antitumor effects was performed using the MTT method. From the tested saponins, &alpha, hederin was biocompatible in normal fibroblasts cells at concentrations between 2&ndash, 10 &mu, g/mL. Its antiproliferative activity was exerted in the concentration range of 10&ndash, 400 &mu, g/mL in cervix ephitelial tumor cells. Similarly, hederagenin presented antiproliferative activity at concentrations between 25&ndash, g/mL. In turn, hederacoside C was shown to be noncytotoxic in normal fibroblasts and cervix ephitelial tumor cell culture at all the tested concentrations. The obtained experimental results were analyzed by &ldquo, Mixture design&rdquo, a specialized form of the response surface method (RSM) provided by the Design Expert 11 software, and the optimal composition of obtained saponins mixture was selected and verified in vitro for antiproliferative activity. The results showed that an optimal saponins mixture has the potential to be used in pharmacological applications.

A thermal analysis study has been performed for the stable free radical 2,2-diphenyl-1-picrylhydrazyl and other ten free radical congeners, together with their corresponding parent hydrazines. Qualitative studies on the decomposition products showed that nitrogen dioxide plays a key role. A mechanistic decomposition pathway is also proposed.

Five new pyrazole acetanilides were synthesized by N-alkylation of pyrazole and its derivatives with 4′-propionyl-2-iodoacetanilide. Compounds 1–5 were characterized by 1H NMR, 13C NMR, IR, UV–Vis, MS, and elemental analysis. X-ray structures of representative compounds 1, 3, and 5 established their conformations and solid-state hydrogen bonding preferences. Acute toxicity, local anesthetic, and antiarrhythmic activities were assessed for compounds 1–5 using established protocols. Lower potencies and lower acute toxicities were recorded relative to lidocaine. Enhanced anesthetic activity of compound 3 was attributed to the presence of the propionyl group in the molecule.

Alignment-free three-dimensional quantitative structure–toxicity relationship models, developed on the basis of GRid INdependent Descriptors (GRIND), on acute toxicity data obtained by (i) oral administration of 25 pyrazolylacetanilides, and (ii) intravenous administration of 15 commercially available Local Anesthetics (LAs) to mice was reported. The most favorable interaction regions extracted from molecular interaction fields obtained with HBA, HBD, hydrophobic, and shape probes were correlated with toxicity data expressed as log[1/(LD50)] by partial Least Square Analysis (PLS). Variable selection was done by fractional factorial design. The best PLS models for set (i) comprises 3LV with r2=0.95 and q2=0.72; for set (ii) comprises 2LV with r2=0.95 and q2=0.58. Internal cross-validation was done by using three random groups of compounds for each set. External predictivity of the second model was checked by a test set consists of eight structurally diverse compounds. The PLS model related to orally administrated set of compounds was compared with the corresponding one related to intravenously administrate drugs. Variables having high impact on each model, positively or negatively correlated with toxicities, were discussed and an attempt was made to link those variables with calculated ADME related properties of compounds, as well as with literature data that describes probable interaction of LA drugs with the homology modeled voltage-gated sodium channels. According to the best of our knowledge this is first reported study that use GRIND methodology in structure–toxicity relationships on whole animals.

The molecular and crystal structures of the lidocaine analogs 2-(pyrazol-1-yl)-2′-methylacetanilide (1), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2′-methylacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-3′-methylacetanilide (3), and 2-(pyrazol-1-yl)-4′-methylacetanilide (4), are reported, with a summary of their pharmacological activities. In this series, the moiety comprising the heterocyclic ring and the amide alkyl linker displays a common conformation. Molecules of 1–4 form identical hydrogen bonded motifs in their crystals, namely linear chains via intermolecular N–H···O=C hydrogen bonding. Moderate anesthetic and anti-arrhythmic potencies recorded for 1–4 relative to lidocaine are countered by their significantly lower toxicities.

X-ray structures of three pharmacologically active lidocaine analogs, containing a common, substituted pyrazole moiety as the basic residue and variously substituted phenyl rings as the hydrophobic residue, have been determined. This isomeric series comprises 2-(3,5-dimethyl-pyrazol-1-yl)-2′-methylacetanilide (1), 2-(3,5-dimethyl-pyrazol-1-yl)-3′-methylacetanilide monohydrate (2), and 2-(3,5-dimethyl-pyrazol-1-yl)-4′-methylacetanilide (3). Crystal data are 1: space group P2 1 /c with a = 4.7617(2), b = 11.5638(4), c = 23.603(1) A, β = 90.736(2)°, Z = 4; 2: P2 1 /c with a = 4.7260(1), b = 13.7001(4), c = 21.7006(6) A, β = 93.425(1)°, Z = 4; 3: P2 1 /n with a = 6.4103(3), b = 24.584(1), c = 8.4449(4) A, β = 100.273(3)°, Z = 4. In 1–3, the amide bond is trans-planar but the basic and hydrophobic residues adopt different orientations relative to this plane. Hydrogen bonding in 1 and 3 is based on C(4) linear arrays whereas in the monohydrate 2, the presence of water gives rise to R (16) ring motifs. A summary of the local anesthetic and anti-arrhythmic properties of 1–3 is provided. X-ray Structures of Pharmacologically Active 2-(3,5-Dimethyl-pyrazol-1-yl)-methylacetanilides Christina Zalaru, Mino R. Caira, Mircea Iovu, and Elena Cristea The title compounds are lidocaine analogs that display local anesthetic and anti-arrhythmic activities. X-ray analyses revealed a range of solid-state conformations among these isomeric compounds as well as variation in hydrogen bonding schemes, namely C(4) (R = o-, p-CH3) and R44(16) (R = m-CH3, monohydrate crystal). 1,1-Os3(CO)9(μ-CO)(phen)

New complexes of Cu(II) with some substituted 2-(3,5-dimethyl-pyrazol-1-yl)-methyl-acetanilides (L) hae been synthesized. The complex compounds, CuL4X2 (where X- = Cl,Br, CH3COO) were characterized by elemental analysis, as well as IR, UV-VIS, EPR spectroscopy. The study evidenced the influence of the position of the methyl group on the benzene ring and also of the anions on the physical properties of the compounds.

The X-ray structures of four pharmacologically active lidocaine analogs, containing substituted pyrazole moieties as the basic residue and an o-nitrophenyl moiety as the hydrophobic residue, have been determined. They are 2-(pyrazol-1-yl)-2′-nitroacetanilide (1), 2-(3,5-dimethyl-pyrazol-1-yl)-2′-nitroacetanilide (2), 2-(3,5-dimethyl-4-iodo-pyrazol-1-yl)-2′-nitroacetanilide (3), and 2-(3,5-dimethyl-4-nitro-pyrazol-1-yl)-2′-nitroacetanilide (4). Crystal data are 1: space group Pn with a = 4.6944(1), b = 22.3890(3), c = 15.7481(2) A, β = 96.810(1)°, Z = 6; 2: P\(\overline {\text{1}} \) with a = 4.7277(2), b = 11.6878(5), c = 12.0355(6) A, α = 87.689(2), β = 85.048(2), γ = 85.975(2)°, Z = 2; 3: I2/a with a = 24.108(5), b = 4.7321(9), c = 25.337(5) A, β = 96.09(3)°, Z = 8; 4: P21 with a = 5.7788(2), b = 8.9844(3), c = 14.0304(5) A, β = 101.611(1)°, Z = 2. Molecules of compound 1 adopt a unique, folded conformation stabilized by intramolecular hydrogen bonds and the crystal structure lacks significant intermolecular interactions. In contrast, molecules of 2–4 adopt common, extended conformations and their crystal structures are based on linear arrays of hydrogen bonded (N—H...O=C) molecules. Compound 3 displayed the highest local anesthetic activity while 2 was the most active in tests for anti-arrhythmic effects.

The Schiff bases obtained from formylmenthone and o-, m-, p-toluidine behave as bidentate ligands with O and N donor atoms in Ni(II) and Cu(II) complexes by the type NiL2 and CuL2.(H2O)2. The donor atoms and the possible geometry for the complexes were assigned by means of chemical, thermodifferential analyses and electronic, EPR and IR spectra

Copper(II) and nickel(II) complexes employing the Schiff bases derived from formylcarvone and ortho and para aminobenzoic acid (L) have been prepared. The complexes of general formula CuL2.2H2O and Nil2.2L have been characterized by elemental analysis, infrared, visible and EPR spectra, and thermodifferential analysis. The metallic ion has determined the type of the complex.

Nine substituted 2-(pyrazol-1-yl)-dialkylacetanilides were synthesized by N-alkylation of pyrazole and its derivatives with several 2-iodoacetanilides. The new compounds exhibited local anesthetic and antiarrhythmic actions. They have been characterized by elemental chemical analysis, UV-Vis, IR, 1H NMR, 13C NMR, SM spectra and pharmacology research.