Cu(II) complexes with heterocyclic substituted thiosemicarbazones: the case of 5-formyluracil. Synthesis,characterization, x-ray structures,DNA interaction studies,and biological activity

Two new 5-formyluracil thiosemicarbazone (H(3)ut) derivatives, Me-H(3)ut (1) and Me(2)-H(3)ut (2), were synthesized by reacting thiosemicarbazides, mono- and dimethylated on the aminic nitrogen, with 5-formyluracil and were subsequently characterized. These ligands, treated with copper chloride and nitrate, afforded three complexes: [Cu(Me-H(3)ut)Cl(2)].H(2)O (3), [Cu(Me(2)-H(3)ut)Cl(2)].H(2)O (4), and [Cu(Me-H(3)ut)(NO(3))(OH(2))(2)]NO(3) (5). The crystal structures of these complexes have been determined by single-crystal X-ray diffraction. In 3 and 4, a similar pentacoordination is present; the copper atom is surrounded by the ligand SNO donor atoms and by two chloride ions. The structure of 5 consists of [Cu(Me-H(3)ut)(NO(3))(OH(2))(2)](+) cations and nitrate anions. The copper coordination (4 + 2) involves the SNO ligand atoms and a water oxygen in the basal plane; the apical positions are occupied by a second water oxygen and by an oxygen of a monodentate nitrate group. Two biochemical techniques, namely DNA titration in the UV-vis region and thermal denaturation, have been employed to probe the details of DNA binding of these compounds. Analysis of the results suggests that our compounds are able to interact with DNA by electrostatic and groove binding but not by intercalation. The compounds have been also tested in vitro on human leukemic cell line U937, but they are not able to inhibit significantly cell proliferation.     

Synthesis and structural characterisation of CdS nanoparticles prepared in a four-components "water-in-oil" microemulsion

Nanostructured semiconductor particles are currently under intense investigation because of their enhanced photoreactivity and photocatalytic properties due to the quantum-size effect and the dependence of the photophysical and photochemical properties on their size as it approaches the exciton diameter. This increasing interest has led to the development of several synthetic procedures to prepare and stabilise uniform crystallites. In this paper, we report a novel synthetic pathway to obtain cadmium sulphide (CdS) nanoparticles in a quaternary "water-in-oil" microemulsion formed by a cationic surfactant cetyltrimethylammonium bromide (CTAB), pentanol, n-hexane and water. The synthesis of CdS in this system is achieved by mixing two microemulsions containing Cd(NO3)2 and Na2S, respectively. The nanocrystals have been characterised by using UV--visible spectroscopy and Transmission Electron Microscopy to investigate the influence of various parameters of the particles' formation and stability in solution. Capping of nanoparticles with suitable organic molecules has been performed in order to increase their stability and afford solubility in a wide range of solvents.     

The Brezis-Nirenberg problem near criticality in dimension 3

We consider the problem of finding positive solutions of Δu+λu+u^q=0 in a bounded, smooth domain Ω in , under zero Dirichlet boundary conditions. Here q is a number close to the critical exponent 5 and 0<λ<λ₁. We analyze the role of Green's function of Δ+λ in the presence of solutions exhibiting single and multiple bubbling behavior at one point of the domain when either q or λ are regarded as parameters. As a special case of our results, we find that if , where λ∗ is the Brezis-Nirenberg number, i.e., the smallest value of λ for which least energy solutions for q=5 exist, then this problem is solvable if q>5 and q−5 is sufficiently small.     

Synthesis and evaluation of stereopure α-trifluoromethyl-malic hydroxamates as inhibitors of matrix metalloproteinases

The total synthesis of trifluoromethyl (Tfm) analogs of known nanomolar matrix metalloproteinases (MMPs) inhibitors has been performed. The synthetic protocol is based on a moderately stereoselective aldol reaction of trifluoropyruvate with an N-acyl-oxazolidin-2-thione for the construction of the core α-Tfm-malic unit. Both the diastereomeric forms of the target α-Tfm-malic hydroxamates showed micromolar inhibitory potency toward MMP-2 and 9, with a substantial drop with respect to the parent unfluorinated compounds.     

Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives

A series of 6- and 6,8-halocoumarin derivatives have been investigated as potential antiproliferative compounds against a panel of tumor and normal cell lines. Cytotoxic effects were determined by the MTT method. To investigate the potential molecular mechanism involved in the cytotoxic effect, apoptosis assay, cell cycle analysis, reactive oxygen species (ROS), and reduced glutathione analysis were performed. Among the screened compounds, coumarins 6,8-dibromo-2-oxo-2H-chromene-3-carbonitrile 2h and 6,8-diiodo-2-oxo-2H-chromene-3-carbonitrile 2k exhibited the most antiproliferative effect in thyroid cancer-derived cells TPC-1. The apoptosis assay showed that both 2h and 2k induced apoptosis in TPC-1 thyroid cancer cells. According to these experiments, both coumarins induced a slight increase in TPC-1 cells in the G2/M phase and a decrease in the S phase. A significant increase in ROS levels was observed in TPC-1 treated with diiodocoumarin 2k, while the dibromocoumarin 2h induced a decrease in ROS in a dose and time-dependent manner.     

Perfluoroaryl Bicyclic Cell‐Penetrating Peptides for Delivery of Antisense Oligonucleotides

Exon‐skipping antisense oligonucleotides are effective treatments for genetic diseases, yet exon‐skipping activity requires that these macromolecules reach the nucleus. While cell‐penetrating peptides can improve delivery, proteolytic instability often limits efficacy. It is hypothesized that the bicyclization of arginine‐rich peptides would improve their stability and their ability to deliver oligonucleotides into the nucleus. Two methods were introduced for the synthesis of arginine‐rich bicyclic peptides using cysteine perfluoroarylation chemistry. Then, the bicyclic peptides were covalently linked to a phosphorodiamidate morpholino oligonucleotide (PMO) and assayed for exon skipping activity. The perfluoroaryl cyclic and bicyclic peptides improved PMO activity roughly 14‐fold over the unconjugated PMO. The bicyclic peptides exhibited increased proteolytic stability relative to the monocycle, demonstrating that perfluoroaryl bicyclic peptides are potent and stable delivery agents.     

New precision measurements of the strong interaction in kaonic hydrogen

The DEAR experiment performed at the DAΦNE electron-positron collider (Frascati, Italy) studied the strong interaction shift and width of the 1s state in kaonic hydrogen using X-ray spectroscopy. The repulsive character of the kaon-proton interaction at threshold was confirmed and the most precise values of the shift and width were obtained. However, high precision data at the percent level are highly requested to further develop the theories and thus our understanding of the low-energy antikaon-nucleon interaction. Therefore, a new series of precision experiments on kaonic hydrogen and kaonic deuterium are planned at LNF.     

Chemometrical strategies for feature selection and data compression applied to NIR and MIR spectra of extra virgin olive oils for cultivar identification

The possibility provided by Chemometrics to extract and combine (fusion) information contained in NIR and MIR spectra in order to discriminate monovarietal extra virgin olive oils according to olive cultivar (Casaliva, Leccino, Frantoio) has been investigated.Linear discriminant analysis (LDA) was applied as a classification technique on these multivariate and non-specific spectral data both separately and jointly (NIR and MIR data together).In order to ensure a more appropriate ratio between the number of objects (samples) and number of variables (absorbance at different wavenumbers), LDA was preceded either by feature selection or variable compression. For feature selection, the SELECT algorithm was used while a wavelet transform was applied for data compression.Correct classification rates obtained by cross-validation varied between 60% and 90% depending on the followed procedure. Most accurate results were obtained using the fused NIR and MIR data, with either feature selection or data compression.Chemometrical strategies applied to fused NIR and MIR spectra represent an effective method for classification of extra virgin olive oils on the basis of the olive cultivar.     

Tricarbonyl rhenium(I) complexes containing a bridging 2,5-diphenyl-1,3,4-oxadiazole ligand: structural, spectroscopic, electrochemical, and computational characterization

The three complexes [Re2(mu-X1)(mu-X2)(CO)6(mu-ppd-kappaN3:kappaN4)] (X1, X2 ) H, 1; X1 ) H, X2 ) Cl, 2; X1, X2 ) Cl, 3; ppd) 2,5-diphenyl-1,3,4-oxadiazole) have been synthesized by different routes, involving the reaction of [Re4(mu3-H)4(CO)12]with ppd for 1, the reaction of 1 with HCl for 2, and the reaction of [ReCl(CO)5] with ppd for 3. The three complexes possess a different number of valence electrons, so the formal Re-Re bond order varies from 2 to 1 to 0 in complexes 1, 2, and 3, respectively. This is reflected in the Re-Re bond distance (277.9, 297.9, and 358.5 pm in the same series)and in the stability of the complexes in the coordinating solvent acetonitrile (t1/2 for ppd displacement 13.6, 4.5, and 3.7 h,for 1, 2, and 3, respectively). Both experimental and calculated structures indicates that coordination induces a distortion from planarity of the diphenyloxadiazole moiety due to the interaction of the equatorial carbonyls with the bridging ppd,which increases on going from 1 to 2 to 3 (dihedral angle between the oxadiazole and the phenyl rings 18.4 degrees, 23.3 degrees, and 45.0 degrees, respectively). The UV spectra show pi-pi* transitions of the oxadiazole ligand (which shift to higher energy on increasing the distortion from the planarity, from 252 to 267 nm) and metal-to-ligand charge transfer absorptions (from 300 to 362 nm). Upon irradiation between 340 and 380 nm, complex 2 only features a weak broad emission at 527 nm(phi)0.02%), whereas upon excitation at 300 nm, the emission typical of free ppd is observed, suggesting photodissociation.Cyclic voltammetry investigations in acetonitrile showed that the three complexes exhibit ligand-centered irreversible reduction peaks (from -1.83 to -1.93 V vs Fc+|Fc), shifted to more positive values with respect to free ppd (-2.50 V). The shift however is smaller than in the analogous derivatives containing 1,2-diazines, suggesting a smaller electron depletion of the heterocycle ligand upon coordination. The complexes also show a metal-centered, bi-electronic, irreversible oxidation peak (from 1.05 to 1.37 V vs Fc+/Fc). A combined density functional and time-dependent density functional (TD DFT)study allowed us to understand the factors affecting the stability of the three complexes and to rationalize their electrochemical and photophysical properties in terms of their electronic structure.     

Thermal analysis of some phytotherapeutic products irradiated with electron beam

The purpose of the present work deals with the evaluation of the electron beam irradiation effects on some natural products based on thermal analysis. Some natural products with therapeutic contributions (artichoke, sea buckthorn, common sage, stonebreaker and cloves) were irradiated with doses up to 9 kGy using accelerated electron beam. The thermal profiles lead to identify three phenomena: dehydration — volatilization, irreversible degradation — molecular reorganization and residue decomposition. The radio-induced degradations determine slight shifts of the temperatures where these phenomena occur. The energetic value of the studied products is affected by e-beam treatment depending on irradiation dose.