Computer simulation of architectural and molecular weight effects on the assembly of amphiphilic linear-dendritic block copolymers in solution

Langevin dynamics simulations are performed on linear-dendritic diblock copolymers containing bead-spring, freely jointed chains composed of hydrophobic linear monomers and hydrophilic dendritic monomers. The critical micelle concentration (CMC), micelle size distribution, and shape are examined as a function of dendron generation and architecture. For diblock copolymers with a linear block of fixed length, it is found that the CMC increases with increasing dendron generation. This trend qualitatively agrees with experiments on linear-dendritic diblock and triblock copolymers with hydrophilic dendritic blocks and hydrophobic linear blocks. The flexibility of the dendritic block is altered by varying the number of spacer monomers between branch points in the dendron. When comparing linear-dendritic diblock copolymers with similar molecular weights, it is shown that increasing the number of spacer monomers in the dendron lowers the CMC due to an increase in flexibility of the dendritic block. Analysis on the micellar structure shows that linear-dendritic diblock copolymers pack more densely than what would be expected for a linear-linear diblock copolymer of the same molecular weight.     

Studies towards the total synthesis of contignasterol

The (17R,20S,22S,24S) C₂₀-C₂₉ segment of contignasterol has been stereoselectively prepared in 8 steps and 40% overall yield from (S)-carvone. Synthetic studies towards contignasterol's C/D ring functionalization/isomerization are also reported.     

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.     

Solvent-Free Microwave-Assisted Organic Reactions Preparation of β-Keto Esters

Microwave technique has been utilised in the preparation of β-keto esters. Two different procedures are described: transesterification of β-keto esters and ring opening of 2,2,6-trimethyl-1,3-dioxin-4-one.     

Compositional and technological features of glazed pottery from Aosta Valley (Italy): a SEM–EDS investigation

Twelve finds from archaeological excavations carried out in the Aosta region (Italy) were studied by scanning electron microscopy coupled with energy-dispersive X-ray detection (SEM–EDS). The archaeological samples were shards of glazed pottery dating from the fourth to the seventh century AD. Analysis of ceramic bodies revealed a general homogeneity in composition among the studied samples and the use of a noncalcareous clay for their manufacture; however, two shards stand out due to their high iron contents. Glazes proved to be high-lead products with more than 70% PbO in all of the samples investigated but one. For the latter, a composition poorer in lead and richer in silicon, aluminium and iron was found. SEM observation of the contact region between body and glaze suggests that the vitreous coatings were mostly obtained by applying the glazing components onto the unfired clay body; moreover, a comparison between clay and glaze compositions suggests the use of a lead compound mixed with a silica-rich material, not a lead compound by itself.     

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.     

Solvent-dependent host–guest complexation of two homologous merocyanines by a water-soluble calix[8]arene: Spectroscopic analysis and structural calculations

The sulfonated calixarene I₈C₁₂ acts as a host for homologous merocyanines Mc1 and Mc2 in organic solvents, exhibiting neither selectivity towards the guest dyes nor solvent dependence of the complexation equilibria. In water, on the contrary, only the lower homologue, Mc1, is solubilized in the presence of the calixarene. A combination of UV–visible and fluorescence spectroscopic and photophysical analysis and MD structural simulation of the calixarene-dye complexes was employed to account for the observations, and suggests that a radical change in the complexation mode occurs upon moving from an organic to an aqueous environment.     

Yoctomole analysis of ganglioside metabolism in PC12 cellular homogenates

We report an ultrasensitive method for the analysis of glycosphingolipid catabolism. The substrate G(M1) and the set of seven metabolites into which it can be degraded (G(A1), G(M2), G(A2), G(M3), LacCer, GlcCer, and Cer) were labeled with the highly fluorescent dye tetramethylrhodamine. CE with LIF detection was used to assay these compounds with 150 +/- 80 yoctomole mass (1 ymol = 10(-24) mol = 0.6 copies) detection limits and 5 +/- 3 pM concentration detection limits. An alignment algorithm based on migration of two components was employed to correct for drift in the separation. The within-day and between-day precision in peak height was 20%, in peak width 15%, and in adjusted migration time 0.03%. After normalization to total sample injected, the RSD in peak height reduced to 2-6%, which approaches the limit set by molecular shot noise in the number of molecules taken for analysis. PC12 cells were incubated with the labeled G(M1). Fluorescent microscopy demonstrated uptake by the cells. CE was used to separate a cellular homogenate prepared from these cells. A set of peaks was observed, which were tentatively identified based on comigration with the standards. Roughly 120 pL of homogenate was injected, which contained a total of 150 zmol of labeled substrate and products. Metabolite that preserves the fluorescent label can be detected at the yoctomole level, which should allow characterization of this metabolic pathway in single cells.     

The preferred reaction path for the oxidation of methanol by PQQ-containing methanol dehydrogenase: addition-elimination versus hydride-transfer mechanism

The catalytic oxidation of methanol to formaldehyde by pyrroloquinoline quinone (PQQ)-containing methanol dehydrogenase (MDH) was investigated at density functional B3LYP level. The still controversial addition-elimination and hydride-transfer reaction mechanisms were analysed. Computations performed in the gas phase and in the protein environment indicated that both suggested reaction sequences involve very high activation barriers. In this situation, the reactions should have scarce probability to occur and the preference for one of the two paths cannot be stated. Here, we will show how some corrections to the successive steps in the addition-elimination mechanism can sensibly decrease the activation barriers height, making possible the determination of the MDH-preferred catalytic path.     

Correlation between molecular orbitals and doping dependence of the electrical conductivity in electron-doped metal-phthalocyanine compounds

We have performed a comparative study of the electronic properties of six different electron-doped metal-phthalocyanine (MPc) compounds (ZnPc, CuPc, NiPc, CoPc, FePc, and MnPc), in which the electron density is controlled by means of potassium intercalation. Despite the complexity of these systems, we find that the nature of the underlying molecular orbitals produces observable effects in the doping dependence of the electrical conductivity of the materials. For all the MPc's in which the added electrons are expected to occupy orbitals centered on the ligands (ZnPc, CuPc, and NiPc), the doping dependence of the conductivity has an essentially identical shape. This shape is different from that observed in MPc materials in which electrons are also added to orbitals centered on the metal atom (CoPc, FePc, and MnPc). The observed relation between the macroscopic electronic properties of the MPc compounds and the properties of the molecular orbitals of the constituent molecules clearly indicates the richness of the alkali-doped metal-phthalocyanines as a model class of compounds for the investigation of the electronic properties of molecular systems.