Structural Characterization of Poly-l-lactic Acid (P(L)LA) and Poly(glycolic acid)(PGA) Oligomers

Structural characterization of poly-l-lactic acid (P(L)LA) and poly(glycolic acid) (PGA) oligomers containing three units was carried out with an atomistic approach. Oligomer structures were first optimized through quantum chemical calculations, using density functional theory (DFT); rotational barriers concerning dihedral angles along the chain were then investigated. Diffusion coefficients of l-lactic acid and glycolic acid in pure water were estimated through molecular dynamic (MD) simulations. Monomer structures were obtained with quantum chemical computation in implicit water using DFT method; atomic charges were fitted with Restrained Electrostatic Potentials (RESP) formalism, starting from electrostatic potentials calculated with quantum chemistry. MD simulations were carried out in explicit water, in order to take into account solvent presence.     

Cyclopropanes and hypervalent iodine reagents: high energy compounds for applications in synthesis and catalysis

One of the major challenges faced by organic chemistry is the efficient synthesis of increasingly complex molecules. Since October 2007, the Laboratory of Catalysis and Organic Synthesis (LCSO) at EPFL has been working on the development of catalytic reactions based on the Umpolung of the innate reactivity of functional groups. Electrophilic acetylene synthons have been developed using the exceptional properties of ethynyl benziodoxolone (EBX) hypervalent iodine reagents for the alkynylation of heterocycles and olefins. The obtained acetylenes are important building blocks for organic chemistry, material sciences and chemical biology. The ring-strain energy of donor-acceptor cyclopropanes was then used in the first catalytic formal homo-Nazarov cyclization. In the case of aminocyclopropanes, the method could be applied in the synthesis of the alkaloids aspidospermidine and goniomitine. The developed methods are expected to have a broad potential for the synthesis and functionalization of complex organic molecules, including carbocycles and heterocycles.     

Near-surface processing on AlGaN/GaN heterostructures: a nanoscale electrical and structural characterization

The effects of near-surface processing on the properties of AlGaN/GaN heterostructures were studied, combining conventional electrical characterization on high-electron mobility transistors (HEMTs), with advanced characterization techniques with nanometer scale resolution, i.e., transmission electron microscopy, atomic force microscopy (AFM) and conductive atomic force microscopy (C-AFM). In particular, a CHF₃-based plasma process in the gate region resulted in a shift of the threshold voltage in HEMT devices towards less negative values. Two-dimensional current maps acquired by C-AFM on the sample surface allowed us to monitor the local electrical modifications induced by the plasma fluorine incorporated in the material.     

Scanning tip measurement for identification of point defects

Self-assembled iron-silicide nanostructures were prepared by reactive deposition epitaxy of Fe onto silicon. Capacitance-voltage, current-voltage, and deep level transient spectroscopy (DLTS) were used to measure the electrical properties of Au/silicon Schottky junctions. Spreading resistance and scanning probe capacitance microscopy (SCM) were applied to measure local electrical properties. Using a preamplifier the sensitivity of DLTS was increased satisfactorily to measure transients of the scanning tip semiconductor junction. In the Fe-deposited area, Fe-related defects dominate the surface layer in about 0.5 μm depth. These defects deteriorated the Schottky junction characteristic. Outside the Fe-deposited area, Fe-related defect concentration was identified in a thin layer near the surface. The defect transients in this area were measured both in macroscopic Schottky junctions and by scanning tip DLTS and were detected by bias modulation frequency dependence in SCM.     

Synthesis and characterization of indium monoselenide (InSe) nanowires

Indium monoselenide (InSe) nanowires were grown by the thermal evaporation method in argon atmosphere without the presence of any catalysts using InSe polycrystalline powder as the source material. No nanostructure growth was observed at deposition temperatures below 580 °C. The nanostructures were discernable at temperatures above 620 °C. Pure InSe nanowires were obtained at the deposition temperature of 660 °C for 50 min. The diameters of the nanowires were from 50 to 240 nm and their lengths were up to several micrometers. X-ray diffraction spectrum reveals that the synthesized products were single-crystalline of the β-phase hexagonal structure of InSe with lattice constants a = 4.006 Å and c = 16.642 Å. The strong peak due to the reflection from the (004) crystal plane reveals that most nanowires grow with a strong preferred orientation.     

Epigallocatechin-3-Gallate Modulates Postoperative Pain by Regulating Biochemical and Molecular Pathways

Treating postoperative (PO) pain is a clinical challenge. Inadequate PO pain management can lead to worse outcomes, for example chronic post-surgical pain. Therefore, acquiring new information on the PO pain mechanism would increase the therapeutic options available. In this paper, we evaluated the role of a natural substance, epigallocatechin-3-gallate (EGCG), on pain and neuroinflammation induced by a surgical procedure in an animal model of PO pain. We performed an incision of the hind paw and EGCG was administered for five days. Mechanical allodynia, thermal hyperalgesia, and motor dysfunction were assessed 24 h, and three and five days after surgery. At the same time points, animals were sacrificed, and sera and lumbar spinal cord tissues were harvested for molecular analysis. EGCG administration significantly alleviated hyperalgesia and allodynia, and reduced motor disfunction. From the molecular point of view, EGCG reduced the activation of the WNT pathway, reducing WNT3a, cysteine-rich domain frizzled (FZ)1 and FZ8 expressions, and both cytosolic and nuclear β-catenin expression, and the noncanonical β-catenin–independent signaling pathways, reducing the activation of the NMDA receptor subtype NR2B (pNR2B), pPKC and cAMP response element-binding protein (pCREB) expressions at all time points. Additionally, EGCG reduced spinal astrocytes and microglia activation, cytokines overexpression and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) pathway, downregulating inducible nitric oxide synthase (iNOS) activation, cyclooxygenase 2 (COX-2) expression, and prostaglandin E2 (PGE2) levels. Thus, EGCG administration managing the WNT/β-catenin signaling pathways modulates PO pain related neurochemical and inflammatory alterations.     

Curing Viscosity of HTPB‐Based Binder Embedding Micro‐ and Nano‐Aluminum Particles

Aluminum is used as a metal fuel in energetic materials for the improvement of propulsion performance and density. Both nano‐sized and micrometer‐sized activated powders represent valuable options in order to improve metal combustion properties, each possessing advantages and drawbacks. These ingredients bear peculiar properties (namely, higher specific surface, coatings, or surface characteristics) which generate high mixing viscosity once suspended in a polymer as well as altered mechanical properties of the final product. Four different powders dispersed in a polymer binder are taken into consideration and the evolution of viscosity in time during the curing process is investigated. The suspending medium is represented by a mixture of hydroxyl‐terminated polybutadiene (HTPB), isophorone diisocyanate (IPDI) and dioctyl adipate (DOA). Viscosity was measured for 5 h on samples under isothermal curing at 60 °C. Non‐isothermal DSC kinetic analyses were also performed using the Kissinger method. It was found that, for the test conditions, a size reduction of metal particles slowed down the increment rate of curing viscosity while some peculiar coatings, such as fatty acids, introduced opposite trends.     

Rapid Quantification of Soyasaponins I and βg in Italian Lentils by High-Performance Liquid Chromatography (HPLC)–Tandem Mass Spectrometry (MS/MS)

In this work, an innovative and fast analytical method for the quantification of soyasaponins I and βg in lentils has been developed. Samples were extracted using 70 % aqueous ethanol at room temperature and then injected into a high-performance liquid chromatography–tandem mass spectrometry system. The correlation coefficients of calibration curves of the analyzed compounds were ≥0.9997. The recoveries obtained by spiking the lentil samples with a standard mixture of soyasaponins I and βg at 50 and 100 mg l^?1 were in the range of 96–101 and 98–103 %, respectively. The validated method was applied to the analysis of 30 lentil samples from central Italy. Soyasaponins I and βg were present in these lentils in concentrations that ranged from 54 to 226 mg kg^?1 and from 436 to 1,272 mg kg^?1, respectively. Our data indicated that lentils cultivated in fields at intermediate altitudes (1,142–1,387 m) showed the highest levels of soyasaponins, a finding confirmed by principal component analysis.     

Indole alkaloids synthesis via a selective cyclization of aminocyclopropanes

The continuous progress in medicinal chemistry requires more versatile synthetic strategies for the generation of large libraries of active compounds and their analogues. As a result, the research for new effective cyclization and cycloaddition reactions is an essential task in organic chemistry. In 2008 we developed the first catalytic formal homo-Nazarov reaction starting from activated cyclopropanes. Herein we report the extension of the catalytic formal homo-Nazarov cyclization to aminocyclopropanes. Highly diastereoselective cyclizations were obtained via an acyliminium intermediate generated through opening of the cyclopropane. An excellent control over the regioselectivity of either the C-C or C-N cyclization in the case of free indoles as nucleophilic partners was achieved. The utility of the developed methodology was demonstrated by the generation of the polycyclic scaffolds of Aspidosperma and Gonioma natural products starting from a common intermediate. Based on this method, a formal total synthesis of the alkaloid aspidospermidine and the total synthesis of the alkaloid goniomitine are presented. Finally, the scope and limitations of our methodology are discussed on an extended range of vinyl-cyclopropyl ketones with cyclic or acyclic carbamates, as well as ethers as donor groups on the cyclopropane.     

Anticancer agents that counteract tumor glycolysis

Can we consider cancer to be a “metabolic disease”? Tumors are the result of a metabolic selection, forming tissues composed of heterogeneous cells that generally express an overactive metabolism as a common feature. In fact, cancer cells have increased needs for both energy and biosynthetic intermediates to support their growth and invasiveness. However, their high proliferation rate often generates regions that are insufficiently oxygenated. Therefore, their carbohydrate metabolism must rely mostly on a glycolytic process that is uncoupled from oxidative phosphorylation. This metabolic switch, also known as the Warburg effect, constitutes a fundamental adaptation of tumor cells to a relatively hostile environment, and supports the evolution of aggressive and metastatic phenotypes. As a result, tumor glycolysis may constitute an attractive target for cancer therapy. This approach has often raised concerns that antiglycolytic agents may cause serious side effects toward normal cells. The key to selective action against cancer cells can be found in their hyperbolic addiction to glycolysis, which may be exploited to generate new anticancer drugs with minimal toxicity. There is growing evidence to support many glycolytic enzymes and transporters as suitable candidate targets for cancer therapy. Herein we review some of the most relevant antiglycolytic agents that have been investigated thus far for the treatment of cancer.