Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue

All over the world, societies are facing rapidly aging populations combined with a growing number of patients suffering from Alzheimer’s disease (AD). One focus in pharmaceutical research to address this issue is on the reduction of the longer amyloid-β (Aβ) fragments in the brain by modulation of γ-secretase, a membrane-bound protease. R-Flurbiprofen (tarenflurbil) was studied in this regard but failed to show significant improvement in AD patients in a phase 3 clinical trial. This was mainly attributed to its low ability to cross the blood–brain barrier (BBB). Here, we present the synthesis and in vitro evaluation of a racemic meta-carborane analogue of flurbiprofen. By introducing the carborane moiety, the hydrophobicity could be shifted into a more favourable range for the penetration of the blood–brain barrier, evident by a logD_7.4 value of 2.0. Furthermore, our analogue retained γ-secretase modulator activity in comparison to racemic flurbiprofen in a cell-based assay. These findings demonstrate the potential of carboranes as phenyl mimetics also in AD research.     

Protonated Porphyrins: Bifunctional Catalysts for the Metal-Free Synthesis of N-Alkyl-Oxazolidinones

The protonation of commercially available porphyrin ligands yields a class of bifunctional catalysts able to promote the synthesis of N-alkyl oxazolidinones by CO₂ cycloaddition to corresponding aziridines. The catalytic system does not require the presence of any Lewis base or additive, and shows interesting features both in terms of cost effectiveness and eco-compatibility. The metal-free methodology is active even with a low catalytic loading of 1 % mol, and the chemical stability of the protonated porphyrin allowed it to be recycled three times without any decrease in performance. In addition, a DFT study was performed in order to suggest how a simple protonated porphyrin can mediate CO₂ cycloaddition to aziridines to yield oxazolidinones.     

Nanocarbons: Opening New Possibilities for Nano-engineered Novel Catalysts and Catalytic Electrodes

Nanocarbons find increasing relevance for the development of advanced, sometimes radically new, catalysts and catalytic electrodes. This perspective contribution discusses the potential of nanocarbons as a new class of catalytic materials, even if carbons (in the form mainly of active carbon materials) are already extensively applied as supports for catalysts. The control of nano-dimension and the improved understanding in tailoring the surface reactivity open new possibilities for their nano-engineering and the development of novel catalytic materials. With focus on the nature of the active sites in nanocarbon catalysts, we discuss here some of the novel possibilities opened by these materials to address the new challenges for catalysis deriving from moving to a more sustainable chemical and energy production.     

Development of a SIMS Method for Isotopic Measurements in Nuclear Forensic Applications

 Methodologies based on secondary ion mass spectrometry (SIMS) for isotopic measurements in nuclear forensic applications relevant to the age determination of Pu particles and isotopic composition of oxygen for geolocation assignment are described. For the age determination of Pu particles, a relative sensitivity factor (RSF) to correct for the different ionisation efficiencies of U and Pu, was obtained by analysing standard Pu materials with known ages. An RSF of 2.41±0.05 was obtained for PuO₂ from measurements on samples with different Pu/U ratios. In a sample of known origin, using this RSF value, the age calculated from the ²³⁸Pu/²³⁴U and ²⁴⁰Pu/²³⁶U ratios agreed well with the reported age of 2.3 years. For geolocation assignment, a new approach based on the measurement of differences in the natural abundance of ¹⁸O and ¹⁶O isotopes and their ratio was developed. The instrumental mass discrimination of the ¹⁸O/¹⁶O ratio was determined using three O-isotope samples of different chemical composition. The measured precision (the standard error of 100 cycles/analysis) obtained for the oxygen isotopic measurement on the samples was typically ±1.1‰.     

Crystallization process on amorphous GeTeSb samples near to eutectic point Ge15Te85

One of most important properties of some tellurium-based chalcogenide glasses is the optical and electrical switching between two states: the glass and the crystalline state. The understanding in these systems of the glass to crystal transition and its transformation kinetics is essential for their application in non-volatile memories. GeTeSb and GeTe amorphous samples of compositions close to the eutectic point Ge₁₅Te₈₅ were obtained by rapid solidification from the liquid state employing melt spinning technique. The glass forming ability of this system, for this cooling technique, is restricted to a small composition range nearby the binary eutectic. The crystallization kinetics of the samples was studied by means of differential scanning calorimetry (DSC) under both isothermal and continuous heating regimes. The quenched samples and the crystallization products have been characterized by X-ray diffraction with Cu(Kα) radiation. The crystallization temperature, activation energy, crystallization enthalpy and the dependence of these properties on concentration are reported. The crystallization study of Ge₁₅Te₈₅ glasses shows: a primary crystallization of Te superimposed with a secondary crystallization of GeTe. The addition of Sb (5 at.%) to the eutectic point Ge₁₅Te₈₅ modifies this behavior: the crystallization of Ge₁₃Sb₅Te₈₂ glasses consists on the crystallization of Te and Ge₂Sb₂Te_5. The crystallization of the ternary glasses was modeled.     

Determination of nuclear graphite impurities by prompt gamma activation analysis to support decommissioning operations

Journal of Radioanalytical and Nuclear Chemistry - Elemental composition of non-irradiated nuclear grade graphite was determined by Prompt Gamma Activation Analysis (PGAA) to quantitively assess...     

On fairness and diversification in WTA and ATP tennis tournaments generation

Annals of Operations Research - Single-elimination (knockout) tournaments are the standard paradigm for both main tennis professional associations, WTA and ATP. Schedules are generated by...     

The effect of adding a bit of Fe to Ag–Ge–Se system

Ag–Ge–Se system is an easy glass former in a wide composition range not far from the Se corner of the equilibrium phase diagram. The existence of a liquid miscibility gap impacts on the glass morphology where Ag-rich zones alternate with Ag depleted ones which size depends on composition. In order to analyze the short range order, 0.5 at.% Fe was added as a probe in the synthesis stage. Mössbauer spectra of these glasses were obtained at room and lower temperatures. Two types of environments were observed. The corresponding Debye temperatures, and the fraction of Fe atoms in each environment were determined. Additionally, magnetic moment was measured as a function of temperature and applied magnetic field. From m(H) and m(T) curves it is evident that the magnetization of the glasses has two components, i.e., a blocked one even up to room temperature that saturates at low field, and a paramagnetic one which does not saturate even at the largest applied field. The Mössbauer spectroscopy results are discussed and correlated to the morphology and magnetic behavior of these glasses.