Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH₂-OXA), ruthenocene-containing (Rc-CH₂-OXA) and benzene-containing (Ph-CH₂-OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.     

Dihydroquinazolinones via A3-Type Reactions of N-Carbamoyliminium Ions

A variant of the A³ coupling reaction was developed utilizing in situ generated N-carbamoyliminium ions. The tandem INCIC/A³-coupling sequence provided a facile one-pot synthesis of dihydroquinazolinone derivatives. The scope of the reaction was demonstrated in solution as well as on solid support. The reaction was further combined with peptide synthesis, S_NAr reactions, CuAAC triazole formation or bromination, providing additional opportunities for further diversification of the dihydroquinazolinone scaffolds.     

Enhancing the Photocatalytic Activity of Sr4Al14O25: Eu2+, Dy3+ Persistent Phosphors by Codoping with Bi3+ Ions

The photocatalytic activity of Bismuth‐codoped Sr₄Al₁₄O₂₅: Eu²⁺, Dy³⁺ persistent phosphors is studied by monitoring the degradation of the blue methylene dye UV light irradiation. Powder phosphors are obtained by a combustion synthesis method and a postannealing process in reductive atmosphere. The XRD patterns show a single orthorhombic phase Sr₄Al₁₄O₂₅: Eu²⁺, Dy³⁺, Bi³⁺ phosphors even at high Bismuth dopant concentrations of 12 mol%, suggesting that Bi ions are well incorporated into the host lattice. SEM micrographs show irregular micrograins with sizes in the range of 0.5–20 μm. The samples present an intense greenish‐blue fluorescence and persistent emissions at 495 nm, attributed to the 5d–4f allowed transitions of Eu²⁺. The fluorescence decreases as Bi concentration increases; that suggest bismuth‐induced traps formation that in turn quench the luminescence. The photocatalytic evaluation of the powders was studied under both 365 nm UV and solar irradiations. Sample with 12 mol% of Bi presented the best MB degradation activity; 310 min of solar irradiation allow 100% MB degradation, whereas only 62.49% MB degradation is achieved under UV irradiation. Our results suggest that codoping the persistent phosphors with Bi³⁺ can be an alternative to enhance their photocatalytic activity.     

Reactivity of 2,3-bis(2-pyridyl)pyrazine with [Re2(CO)8(CH3CN)2]: Molecular structures of [Re2(CO)8(C14H10N4)] and [Re2(CO)8(C14H10N4)Re2(CO)8]

The reaction of the labile compound [Re₂(CO)₈(CH₃CN)₂] with 2,3-bis(2-pyridyl)pyrazine in dichloromethane solution at reflux temperature afforded the structural dirhenium isomers [Re₂(CO)₈(C₁₄H₁₀N₄)] (1 and 2), and the complex [Re₂(CO)₈(C₁₄H₁₀N₄)Re₂(CO)₈] (3). In 1, the ligand is σ,σ′-N,N′-coordinated to a Re(CO)₃ fragment through pyridine and pyrazine to form a five-membered chelate ring. A seven-membered ring is obtained for isomer 2 by N-coordination of the 2-pyridyl groups while the pyrazine ring remains uncoordinated. For 2, isomers 2a and 2b are found in a dynamic equilibrium ratio [2a]/[2b]  =  7 in solution, detected by ¹H NMR (−50 °C, CD₃COCD₃), coalescence being observed above room temperature. The ligand in 3 behaves as an 8e-donor bridge bonding two Re(CO)₃ fragments through two (σ,σ′-N,N′) interactions. When the reaction was carried out in refluxing tetrahydrofuran, complex [Re₂(CO)₆(C₁₄H₁₀N₄)₂] (4) was obtained in addition to compounds 1-3. The dinuclear rhenium derivative 4 contains two units of the organic ligand σ,σ′-N,N′-coordinated in a chelate form to each rhenium core. The X-ray crystal structures for 1 and 3 are reported.     

Identification of lead pigments in nanosamples from ancient paintings and polychromed sculptures using voltammetry of nanoparticles/atomic force microscopy

Voltammetry of nanoparticles coupled with atomic force microscopy was used to identify lead pigments in nanosamples proceeding from works of art. Upon mechanical attachment of few nanograms of sample to a graphite plate, well-defined voltammetric responses were obtained for lead orange, lead yellow, lead white, litharge, minium, Naples yellow, and tin-lead yellow, allowing for an unambiguous identification of such pigments. Atomic force images provide evidence for the occurrence of pigment-characteristic reduction processes accompanied by metal deposition on the graphite substrate. Electrochemical parameters are used for pigment identification. Application to the method for identifying lead pigments in different model binder + pigment specimens and pictorial samples from the canvas painting collection (anonymous, 17th century) of the Saint Joseph Church in Taormina (Italy), the frescoes painted by Antonio Acisclo Palomino y Velasco (1698) in the vault of the Sant Joan del Mercat church in València (Spain) and an anonymous polychromed sculpture (16th century) representing a Martyr Saint from Alacant (Spain) is described.     

Mixed-mode liquid chromatography coupled to tandem mass spectrometry for the analysis of aminoglycosides in meat

A novel LC-MS/MS method has been developed for the determination of 13 aminoglycoside antibiotics in meat products. Among the chromatographic columns tested, the mixed-mode Obelisc R provided the best performance. Electrospray has been used for the coupling of the LC and the effect of temperature on the ionization has been evaluated. The mass spectra of AGs have been studied in order to select the most adequate precursor and product ions for quantitation and confirmation in SRM mode, showing that the single charged [M+H]⁺ provided better precisions than the double charged [M+2H]²⁺. Accurate mass measurements have been performed in order to confirm the molecular composition of the product ions, allowing the establishment of a new mechanism for some product ions of STR and DHSTR. A sample treatment based on an extraction and a SPE clean-up has been applied to a wide variety of meat products such as frankfurters; sausages; and minced meat of pork, veal, and chicken. Method limits of quantitation in the low microgram per kilogram level (1–50 μg kg^?1), precisions %RSD below 15 % and accuracies expressed as relative errors below 23 % have been obtained, making the proposed method suitable for routine analysis.     

Nucleation,Crystallization, and Thermal Fractionation of Poly (ε‐Caprolactone)‐Grafted‐Lignin: Effects of Grafted Chains Length and Lignin Content

Poly(ε‐caprolactone)‐grafted‐lignin (PCL‐g‐lignin) copolymers with 2 to 37 wt % lignin are employed to study the effect of lignin on the morphology, nucleation, and crystallization kinetics of PCL. Lignin displays a nucleating action on PCL chains originating an intersecting lamellar morphology. Lignin is an excellent nucleating agent for PCL at low contents (2–5 wt %) with nucleation efficiency values that are close to or >100%. This nucleating effect increases the crystallization and melting temperature of PCL under nonisothermal conditions and accelerates the overall isothermal crystallization rate of PCL. At lignin contents >18 wt %, antinucleation effects appear, that decrease crystallization and melting temperatures, reduce crystallinity degree, hinder annealing during thermal fractionation and significantly retard isothermal crystallization kinetics. The results can be explained by a competition between nucleating effects and intermolecular interactions caused by hydrogen bonding between PCL and lignin building blocks. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 1736–1750