Determination of the Peptide AWRK6 in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) and Its Application to Pharmacokinetics.

AWRK6 was a synthesized peptide developed based on the natural occurring peptide dybowskin-2CDYa, which was discovered in frog skin in our previous study. Here, a quantitative determination method for AWRK6 analysis in rat plasma by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established and validated following U.S. FDA guidelines. A combination of plasma precipitation and liquid-liquid extraction was applied for the extraction. For pharmacokinetics study, the rats were administrated with AWRK6 via intraperitoneal and intravenous injection. The prepared plasma samples were separated on an ODS column and analyzed by tandem MS using precursor-to-product ion pairs of m/z: 533.4→84.2 for AWRK6 and m/z: 401.9→101.1 for internal standard Polymyxin B sulfate in multiple reaction monitoring mode. AWRK6 concentrations in rat plasma peaked at about 1.2 h after intraperitoneal injections at 2.35, 4.7 and 9.4 mg/kg bodyweight. The terminal half-life was around 2.8 h. The absolute bioavailability of AWRK6 was 50% after 3 doses via injection, and the apparent volume of distribution was 4.884 ± 1.736 L. The obtained determination method and pharmacokinetics profiles of AWRK6 provides a basis for further development, and forms a benchmark reference for peptide quantification.

Operando potassium K-edge X-ray absorption spectroscopy: investigating potassium catalysts during soot oxidation.

The chemical and structural nature of potassium compounds involved in catalytic soot oxidation have been studied by a combination of temperature programmed oxidation and operando potassium K-edge X-ray absorption spectroscopy experiments. These experiments are the first known operando studies using tender X-rays (∼3.6 keV) under high temperature oxidation reaction conditions. X-ray absorption near edge structure analysis of K2CO3/Al2O3 catalysts during heating shows that, at temperatures between 100 and 200 °C, potassium species undergo a structural change from an initial hydrated K2CO3·xH2O and KHCO3 mixture to well-defined K2CO3. As the catalyst is heated from 200 °C to 600 °C, a feature associated with multiple scattering shifts to lower energy, indicating increased K2CO3 dispersion, due to its mobility at high reaction temperature. This shift was noted to be greater in samples containing soot than in control experiments without soot and can be attributed to enhanced mobility of the K2CO3, due to the interaction between soot and potassium species. No potassium species except K2CO3 could be defined during reactions, which excludes a potential reaction mechanism in which carbonate ions are the active soot-oxidising species. Simulations of K-edge absorption near edge structures were performed to rationalise the observed changes seen. Findings showed that cluster size, unit cell distortions and variation in the distribution of potassium crystallographic sites influenced the simulated spectra of K2CO3. While further simulation studies are required for a more complete understanding, the current results support the hypothesis that changes in the local structure on dispersion can influence the observed spectra. Ex situ characterisation was carried out on the fresh and used catalyst, by X-ray diffraction and X-ray photoelectron spectroscopy, which indicated changes to the carbonate species, in line with the X-ray absorption spectroscopy experiments.

PEI-Coated Fe3O4 Nanoparticles Enable Efficient Delivery of Therapeutic siRNA Targeting REST into Glioblastoma Cells.

Glioblastomas (GBM) are the most frequent brain tumors lacking efficient treatment. The increasingly elucidated gene targets make siRNA-based gene therapy a promising anticancer approach, while an efficient delivery system is urgently needed. Here, polyethyleneimine (PEI)-coated Fe3O4 nanoparticles (NPs) have been developed and applied for siRNA delivery into GBM cells to silence repressor element 1-silencing transcription factor (REST). The prepared PEI-coated Fe3O4 NPs were characterized as magnetic nanoparticles with a positive charge, by transmission electronic microscopy, dynamic light-scattering analysis and a magnetometer. By gel retardation assay, the nanoparticles were found to form complexes with siRNA and the interaction proportion of NP to siRNA was 2.8:1. The cellular uptake of NP/siRNA complexes was verified by prussian blue staining, fluorescence labeling and flow cytometry in U-87 and U-251 GBM cells. Furthermore, the REST silencing examined by realtime polymerase chain reaction (PCR) and Western blotting presented significant reduction of REST in transcription and translation levels. Upon the treatment of NP/siRNA targeting REST, the GBM cell viabilities were inhibited and the migration capacities were repressed remarkably, analyzed by cell counting kit-8 and transwell assay separately. In this study, we demonstrated the PEI-coated Fe3O4 nanoparticle as a vehicle for therapeutic siRNA delivery, at an appropriate NP/siRNA weight ratio for REST silencing in GBM cells, inhibiting cell proliferation and migration efficiently. These might represent a novel potential treatment strategy for GBM.

Topochemical polymerization in self-assembled rodlike micelles of bisurea bolaamphiphiles.

Rod-like micelles, formed from bolaamphiphiles with oligo(ethylene oxide) hydrophilic outer segments and a hydrophobic segment with diacetylene flanked by two urea moieties, were covalently fixated by topochemical photopolymerization to high degrees of polymerization by optimizing the hydrophobic core and the hydrophilic periphery of the bolaamphiphiles. Analysis of the polymerized product with dynamic light scattering in chloroform showed degrees of polymerization of approximately 250. Cryo-TEMof bolaamphiphiles before and after UV irradiation showed that the morphology of the rods was conserved upon topochemical polymerization.

Coordination properties of ionic liquid-mediated chromium(II) and copper(II) chlorides and their complexes with glucose.

The structural and coordination properties of complexes formed upon the interaction of copper(II) and chromium(II) chlorides with dialkylimidazolium chloride (RMIm(+)Cl(-)) ionic liquids and glucose are studied by a combination of density functional theory (DFT) calculations and X-ray absorption spectroscopy (XAS). In the absence of the carbohydrate substrate, isolated mononuclear four-coordinated MeCl(4)(2-) species (Me = Cu, Cr) dominate in the ionic liquid solution. The organic part of the ionic liquid does not directly interact with the metal centers. The interactions between the RMIm(+) cations and the anionic metal chloride complexes are limited to hydrogen bonding with the basic Cl(-) ligands and the overall electrostatic stabilization of the anionic metal complexes. Exchange of Cl(-) ligands by a hydroxyl group of glucose is only favorable for CrCl(4)(2-). For Cu(2+) complexes, the formation of hydrogen bonded complexes between CuCl(4)(2-) and glucose is preferred. No preference for the coordination of metal chloride species to specific hydroxyl group of the carbohydrate is found. The formation of binuclear metal chloride complexes is also considered. The reactivity and selectivity patterns of the Lewis acid catalyzed reactions of glucose are discussed in the framework of the obtained results.

Acid and base catalysed reactions in one pot with site-isolated polyHIPE catalysts.

The polyHIPE catalysts based on styrene, vinyl benzyl chloride, and divinylbenzene co-polymerisation were functionalised with carboxylic and tertiary amine groups. Catalyst characterisation showed covalent bonding of the graft polymers. The macroporous and highly interconnected structure of polyHIPEs allows isolation of the acid and base functional groups and allows the presence of these otherwise incompatible functionalities on the same catalyst. The functionalised polyHIPE catalysts were shown to perform two reactions; (i) acid-catalysed acetal hydrolysis and (ii) base-catalysed Knoevenagel condensation in one-pot with 97% yield. The yield obtained is substantially higher than that observed with the homogeneous or resin polymer type catalysts due to the compartmentalisation of the active sites and improved mass transfer through the open porous polyHIPE structure.

A hydrothermally stable ytterbium metal-organic framework as a bifunctional solid-acid catalyst for glucose conversion.

Yb6(BDC)7(OH)4(H2O)4 contains both bridging hydroxyls and metal-coordinated waters, possessing Brønsted and Lewis acid sites. The material crystallises from water at 200 °C. Using the solid as a heterogenous catalyst, glucose is converted into 5-hydroxymethylfurfural, via fructose, with a total selectivity of ∼70% after 24 hours at 140 °C in water alone: the material is recyclable with no loss of crystallinity.

2D boron nitride nanosheets (BNNS) prepared by high-pressure homogenisation: structure and morphology.

2D Boron Nitride Nano-sheets (BNNS) were prepared using a high-pressure homogenisation process to exfoliate bulk hexagonal boron nitride (h-BN). The effectiveness of this process was studied by characterising bulk h-BN and BNNS post-processing using numerous techniques. The BNNS produced was composed of a mixture of sheets having lengths on the nanometre (nm) scale, but lateral thicknesses on the micron (µm) length scale. The product was a macro-porous material containing slit-like pores with a surface area of 170 m2 g-1. It had a polycrystalline structure with d002 = 0.335 nm and L002 = 2 nm. From the sharp E2g peak in the Raman spectrum at 1360 cm-1 (FWHM = 12.5 cm-1), the sheets had a low defect density and were highly exfoliated. X-Ray photoelectron spectroscopy (XPS) studies detected B-OH and N-H groups on the BNNS surface and the presence of residual surfactant. Contact angle measurements (60°± 3° (0 s); 40°± 2° (10 s)) confirmed a hydrophilic surface. The BNNS was thermally stable under oxidative conditions up to 323 °C.

Exceptionally Efficient and Recyclable Heterogeneous Metal-Organic Framework Catalyst for Glucose Isomerization in Water.

Heterogeneous catalysts are desired for the conversion of glucose, the most abundant sugar in renewable biomass, but presently their synthesis requires highly toxic chemicals with long synthesis times. We report the conversion of glucose into fructose and 5-hydroxymethylfurfural on a heterogeneous catalyst that is stable and selective and operates in the most environmentally benign solvent, water. We used a bifunctional solid with Lewis and Brønsted acid sites by partially replacing the organic linker of the zirconium organic framework UiO-66 with 2-monosulfo-benzene-1,4-dicarboxylate. This catalyst showed high product selectivity (90 %) to 5-hydroxymethylfurfural and fructose at 140 °C in water after a reaction time of 3 h. It was recyclable and showed only a minor loss in activity after the third recycle, offering a realistic solution for the bottleneck glucose isomerization reaction for scale-up and industrial application of biomass utilization.

A computational study of the mechanism of CO oxidation by a ceria supported surface rhodium oxide layer.

A mechanism of CO oxidation by a thin surface oxide of Rh supported on ceria is proposed: CO is oxidized by the Rh-oxide film, which is subsequently reoxidized by a ceria surface O atom. The proposed mechanism is supported by in situ Raman spectroscopic investigations.

Dual template synthesis of a highly mesoporous SSZ-13 zeolite with improved stability in the methanol-to-olefins reaction.

The dual template synthesis of zeolite SSZ-13 by use of trimethyl-adamantanammonium hydroxide and a diquaternary-ammonium mesoporogen induces considerable mesoporosity without impeding zeolite microporosity. The strongly improved accessibility of Brønsted sites in mesoporous SSZ-13 increases its stability during application as an acid catalyst in the methanol-to-olefins reaction.

Phosphotungstic acid encapsulated in metal-organic framework as catalysts for carbohydrate dehydration to 5-hydroxymethylfurfural.

MIL-101, a chromium-based metal-organic framework, is known for its very large pore size, large surface area and good stability. However, applications of this material in catalysis are still limited. 5-Hydroxymethylfurfural (HMF) has been considered a renewable chemical platform for the production of liquid fuels and fine chemicals. Phosphotungstic acid, H3PW12O40 (PTA), encapsulated in MIL-101 is evaluated as a potential catalyst for the selective dehydration of fructose and glucose to 5-hydroxymethylfurfural. The results demonstrate that PTA/MIL-101 is effective for HMF production from fructose in DMSO and can be reused. This is the first example of the application of a metal-organic framework in carbohydrate dehydration.