Characterization of a highly stable zwitterionic hydrophilic interaction chromatography stationary phase based on hybrid organic–inorganic particles

We have characterized a sulfobetaine stationary phase based on 1.7 μm ethylene-bridged hybrid organic–inorganic particles, which is intended for use in hydrophilic interaction chromatography. The efficiency of a column packed with this material was determined as a function of flow rate, demonstrating a minimum reduced plate height of 2.4. The batch-to-batch reproducibility was assessed using the separation of a mixture of acids, bases, and neutrals. We compared the retention and selectivity of the hybrid sulfobetaine stationary phase to that of several benchmark materials. The hybrid sulfobetaine material gave strong retention for polar neutrals and high selectivity for methyl groups, hydroxy groups, and configurational isomers. Large differences in cation and anion retention were observed among the columns. We characterized the acid and base stability of the hybrid sulfobetaine stationary phase, using accelerated tests at pH 1.3 and 11.0, both at 70°C. The results support a recommended pH range of 2–10. We also investigated the performance of columns packed with this material for metal-sensitive analytes, comparing conventional stainless steel column hardware to hardware that incorporates hybrid surface technology to mitigate interactions with metal surfaces. Compared to the conventional columns, the hybrid surface technology columns showed a greatly improved peak shape.     

Intra- and Inter-molecular Sulf- hydryl Hydrogen Bonding: Facilitating Proton Transfer Events for Determination of pH in Sea Water

This work presents the electrochemical response of a 2-(methylthio)phenol glassy carbon based electrode for a promising voltammetric pH sensor in both buffered and low-buffered solutions. Electropolymerization of the redox species was performed with the resulting polymer presenting a Nernstian response in buffered media, with a sensitivity of 51 mV/pH unit. The effectiveness of the sulfhydryl bond to facilitate proton transfer from the bulk solution to the phenol molecules has been confirmed, providing an accurate pH measurement of 8.28 in sea water media, compared to that measured with a calibrated glass pH probe of 8.30.     

Excitation dependent quenching of luminescence in LED phosphors

Droop, the decrease of efficiency with increased power density, became a major topic with InGaN LEDs, after its introduction in 2007. This paper provides insight into droop in localized center luminescence phosphors, exemplified here by Eu²⁺ doped materials. This topic is of increasing importance, as high brightness blue LEDs have reached outputs >1 W/mm². The nonlinearities in phosphor quantum efficiency result in drive‐dependent color point shift and reduction of overall efficiency of phosphor converted white LEDs which utilize Eu²⁺ activated phosphors. The efficiency quenching can be traced back to two processes, well‐known in laser physics, excited state absorption or/and cross relaxation by Foerster/Dexter transfer. Both processes lead to reduction in phosphor efficiency, but they can be differentiated. Understanding the root cause of efficiency quenching opens ways to minimize the practical consequences. (© 2016 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Investigating microcrystalline cellulose crystallinity using Raman spectroscopy

Cellulose - Microcrystalline cellulose (MCC) is a semi-crystalline material with inherent variable crystallinity due to raw material source and variable manufacturing conditions. MCC crystallinity...     

A flow system for hydrogen peroxide production at reticulated vitreous carbon via electroreduction of oxygen

In this work, a reticulated vitreous carbon electrode (RVCE, 96.5 % porosity, 24 cm^?1) was modified with 2-anthraquinonyl groups to electrocatalytically reduce dissolved oxygen in neutral aqueous solution (0.1 M phosphate buffer solution supported with 3 M potassium chloride, pH of 6.7) to hydrogen peroxide (H₂O₂) at 25 °C under atmospheric pressure. The obtained current density was ca. 3 mA cm^?2. For the first time, the oxygen reduction was investigated on a novelly designed RVCE housed in a gravity-feed flow system. Fractional current conversions obtained on the RVC flow cell were compared and contrasted with those on a two-dimensional electrode, viz. a tubular flow electrode. The modified-on catalyst has the benefit in terms of easy separation of the product from the catalyst. The in situ generated low concentration of H₂O₂ provides potential applications to water purification processes and disinfection for water and food.     

Long‐Wavelength Fluorescent Reporters for Monitoring Protein Kinase Activity

In vivo optical imaging must contend with the limitations imposed by the optical window of tissue (600–1000 nm). Although a wide array of fluorophores are available that are visualized in the red and near‐IR region of the spectrum, with the exception of proteases, there are few long wavelength probes for enzymes. This situation poses a particular challenge for studying the intracellular biochemistry of erythrocytes, the high hemoglobin content of which optically obscures subcellular monitoring at wavelengths less than 600 nm. To address this, tunable fluorescent reporters for protein kinase activity were developed. The probing wavelength is preprogrammed by using readily available fluorophores, thereby enabling detection within the optical window of tissue, specifically in the far‐red and near‐IR region. These agents were used to monitor endogenous cAMP‐dependent protein kinase activity in erythrocyte lysates and in intact erythrocytes when using a light‐activatable reporter.     

Replacement of the Cobalt Center of Vitamin B12 by Nickel: Nibalamin and Nibyric Acid Prepared from Metal-Free B12 Ligands Hydrogenobalamin and Hydrogenobyric Acid

The (formal) replacement of Co in cobalamin ( Cbl ) by Ni^II generates nibalamin ( Nibl ), a new transition-metal analogue of vitamin B₁₂. Described here is Nibl , synthesized by incorporation of a Ni^II ion into the metal-free B₁₂ ligand hydrogenobalamin ( Hbl ), itself prepared from hydrogenobyric acid ( Hby ). The related Ni^II corrin nibyric acid ( Niby ) was similarly synthesized from Hby , the metal-free cobyric acid ligand. The solution structures of Hbl , and Niby and Nibl , were characterized by spectroscopic studies. Hbl features two inner protons bound at N2 and N4 of the corrin ligand, as discovered in Hby . X-ray analysis of Niby shows the structural adaptation of the corrin ligand to Ni^II ions and the coordination behavior of Ni^II. The diamagnetic Niby and Nibl , and corresponding isoelectronic Co^I corrins, were deduced to be isostructural. Nibl is a structural mimic of four-coordinate base-off Cbls , as verified by its ability to act as a strong inhibitor of bacterial adenosyltransferase.     

Bucillamine Inhibits UVB-Induced MAPK Activation and Apoptosis in Human HaCaT Keratinocytes and SKH-1 Hairless Mouse Skin

Ultraviolet B (UVB) radiation is known as a culprit in skin carcinogenesis. We have previously reported that bucillamine (N-[2-mercapto-2-methylpropionyl]-L-cysteine), a cysteine derivative with antioxidant and anti-inflammatory capacity, protects against UVB-induced p53 activation and inflammatory responses in mouse skin. Since MAPK signaling pathways regulate p53 expression and activation, here we determined bucillamine effect on UVB-mediated MAPK activation in vitro using human skin keratinocyte cell line HaCaT and in vivo using SKH-1 hairless mouse skin. A single low dose of UVB (30 mJ cm⁻²) resulted in increased JNK/MAPK phosphorylation and caspase-3 cleavage in HaCaT cells. However, JNK activation and casaspe-3 cleavage were inhibited by pretreatment of HaCaT cells with physiological doses of bucillamine (25 and 100 µm ). Consistent with these results, bucillamine pretreatment in mice (20 mg kg⁻¹) inhibited JNK/MAPK and ERK/MAPK activation in skin epidermal cells at 6–12 and 24 h, respectively, after UVB exposure. Moreover, bucillamine attenuated UVB-induced Ki-67-positive cells and cleaved caspase-3-positive cells in mouse skin. These findings demonstrate that bucillamine inhibits UVB-induced MAPK signaling, cell proliferation and apoptosis. Together with our previous report, we provide evidence that bucillamine has a photoprotective effect against UV exposure.     

Discovery of Chemicals to Either Clear or Indicate Amyloid Aggregates by Targeting Memory‐Impairing Anti‐Parallel Aβ Dimers

Amyloid‐β (Aβ) oligomers are implicated in Alzheimer disease (AD). However, their unstable nature and heterogeneous state disrupts elucidation of their explicit role in AD progression, impeding the development of tools targeting soluble Aβ oligomers. Herein parallel and anti‐parallel variants of Aβ(1–40) dimers were designed and synthesized, and their pathogenic properties in AD models characterized. Anti‐parallel dimers induced cognitive impairments with increased amyloidogenesis and cytotoxicity, and this dimer was then used in a screening platform. Through screening, two FDA‐approved drugs, Oxytetracycline and Sunitinib, were identified to dissociate Aβ oligomers and plaques to monomers in 5XFAD transgenic mice. In addition, fluorescent Astrophloxine was shown to detect aggregated Aβ in brain tissue and cerebrospinal fluid samples of AD mice. This screening platform provides a stable and homogeneous environment for observing Aβ interactions with dimer‐specific molecules.     

Synthesis of Novel C/D Ring Modified Bile Acids

Bile acid receptors have been identified as important targets for the development of new therapeutics to treat various metabolic and inflammatory diseases. The synthesis of new bile acid analogues can help elucidate structure–activity relationships and define compounds that activate these receptors selectively. Towards this, access to large quantities of a chenodeoxycholic acid derivative bearing a C-12 methyl and a C-13 to C-14 double bond provided an interesting scaffold to investigate the chemical manipulation of the C/D ring junction in bile acids. The reactivity of this alkene substrate with various zinc carbenoid species showed that those generated using the Furukawa methodology achieved selective α-cyclopropanation, whereas those generated using the Shi methodology reacted in an unexpected manner giving rise to a rearranged skeleton whereby the C ring has undergone contraction to form a novel spiro–furan ring system. Further derivatization of the cyclopropanated steroid included O-7 oxidation and epimerization to afford new bile acid derivatives for biological evaluation.