Preparation and Characterization of Forsterite (Mg2SiO4) Xerogels

Mg2SiO4 gels were prepared from alkoxide precursors, and the formation of the forsterite crystal phase was studied after heat treatments up to 1200°C. Prehydrolyzed TEOS in solution with 2-methoxyethanol was mixed with Mg(OEt)2, and the solution was hydrolyzed using excess water. The resultant gels were dried at 100°C to form xerogels which were subsequently powdered. These powders were characterized using thermal analysis (DTA and TGA), surface area analysis (BET), X-ray diffraction (XRD) and transmission electron microscopy (TEM).DTA and XRD indicated that forsterite crystallized at 770°C, and by 1000°C the powders were predominantly crystalline. BET gave powder surface areas between 400 and 550 m2 g–1. TEM revealed angular particles with sizes between 0.2 and 2 m. The low temperature of crystallization of forsterite indicates a high degree of intimate mixing between the precursor alkoxides, although XRD indicated some degree of inhomogeneity.     

Palladium-Catalyzed Carbonylation and Coupling Reactions of Aryl Chlorides and Amines

The palladium-catalyzed amidation of electron-deficient aryl chlorides proceeds readily in the presence of low CO pressures and a slight excess of an iodide salt. The rates of amidation are accelerated over those without added salt, and iodide is preferred over bromide or chloride. More electron-rich aryl chlorides were not effectively amidated, either with or without added iodide. We postulate that an intermediate anionic palladium(0) iodide complex is responsible for the enhanced reactivity.     

Approaches for the detection and analysis of antidrug antibodies to biopharmaceuticals: A review

Antibody-based therapeutic agents and other biopharmaceuticals are now used in the treatment of many diseases. However, when these biopharmaceuticals are administrated to patients, an immune reaction may occur that can reduce the drug's efficacy and lead to adverse side-effects. The immunogenicity of biopharmaceuticals can be evaluated by detecting and measuring antibodies that have been produced against these drugs, or antidrug antibodies. Methods for antidrug antibody detection and analysis can be important during the selection of a therapeutic approach based on such drugs and is crucial when developing and testing new biopharmaceuticals. This review examines approaches that have been used for antidrug antibody detection, measurement, and characterization. Many of these approaches are based on immunoassays and antigen binding tests, including homogeneous mobility shift assays. Other techniques that have been used for the analysis of antidrug antibodies are capillary electrophoresis, reporter gene assays, surface plasmon resonance spectroscopy, and liquid chromatography-mass spectrometry. The general principles of each approach will be discussed, along with their recent applications with regards to antidrug antibody analysis.     

Precision and control in polymer synthesis why it's important and some recent examples of how to do it

This paper discusses some of the reasons why precision and control in polymer synthesis is of importance. By way of illustration it describes in outline recent results from the authors' laboratories in three areas. Namely; the controlled syntheses of poly(arylene vinylene)s and the influence of cis/trans vinylene content on luminescence in such polymers; the living polymerisation of highly functionalised polymers in water and the regulation of the crystallisation of calcium carbonate from water by the resultant well-defined water soluble polymers; and a simple route to hyperbranched polymers and the influence of the structure and topology of the products on solution properties. In each case the influence of control of architecture on properties will be discussed.     

Constraining Cyclic Peptides To Mimic Protein Structure Motifs

Many proteins exert their biological activities through small exposed surface regions called epitopes that are folded peptides of well‐defined three‐dimensional structures. Short synthetic peptide sequences corresponding to these bioactive protein surfaces do not form thermodynamically stable protein‐like structures in water. However, short peptides can be induced to fold into protein‐like bioactive conformations (strands, helices, turns) by cyclization, in conjunction with the use of other molecular constraints, that helps to fine‐tune three‐dimensional structure. Such constrained cyclic peptides can have protein‐like biological activities and potencies, enabling their uses as biological probes and leads to therapeutics, diagnostics and vaccines. This Review highlights examples of cyclic peptides that mimic three‐dimensional structures of strand, turn or helical segments of peptides and proteins, and identifies some additional restraints incorporated into natural product cyclic peptides and synthetic macrocyclic peptidomimetics that refine peptide structure and confer biological properties.     

Characterizing Methyl‐Bearing Side Chain Contacts and Dynamics Mediating Amyloid β Protofibril Interactions Using 13Cmethyl‐DEST and Lifetime Line Broadening

Many details pertaining to the formation and interactions of protein aggregates associated with neurodegenerative diseases are invisible to conventional biophysical techniques. We recently introduced ¹⁵N dark‐state exchange saturation transfer (DEST) and ¹⁵N lifetime line‐broadening to study solution backbone dynamics and position‐specific binding probabilities for amyloid β (Aβ) monomers in exchange with large (2–80 MDa) protofibrillar Aβ aggregates. Here we use ¹³C_methyl DEST and lifetime line‐broadening to probe the interactions and dynamics of methyl‐bearing side chains in the Aβ‐protofibril‐bound state. We show that all methyl groups of Aβ40 populate direct‐contact bound states with a very fast effective transverse relaxation rate, indicative of side‐chain‐mediated direct binding to the protofibril surface. The data are consistent with position‐specific enhancements of ¹³C_methyl‐${R{{{\rm tethered}\hfill \atop 2\hfill}}}$ values in tethered states, providing further insights into the structural ensemble of the protofibril‐bound state.     

Fuctionalization of Linear and Angular Phenothiazine and Phenoxazine Ring Systems via Pd(0)/XPhos Mediated Suzuki‐Miyaura Cross‐coupling Reactions

Chloro‐substituted phenothiazines and phenoxazines were successfully derivatized with phenylboronic and styrylboronic acids using Suzuki–Miyaura cross‐coupling reaction catalyzed by Pd(0)/XPhos for the first time in good yields. The protocol employed 4 mol% Pd and 7 mol% XPhos with K₃PO₄ in acetonitrile at 80°C. The reaction condition is compatible with carbonyl and unprotected N–H groups in substrates. Structural assignments were established by combined spectroscopic (UV, IR, ¹H, and ¹³C NMR), MS, and elemental analytical data.     

Dry Reforming of Methane on a Highly‐Active Ni‐CeO2 Catalyst: Effects of Metal‐Support Interactions on C−H Bond Breaking

Ni‐CeO₂ is a highly efficient, stable and non‐expensive catalyst for methane dry reforming at relative low temperatures (700 K). The active phase of the catalyst consists of small nanoparticles of nickel dispersed on partially reduced ceria. Experiments of ambient pressure XPS indicate that methane dissociates on Ni/CeO₂ at temperatures as low as 300 K, generating CH_x and CO_x species on the surface of the catalyst. Strong metal–support interactions activate Ni for the dissociation of methane. The results of density‐functional calculations show a drop in the effective barrier for methane activation from 0.9 eV on Ni(111) to only 0.15 eV on Ni/CeO_2?x(111). At 700 K, under methane dry reforming conditions, no signals for adsorbed CH_x or C species are detected in the C 1s XPS region. The reforming of methane proceeds in a clean and efficient way.     

Relative quantification of long chain branching in essentially linear polyethylenes

The aim of this work is to describe a method whereby low levels of long chain branching, LCB, can be quantified on a relative basis for whole, unfractionated, and essentially linear ethylene/α-olefin copolymers. The method is based on a well established, relatively fast and robust experiment, namely the measurement of the linear viscoelastic properties by a single, isothermal, small amplitude oscillatory shear experiment. The analysis of the data is predicated on the use of the so-called van Gurp-Palmen plots (the phase angle, δ (=tan⁻¹(G″/G′)), plotted against the absolute value of the dynamic complex modulus, |G∗| = (G′²+G″²)^1/2). From this plot, the value of δ at |G∗| = 10 kPa is recorded, and it is demonstrated that the amount of LCB inversely correlates with such value of the phase angle, δ. Depending on the desired frequency range, the experiment duration varies between 15 and 60 min rendering this technique well suited for high throughput parallel testing. Its applicability is critically examined with a wide variety of commercial ethylene/α-olefin copolymers. Moreover, we have improved on the long chain branching index (LCBI) proposed by Shroff and Mavridis [Shroff RN, Mavridis H. Long-chain-branching index for essentially linear polyethylenes. Macromolecules 1999;32:8454-64] by basing it on data of truly linear polyethylenes (hydrogenated anionically synthesized polybutadienes) instead of apparently linear commercial polyethylenes.     

Using chemical probes to investigate the sub-inhibitory effects of azithromycin

The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.