Influence of synthesis route on the properties of doped lanthanum cobaltite and its performance as an electrochemical reactor for the partial oxidation of natural gas

La(0.6)Sr(0.4)Co(0.2)Fe(0.8)O(3-delta)(LSCF) perovskite powders have been synthesised by solid-state reaction, co-precipitation, drip pyrolysis and citrate gel routes, and characterised using XRF, XRD, SEM and BET. Co-precipitation using oxalic acid or aqueous ammonia as precipitant failed to achieve the correct chemical composition. Perovskite structures were achieved in all other cases. Surface areas ranging from 0.6 to 17.4 m(2) g(-1) were obtained, which was reflected in the different microstructures observed. The citrate gel product exhibited a convoluted network morphology resulting in its large surface area. Thin-walled (approximately 200 microm) tubular membranes have been manufactured from the LSCF powders using viscous plastic processing. The tubes have been characterised using a custom-built gas analysis rig with on-line mass spectrometry. Porosity levels of the membranes were found to be very low (<0.1%). The spontaneous oxygen flux across the tubular membranes was determined as a function of temperature. Oxygen permeation rates ranged from 0.1 to 0.3 micromol cm(-2) s(-1) at 1273 K. The catalytic behaviour of the LSCF tubes towards methane oxidation has been studied using temperature programmed reaction and conventional catalytic measurements. The tubes favoured combustion reactions, with smaller amounts of partial oxidation and oxidative coupling products observed. Powder coatings have been incorporated to establish the effect of increasing surface area.     

Activity-based chemical proteomics accelerates inhibitor development for deubiquitylating enzymes

Converting lead compounds into drug candidates is a crucial step in drug development, requiring early assessment of potency, selectivity, and off-target effects. We have utilized activity-based chemical proteomics to determine the potency and selectivity of deubiquitylating enzyme (DUB) inhibitors in cell culture models. Importantly, we characterized the small molecule PR-619 as a broad-range DUB inhibitor, and P22077 as a USP7 inhibitor with potential for further development as a chemotherapeutic agent in cancer therapy. A striking accumulation of polyubiquitylated proteins was observed after both selective and general inhibition of cellular DUB activity without direct impairment of proteasomal proteolysis. The repertoire of ubiquitylated substrates was analyzed by tandem mass spectrometry, identifying distinct subsets for general or specific inhibition of DUBs. This enabled identification of previously unknown functional links between USP7 and enzymes involved in DNA repair.     

PEG- and peptide-grafted aliphatic polyesters by click chemistry

Novel aliphatic polyesters with pendent acetylene groups were prepared by controlled ring-opening polymerization and subsequently used for grafting poly(ethylene glycol) and oligopeptide moieties by the Cu(I)-catalyzed addition of azides and alkynes, a type of "click" chemistry. These aliphatic polyesters possess an acetylene graft density that can be tailored by ring-opening copolymerization of alpha-propargyl-delta-valerolactone (1) with epsilon-caprolactone. Since the mild conditions associated with the click reaction are shown to be compatible with the polyester backbone, this method is a generally useful means for grafting numerous types of functionality onto aliphatic polyesters. The amphiphilic graft polyesters prepared in this study are shown to be biocompatible by in vitro cytotoxicity evaluation, suggesting their suitability for a range of biomaterial applications.     

Efficient syntheses of 1,2,3,4,4a,5-hexahydro-pyrazino[2,1-c][1,4]benzothiazine-6,6-dioxide

Expeditious routes to 1,2,3,4,4a,5-hexahydro-pyrazino[2,1-c][1,4]benzothiazine-6,6-dioxide, a methylenesulfone-constrained arylpiperazine, have been developed. The key step forms the tricyclic system in a cascade of reactions via a 1,4-addition, nitrogen alkylation, and aromatic substitution sequence.     

Marine mammal blubber reference and control materials for use in the determination of halogenated organic compounds and fatty acids

The National Institute of Standards and Technology (NIST) has a diverse collection of control materials derived from marine mammal blubber, fat, and serum. Standard Reference Material (SRM) 1945 Organics in Whale Blubber was recertified for polychlorinated biphenyl (PCB) congeners, organochlorine pesticides, and polybrominated diphenyl ether (PBDE) congeners. SRM 1945 has also been assigned mass fraction values for compounds not frequently determined in marine samples including toxaphene congeners, coplanar PCBs, and methoxylated PBDE congeners which are natural products. NIST also has assigned mass fraction values, as a result of interlaboratory comparison exercises, for PCB congeners, organochlorine pesticides, PBDE congeners, and fatty acids in six homogenate materials produced from marine mammal blubber or serum. The materials are available from NIST upon request; however, the supply is very limited for some of the materials. The materials include those obtained from pilot whale blubber (Homogenates III and IV), Blainville’s beaked whale blubber (Homogenate VII), polar bear fat (Homogenate VI), and California sea lion serum (Marine Mammal Control Material-1 Serum) and blubber (Homogenate V).     

Measuring the intra-individual variability of the plasma proteome in the chicken model of spontaneous ovarian adenocarcinoma

The domestic chicken (Gallus domesticus) has emerged as a powerful experimental model for studying the onset and progression of spontaneous epithelial ovarian cancer (EOC) with a disease prevalence that can exceed 35% between 2 and 7 years of age. An experimental strategy for biomarker discovery is reported herein that combines the chicken model of EOC, longitudinal plasma sample collection with matched tissues, advanced mass spectrometry-based proteomics, and concepts derived from the index of individuality (Harris, Clin Chem 20: 1535–1542, 1974). Blood was drawn from 148 age-matched chickens starting at 2.5 years of age every 3 months for 1 year. At the conclusion of the 1 year sample collection period, the 73 birds that remained alive were euthanized, necropsied, and tissues were collected. Pathological assessment of resected tissues from these 73 birds confirmed that five birds (6.8%) developed EOC. A proteomics workflow including in-gel digestion, nanoLC coupled to high-performance mass spectrometry, and label-free (spectral counting) quantification was used to measure the biological intra-individual variability (CV_W) of the chicken plasma proteome. Longitudinal plasma sample sets from two birds within the 73-bird biorepository were selected for this study; one bird was considered “healthy” and the second bird developed late-stage EOC. A total of 116 proteins from un-depleted plasma were identified with 80 proteins shared among all sample sets. Analytical variability (CV_A) of the label-free proteomics workflow was measured using a single plasma sample analyzed five times and was found to be ≥CV_W in both birds for 16 proteins (20%) and in either bird for 25 proteins (31%). Ovomacroglobulin (ovostatin) was found to increase (p < 0.001) over a 6 month period in the late-stage EOC bird providing an initial candidate protein for further investigation.     

A Chemical Probe for Dehydrobutyrine

Bacterial phosphothreonine lyases, or phospholyases, catalyze a unique post‐translational modification that introduces dehydrobutyrine (Dhb) or dehydroalanine (Dha) in place of phosphothreonine or phosphoserine residues, respectively. We report the use of a phospha‐Michael reaction to label proteins and peptides modified with Dha or Dhb. We demonstrate that a nucleophilic phosphine probe is able to modify Dhb‐containing proteins and peptides that were recalcitrant to reaction with thiol or amine nucleophiles under mild aqueous conditions. Furthermore, we used this reaction to detect multiple Dhb‐modified proteins in mammalian cell lysates, including histone H3, a previously unknown target of phospholyases. This method should prove useful for identifying new phospholyase targets, profiling the biomarkers of bacterial infection, and developing enzyme‐mediated strategies for bioorthogonal labeling in living cells.     

Activation of Platinum(IV) Prodrugs By Motexafin Gadolinium as a Redox Mediator

Water‐soluble platinum(IV) prodrugs, which proved kinetically stable to reduction in the presence of physiological concentration of ascorbate, were quickly reduced to their active form, oxaliplatin, when co‐incubated with a macrocycle metallotexaphyrin (i.e., Motexafin Gadolinium (MGd)). The reduction of Pt^IV to Pt^II promoted by MGd occurs in cell culture as well, leading to an increase in the antiproliferative activity of the Pt^IV species in question. The mediated effect is proportional to the concentration of MGd and gives rise to an enhancement when the prodrug is relatively hydrophilic. MGd is known to localize/accumulate preferentially in tumor tissues. Thus, the present “activation by reduction” approach may allow for the cancer‐selective enhancement in the cytotoxicity of Pt^IV prodrugs.     

Structural properties of ultra-small thorium and uranium dioxide nanoparticles embedded in a covalent organic framework

We report the structural properties of ultra-small ThO₂ and UO₂ nanoparticles (NPs), which were synthesized without strong binding surface ligands by employing a covalent organic framework (COF-5) as an inert template. The resultant NPs were used to observe how structural properties are affected by decreasing grain size within bulk actinide oxides, which has implications for understanding the behavior of nuclear fuel materials. Through a comprehensive characterization strategy, we gain insight regarding how structure at the NP surface differs from the interior. Characterization using electron microscopy and small-angle X-ray scattering indicates that growth of the ThO₂ and UO₂ NPs was confined by the pores of the COF template, resulting in sub-3 nm particles. X-ray absorption fine structure spectroscopy results indicate that the NPs are best described as ThO₂ and UO₂ materials with unpassivated surfaces. The surface layers of these particles compensate for high surface energy by exhibiting a broader distribution of Th–O and U–O bond distances despite retaining average bond lengths that are characteristic of bulk ThO₂ and UO₂. The combined synthesis and physical characterization efforts provide a detailed picture of actinide oxide structure at the nanoscale, which remains highly underexplored compared to transition metal counterparts.

ThO₂ and UO₂ nanoparticles synthesized using a COF-5 template exhibit unpassivated surfaces and provide insight into nanoscale properties of actinides.     

A facile,one-pot procedure for the formation of benzimidazoles from esters using DABAL-Me3, an air stable source of AlMe3

A convenient, single-step, efficient synthesis of benzimidazoles from esters and diamines is reported. The methodology uses an air stable form of trimethylaluminum referred to as DABAL-Me₃ and is compatible with a wide range of functional groups, including acid-sensitive protecting groups.