Gas and particle circulation in an internally circulating fluidized bed membrane reactor cold model

A cold model study was carried out of an internally circulating fluidized bed membrane reactor for hydrogen production by steam reforming. This configuration facilitates a novel process in which air is introduced for autothermal operation, while avoiding diluting the hydrogen in the gas stream by nitrogen. A column of diameter 230 mm and height 2.4 m contained a membrane box of square cross-section. Gas circulation was investigated by injecting helium tracer into the top of the bed above the membrane box and detecting its concentration in the annulus and lower membrane box by a thermal conductivity detector. Solids circulation was determined from the downward velocity of particles in the annulus. The major resistance to solids circulation was found to be at the passage connecting the outer downflow to the inner upflow compartment. A ring distributor helped overcome this resistance.     

Reversible H2 storage using a SAPO-34 zeolite layer

A SAPO-34 zeolite membrane was made essentially impermeable to high-pressure hydrogen at room temperature by adsorbing methanol in the SAPO-34 layer. Hydrogen permeance decreased three orders of magnitude when the methanol feed activity was 0.1, and it decreased more than six orders of magnitude when the methanol feed activity was higher than 0.85 at 293 K. The hydrogen permeance at 293 K was below 10⁻¹⁴ mol/m² s Pa for at least five days for a H₂ feed pressure of 6.6 MPa. At higher temperatures, methanol desorbed and the H₂ flux increased. The hydrogen permeance could be controlled by the activity of the methanol on the feed side. These results demonstrate that the SAPO-34 membrane had low fluxes through defects, and H₂ flow through these defects was blocked by capillary condensation of methanol at high methanol activities.     

Host Recognition by the Specialist Hoverfly <Emphasis Type="Italic">Microdon mutabilis</Emphasis>, a Social Parasite of the Ant <Emphasis Type="Italic">Formica lemani</Emphasis>

The larva of the hoverfly Microdon mutabilis is a specialist social parasite of the ant Formica lemani that is adapted to local groups of F. lemani colonies but mal-adapted to colonies of the same species situated only a few hundred meters away. At a study site in Ireland, F. lemani shares its habitat with four other ant species. All nest under stones, making the oviposition choice by M. mutabilis females crucial to offspring survival. In this study, we tested the hypothesis that, as an extreme specialist, M. mutabilis should respond to cues derived from its host rather than from its microenvironment, a phenomenon that has hitherto only been addressed in the context of herbivorous insects and their parasitoids. In behavioral assays, M. mutabilis females reacted to volatiles from F. lemani colonies by extending their ovipositors, presumably probing for an oviposition substrate. This behavior was not observed toward negative controls or volatiles from colonies of Myrmica scabrinodis, the host ant of the closely related Microdon myrmicae. Coupled gas chromatography-electroantennography (GC-EAG) that used antennal preparations of M. mutabilis located a single physiologically active compound within an extract of heads of F. lemani workers. Coupled GC-mass spectrometry (GC-MS) tentatively identified the compound as a methylated methylsalicylate. GC co-injection of the extract with authentic samples showed that of the four possible isomers (methyl 3-, 4-, 5-, and 6-methylsalicylate), only methyl 6-methylsalicylate co-eluted with the EAG-active peak. Furthermore, the response to methyl 6-methylsalicylate was four times higher than to those of the other isomers. Coupled GC-EAG and GC-MS also revealed physiological responses to two constituents, 3-octanone and 3-octanol, of the M. scabrinodis alarm pheromone. However, the behavioral trials did not reveal any behavior that could be attributed to these compounds. Results are discussed in the context of four phases of host location behavior, and of the characteristics, which volatile cues should provide to be useful for an extreme specialist such as M. mutabilis.     

Evolution of a fourth generation catalyst for the amination and thioetherification of aryl halides

Many active pharmaceuticals, herbicides, conducting polymers, and components of organic light-emitting diodes contain arylamines. For many years, this class of compound was prepared via classical methods, such as nitration, reduction and reductive alkylation, copper-mediated chemistry at high temperatures, addition to benzyne intermediates, or direct nucleophilic substitution on particularly electron-poor aromatic or heteroaromatic halides. However, during the past decade, palladium-catalyzed coupling reactions of amines with aryl halides have largely supplanted these earlier methods. Successive generations of catalysts have gradually improved the scope and efficiency of the palladium-catalyzed reaction. This Account describes the conceptual basis and utility of our latest, "fourth-generation" palladium catalyst for the coupling of amines and related reagents with aryl halides. In the past five years, we have developed these catalysts using the lessons learned from previous generations of catalysts developed in our group and in other laboratories. The ligands on the fourth-generation catalyst combine the chelating properties of the aromatic bisphosphines of the second-generation systems with the steric properties and strong electron donation of the hindered alkylphosphines of the third-generation systems. The currently most reactive catalyst in this class is generated from palladium and a sterically hindered version of the Josiphos family of ligands that possesses a ferrocenyl-1-ethyl backbone, a hindered di-tert-butylphosphino group, and a hindered dicyclohexylphosphino group. This system catalyzes the coupling of aryl chlorides, bromides, and iodides with primary amines, N-H imines, and hydrazones in high yield. The reaction has broad scope, high functional group tolerance, and nearly perfect selectivity for monoarylation. It also requires the lowest levels of palladium that have been used for C-N coupling. In addition, this latest catalyst has dramatically improved the coupling of thiols with haloarenes to form C-S bonds. Using ligands that lacked one or more of the structural elements of the most active catalyst, we examined the effects of individual structural elements of the Josiphos ligand on catalyst activity. This set of studies showed that each one of these elements contributes to the high reactivity and selectivity of the catalyst containing the hindered, bidentate Josiphos ligand. Finally, we examined the effect of electronic properties on the rates of reductive elimination to distinguish between the effect of the properties of the M-N sigma-bond and the nitrogen electron pair. We have found that the effects of electronic properties on C-C and C-N bond-forming reductive elimination are similar. Because the amido ligands contain an electron pair, while the alkyl ligands do not, we have concluded that the major electronic effect is transmitted through the sigma-bond.     

Evaluation of solvent accessibility epitopes for different dehydrogenase inhibitors

Knowledge about the orientation of ligands or inhibitors bound to a protein is vital for the development of new drugs. It was recently shown that solvent accessibility epitopes for protein ligands can be mapped by transferring magnetization from water molecules to the ligand to derive the ligand orientation. This is based on the fact that NMR signals of ligands arising from magnetization transferred from solvent molecules via the protein have a different sign from those arising from direct magnetization transfer from bulk water. Herein we critically evaluate the applicability of solvent accessibility mapping to derive binding orientations for ligands of two dehydrogenases (AKR1C3 and HSD17beta1) with very different binding pockets, including complexes in which the ligand is buried more deeply inside the protein. We also evaluate the possibility of using co-solvents, such as DMSO, for magnetization transfer.     

Bacterial inactivation and organic oxidation via immobilized photo-Fenton reagent on structured silica surfaces

A woven inorganic silica fabric loaded with Fe-ions (EGF-Fe) was tested under simulated solar light during hydroquinone degradation. The abatement of hydroquinone was observed to attain about 80% within 3 h. The photo-catalyst was also tested to inactive Escherichia coli K12 at “natural” pH and in the presence of a low concentration of H₂O₂. Addition of H₂O₂ (10 mg L⁻¹) did not by itself to bacterial inactivation. Total bacterial inactivation was mediated by EGF-Fe fabrics in the presence of H₂O₂ (10 mg L⁻¹) under solar light irradiation. A sample containing active (culturable) bacteria (10⁵ CFU mL⁻¹) decreased to values <1 CFU mL⁻¹ within 3 h reaction. Fe-mediated homogeneous process decreased the bacterial CFU content by about two orders of magnitude within 4 h. During the degradation of hydroquinone only a small amount of iron ions were found in solution of about 1.2 mg L⁻¹, within 90 min decreasing to values ≤0.5 mg L⁻¹ after 180 min. The leaching of Fe-ions did not affect the photo-catalyst performance since EGF-Fe fabric did not deactivate after five or more cycles. The Fe-ions founds in solution mineralized hydroquinone to levels below 37% of its initial content. The present study presents the first report on the beneficial role of a heterogeneous iron supported catalyst leading to efficient bacterial inactivation in aqueous solution with iron leaching <0.1 mg L⁻¹, the detection limit for Fe-analysis in solution. No bacterial re-growth was observed during a post-irradiation period up to 24 h in the dark.     

Challenges in modern drug discovery: a case study of boceprevir, an HCV protease inhibitor for the treatment of hepatitis C virus infection

More than 170 million people worldwide are affected by the hepatitis C virus (HCV). The disease has been described as a "silent epidemic" and "a serious global health crisis". HCV infection is a leading cause of chronic liver disease such as cirrhosis, carcinoma, or liver failure. The current pegylated interferon and ribavirin combination therapy is effective in only 50% of patients. Its moderate efficacy and apparent side effects underscore the need for safer and more effective treatments. The nonstructural NS3 protease of the virus plays a vital role in the replication of the HCV virus. The development of small molecule inhibitors of NS3 protease as antiviral agents has been intensively pursued as a viable strategy to eradicate HCV infection. However, it is a daunting task. The protease has a shallow and solvent-exposed substrate binding region, and the inhibitor binding energy is mainly derived from weak lipophilic and electrostatic interactions. Moreover, lack of a robust in vitro cell culture system and the absence of a convenient small animal model have hampered the assessment of both in vitro and in vivo efficacy of any antiviral compounds. Despite the tremendous challenges, with access to a recently developed cell-based replicon system, major progress has been made toward a more effective small molecule HCV drug. In our HCV program, facing no leads from our screening effort, a structure-based drug design approach was carried out. An alpha-ketoamide-type electrofile was designed to trap the serine hydroxyl of the protease. Early ketoamide inhibitors mimicked the structures of the peptide substrates. With the aid of X-ray structures, we successfully truncated the undecapeptide lead that had a molecular weight of 1265 Da stepwise to a tripeptide with a molecular weight of 500 Da. In an attempt to depeptidize the inhibitors, various strategies such as hydrazine urea replacement of amide bonds and P2 to P4 and P1 to P3 macrocyclizations were examined. Further optimization of the tripeptide inhibitors led to the identification of the best moieties for each site: primary ketoamide at P', cyclobutylalanine at P1, gem-dimethylcyclopropylproline at P2, tert-leucine at P3, and tert-butyl urea as capping agent. The combination of these led to the discovery of compound 8 (SCH 503034, boceprevir), our clinical candidate. It is a potent inhibitor in both enzyme assay (Ki* = 14 nM) and cell-based replicon assay (EC 90 = 0.35 microM). It is highly selective (2200x) against human neutrophil elastase (HNE). Boceprevir is well tolerated in humans and demonstrated antiviral activity in phase I clinical trials. It is currently in phase II trials. This Account details the complexity and challenges encountered in the drug discovery process.     

Mathematical modelling of temperature induced moisture migration in bulk powders

This paper reviews the importance of temperature gradient induced moisture diffusion in powder beds. Redistribution of moisture by this mechanism is important for a wide variety of products, especially those which are crystalline in nature. Moisture transfer in these products can result in very high local water activity and lead to microbial spoilage and caking problems. A conceptual model was developed for heat and moisture transfer due to the application of thermal gradients across a one-dimensional powder bed. The validity of the key assumptions in the model formulation were demonstrated and a mathematical model was derived and solved numerically. The model was validated against experimental data collected using crystalline lactose powders as a working example.     

Microstructure and Creep Behavior of Silicon Nitride and SiAlONs

Microstructural evolution of silicon nitride (Si₃N₄) and SiAlON materials and its influence on creep resistance is reviewed. Grain size, grain morphology, and the ratio of α- to β-phase grains play a part in resistance to creep. The glassy, intergranular phase typically has the strongest influence on creep. Creep data are usually obtained using uniaxial tensile or compressive tests, where creep in tension is controlled by cavitation and grain boundary sliding controls creep in compression. The impression creep methodology is also reviewed. An additional creep mechanism, dilation of the SiAlON grain structure, was found to be active in impression creep.