ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.     

Freestanding, Micromachined, Multimode Silicon Optical Waveguides at lambda = 1.3 mum for Microelectromechanical Systems Technology

Freestanding, multimode optical channel waveguides formed by micromachining silicon are demonstrated. Fabrication utilizes standard microelectromechanical systems (MEMS) technology. Losses in the 0.57-0.80-dB/cm range are measured for channel waveguides with an air-silicon-air structure, whereas losses in the 1.12-1.52-dB/cm range are measured for channel waveguides with a SiO(2)-silicon-SiO(2) structure. Freestanding channel waveguides, along with optical fibers and other MEMS structures, can readily be mounted on a silicon MEMS platform to provide optimal alignment for maximizing optical coupling, and they are thus expected to be useful in devices that involve light and MEMS structures.     

The origin of the support effect in supported metal oxide catalysts: in situ infrared and kinetic studies during methanol oxidation

The strong influence of the oxide support upon the turn-over frequency (TOF) of methanol oxidation over supported metal oxide catalysts has been well documented in recent years. However, the mechanistic origins (adsorption equilibrium of methanol to methoxy species, rate-determining methoxy surface decomposition, or product desorption equilibrium) of this interesting phenomenon are not completely understood. In order to obtain additional insight, the steady-state surface concentrations of adsorbed methoxy intermediates on monolayer catalysts (8 V atoms nm⁻²) of V₂O₅/(TiO₂, CeO₂, Al₂O₃ and ZrO₂) have been quantified with in situ transmission infrared spectroscopy/mass spectrometry. Calculations of the adsorption equilibrium constant, K_ads, show a six times increase for vanadia on oxide supports of Al < Ti < Zr < Ce, whereas the methoxy surface decomposition rate constant, k_rds (rds = rate-determining step), shows a 22 times increase in value over these same catalysts. Thus, changes in both the adsorption equilibrium and the methoxy decomposition properties of supported metal oxide catalysts appear to be responsible for the support effect, although the methoxy decomposition is clearly the reaction step that is more sensitive to the specific metal oxide support. More fundamentally, the support effect appears to correlate with the electronegativity of the support cation, which is proposed to have influence upon the rate of methoxy decomposition through hydride abstraction and on the steady-state equilibrium adsorption capacity of methanol to surface methoxy intermediates through the basicity of the bridging V–O–support bond (the adsorption site).     

In situ IR,Raman, and UV-Vis DRS spectroscopy of supported vanadium oxide catalysts during methanol oxidation

The application of in situ Raman, IR, and UV-Vis DRS spectroscopies during steady-state methanol oxidation has demonstrated that the molecular structures of surface vanadium oxide species supported on metal oxides are very sensitive to the coordination and H-bonding effects of adsorbed methoxy surface species. Specifically, a decrease in the intensity of spectral bands associated with the fully oxidized surface (V⁵⁺) vanadia active phase occurred in all three studied spectroscopies during methanol oxidation. The terminal V = O (∼1030 cm⁻¹) and bridging V–O–V (∼900–940 cm⁻¹) vibrational bands also shifted toward lower frequency, while the in situ UV-Vis DRS spectra exhibited shifts in the surface V⁵⁺ LMCT band (>25,000 cm⁻¹) to higher edge energies. The magnitude of these distortions correlates with the concentration of adsorbed methoxy intermediates and is most severe at lower temperatures and higher methanol partial pressures, where the surface methoxy concentrations are greatest. Conversely, spectral changes caused by actual reductions in surface vanadia (V⁵⁺) species to reduced phases (V³⁺/V⁴⁺) would have been more severe at higher temperatures. Moreover, the catalyst (vanadia/silica) exhibiting the greatest shift in UV-Vis DRS edge energy did not exhibit any bands from reduced V³⁺/V⁴⁺ phases in the d–d transition region (10,000–30,000 cm⁻¹), even though d–d transitions were detected in vanadia/alumina and vanadia/zirconia catalysts. Therefore, V⁵⁺ spectral signals are generally not representative of the percent vanadia reduction during the methanol oxidation redox cycle, although estimates made from the high temperature, low methoxy surface coverage IR spectra suggest that the catalyst surfaces remain mostly oxidized during steady-state methanol oxidation (15–25% vanadia reduction). Finally, adsorbed surface methoxy intermediate species were easily detected with in situ IR spectroscopy during methanol oxidation in the C–H stretching region (2800–3000 cm⁻¹) for all studied catalysts, the vibrations occurring at different frequencies depending on the specific metal oxide upon which they chemisorb. However, methoxy bands were only found in a few cases using in situ Raman spectroscopy due to the sensitivity of the Raman scattering cross-sections to the specific substrate onto which the surface methoxy species are adsorbed. This revised version was published online in August 2006 with corrections to the Cover Date.     

Separation of conglomerate forming enantiomers using a novel continuous preferential crystallization process

Providing enantiomerically pure products is of key importance in the fine chemicals, food, and pharmaceutical industries. A continuous preferential crystallization process is presented that allows the separation of conglomerate forming enantiomers in a stable, robust, and flexible way. This is achieved by coupling two continuous crystallizers by exchanging their clear liquid phases. Each crystallizer is connected to a suspension mill responsible for in situ seed generation through particle breakage. The dynamic and steady‐state behavior of this process is extensively analyzed for racemic feed streams through process simulations, and parameter regions, which yield pure enantiomers in both crystallizers, are identified. For enriched feed streams, it is further shown when this novel flow sheet is capable of outperforming an ideal batch process in terms of solvent consumption per unit mass of desired enantiopure product produced. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2810–2823, 2015     

Investigation of the microcracking behavior of bismaleimide composites during thermal aging

Samples of 16-ply, quasi-isotropic bismaleimide composites were aged in convection ovens at 150°C, 177°C, and 204°C for up to 16,000 hours. As a measure of degradation, transverse microcrack density was characterized as a function of time, temperature, and ply depth. Times required to reach onset and saturation crack density were delayed on the tool side of the laminate, for lower temperatures, and for deeper ply depths. Saturation crack densities ranged from 35 cracks/cm to 46 cracks/cm, depending on ply depth. Master curves were constructed for each ply level to express all time-temperature data for that ply as a single reference curve. A mass transfer analysis further suggests that diffusion is the controlling mechanism in the degradation process. Finally, a prediction of the degradation behavior in the 120,000-h lifetime of the HSCT aircraft for a sustained temperature of 150°C indicates that ∼13 plies will have reached initiation in a quasi-isotropic laminate.     

Iterative model-based experimental design for spherical agglomeration processes

Spherical agglomeration (SA) is a process intensification strategy, which can reduce the number of unit operations in pharmaceutical manufacturing. SA merges drug substance crystallization with drug product wet granulation, reducing capital, and operating costs. However, SA is a highly nonlinear process, thus for its efficient operation model-based design and control strategies are beneficial. These require the development of a high-fidelity process model with appropriately estimated parameters. There are two major problems associated with the development of a high-fidelity process models—(i) selection of the appropriate model corresponding to the underlying process mechanisms, and (ii) accurate estimation of the parameters. This work focuses on the identification of the best fitting model that correlates with experimental observations using cross-validation experiments. Further, an iterative model-based experimental design strategy is developed, which uses D-optimal experimental design criterion to minimize the number of experiments necessary to obtain accurate parameter estimates.     

Applying just-in-time in a wafer fab: a case study

The successful application of the just-in-time (JIT) manufacturing management philosophy within a wafer fab photoresist wet chemistry area is described. The JIT techniques that were applied included lot-size reduction, setup-time reduction, layout changes for improved work flow, and improved operator flexibility. These set the stage for the implementation of a demand-pull system that resulted in significant decreases in cycle times as well as corresponding decrease in inventory levels. Aspects related to quality improvement as well as other long-term issues are also discussed     

The recycle of sulfuric acid and xylose in the prehydrolysis of corn stover

Ethanol may be produced from agricultural residues by using a two-stage acid hydrolysis followed by acid recovery, fermentation, and distillation. With sulfuric acid as a catalyst, xylose-rich and glucose-rich streams can be obtained from corn stover in the prehydrolysis and hydrolysis steps, respectively. After acid separation, the sugar solutions are fermented to ethanol and concentrated by distillation.The acid recovery and distillation steps are the most expensive portions of the process; therefore, any reduction in the requirements for these steps will significantly improve the economics of the overall process. One means by which this may be accomplished is the addition of a recycle stream in the prehydrolysis step. The result will be an increased xylose concentration in the the prehydrolyzate fluid, which will reduce the acid recovery and distillation costs for each unit of ethanol produced. Thus, both capital and operating costs can be lowered while the net energy production is increased.In this investigation, the prehydrolysis step was carried out in a batch reactor at a temperature of 100 °C and a reaction time of 80 min. A 2-1. reaction vessel was used for the first two batches, each of which resulted in approx. 600 milliliters (ml) of prehydrolyzate fluid. This fluid, consisting primarily of xylose dissolved in the dilute sulfuric acid solution, was then mixed in varying ratios with fresh acid and used as the acid catalyst in later experiments to determine the effects of recycle on sulfuric acid activity and xylose concentration. In one set of recycle experiments, the activity of the recycled acid was as much as 90% of the activity of fresh acid on a volume per volume basis. Because the recycled fluid contained approx. 3% xylose, the xylose concentrations obtained in these experiments depended on the ratio of recycled acid to fresh acid. Concentrations averaged 27.5 grams per liter (g/l) for an acid residence time of 80min and 51.4 g/l for an acid residence time of 160 min.The effect of the increased concentration of xylose on the economics of a 4.5 × 10⁶ gallon per year ethanol plant were estimated to be a 16% reduction in capital costs and a 17% reduction in operating costs. For corn stalks at $25 per ton and ethanol at $1.185 per gallon (ga), the estimated rate of return on investment would increase from 3.4% without recycle to 18.0% with recycle.