Tremorgenic Indole Alkaloids. 10. An Improved Asymmetric Synthesis of a Tricyclic Common Intermediate

An efficient third-generation asymmetric synthesis of tricyclic lactone (+)-1, designed to serve as the common intermediate for construction of the indole tremorgens, has been developed. The major challenge was stereocontrolled introduction of the vicinal quaternary methyl groups. Our initial approaches employed enolate chemistry to install the second methyl moiety; herein we exploit instead a hydroxyl-directed Simmons-Smith cyclopropanation followed by reductive opening of the three-membered ring. The new 15-step synthesis proceeds in 8.3% overall yield, nearly an eightfold increase over the second-generation route, and is amenable to large-scale production of (+)- 1.      

Computational Approaches for Studying the Granular Dynamics of Continuous Blending Processes, 2 – Population Balance and Data‐Based Methods

The application of computationally inexpensive modeling methods for a predictive study of powder mixing is discussed. A multidimensional population balance model is formulated to track the evolution of the distribution of a mixture of particle populations with respect to position and time. Integrating knowledge derived from a discrete element model, this method can be used to predict residence time distribution, mean and relative standard deviation of the API concentration in a continuous mixer. Low‐order statistical models, including response surface methods, kriging, and high‐dimensional model representations are also presented. Their efficiency for design optimization and process design space identification with respect to operating and design variables is illustrated.

     

The Structures of Gd(III) Chelates Conjugated at the Periphery of 3-(1’-Hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH) Have a Significant Impact on the Imaging and Therapy of Cancer

3-(1’-Hexyloxyethyl)-3-devinyl-pyropheophorbide-a (HPPH or Photochlor), a tumor-avid chlorophyll-a derivative currently undergoing human clinical trials, was conjugated at various peripheral positions (position-17 or 20) of HPPH with either Gd(III)-aminobenzyl-DTPA (Gd(III) DTPA) or Gd(III)-aminoethylamido-DOTA (Gd(III) DOTA). The corresponding conjugates were evaluated for in vitro PDT efficacy, T₁, T₂ relaxivities, in vivo fluorescence, and MR imaging under similar treatment parameters. Among these analogs, the water-soluble Gd(III)-aminoethylamido-DOTA linked at position-17 of HPPH, i. e., HPPH-17-Gd(III) DOTA, demonstrated strong potential for tumor imaging by both MR and fluorescence, while maintaining the PDT efficacy in BALB/c mice bearing Colon-26 tumors (7/10 mice were tumor free on day 60). In contrast to Gd(III) DTPA (Magnevist) and Gd(III) DOTA (Dotarem), the HPPH-Gd(III) DOTA retains in the tumor for a long period of time (24 to 48 h) and provides an option of fluorescence-guided cancer therapy. Thus, a single agent can be used for cancer-imaging and therapy. However, further detailed pharmacokinetic, pharmacodynamic, and toxicological studies of the conjugate are required before initiating Phase I human clinical trials.     

Processing and electromechanical properties of high-coercive field ZnO-doped PIN-PZN-PT ceramics

This study explores sintering and piezoelectricity of ZnO-doped perovskite Pb(In_1/2Nb_1/2)O₃-Pb(Zn_1/3Nb_2/3)O₃-PbTiO₃ (PIN-PZN-PT) ceramics. The enhanced densification of ZnO-doped PIN-PZN-PT is attributed to the formation of oxygen vacancies by the incorporation of Zn²⁺ into the perovskite B-site and increased rate of bulk diffusion relative to undoped PIN-PZN-PT. Incorporation of Zn²⁺ into the perovskite lattice increased the tetragonal character of PIN-PZN-PT as demonstrated by tetragonal peak splitting and increased Curie temperature. Sintering in flowing oxygen reduced the solubility of Zn²⁺ in the perovskite lattice and resulted in rhombohedral PIN-PZN-PT. Sintering in oxygen prevented secondary phase formation which resulted in a high-piezoelectric coefficient (d₃₃ – 550 pC/N), high-coercive field (E_c – 13 kV/cm), and high-rhombohedral to tetragonal phase transition temperature (T_r-t – 165°C). We conclude that ZnO-doped PIN-PZN-PT ceramics are excellent candidates for high-power transducer applications.     

Novel processing,testing and characterization of copper/carbon nanotube (Cu/CNT) yarn composite conductor

Sustainable electrified aircraft propulsion (EAP) is likely to lead to an increase in the electrical wiring contained within a single aircraft. Since the electrical resistance and mass of copper (Cu) conductors are associated with power losses, it is desirable to design high-conductivity lightweight conductor materials, thus reducing the mass of components like motor windings, low-voltage signal cables, and transmission cables for data and power to improve the overall energy efficiency. This paper describes a unique framework for manufacturing metalized carbon nanotube (CNT) composite conductors, measuring their electrical conductivity and strength, and modeling the overall conductivity and current sharing within such composites. Tensile testing was conducted on the processed composite conductor cables with the use of acoustic emission and electrical resistivity to determine stress-dependent-failure mechanisms while monitoring the electrical conductivity. The average of measured electrical conductivities of annealed Cu/CNT samples from batch 5 was greater than theoretical predictions by 9.8 percent and was also greater than the conductivity of pure annealed Cu by 4.8 percent and had comparable ultimate tensile strengths. Additionally, those Cu/CNT samples provide a 13.5% weight saving over current state of the art copper wires. Theories explaining improved intrinsic conductivity are discussed.     

Incorporation of postconsumer polyurethane foam into a polymer/clay aerogel matrix

The feasibility of incorporating ground recycled polyurethane (PU) foam into clay/polymer aerogels was demonstrated, and a range of compositions were prepared and characterized to determine the effect of variation in the formulations on density and mechanical properties of the resulting materials. This study followed a modified combinatorial approach. Initially, experiments were performed in water using either sodium exchanged montmorillonite or laponite clay, poly(vinyl alcohol) (PVOH) solution as the polymer binder, and the recycled PU foam. Freezing and freeze‐drying the aqueous gels produced aerogels, which were characterized through density and mechanical testing, scanning electron microscopy, and thermal gravimetric analysis. The study was expanded by exploring alternative binder chemistries, including the use of an alginate polymer in place of the PVOH or adding a polyisocyanate as a crosslinking agent for PVOH. The effect of recycled PU foam content, clay type and level, and binder type and level on the mechanical properties of the aerogels were determined and will be discussed herein. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42586.     

Melt Rheological Behavior and Creep Response of EVA/TPU Blends: Exploring the Effect of Electron Beam Irradiation and Peroxide Cross-linking

The present study focuses on the variation of the melt rheological characteristics and the creep behavior of both electron beam-cross-linked and peroxide-cured ethylene vinyl acetate/thermoplastic polyurethane blends. The variation of complex viscosity, complex modulus, storage modulus, and loss modulus was evaluated over a wide range of frequency and strain amplitude using rubber process analyzer and the effect of radiation dose and peroxide concentration was investigated in detail. The creep study using dynamic mechanical analyzer shows that the creep behavior of the blends significantly improves after cross-linking and the creep compliance gradually decreases with the increasing radiation dose and peroxide content. An attempt was also made to pursue a comparative rheological and creep study among the peroxide-cured, electron beam-cross-linked and the coagent-treated dynamically vulcanized samples.     

Characterization of Morphological Changes in Agglomerates Subject to Condensation and Evaporation Using Multiple Fractal Dimensions

Multiple fractal dimensions are used to characterize morphological changes that occur when an aerosol composed of irregularly shaped agglomerates is subject to condensation followed by evaporation. The agglomerates change from a branched, chainlike structure to a more regular, near-spherical or clumplike structure reflected in a decrease in the structural fractal dimension. The textural fractal dimension remains constant because the primary particles, of which the agglomerates are composed, do not change in shape. The degree of supersaturation and the number of condensation-evaporation cycles that the aerosol undergoes are major factors that influence morphological change. Even at low supersaturations, increasing the number of condensation-evaporation cycles makes the agglomerates more regular and thus decreases the structural fractal dimension. The transition point in the Richardson plot is a good indicator of the size of the primary particles in the agglomerate.