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Sulfur poisoning of PdCu membrane alloys has promoted new alloy development that requires quantitative understanding of the thermodynamics of the Pd–Cu–S system. This study attempts to develop a self-consistent thermodynamic description of the Pd-rich Pd–S binary system using the CALPHAD approach, based on available phase equilibrium information and thermochemistry data. The optimized phase diagram and enthalpies of formation agree well with the experimental values and first-principles calculations. The phase stability of this system is further investigated using first-principles calculations, confirming that the five intermetallic compounds reported are stable phases. The present density functional theory (DFT) calculations using various exchange–correlation functionals, pseudo-potentials and settings demonstrate that using the PBEsol functional reproduces the experimental enthalpies and phase stability of S, Pd and Pd–S compounds acceptably, and is able to reproduce the lattice parameters nearly perfectly.

Vanadium is a refractory metal with high melting point (1910 °C) that has good structural strength, good room-temperature corrosion resistance, and low thermal neutron-absorption cross section. Vanadium is primarily used as a steel additive to improve the strength of steels by forming stable nitrides and carbides. Addition of yttrium to vanadium alloys can improve the oxidation resistance and mechanical properties. In this work, three binary systems, V-Ce, V-La, and V-Y, were thermodynamically assessed based on the ASM Binary Alloy Phase Diagrams using CALPHAD approach. Self-consistent thermodynamic descriptions for all three systems were obtained.

Molybdenum is a refractory metal that is typically used for high-temperature applications due to its high melting point (2615 °C), high-temperature strength, low thermal-expansion coefficient, and high thermal conductivity. The alloying of rare earth elements to molybdenum can help improve oxidation resistance as well as strengthening the alloy via dispersion strengthening due to formation of rare earth oxides. In this study, two binary systems, Mo-Ce and Mo-Y, were thermodynamically assessed based on limited phase equilibria information available in the literature. Self-consistent thermodynamic descriptions for both systems were obtained using the CALPHAD method.

The purpose of this work is to predict elastic and thermodynamic properties of chromium-based alloys based on first-principles calculations and to demonstrate an appropriate computational approach to develop new materials for high-temperature applications in energy systems. In this study, Poisson ratio is used as a screening parameter to identify ductilizing additives to the refractory alloys. The results predict that elements such as Ti, V, Zr, Nb, Hf, and Ta show potential as ductilizers in Cr while Al, Ge, and Ga are predicted to decrease the ductility of Cr. Experimental evidence, where available, validates these predictions. The purpose of this work is to predict elastic and thermodynamic properties of chromium-based alloys based on first-principles calculations and to demonstrate an appropriate computational approach to develop new materials for high-temperature applications in energy systems. In this study, Poisson ratio is used as a screening parameter to identify ductilizing additives to the refractory alloys. The results predict that elements such as Ti, V, Zr, Nb, Hf, and Ta show potential as ductilizers in Cr while Al, Ge, and Ga are predicted to decrease the ductility of Cr. Experimental evidence, where available, validates these predictions.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating basic biaryl P4 groups, producing highly potent inhibitors with significant anticoagulant activities and encouraging oral pharmacokinetic profiles.

This paper presents the results of plant-site experiments conducted on several natural-gas-fired, reverberatory aluminum furnaces to evaluate overall energy efficiency and to analyze major sources of heat loss, providing an overall picture of current aluminum melting furnaces in the US aluminum industry. Thermodynamic analyses were done for energy utilization according to energy balance and compared with the measured data. Our experimental results indicate that the effective energy efficiency in most melting furnaces measured is around 26–29%, and the major heat loss through flue gas is between 35% and 50%. The energy availability concept is introduced to predict the maximum energy potential and minimum flue gas heat loss in this type of aluminum furnace. Pollutant formation and control of nitrogen oxides and greenhouse gas are discussed. Methods that may improve energy efficiency and reduce pollutant emissions from melting operations are also addressed.

Nickel and cobalt silicides have formation and/or stability issues when forming in the presence of Ge. Additions of Ge increase the temperature at which a low resistance CoSi"2 is formed due to phase separation into CoSi"2 and Ge-rich Si-Ge grains. With Ni, additions of Ge decrease the temperature at which NiSi converts to a NiSi"2, lead to agglomeration at a lower temperature and lead to germanosilicide formation. Nickel has a ''must not exceed'' critical temperature that decreases with increasing Ge concentration, and Co has a minimum critical temperature that increases with increasing germanium concentration. Neither silicide is ideal for doped Si-Ge contacts, where the germanium compositions are in excess of 20%. The insertion of a layer of pure Si above the Si-Ge is a promising integration option for forming a robust silicide on Si-Ge substrates. The phase formation and stability of pure Co on Si-20%Ge substrates with Si caps of thickness from 200 to 1000A were studied and it was shown that a 400A Si cap on Si-20%Ge leads to low resistance CoSi"2.

Furan-2-ylmethyl, thien-2-ylmethyl and pyrrol-2-ylmethyl tosylacetates undergo facile decarboxylative Claisen rearrangement upon exposure to N,O-bis(trimethylsilyl)acetamide-potassium acetate to yield the corresponding 2,3-disubstituted heteroaromatic products in good yield. However, for 1-(thien-2-yl)ethyl tosylacetates and substrates derived from 3-(hydroxyalkyl)indoles rearomatisation does not occur.

We have identified a new class of catalysts for the asymmetric reduction of prochiral ketones by borane. Key to the architecture of effective catalysts is an N–PO structural unit which may be part of a phosphinamide, phosphonamide or a related structure. Such catalysts are simple to prepare, are often crystalline solids and may be recovered from reduction reactions and reused. The catalysts act essentially as Lewis bases, serving to increase the reactivity of borane by electron donation. The incorporation of a hydroxy group into the catalyst provides an adjacent Lewis acid site upon reaction with borane and thus affords a superior catalyst capable of asymmetric inductions of up to 92% ee.

Single crystals of magnesium zinc dianti­mony, Mg1.59 (1)Zn1.41 (1)Sb2, were grown by a reaction of elemental Mg, Zn and Sb in an excess of Zn acting as a flux. The compound crystallizes with the trigonal anti-La2O3 type (Pearson code hP5). The structure can be regarded as a substitutional derivative of α-Mg3Sb2 by replacing some of the Mg atoms in the tetra­hedral postion (site symmetry 3m.) with Zn atoms. The other two atoms in the asymmetric unit also occupy special positions, viz. Mg (\overline{3}m.) and Sb (3m.).

In order to probe structure-activity relationships in the epothilone area, two series of epothilone B analogues have been designed and synthesized. The first series containing an oxazole moiety in place of a thiazole on the side chain was constructed by utilizing key intermediates 7–9 or 10, 12, and 13 (Scheme 1), whereas the second series containing an ethano group instead of the gem-dimethyl group at position 4 was synthesized from fragments 42 and 43. A Yamaguchi-type macrolactonization reaction was used to construct the macrocycle from a secoacid, which was assembled, in both cases, by means of a) an aldol reaction, b) an Enders alkylation, and c) a Wittig-type reaction. This convergent strategy provided access to oxazole analogues 2,4,29–32 and 4,4-ethano derivatives 3,40,60–63 for biological studies.

For structure-activity relationship studies, two series of epothilone A (1) analogues have been designed and synthesized, one containing an oxazole moiety instead of the thiazole heterocycle and the other containing a spirocyclopropane moiety in place of the gem-dimethyl group at position C-4 (4,4-ethano-epothilones). The olefin metathesis strategy in solution was utilized for the chemical synthesis of these compounds starting with key building blocks 7–9 for the oxazole series (compounds 2, 14–18, 21–26) and building blocks 8, 30, and 31 for the 4,4-ethano series (compounds 3,39–43, 46–51). The convergent strategy towards the designed epothilone A series involved a) an aldol condensation reaction, b) an esterification reaction, c) an olefin metathesis reaction catalyzed by [RuCl2(=CHPh)-(PCy3)2], and d) epoxidation of the macrocycle double bond.

A study is presented of the optimal crossover duct location and width to obtain consistent branched detonation transition from one detonation tube to another. On a Pulsed Detonation Engine (PDE) with detonation branching, the duct location at which the detonation crosses from one (primary) tube to a branched (secondary) tube impacts the number of successful detonations. In this paper, a comparison is made of the effects of the location and width of the crossover duct for hydrogen, ethylene and an n-alkane. The crossover location is varied from the aft end of the detonation tube to the middle of the detonation tube while the crossover width is varied from 2.5 in to 0.5 in. Detonation wave speeds are measured and compared to Chapman-Jouguet velocities in order to determine successful detonations. Regardless of crossover location, all three fuels are demonstrated 100% of the time to transition between 2 in detonation tubes with a crossover width of 2 in. With a mid-location crossover duct, all three fuels are demonstrated 100% of the time to transition detonations between 2 in detonation tubes with a crossover width between 1.75 in and 2.5 in.

A number of new catalysts for the asymmetric reductions of ketones by borane are described. The highest accelerations are achieved by catalysts in which the phosphinamide (R 2 NPO) unit can adopt a planar geometry. This observation has provided an insight into the mechanism of catalysis.

During a synthesis of 16-desmethylepothilone B new methods for the convergent and highly stereoselective synthesis of epothilone B and analogues were developed.

As part of an on-going lead optimisation effort, a cross screening exercise identified an aryl sulphonyl amide hit that was optimised to afford a highly potent series of ghrelin receptor agonists.

The main objectives of current work were (1) to compare the effects of monophasic or biphasic electrical field stimulation on structure and function of engineered cardiac organoids based on enriched cardiomyocytes (CM) and (2) to determine if electrical field stimulation will enhance electrical excitability of cardiac organoids based on multiple cell types. Organoids resembling cardiac myofibers were cultivated in Matrigel-coated microchannels fabricated of poly(ethylene glycol)-diacrylate. We found that field stimulation using symmetric biphasic square pulses at 2.5 V/cm, 1 Hz, 1 ms (per pulse phase) was an improved stimulation protocol, as compared to no stimulation and stimulation using monophasic square pulses of identical total amplitude and duration (5 V/cm, 1 Hz, 2 ms). This was supported by the highest success rate for synchronous contractions, low excitation threshold, the highest cell density, and the highest expression of Connexin-43 in the biphasic group. Subsequently, enriched CM were seeded on the networks of (1) cardiac fibroblasts (FB), (2) D4T endothelial cells (EC), or (3) a mixture of FB and EC that were precultured for 2 days prior to the addition of enriched CM. Biphasic field stimulation was also effective at improving electrical excitability of these cardiac organoids by improving the three-dimensional organization of the cells, increasing cellular elongation and enhancing Connexin-43 presence.

A series of small molecule orally bioavailable ghrelin receptor agonists have been identified through systematic optimisation of a high throughput screening hit.

Structure and property based drug design was exploited in the synthesis of sulfonamidopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating biaryl P4 groups, producing highly potent inhibitors with encouraging oral pharmacokinetic profiles and significant but sub-optimal anticoagulant activities.

A silyl-modified variant of the Bellus–Claisen rearrangement is described; the generality of this rearrangement has been demonstrated with a range of allylic amines and ketenes.

Structure-based drug design was exploited in the synthesis of 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group with acyclic tertiary amide termini. Optimized hydrophobic contacts of one amide substituent in P4 were complemented by hydrophobicity-modulating features in the second, producing potent fXa inhibitors including examples with excellent anticoagulant properties.

A series of novel, non-basic 3-(6-chloronaphth-2-ylsulfonyl)aminopyrrolidin-2-one-based factor Xa (fXa) inhibitors, incorporating an alanylamide P4 group, was designed and synthesised. Within this series, the N-2-(morpholin-4-yl)-2-oxoethyl derivative 24 was shown to be a potent, selective fXa inhibitor with good anticoagulant activity. Moreover, 24 possessed highly encouraging rat and dog pharmacokinetic profiles with excellent oral bioavailabilities in both species.

The macrolactonization-based strategy for the total synthesis of epothilones has been streamlined and improved to a high level of efficiency and stereoselectivity. This strategy has been applied to the construction of vinyl iodide 19 which served as a common intermediate for the synthesis of a series of natural and designed epothilones including an epothilone B10 (3), epothilone F (5), 16-desmethylepothilone B (14), pyridine epothilones 57 a–57 g, dimeric epothilones 59 and 61, and benzenoid epothilones 63 a–63 g.

The increasing popularity of ring-closing metathesis (RCM) can be attributed to the development of transition metal complexes 1, 2 and 3 as initiators. These compounds efficiently promote the RCM process, are compatible with a wide range of chemical functionalities and can be used without recourse to rigorously controlled reaction conditions. In this chapter, applications of this technology to the preparation of the 16-membered macrolactone core of the epothilones culminating in the total synthesis of epothilones A, B and E will be presented. The preparation of a diverse array of analogs using both solution and solid-phase techniques will also be discussed. The use of the cyclopentadienyl titanium complexes 93 and 110 for olefination/olefin metathesis will also be described, with particular emphasis on their potential in the synthesis of polyether natural products.

A library of epothilone A and B analogues, which was constructed by solid-phase combinatorial synthesis using SMART Microreactors and solution chemistry, was screened in two different tubulin binding assays. Selected compounds were subjected to cytotoxicity studies against a number of cell lines, including Taxol-resistant cells. Important structure–activity relationship emerged from these studies, which sets the stage for further discoveries and developments in the anticancer field.

During a synthesis of 16-desmethylepothilone B new methods for the convergent and highly stereoselective synthesis of epothilone B and analogues were developed.

Excerpt Calcium may be deposited within the cardiac tissue or precipitated directly into the endocardium. Healthy tissue never shows calcium salts deposited. Deposition of the calcium salts in dead...