Chemotherapeutic agents. XII [1]. Synthesis of Pyrimidines and Fused Pyrimidines as leishmanicides and herbicides

Various bicyclic ( 2 , 3 ) and tricyclic ( 4 , 5 ) heterocycles were prepared by the reaction of 1a , c with dihaloalkanes and polynitrohalobenzene separately. Electrophilic substitution on 1a–c with different alkyl halides yielded mono and dialkyl pyrimidiens ( 6–20 ). Nucleophilic substitution reactions on 18 and 21 with amine and hydrazine separately yielded 22–31 , 21a , b and 41c . Reaction of 25a with ethyl ethoxymethylenecyanoacetate and chloroacetyl chloride separately provided bicyclic compounds 32 and 33 . Condensation-cyclization of 25a with formic, acetic and nitrous acid separately yielded 34a , b and 35 . Reaction of 26a with ethylthiocylycolate and thiourea separately provided 36a and 39 . The latter was alkylated with methyl iodide to 40 . An attempt to cyclize 29a and 30a with thionyl chloride provided bicyclic compounds 37a , b and an uncyclic product 38 . Some of the compounds were screened for leishmanicidal and herbicidal activities and a few of them exhibited significant activity. Leishmaniasis is considered to be one of the most devastating diseases and is ominous to tropical countries. The high toxicity of leishmanicidal drugs in current use, aroused considerable interest to develop new safer and effective chemotherapeutic agents. The only drug pyrimethamine [2] is the representative of pyrimidine derivatives, known as leishmanicides but low order of activity at high dose failed to retain in the clinic. Based on our past experiences in rational designing of leishmanicidal pyrimidine analogs, incorporation of levamisole pharmacophore either in flexible or rigid forms is indispensable for potential activity [1,3] against visceral leishmaniasis. These observations induced an impetus to synthesize pyrimidine analogs as potential leishmanicides.     

The effect of microencapsulated phase change materials on the rheology of geopolymer and Portland cement mortars

The effect of microencapsulated phase-change materials (MPCM) on the rheological properties of pre-set geopolymer and Portland cement mortars was examined. Microcapsules with hydrophilic and hydrophobic shells were compared. The shear rate dependency of the viscosities fitted well to a double Carreau model. The zero shear viscosities are higher for geopolymer mortar, illustrating poorer workability. The time evolution of the viscosities was explored at shear rates of 1 and 10 s⁻¹. New empirical equations were developed to quantify the time-dependent viscosity changes. The highest shear rate disrupted the buildup of the mortar structures much more than the lower shear rate. Microcapsules with a hydrophobic shell affect the rheological properties much less than the microcapsules with a hydrophilic shell, due to the higher water adsorption onto the hydrophilic microcapsules. Shear forces was found to break down the initial structures within geopolymer mortars more easily than for Portland cement mortars, while the geopolymer reaction products are able to withstand shear forces better than Portland cement hydration products. Initially, the viscosity of geopolymer mortars increases relatively slowly during due to formation of geopolymer precursors; at longer times, there is a steeper viscosity rise caused by the development of a 3D-geopolymer network. Disruption of agglomerates causes the viscosities of portland cement mortars to decrease during the first few minutes, after which the hydration process (increasing viscosities) competes with shear-induced disruption of the structures (decreasing viscosities), resulting in a complex viscosity behavior.     

Consolidation of advanced composites having volatile generation

Processing polyimide-based thermosetting matrix composites is complicated because of gaseous volatiles produced during the polymerization and crosslinking reactions. This process involves complex interactions between part geometry, temperature and force cycles, and matrix/fiber properties. A simple model for the consolidation process that treats these composites as a three-phase system consisting of fiber, resin, and volatile has been developed. This model has been applied to compression molding process for constant thickness laminates and the predictions agree well with experiments. Further extension to handle three-dimensional parts and the required numerical techniques have also been developed.     

Design of vessels subjected to external pressure

An analytical procedure, developed to simulate the graphic method for the design of vessels subjected to external pressure or vacuum, suggested by the ASME Code, Section VIII, Division 1, is presented in this contribution. A comprehensive computer program based on this method is also presented. The program also covers the design of stiffener rings. The procedure can be easily extended to include other international standards such as the British and German codes, since the method is based on the concept of the number of lobes at collapse. The method produced reproducible results over the entire range of L/D₀ and D₀/t ratios of the code. The deviation observed at any point in this range is less than 0.5% for factor A. The variation in allowable pressure is less than 2%.     

Mining the Wheat Grain Proteome

Bread wheat is the most widely cultivated crop worldwide, used in the production of food products and a feed source for animals. Selection tools that can be applied early in the breeding cycle are needed to accelerate genetic gain for increased wheat production while maintaining or improving grain quality if demand from human population growth is to be fulfilled. Proteomics screening assays of wheat flour can assist breeders to select the best performing breeding lines and discard the worst lines. In this study, we optimised a robust LC–MS shotgun quantitative proteomics method to screen thousands of wheat genotypes. Using 6 cultivars and 4 replicates, we tested 3 resuspension ratios (50, 25, and 17 µL/mg), 2 extraction buffers (with urea or guanidine-hydrochloride), 3 sets of proteases (chymotrypsin, Glu-C, and trypsin/Lys-C), and multiple LC settings. Protein identifications by LC–MS/MS were used to select the best parameters. A total 8738 wheat proteins were identified. The best method was validated on an independent set of 96 cultivars and peptides quantities were normalised using sample weights, an internal standard, and quality controls. Data mining tools found particularly useful to explore the flour proteome are presented (UniProt Retrieve/ID mapping tool, KEGG, AgriGO, REVIGO, and Pathway Tools).     

Antimicrobial resistance and phage and molecular typing of Salmonella strains isolated from food for human consumption in Spain

The aims of this study were to ascertain the population structure and antimicrobial susceptibility of Salmonella enterica serovars isolated in 2002 from food in 16 Spanish regions. Serovars were characterized by serotyping, phage typing, antimicrobial susceptibility, and pulsed-field gel electrophoresis (PFGE) typing, and 264 nonrelated strains were selected for further analysis. The main sources were eggs and their derivatives (21.6% of strains), poultry and related products (16.6%), and seafood (16.3%). High serotype diversity was detected (51 serotypes); the most common were Enteritidis (n = 96, 36.3%) and Typhimurium (n = 53, 20.1%), followed by a miscellaneous group of 49 different serotypes (n = 115, 43.5%). A 15% increase in Salmonella Enteritidis isolation was observed. Common phage types for Salmonella Enteritidis were PT1 (41.6% of isolates), PT4 (9.4%), PT6 (9.4%), and PT6a (9.4%), and common types for Salmonella Typhimurium were DTU302 (18.8%), DT104 (15.1%), and DT104B (13.2%). Salmonella Enteritidis strains were categorized into eight PFGE types with a similarity of 81 to 96%, and 73.9% of the strains were grouped into just one cluster. Salmonella Typhimurium isolates were divided into 13 PFGE types with a similarity of 64 to 86%, and one predominant clone contained 41.5% of the strains. Resistance rates for Salmonella Enteritidis, Salmonella Typhimurium, and the miscellaneous group were, respectively, 8.3, 69.8, and 13.9% for ampicillin, 3.1, 52.8, and 59% for streptomycin, 40.6, 22.6, and 10.4% for nalidixic acid, 15.6, 71.7, and 31.1% for tetracycline, 7.3, 18.8, and 9.5% for trimethoprim-sulfamethoxazole, 0, 50.9, and 4.3% for chloramphenicol, and 6.2, 71.7, and 17.4% for multiple (at least four) antimicrobials. All the strains remained susceptible to other beta-lactams and fluoroquinolones. Surveillance of S. enterica isolated from food is strongly recommended to reduce community exposure to antimicrobial resistant strains.     

Effects of dietary supplements of zinc-methionine on milk production,udder health and zinc metabolism in dairy goats

Twenty-two Murciano-Granadina dairy goats were used to investigate the effects of organic Zn supplementation of a diet containing a high level of inorganic Zn. Goats were kept in pens, machine milked once a day throughout lactation and fed a diet based on a dehydrated mixture of whole-plant maize and alfalfa ad libitum, alfalfa pellets, barley grain and a concentrate mixture. Treatments were: (1) control, and (2) supplemented with 1 g/d Zn-Methionine (Zn-Met) included in the concentrate mixture. After parturition, goats were blocked in week 3 and dietary treatments were applied until week 23. From weeks 3-20, feed intake, milk yield, milk composition, milk somatic cell count (SCC), and udder health were measured. In week 21, all goats were injected intraperitoneally with 1 g/d DL-methionine for 5 d to establish the effects of methionine under the conditions of udder stress induced by hand milking on the second day. During weeks 22 and 23, diet digestibility, and N and Zn balance were determined. Dry matter intake, milk yield, and milk contents of total solids, fat, total and true protein, and casein did not differ between treatments, but whey protein and non-protein nitrogen contents were significantly lower for the Zn-Met group. Milk SCC tended to decrease as a result of Zn-Met supplementation but differences between treatments were not significant when halves with persistent infection were excluded. Hand milking increased SCC in both groups, but udders of supplemented goats showed a lower reaction. Apparent absorption of N significantly increased and Zn retention tended to increase in Zn-Met supplemented goats. We conclude that Zn-Met supplementation can enhance resistance to udder stress in dairy goats. Effects were attributed to the organic Zn and not to the methionine component. Zn retention and protein utilization were also improved by the Zn-Met supplement.     

Selective synthesis of alcohols from syngas and hydroformylation of ethylene over supported cluster-derived cobalt catalysts

Hydroformylation of ethylene and CO hydrogenation were studied over cobalt-based catalysts derived from reaction of Co₂(CO)₈ with ZnO, MgO and La₂O₃ supports. At 433 K a similar activity sequence was reached for both reactions: Co/ ZnO > Co/La₂O₃ > Co/MgO. This confirms the deep analogy between hydroformylation and CO hydrogenation into alcohols. In the CO hydrogenation the selectivity towards alcohol mixture (C₁-C₃) was found to be near 100% at 433 K for a conversion of 6% over the Co/ZnO catalyst; this catalyst showed oxo selectivity higher than 98% in the hydroformylation of ethylene. Magnetic experiments showed that no metallic cobalt particles were formed at 433 K. It is suggested that the active site for the step that is common to both reactions is related to the surface homonuclear Co²⁺/[Co(CO)₄]^– ion-pairing species.     

Improved energy recovery from dark fermented cane molasses using microbial fuel cells

A major limitation associated with fermentative hydrogen production is the low substrate conversion efficiency. This limitation can be overcome by integrating the process with a microbial fuel cell (MFC) which converts the residual energy of the substrate to electricity. Studies were carried out to check the feasibility of this integration. Biohydrogen was produced from the fermentation of cane molasses in both batch and continuous modes. A maximum yield of about 8.23 mol H₂/kg COD_removed was observed in the batch process compared to 11.6 mol H₂/kg COD_removed in the continuous process. The spent fermentation media was then used as a substrate in an MFC for electricity generation. The MFC parameters such as the initial anolyte pH, the substrate concentration and the effect of pre-treatment were studied and optimized to maximize coulombic efficiency. Reductions in COD and total carbohydrates were about 85% and 88% respectively. A power output of 3.02 W/m³ was obtained with an anolyte pH of 7.5 using alkali pre-treated spent media. The results show that integrating a MFC with dark fermentation is a promising way to utilize the substrate energy.     

Low-Temperature Sintering of La(Ca)CrO3 Powder Prepared through the Combustion Process

Ultrafine La(Ca)CrO₃ (LCC) powder was prepared through the glycine–nitrate gel combustion process. It was shown for the first time that the use of relatively inexpensive CrO₃ as a starting material for chromium has potential for the bulk preparation of sinter-active LCC powder. As-prepared powder, when calcined at 700°C, resulted in LCC along with a small amount of CaCrO₄. The calcined powder was found to be composed of soft agglomerates with a particle size of ≈70–290 nm. The cold pressing and sintering of the calcined powder at 1200°C resulted in the mono-phasic La_0.7Ca_0.3CrO₃ with density ≈98% of its theoretical value. This is the lowest sintering temperature ever reported for La_0.7Ca_0.3CrO₃. The conductivity of the sintered La_0.7Ca_0.3CrO₃ at 1000°C was found to be ≈57 S/cm in air. The sintering and electrical behavior achieved for La_0.7Ca_0.3CrO₃ may find application as an interconnect material for high-temperature solid oxide fuel cells if problems with chemical expansion and poor conductivity in fuel can be overcome.