Coordination networks of Cu2+ ions with 1,3-bis[2-(4-pyridyl)ethyl]benzene : strong structure-directing role of the counter ion (nitrate, acetate and sulphate), leading to clusters, sheets and chains

Date of Acceptance: 16/10/2015

New methods for the asymmetric synthesis of α-alkylated ketones and 1,3-amino alcohols

A large number of optically active drugs and natural products contain α-functionalised ketones or simple derivatives thereof. Furthermore, chiral α-alkylated ketones are useful synthons and have found widespread use in total synthesis. The asymmetric alkylation of ketones represents one of the most powerful and longstanding procedures in organic chemistry. Surprisingly, however, only one effective methodology is available, and this involves the use of chiral auxiliaries. This is discussed in Chapter 1, which also provides a background of other key topics discussed throughout the thesis. Expanding on the existing methodology of chiral auxiliaries, Chapter 2 details the synthesis of a novel chiral auxiliary containing a pyrrolidine ring and its use in the asymmetric preparation of α-alkylated ketones with good enantioselectivity. The synthesis of racemic α-alkylated ketones as reference standards for GC chromatography is also reported in this chapter. Chapter 3 details a new approach to chiral α-alkylated ketones using an intermolecular chirality transfer methodology. This approach employs the use of simple non-chiral dimethylhydrazones and their asymmetric alkylation using the chiral diamine ligands, (+)- and (-)-sparteine. The methodology described represents the first example of an asymmetric alkylation of non-chiral azaenolates. Enantiomeric ratios up to 83 : 17 are observed. Chapter 4 introduces the first aldol-Tishchenko reaction of an imine derivative for the preparation of 1,3-aminoalcohol precursors. 1,3-Aminoalcohols can be synthesised via indirect routes involving various permutations of stepwise construction with asymmetric induction. Our approach offers an alternative highly diastereomeric route to the synthesis of this important moiety utilising N-tert-butanesulfinyl imines in an aldol-Tishchenko-type reaction. Chapter 5 details the experimental procedures for all of the above work. Chapter 6 discusses the results of a separate research project undertaken during this PhD. 2-alkyl-quinolin-4-ones and their N-substituted derivatives have several important biological functions such as the role of Pseudomonas quinolone signal (PQS) in quorum sensing. Herein, we report the synthesis of its biological precursor, 2-heptyl-4-hydroxy-quinoline (HHQ) and possible isosteres of PQS; the C-3 Cl, Br and I analogues. N-Methylation of the iodide was also feasible and the usefulness of this compound showcased in Pd-catalysed cross-coupling reactions, thus allowing access to a diverse set of biologically important molecules.

Annotated record of the detailed examination of Mn deposits from DSDP Site 41, Leg 5 (Cores 5-41-1, 5-41-5)

Site 41 marks the transition from the North Pacific gyral to the Equatorial Current System. The JOIDES Pacific Advisory Panel selected a site at this latitude along the longitudinal profile of 140°W in order to obtain information on the history of migrations of these current systems.

Novel free fatty acid receptor 1 (GPR40) agonists based on 1,3,4-thiadiazole-2-carboxamide scaffold

Free fatty acid receptor 1 (FFA1), previously known as GPR40 is a G protein-coupled receptor and a new target for treatment of type 2 diabetes. Two series of FFA1 agonists utilizing a 1,3,4-thiadiazole-2-caboxamide scaffold were synthetized. Both series offered significant improvement of the potency compared to the previously described 1,3,4-thiadiazole-based FFA1 agonists and high selectivity for FFA1. Molecular docking predicts new aromatic interactions with the receptor that improve agonist potency. The most potent compounds from both series were profiled for in vitro ADME properties (plasma and metabolic stability, LogD, plasma protein binding, hERG binding and CYP inhibition). One series suffered very rapid degradation in plasma and in presence of mouse liver microsomes. However, the other series delivered a lead compound that displayed a reasonable ADME profile together with the improved FFA1 potency.

Preparation and characterization of Pr0.6Sr0.4FeO3-δ-Ce0.9Pr0.1O2-δ nanofiber structured composite cathode for IT-SOFCs

In this work, Pr_0.6Sr_0.4FeO_3-δ -Ce_0.9Pr_0.1O_2-δ (PSFO-CPO) nanofibers were synthesized by a one-step electrospin technique for use in intermediate-temperature solid oxide fuel cell (IT-SOFC) applications. PSFO-CPO nanofibers were produced with a diameter of about 100nm and lengths exceeding tens of microns. The thermal expansion coefficient (TEC) matches with standard GDC electrolytes and the resulting conductivity also satisfies the needs of IT-SOFCs cathodes. EIS analysis of the nanofiber structured electrode gives a polarization resistance of 0.072Ωcm² at 800°C, smaller than that from the powdered cathode with the same composition. The excellent electrochemical performance can be attributed to the well-constructed microstructure of the nanofiber structured cathode, which promotes surface oxygen diffusion and charge transfer processes. All the results imply that the one-step electrospin method is a facile and practical way of improving the cathode properties and that PSFO-CPO is a promising cathode material for IT-SOFCs.

Synthesis of Pr0.6Sr0.4FeO 3-δ -xCe0.9Pr0.1O 2-δ cobalt-free composite cathodes by a one-pot method for intermediate-temperature solid oxide fuel cells

Cobalt-free composite cathodes consisting of Pr_0.6Sr_0.4FeO _3-δ -xCe_0.9Pr_0.1O _2-δ (PSFO-xCPO, x = 0-50 wt%) have been synthesized using a one-pot method. X-ray diffraction, scanning electron microscopy, thermal expansion coefficient, conductivity, and polarization resistance (R _P ) have been used to characterize the PSFO-xCPO cathodes. Furthermore the discharge performance of the Ni-SSZ/SSZ/GDC/PSFO-xCPO cells has been measured. The experimental results indicate that the PSFO-xCPO composite materials fully consist of PSFO and CPO phases and posses a porous microstructure. The conductivity of PSFO-xCPO decreases with the increase of CPO content, but R _P of PSFO-40CPO shows the smallest value amongst all the samples. The power density of single cells with a PSFO-40CPO composite cathode is significantly improved compared with that of the PSFO cathode, exhibiting 0.43, 0.75, 1.08 and 1.30 W cm^-2 at 650, 700, 750 and 800 °C, respectively. In addition, single cells with the PSFO-40CPO composite cathode show a stable performance with no obvious degradation over 100 h when operating at 750 °C.

Energy transfer rates and population inversion investigation of sup(1)Gsub(4) and sup(1)Dsub(2) excited states of Tmsup(3+) in Yb:Tm:Nd:KYsub(3)Fsub(10) crystals

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Exploring associations between violent discipline and aggressive behavior in children ages 4-5 in The Republic of Nicaragua: A secondary data analysis of the 2011 Demographic and Health Survey

Thesis (Master's)--University of Washington, 2016-06

6-(4-Aminophenyl)-4,5-dihydro-3(2H)-pyridazinone - An important chemical moiety for development of cardioactive agents: A review

6-(4-Aminophenyl)-4,5-dihydro-3(2H)-pyridazinone moiety is a vital structural part of many cardio-active pyridazinone derivatives which are either in clinical use or have been tested in clinical trials. These include imazodan, CI-930, pimobendan, indolidan, levosimendan, SK&F-93741, Y-590, meribendan, NSP-804, NSP-805, bemoradan, senazodan, amipizone, prinoxodan, SKF 95654, siguazodan and KF 15232. This article briefly reviews relevant literature on various reports on the synthesis and use of this moiety for development of cardio-active agents

Lack of Galectin-3 Disturbs Mesenteric Lymph Node Homeostasis and B Cell Niches in the Course of Schistosoma mansoni Infection

Galectin-3 is a beta-galactoside-binding protein that has been shown to regulate pathophysiological processes, including cellular activation, differentiation and apoptosis. Recently, we showed that galectin-3 acts as a potent inhibitor of B cell differentiation into plasma cells. Here, we have investigated whether galectin-3 interferes with the lymphoid organization of B cell compartments in mesenteric lymph nodes (MLNs) during chronic schistosomiasis, using WT and galectin-3(-/-) mice. Schistosoma mansoni synthesizes GalNAc beta 1-4(Fuc alpha 1-3) GlcNAc(Lac-DiNAc) structures (N-acetylgalactosamine beta 1-4 N-acetylglucosamine), which are known to interact with galectin-3 and elicit an intense humoral response. Antigens derived from the eggs and adult worms are continuously drained to MLNs and induce a polyclonal B cell activation. In the present work, we observed that chronically-infected galectin-3(-/-) mice exhibited a significant reduced amount of macrophages and B lymphocytes followed by drastic histological changes in B lymphocyte and plasma cell niches in the MLNs. The lack of galectin-3 favored an increase in the lymphoid follicle number, but made follicular cells more susceptible to apoptotic stimuli. There were an excessive quantity of apoptotic bodies, higher number of annexin V(+)/PI(-) cells, and reduced clearance of follicular apoptotic cells in the course of schistosomiasis. Here, we observed that galectin-3 was expressed in nonlymphoid follicular cells and its absence was associated with severe damage to tissue architecture. Thus, we convey new information on the role of galectin-3 in regulation of histological events associated with B lymphocyte and plasma cell niches, apoptosis, phagocytosis and cell cycle properties in the MLNs of mice challenged with S. mansoni.

Requirement for PLC gamma 2 in IL-3 and GM-CSF-Stimulated MEK/ERK Phosphorylation in Murine and Human Hematopoietic Stem/Progenitor Cells

Even though the involvement of intracellular Ca(2+) (Ca(i)(2+)) in hematopoiesis has been previously demonstrated, the relationship between Ca(i)(2+) signaling and cytokine-induced intracellular pathways remains poorly understood. Herein, the molecular mechanisms integrating Ca(2+) signaling with the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in primary murine and human hematopoietic stem/progenitor cells stimulated by IL-3 and GM-CSF were studied. Our results demonstrated that IL-3 and GM-CSF stimulation induced increased inositol 1,4,5-trisphosphate (IP(3)) levels and Ca(i)(2+) release in murine and human hematopoietic stem/ progenitor cells. In addition, Ca(i)(2+) signaling inhibitors, such as inositol 1,4,5-trisphosphate receptor antagonist (2-APB), PKC inhibitor (GF109203), and CaMKII inhibitor (KN-62), blocked phosphorylation of MEK activated by IL-3 and GM-CSF, suggesting the participation of Ca(2+)-dependent kinases in MEK activation. In addition, we identify phospholipase C gamma 2 (PLC gamma 2) as a PLC gamma responsible for the induction of Ca(2+) release by IL-3 and GM-CSF in hematopoietic stem/progenitor cells. Furthermore, the PLCg inhibitor U73122 significantly reduced the numbers of granulocyte-macrophage colony-forming units after cytokine stimulation. Similar results were obtained in both murine and human hematopoietic stem/progenitor cells. Taken together, these data indicate a role for PLC gamma 2 and Ca(2+) signaling through the modulation of MEK in both murine and human hematopoietic stem/ progenitor cells. J. Cell. Physiol. 226: 1780-1792, 2011. (C) 2010 Wiley-Liss, Inc.