Bikkavilli Rama Kamesh. / "August 2004." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (p. 212-223) / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

The kinetics and mechanism of the reactions of (tmpa)W-(CO)^ and (tmen)W(CO)^ (tmpa = N,N,N',N'-tetramethy1-1,3-diaminopropane and tmen = N,N,N1,N1-tetramethylethylenediamine) with four phosphorus donor ligands (triisopropyl phosphite, triphenyl phosphite, triphenylphosphine and "constrained phosphite", 4-methyl-2,6,7-trioxa-l-phosphabicylo[2.2.2]octane) in xylene have been investigated in detail. These reactions were found to take place by the ring-opening of the bidentate ligand in a reversible step which leads to the formation of a five-coordinate intermediate of the type [(h^-tmpa)W(CO)or [(h^-tmen)W(CO). The intermediate then reacts with one molecule of phosphorus ligand, L, to form a six-coordinate intermediate, which can either expel the bidentate ligand and react with another molecule of L leading to the formation of a new disubstituted tungsten tetracarbonyl or go through a ring-reclosure step to form a seven-coordinate activated com-2 2plex or intermediate of the type [(h -tmpa)W(CO)^(L)] or [(h - tmen)W(CO)^(L)] which then regenerates the substrate through the expulstion of the L molecule. This mechanism is consistent with the observed rate behavior in these systems. For the reaction of (tmpa)W(CO)^ with the "constrained phosphite", an intermediate of the type [(h1-tmpa)W(CO)4P(OCH2)3CCH3] was isolated and identified.

Accumulating evidence has indicated that microbial infection could intensify allergic responses. Previous findings demonstrated that eosinophil activation could be elicited by bacterial and viral conserved molecular pattern through TLR. Recently, two cytoplasmic pattern recognition receptors, NLR protein NOD1 and NOD2, have been discovered and the important roles in innate immunity have been elucidated. Eosinophils alone have little responses upon the stimulation with ligands of NOD1 and NOD2. Since airway eosinophils increase in more numbers of asthmatic patients compared to control subjects, we investigated the co-culture system of eosinophils and human bronchial epithelial cells to illustrate the potential immunopathological roles of NOD1 and NOD2 in asthma processes. In the co-culture system, NOD1 ligand gamma-D-Glu-mDAP (iE-DAP) and NOD2 ligand muramyl dipeptide (MDP) could upregulate cell surface expression of CD1 8 and ICAM-1 on eosinophils and ICAM-1 and vascular cell adhesion molecule-1 (VCAM-1) on bronchial epithelial cells, as well as induce chemokines CCL2 and CXCL8 release. These findings therefore imply the direct interaction and activation between the two cells upon NOD1 and NOD2 ligand stimulation. / Allergic diseases are prevalent and their incidences have been increasing worldwide. Eosinophils are the principal effector cells for the late phase response in allergic inflammation. The infiltration of eosinophils together with other inflammatory cells at the local inflammatory sites is the major characteristic in allergic inflammation. However, the detailed innnunopathological responses and mechanisms of the activation of eosinophils in allergic inflammation are not well defined. In the present study, we investigated and attempted to elucidate the mechanisms of eosinophil activation induced by various stimuli, including thymic stromal lymphopoietin (TSLP), the novel interleukin (IL)-12 family cytokine IL-27, and ligands of nucleotide-binding oligomerization domain (NOD) like receptor (NLR) protein NOD1 and NOD2 upon interaction with bronchial epithelial cells. / In conclusion, the above findings demonstrated that eosinophils could be potently activated by diverse stimuli and regulated by multiple intracellular regulatory mechanisms. The elucidation of eosinophil activation may offer new therapeutic stategies and clues for the treatment of allergic diseases. / Recently, the novel IL-12 family member IL-27 was found to regulate immune responses, exerting either stimulation or suppression effects. We found that eosinophils constitutively expressed IL-27 receptor heterodimer, gp130 and WSX-1. IL-27 could prolong eosinophil survival by reducing apoptosis, modulate the expression of adhesion molecules to facilitate eosinophil adhesion and accumulation, and induce the release of proinflammatory cytokines IL-6, tumor necrosis factor (TNF)-aalpha IL-1beta and chemokines CCL2, CXCL8 and CXCL1. The stimulatory effects of IL-27 on eosinophils could not be abrogated by IL-25, hematopoietic cytokine granulocyte-macrophage colony stimulating factor (GM-CSF) and toll-like receptor (TLR) 4 ligand lipopolysaccharide (LPS). These findings were different from the effects of IL-27 and LPS on monocytes. Intracellular signaling mechanistic studies showed that IL-27-mediated eosinophil activation was differentially regulated by MAPKs and NF-kappaB. Based on the above results, IL-27 could play crucial roles in allergic diseases by the activation of eosinophils via differential intracellular signaling cascades. However, IL-27 has been shown to suppress allergic diseases in mouse models. According to our findings of its activating effects on human eosinophils, IL-27 may play pleiotropic roles in human allergic responses. / TSLP is a novel IL-7-like cytokine highly expressed by bronchial epithelial cells and skin keratinocytes in allergic diseases. TSLP acts as a master switch for allergic inflammation through the activation of dendritic cells and mast cells for initiating inflammatory Th2 responses. To elucidate the immunological cascades of epithelium/keatinocyte-eosinophil mediated allergic inflammation, we examined the modulating effects of TSLP on human eosinophils. We observed that human eosinophils constitutively expressed TSLP receptor complex comprising TSLP-binding chain TSLPR and IL-7Ralpha chain. TSLP could significantly delay eosinophil apoptosis, up-regulate the cell surface expression of adhesion molecule CD18 and intercellular adhesion molecule-1 (ICAM-1) but down-regulate L-selectin, enhance eosinophil adhesion to fibronectin, and induce the release of inflammatory cytokine 1L-6 and chemokines CXCL8, CXCL1 and CCL2. All these effects were concentration-dependent and TSLP-specific. TSLP regulated the above effects through the activation of extracellular signal-regulated protein kinase (ERK), p38 mitogen activated protein kinase (MAPK) and nuclear factor (NF)-kappaB signaling pathway, but not signal transducer and activator of transcription (STAT)-5 and STAT-3 which were usually activated in other effector cells upon TSLP stimulation. Collectively, the above findings elucidated the pro-allergic mechanisms of TSLP via the activation of distinct intracellular signaling pathways in eosinophils. / Hu, Shuiqing. / Adviser: Wong Chin Kwok. / Source: Dissertation Abstracts International, Volume: 72-04, Section: B, page: . / Thesis (Ph.D.)--Chinese University of Hong Kong, 2010. / Includes bibliographical references (leaves 176-216). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.

L'accroissement des connaissances, structurales et fonctionnelles, des protéines nous donne désormais une vision plus précise des phénomènes d'interaction. L'utilisation de ces informations pour le développement de ligands permettrait d'obtenir de nouveaux composés, capables d'interagir avec diverses cibles d'intérêt, et d'améliorer notre compréhension de ces interactions. Ce travail présente le développement d'une nouvelle méthode de conception de ligands protéiques, laquelle repose sur le transfert d'un groupe de résidus, appartenant à un ligand connu et contribuant de façon importante à la liaison avec une cible d'intérêt, sur une protéine hôte, de moins de 100 résidus (mini-protéines). L'identification de protéines hôtes, aptes à reproduire l'interaction après transfert du motif, est réalisée de manière systématique à partir des structures présentes dans la PDB. L'approche a été appliquée pour le développement de ligands du canal Kv1.2, à partir de connaissances structurales et fonctionnelles de l'interaction de ce même canal avec la toxine BgK. Trois ligands, possédant des constantes d'inhibition micro molaires, ont été ainsi conçus. Ces résultats démontrent la possibilité de mettre en application une méthode de conception de ligands, basée sur le transfert de motifs de « hotspots », sur une plateforme structurale de nature protéique, dont les aspects stérique et électrostatique sont compatibles avec une interaction donnée.

La thèse présente de nouvelles stratégies dans la chimie métallo-supramoléculaire en utilisant, (1) des nouveaux précurseurs de cuivre (II) avec des positions basales accessibles, qui peuvent favoriser l'échange magnétique, et qui présentent aussi des sphères de coordinations flexibles pour l'obtention des matériaux magnétiques et photo magnétiques; (2) des ligands cyano-bisphosphonates pour l'obtention de réseaux étendus en utilisant la stratégie building-block; (3) des ligands tris-phosphonato-triazine pour l'obtention des complexes avec des centres paramagnétiques Cu(II), Mn(II) et Co(II) en utilisant des fragments M(hfac)2 (hfac = hexafluoro-acétylacétonate). Des nouveaux clusters hétérométalliques ont été obtenus en utilisant comme building-block [Co(CN)6]3-[Cr(CN)6]3-,[Mo(CN)8]4-, [W(CN)8]4- et précurseurs de cuivre (II), synthétisés à partir d'une base de Schiff tridentate qui peut permettre l'accès du connecteur dans le plan basal. Nous présenterons dans la thèse les résultats obtenus avec le ligand 1-Cyanométhylène-bis(5,5-diméthyl-2-oxo-1,3,2-dioxaphosphorinane ). Une série de complexes homométalliques a été synthétisée et caractérisée à l'état solide par diffraction des rayons X sur monocristal. La réaction de ces unités de construction avec un deuxième centre métallique conduit à des systèmes supramoléculaires étendus.

Thesis (Ph. D.)--University of Missouri--Columbia, 2001. / Typescript. Vita. Includes bibliographical references (leaves 228-272). Also available on the Internet.

This thesis details the synthesis and coordination chemistry of twenty-five nitrogencontaining heterocyclic ligands, nineteen of which were previously unreported compounds. These ligands were designed for use as synthons for the formation of molecular cages, so contain multiple coordination sites capable of bridging multiple metal atoms. The majority of molecular cages in the literature are formed by rigid bridging ligands, whereas the ligands studied in this research incorporate a higher level of flexibility, thereby lessening the degree of control over the self-assembly process and increasing the number of possible structures that can be formed upon reaction of these ligands with meal salts. Three of the new ligands synthesised were two-armed bridging ligands, which were reacted with a wide variety of metal salts to investigate what self-assembly products were formed. The complexes characterised include a M₃L₃ cyclic trimer, a range of coordination polymers of varying dimensionality, a range of dimeric products and a series of M₄L₆ cage-like molecular squares. However, the majority of ligands studied were three-armed, potentially tripodal compounds, which were envisaged as potential components of M₃L₂ or M₆L₄ molecular cages. The products of self-assembly of these ligands with various metals salts were shown to include a variety of discrete tri- and tetranuclear complexes, a range of coordination polymers of varying dimensionality and interpenetration, and a complex M₆L₄ assembly that appears to be a collapsed coordination cage. Unfortunately some of the ligands synthesised were shown to decompose in the presence of various metal salts, a phenomenon already identified in the literature. Analogues of these decomposition products were synthesised deliberately to identify the potential of a known tridentate ligand as a metallosupramolecular synthon. ¹H NMR spectroscopy, mass spectrometry, elemental analysis, thermogravimetric analysis and X-ray crystallography were used to study the compounds synthesised. The crystal structures of five ligands and fifty-one complexes are discussed.

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N,N&rsquo / -bis(ferrocenylmethylene)ethylenediamine was prepared from the reaction of ferrocenecarboxaldehyde and ethylenediamine and characterized by IR, Raman, 1H and 13C-NMR spectroscopy. The electrochemical behaviour of this ligand was also studied for the first time by cyclic voltammetry. Diferrocenyl diimine ligand was used in the thermal substitution of 1,5-cyclooctadiene in Cr(CO)4(2:2-1,5-cyclooctadiene) at 38&deg / C in toluene for two hours to form the tetracarbonyl[N,N&rsquo / -bis(ferrocenylmethylene)ethylenediamine]chromium(0), [Cr(CO)4(BFEDA)]. This complex was succesfully isolated and crystallized from its 1:1 toluene/dichloromethane solution and characterized by elemental analysis, MS, IR, 1H, 13C-NMR spectroscopy. Electrochemical behaviour of the complex was also studied by cyclic voltammetry and the mechanism of electrode reaction was investigated by in-situ UV-VIS and IR spectroscopy measurements. This new complex has the iron atom of ferrocene unit in conjugation with the chromium metal center and, therefore, shows an electronic communication between two metal atoms.