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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Synthesis, characterisation and reactivity studies of novel strained [n]carbametallocenophanes (n = 2,3) containing cobalt and nickel

Baljak, Sladjana January 2013 (has links)
The synthesis and characterisation of novel [2]dicarbacobaltocenophanes is described and their thermal reactivity studied, which led to unexpected reactivity, including C-C bond cleavage, disproportion and dimerisation. Additionally, chiral polyelectolytes were obtained, when the poly(cobaltocenoethylene) (PCE) was oxidised in the presence of chiral amino-acid based surfactants. The synthesised oligopolycobaltocene, which was formed by the ring-opening polymerisation (ROP) also exhibited chiral propel1ies in the oxidised state when chiral surfactants were chosen as counter anions. The first strained [3 ]tricarbanickelocenophane, with a flexible hydrocarbon-bridge was obtained via the 'fly-trap' method. Its detailed charactelisation is reported. Moreover, the reactivity of the [3]tricarbanickelocenophane towards NHCs as well as P- and N-donor ligands was studied . High-molecular weight cyclic polymers were obtained from the reaction of [3]tricarbanickelocenophane in pyridine, while the reaclion of the monomer and NaCp in different ratios afforded both cyclic and linear oligomers, respectively. Additionally, a cross-linked nickel-containing polymer was formed when the [3]tricarbanickelocenphane was heated to 80 DC in the absence of solvent. The pyrolysis of this material afforded magnetic ceramics, which were subject to fUl1her study . Furthermore the thermal reactivity of the cyclohexylsubstituted [2]dicarba ferrocenophane and the potential photolytic initiated ROP of [1 ]stalU1aferrocenophane have been explored.
2

ASR in the presocratics and Plato

Bargrave-Weaver, Derek January 1956 (has links)
I intend in this dissertation to enquire into the ideas held by the Pre-Socratics and Plato about the nature and properties of the substances that we now call 'gases' - a word invented by van Helmont (1577 1644), a pioneer of modern chemistry, who was the first man to recognise the nature of gases other than air. Before his time, and indeed for some time after, man had no idea of what gases really are, and what gives them their properties. !et the Greeks did realise that there are certain things that, although they are invisible and intangible, and therefore fail to pass two of the typical tests for reality used by the early 'scientists', are, nevertheless, real substances. ~Nb.at led to this discovery, how did they interpret it, and how far was that interpretation in accord with modern theory? These are the questions that i hope to answer.
3

Customising lactacystins : studies towards the total synthesis of lactacystin and its analogues

Horton, Alexandra January 2015 (has links)
This thesis consists of four chapters. The first contains a literature review of the isolation, previous total syntheses, biological activity and structure activity relationships of lactacystin and its analogues. Chapter two discusses our work towards the total synthesis of lactacystin and its analogues starting from three different amino acids. Chapter three contains the experimental details of our work, and the final chapter contains the details of our work on the biological testing of some of our advanced intermediates towards deoxylactacystin. Our synthetic approach towards lactacystin and its analogues starts from a simple amino acid derivative; using different amino acid derivatives as starting material, the C5 position is easily altered. The starting material is then advanced to a suitable diester for Dieckmann cyclization to form the lactam core found in the natural product. The next key step in our approach follows Mander’s acylation protocol to form the C5 quaternary centre using methyl cyanoformate to install a methyl ester group in a selective manner. This step results in the fully functionalized core of lactacystin. At this stage we had two possible routes. First, we investigated the reduction of the ketone at C6 followed by attempted decarboxylation at C7; this route ultimately proved unsuccessful. The second route inverted the reaction order; performing the decarboxylation at C7 first followed by attempts to reduce the ketone at C6. The reduction was unsuccessful and so a thiomethyl derivative was employed to allow the ketone to be successfully reduced followed by removal of the thiomethyl group using Raney nickel. Chapter four has been written as a stand-alone chapter. Four advanced intermediates towards deoxylactacystin were chosen to undergo biological testing. Compounds were tested for their anti-proliferative effects against the HL-60 cell line using an MTS assay and their ability to inhibit the chymotrypsin-like activity in the 20S proteasome.
4

Investigations into the manipulation of 1,2,3-triazoles and towards an asymmetric 'click' reaction of meso bis-alkynes

Harvey, James Martin January 2015 (has links)
This thesis describes the synthetic approaches undertaken to generate various substituted 1,2,3-triazoles and a small group of bis alkyne-containing compounds, followed by their attempted application in an asymmetric ‘click’ reaction. The first chapter gives an outline to the importance of desymmetrization within organic synthesis, providing examples of the types of stereoselective reactions found within the literature. Attention is then focused on the field of ‘click’ chemistry, specifically the copper-catalysed azide-alkyne cycloaddition (CuAAC), its mechanistic studies and recent applications. Chapter two contains the results and discussion of the project and begins with the application of the CuAAC reaction to produce a simple 1,4-disubstituted 1,2,3-triazole from its two coupling partners, an azide and an alkyne, in near quantitative yields. The 1,4-disubstituted triazole is then transformed to its corresponding triazolium salt, with the longer alkyl chains only giving 40-45% product. They are then reacted with potassium tert-butoxide to generate the 1,5-disubstituted 1,2,3-triazole in yields of 83% or above. The reaction steps were optimised to give a standard procedure for the conversion of 1,4- to 1,5-triazoles, with a small series of test reactions giving overall yields of up to 90%. The second section of the results and discussion chapter centres on the development of meso bis-alkynes which were to be used in the evaluation of an asymmetric ‘click’ reaction. A number of synthetic approaches to these compounds are described, with most falling short of their final target compound, and either needing further work or a redesign of the target compound itself. One target compound, meso-1,2-bis-(prop2-yn-1-ol)benzene 29, was synthesised and a series of further meso bis-alkynes produced by various additions to the propargylic alcohol. Evaluation of the asymmetric ‘click’ reaction using this group of compounds under a wide selection of reaction conditions gave no successful results, all returning only starting material. Chapter two concludes with a brief summary of future work. Finally, chapter 3 contains full experimental details for the synthetic studies carried out in the preceding chapters.
5

Studies towards a total synthesis of Hippeastrine

Helary, Johanna Myriam January 2015 (has links)
Tricarbonyl(ŋ5 -carboxylic acid methyl ester)iron(1+) hexafluorophosphate(1−) (97) was easily prepared in a moderate yield by a tandem Wittig-Michael addition using (3-methoxycarbonylallyl)triphenylphosphonium bromide (94). The resulting cyclohexa-1,3-dienecarboxylic acid methyl ester (95) was complexed with Fe2(CO)9 to obtain tricarbonyl(cyclohexa-1,3-dienecarboxylic acid methyl ester)iron(0) (96) was converted into the highly electrophilic tricarbonyl(ŋ5 -carboxylic acid methyl ester)iron(1+) hexafluorophosphate(1−) by hydride abstraction using triphenylcarbenium hexafluorophosphate (97). 4-Bromo-1,2-(methylenedioxy)benzene (132), 6-bromopiperonylic acid (98) and 2-bromo-5-methoxy benzoic acid (140) were converted into aryllithium reagents through lithiumbromide exchange by treatment with n-butyllithium. Lithiation and deuteration of 6-bromopiperonylic acid (98) , 2-bromobenzoic acid (136) and of 2-bromo-5-methoxybenzoic acid (140) were investigated by using various reagents such as n-butyllithium, LiHMDS and NaH to find the best route for the arylation of 98 to go onwards our target (+/−)-hippeastrine (107 and 108). Tricarbonyl[ŋ4-1-methyl ester-5-(3',4'-methylenedioxy)phenylcyclohexa- 1,3-diene]iron(0) (134) was prepared by preparing the aryllithium reagent 132 by lithium-bromide exchange and converting it into an organocuprate nucleophile with copper(I) bromide. Arylation with the cation 97 resulted in the formation of the complex 134. Tricarbonyl[ŋ4 -1-methyl ester-5- (3',4'-methylenedioxy-6'-carboxyphenyl)cyclohexa- 1,3-diene]iron(0) (99) was synthesised in the same way as complex (134), using the lithiated 6-bromopiperonylic acid (98) as the reagent. The structures of the compounds were determined by IR, 1HNMR, 13C-NMR spectroscopy and mass spectrometry.
6

Tryptophan oxidation by the heme-containing dioxygenases

Booth, Elizabeth Suzanne January 2016 (has links)
In biology, the kynurenine pathway is the major degradation pathway of tryptophan (L-Trp). The first and rate-limiting step is the oxidation of L-Trp to N-formylkynurenine (NFK). The mechanism of this oxygen-dependent reaction has not been established, but is catalysed by two heme-containing dioxygenase enzymes: indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). Early proposals suggested a base-catalysed abstraction mechanism, but most of the recent studies argue against that. Instead, formation of a ferryl (Compound II intermediate) seems more likely. In this thesis, aspects of the reaction mechanism have been investigated. A Compound II intermediate was detected during the oxidation of L-Trp by hIDO using stopped flow photodiode array spectroscopy. A Compound II intermediate was also detected during the oxidation of a number of different tryptophan analogues. The results suggest a common mechanism of oxidation between L-Trp and other substrates of hIDO. The difference in reactivity between the tryptophan analogues 5-hydroxy-tryptophan and 5-methoxy-tryptophan with hIDO have been interpreted to indicate that initial oxygen atom insertion occurs by radical rather than electrophilic addition. An intermediate was detected during the oxidation of L-Trp by hTDO and XcTDO. The spectrum of this intermediate did not appear to be characteristic of a Compound II based on comparison with the spectrum of Compound II from hIDO. Weaker binding of L-Trp to both hTDO and XcTDO has been used to interpret these results. It is suggested that Compound II in TDO has a different spectrum or that the rate-limiting step is altered and an alternative catalytic intermediate accumulates. Crystal trials have been conducted for hIDO and hTDO, with some conditions producing micro-crystals. The structure of XcTDO in complex with potassium cyanide and L-Trp was solved. The binding mode of L-Trp within the distal pocket does not correlate with the L-Trp binding mode in the published ferrous XcTDO- L-Trp binary complex structure. Oxidation of L-Trp by ferric TDO without the addition of reducing agent was investigated. The results suggest the recruitment of hydrogen peroxide from solution to activate ferric heme. A summary of the mechanistic information gathered from all of the above experiments is presented.
7

Computational study of radiation-induced defects in topaz

Krizek, E. A. R. January 2015 (has links)
This purely theoretical investigation considered the irradiation induced and other intrinsic defects that may form colour centres in topaz. Topaz is an aluminium ouro/hydroxy-silicate and undergoes a colourless to blue optical transformation during irradiative treatment. The depth of hue and quality of the colour is dependent on the type of radiation used, whether thermal annealing was involved, and the origin of the samples. Since the colour centres for any of these processes are not well understood for topaz, a detailed investigation into all likely defects cited in the literature was performed. Ground state electronic structure calculations, using full electron basis sets and hybrid functionals, were performed using the CRYSTAL and CP2K codes, to gain the relative stabilities and structural properties of optimised open shell defect models; as well as the density of states, localised spin densities, and certain EPR parameters. The molecule dynamics time-dependent density functional theory (MD TD-DFT) scheme within the CP2K code was used to generate calculated UV-Vis spectra to compare with experimental data supplied by literature.
8

Enzyme inspired proton reduction catalysts

Ghosh, S. January 2015 (has links)
This thesis demonstrates electrocatalytic proton reduction by a variety of molecular catalysts including biomimetic models of [FeFe]-hydrogenase enzyme. Hydrogenases are group of metalloenzymes capable of reversible reduction of protons into dihydrogen and are divided into three groups according to the metal content in their active sites namely [FeFe]-hydrogenase, [NiFe]-hydrogenase and [Fe]-hydrogenase. The principle objective of this work has been the development of efficient iron-based electrocatalysts that can catalyse the reduction of protons at reasonably mild potentials. Chapter 1 provides an overview of electrocatalytic proton reduction by earthabundant metal complexes together with a brief discussion of hydrogenase enzymes and model complexes developed to mimic the function of the [FeFe]- hydrogenase. The synthesis, characterisation and catalytic properties of diiron biomimetics containing various diamines and diphosphines are detailed in Chapters 2-5. Most of these ligands are electrochemically non-innocent and were used in order to mimic the function of the [FeFe]-hydrogenase active site as the later also bonded to an additional redox co-factor which relays electron to-from the diiron centre during catalysis. Chapters 6-7 detail the synthesis, structure and electrocatalytic proton reduction ability of octahedral and square-pyramidal mononuclear iron complexes. These complexes have certain features of the active site of [FeFe]-hydrogenase and are shown to be efficient catalysts for the reduction of protons. Chapters 8-10 detail electrocatalytic proton reduction by low-valent iron carbonyl clusters. All have an electronegative main group element directly bonded to the cluster core which provides a site for acidic hydrogen to interact with metalbound basic hydride during catalysis. Electrocatalytic proton reduction by related triruthenium 2-aminopyridinate clusters has also been described in Chapter 10.
9

Towards the synthesis of selective CDK7 inhibitors as potential anti-cancer drugs

Kroll, Sebastian Herbert Benjamin January 2011 (has links)
Cyclin-dependent kinase 7 (CDK7) exhibits an interesting target for an anti-cancer therapy approach. CDK7’s triple role in phosphorylation (cell cycle, transcription, estrogen receptor (ER)) in cell regulation makes this kinase interesting. Phosphorylation of cell cycle CDK’s via its CAK-complex, of Ser-5 in RNA-PolII as part of the TFIIH-complex and phosphorylation of Ser-118 in ER all show the importance of this enzyme. Given that CDKs are over-expressed in many cancers, selective inhibition of CDK7 should result in cell cycle arrest and apoptosis predominately in tumour cells. Previously, BS-181 (Figure 0.1) has been reported as the first CDK7 selective inhibitor, which displayed a good in vitro and in vivo profile.1 Based on this initial lead compound, a library of rational-designed analogues was synthesised. Much of this library was based on a computer-aided-drug-design (CADD) approach by docking, which gave valuable insights in possible binding modes and helped to focus targeting the whole active site. [Molecular structure diagrams appear here. To view, please open pdf attachment] Figure 0.1: BS-181 and new analogues. Several of these novel inhibitors showed excellent selectivity versus CDK2 in particular, and potency against CDK7 in the 30 – 60 nM range for their IC50-values. Cellular assays confirmed the growth inhibitory properties of these new compounds, with GI50-values in the low μM range. This work also demonstrates what functional groups were tolerated in the 3-,5- and 7-position.
10

Multi-dimensional fluorescence microscopy for Förster resonance energy transfer studies of cell signaling

Grant, David Mitchell January 2008 (has links)
This thesis discusses the development of novel multi-dimensional fluorescence microscopy, particularly fluorescence lifetime imaging (FLIM) technology, and its application to imaging Förster Resonance Energy Transfer (FRET) events in live cells. Particular emphasis is placed on imaging activation of Ras family GTP-ases and binding to their effectors, including Phospholipase C Epsilon (PLCε). The early part of the thesis discusses FLIM-FRET experiments performed using a standard confocal microscope with time correlated single photon counting (TCSPC) to image interactions between PLCε and Ras. These early experiments suggested a weak interaction but this mode of imaging was too slow to capture dynamics of Ras activation in live cells. The long acquisition times required by the TCSPC microscope prompted the development of a high speed FLIM microscope using wide-field time-gated imaging, which was combined with a Nipkow disc confocal scan head to achieve optical sectioning. This system was characterised and its performance compared with commercially available TCSPC FLIM microscopes, demonstrating the enhancement in imaging speed for comparable accuracy of lifetime determination. This new microscope was subsequently applied to study the activation of the H-Ras oncogene in live cells following EGF stimulation. The latter part of the thesis discusses the development of a second novel microscope system for multiplexed FRET studies – using both FLIM and spectral ratiometric imaging to monitor two different FRET pairs expressed within a single live cell. A CFP-YFP cameleon FRET biosensor was used to probe calcium signals in cells expressing different PLC isoforms and this was complemented by several novel Ras activation sensors that were designed using fluorescent proteins in the red end of the visible spectrum. Calibration experiments were carried out to determine the optimal fluorophores and filter sets for imaging multiplexed biosensors and the potential for imaging dynamics of calcium flux and Ras activation within the same cell were investigated.

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