Gas phase studies by the sodium diffusion flame methodBoak, David Stewart January 1969 (has links)
No description available.
Insights into the structures and dynamics of the pathogen secreted effectors AVR3A11 and TARP through the application of NMR spectroscopyTolchard, James January 2014 (has links)
The lifecycles of obligate pathogenic and parasitic microorganisms depend on a myriad of interactions with their hosts at the molecular level. The class of bacterial proteins directly responsible for these inter-organism interactions have been termed effector proteins and can function in either an extracellular or, once secreted into the host cell, an intracellular environment. Primarily through the use of nuclear magnetic resonance spectroscopy (NMR), I have investigated the biophysical properties of two such bacterial effector proteins. TARP (translocated actin recruiting protein) is a largely disordered 100 kDa effector, common to all chlamydial species, which functions to remodel the host actin cytoskeleton to facilitate the internalisation of the chlamydial cell. Using constructs of TARP comprising an expected actin binding domain, I have shown through NMR chemical shift indexing and 15N relaxation that although the unbound domain is intrinsically disordered a short region, which aligns to other helical actin binding domains, maintains some helical propensity. Furthermore, these residues map to chemical shift variations in the bound state and the Kd for the interaction has also been determined using isothermal titration calorimetry. AVR3a11 is an 8 kDa effector from the pepper pathogen Phytophthora capsici that has been shown to inhibit plant programmed cell death. Using a combination of 2D and 3D NMR experiments I have assigned the majority of the backbone and side-chain resonances from the structured regions of AVR3a11. Through the acquisition and analysis of 13C and 15N edited HSQCNOESY spectra I have also calculated a water refined, structural ensemble for AVR3a11. Additionally, analysis of the slow (H:D exchange) and fast (T1, T2 and heteronuclear NOE) dynamic regimes, describes AVR3a11 as a relatively tightly folded helical bundle which also exhibits a significant degree of conformational exchange.
Molecular machines constructed from multichromophore arraysGonzález Lucas, Daniel January 2014 (has links)
Our long-term ambitious goal is to construct molecular assemblies or machines of unprecedented complexity leading to unique function. Porphyrins and phthalocyanines have been selected as the building blocks for the construction of the targeted molecular machines. The synthesis of different porphyrin/phthalocyanine building blocks is introduced with particular emphasis on the introduction of central metal/metalloid elements such as ruthenium, indium and lanthanides. The linking of porphyrins to give covalent assemblies suitable for elaboration into machine-like arrays is then described. The synthesis of an array in which four porphyrin units surround a central porphyrin core is described, alongside modifications to the strategy that permits differential metal substitution. Strategies for face-to-face elaboration of machine-like structures from the previously described covalent multiporhyrin array are discussed. Although unsuccessful, a separate reaction pathway is described that leads to controlled formation of triple-decker structures. Model diporphyrins, linked through flexible spacers, are smoothly metallated with lanthanum. Complementary phthalocyanine macrocycles are then easily inserted, giving high yields of triple decker molecules. The synthesis and materials are discussed, and the novel structures are characterised by absorption spectroscopy, NMR spectroscopy and crystallography. The versatility and generality of the strategy are demonstrated by synthesis of analogues that incorporate more heavily functionalised central (phthalocyanine) macrocycles. Rotation is hindered (NMR) in these cases. Finally, preliminary assessment of extension of this approach towards higher-order stacks is described, alongside variation of the linking lanthanides to include magnetic elements such as dysprosium.
Hyerbranched polydendrons : a new macromolecular architectureHatton, Fiona January 2014 (has links)
A novel architecture ‘hyperbranched polydendrons’ (hyp-polydendrons) was produced via the synthesis of low generation dendron initiators for ATRP and subsequent copolymerisation of vinyl and divinyl monomers, to give large polymeric macromolecules containing dendron moieties at the end of each primary chain. Subsequent studies of such materials were performed to assess their ability to form nanoparticles via a nanoprecipitation approach, utilising organic solvent and aqueous nanoparticle formation. It was found that the branched polymers were superior to the linear polymer analogues when assessing their nanoprecipitation behaviour. Mixed initiator hyp-polydendrons were also synthesised by the statistical incorporation of different functionality initiators into the reaction mixture. Here a G2 dendron and different PEG macroinitiators were mixed statistically to produce a series of materials where the primary chain length of the monomer HPMA was also varied. This led to a series of nanoparticles which showed a variation of internal environments when studied using different fluorescent dyes (Nile red and pyrene). Initial pharmacological experiments were promising, however, the initial set of materials did not show prolonged stability in physiologically relevant conditions when using a short PEG macroinitiator (750PEG). Extending the length of the PEG chain (2000PEG initiator) in the mixed polymerisations produced a range of materials with varying solubilities and, therefore, nanoprecipitation behaviour. Nanoparticles were formed which were stable under physiologically relevant conditions and were studied for their cytotoxicity and transcellular permeability in Caco- 2 cells. These materials showed limited toxicity at the concentrations studied and enhanced permeation though the Caco-2 cell monolayer, which is a model of the intestinal epithelial cells. Further studies of the nanoprecipitation behaviour of different molecular weight fractions of the hyp-polydendrons were conducted. This involved separation of molecular weight fractions by dialysis of the hyp-polydendrons against two different good solvents, leading to two HMW fractions and two LMW fractions. Analysis of the nanoprecipitation behaviour of these fractions showed that the HMW fractions produced particles with more narrow PdIs, and the mixing of a low amount of a HMW fraction (1 wt%) with a linear polymer improved the nanoprecipitation behaviour hugely. Encapsulation of two different guest molecules via nanoprecipitation was assessed using FRET, which can report on the proximity of two fluorophores. Dual loading of the particles with DiO and DiI in a 1:1 ratio gave particles which exhibited a FRET signal, therefore indicating that the two fluorophores were located in the same nanoparticle. Somewhat unexpectedly it was found that upon mixing of the two singly loaded particles the observed FRET ratio increased over time until it reached a similar value obtained within the dual loaded nanoparticles. This was possibly due to nanoparticle-nanoparticle collisions. Therefore hyp-polydendrons were produced and utilised to form nanoparticles via a nanoprecipitation approach. Loading of the nanoparticles was achieved and pharmacological benefits were observed for some of the nanoparticle samples, suggesting future benefits for these polymer architectures in nanomedicine applications.
Understanding the self-assembly process and tunability of the final properties of dipeptide-based low molecular weight hydrogelsRaeburn, Jaclyn January 2014 (has links)
Reported in this thesis is the ability to prepare a number of dipeptide-conjugate hydrogels with tunable final properties, through judicious choice of the assembly conditions and gelator structure. Gelation of these materials can be triggered by solvent-mediated, pH-triggered, UV-triggered and electrochemically-induced means to give different mechanical properties. Subtle changes in the assembly conditions can evoke changes in the final properties - something that was evident across a range of gelator systems and methods of triggering gelation. UV and electrochemical methods demonstrated the ability to spatially and temporally control gelation, which could be of potential use to biosensor and cell culturing applications. Molecular rotors could be employed to monitor the kinetics of the gelation process, indicating an evolution in self-assembled structure around the pKa of a gelator. This thesis highlights the importance of the self-assembly process on the final properties of dipeptide-conjugate gels. A better understanding of this process will be beneficial for gelator design. Where specific hydrogel properties are needed, the gelator will be tunable for a desired application by manipulating the assembly conditions.
Photodynamic and photothermal human cancer cell killing using gold nanoparticlesChadwick, Samantha January 2015 (has links)
Cells from a human fibroblast cell line (HeLa) were used to explore the role of photothermal and photodynamic effects of laser irradiation using plasmonic gold nanoparticles. The two types of spherical gold nanoparticles used were (i) citrate- stabilised and (ii) peptide stabilised particles. These particles were prepared following standard protocols and characterised by a range of methods including TEM, UV-vis spectroscopy and dynamic centrugal sedimentation. Different sizes of particles were prepared and the effect of size was investigated. Cellular uptake of the nanoparticles prior to exposure to laser light was quantified by TEM and by ICP-AES. Cell cultures were exposed to a laser of a wavelength within the plasmon band of the gold nanoparticles (520 nm), and cell death was monitored by optical microscopy using the standard Trypan blue exclusion assay. The total energy transfer from the laser to the cell culture was estimated based on the extinction coefficient of the nanoparticles and also measured directly by UV-vis spectroscopy. Heating profiles for a range of laser intensities and exposure times were calculated. The temperature at which thermal cell death occurs was estimated by exposing the cells to a heated water bath and monitoring viability. Conditions were established to demarcate photothermal from photodynamic cell death, and a photodynamic mechanism was suggested based on the photochemical production of singlet oxygen. The plausibility of this mechanism was demonstrated by quantitative studies of singlet oxygen formation by laser irradiation of gold nanoparticles dispersed in water.
Single molecule electronics in ionic liquid mediaKay, Nicola Julie January 2012 (has links)
The field of single molecule electronics, where the charge transport properties of a variety of single molecular systems are investigated, has vastly increased in popularity over the last decade. This thesis in particular explores the single molecule conductance and electron transfer over a range of molecules in a room temperature ionic liquid medium. Prior to the work contained in this thesis, no conductance measurements of a single molecule had been recorded in a room temperature ionic liquid medium, to the best of our knowledge. Due to the novelty of room temperature ionic liquids in this field, it was decided that alkanedithiols would be an ideal starting point, largely due to their simplicity and reputation as a model system in single molecule electronics. Ionic liquids have several notable advantages as a medium in such measurements and the aim of the research contained in this thesis is first to show that ionic liquids are indeed a viable medium and secondly, to demonstrate their advantages over more widely used, conventional aqueous or organic media. The redox active molecular wire pyrrolo-tetrathiafulvalene is a particular molecule which would highlight the benefits of an ionic liquid medium, as it has a redox transition which is outside of the potential window available to aqueous electrolytes. Single molecule conductance measurements were obtained using a scanning tunnelling microscope (STM), in particular, the current-distance I(s) technique, and for alkanedithiols also the STM break junction technique. The electrochemistry of pyrrolo-tetrathiafulvalene was investigated using cyclic voltammetry and a monolayer of pyrrolo-tetrathiafulvalene was characterised using polarisation modulation infrared reflection absorption spectroscopy (PM-IRRAS).
Study of spontaneous polymerisation inhibitionNewby, Thomas Edward January 2014 (has links)
Spontaneous polymerisation is an unwanted reaction, prevented by inhibitor molecules. In order to observe the inhibition of spontaneous polymerisation by different molecules, a small scale dilatometry experiment was developed. This was used to screen structurally related molecules to 2-nitrophenol to determine what structural features give rise to inhibition properties. Compounds with an intramolecular hydrogen bond demonstrated more efficient inhibition of polymerisation. The product mixture of styrene inhibited by 2-nitrophenol was analysed to determine the reaction pathway. Column chromatography, MS and NMR were used to determine the structure of two intermediates, 2-aminophenol and a compound derived from a Diels Alder styrene initiator and 2-nitrophenol. The proposed intermediate, 2-nitrosophenol, was synthesised and its stability in styrene was determined. The products of reaction between 2-nitrosophenol and styrene at room temperature were proposed by comparing results with the reaction between styrene and nitrosobenzene. The main product of the inhibition by 2-nitrosophenol, was also determined to be 2-aminophenol, suggesting that 2-aminophenol formed from inhibition by 2-nitrophenol goes via 2-nitrosophenol. Other intermediates and products identified were also screened in the dilatometry setup. They show inhibition properties at high concentration, but at more realistic concentrations, they did not inhibit styrene polymerisation. An overall mechanism for the inhibition of styrene polymerisation by 2-nitrophenol, was proposed based on the data obtained.
α-formylations with chiral chloroiminium saltsHassan, Jamal January 2014 (has links)
The synthesis of quaternary carbon centres is a challenging task in organic chemistry, and this is believed to be due to the significant amount of ‘steric crowding’ involved in the creation of a quaternary carbon centre. This thesis discusses the discovery and development of a new method for the preparation of α-formyl ketones containing an α-quaternary carbon centre. Ketone substrates were reacted with the Vilsmeier reagent (chloromethylene) dimethylammnonium chloride (generated in situ from DMF and oxalyl choride) followed by work up with aqueous base (NaHCO3) to afford α-formyl ketones (8-88% yield). This methodology was extended to the asymmetric α-formylation of α-methyl indanone and α-methyl tetralone using chiral chloroiminium salts derived from (S)-proline. The asymmetric reactions gave enantiomeric excesses of up to 68%.
The state of ³⁵S in alkali chloride crystalsKasrai, Masoud January 1968 (has links)
No description available.
Page generated in 0.0628 seconds