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Studies on organic electron donors and their applications in chemistry
Get PDFElectron transfer reactions using organic donors have been and are still successfully applied in the Murphy group to perform reductions usually requiring heavy metals. This thesis focuses on several organic electron donors used to: (i) promote the cross-coupling reaction between aryl halides and benzene, which was also studied with computational experiments, (ii) cleave carbon-oxygen bonds and (iii) reduce nitrobenzenes and azobenzenes.;In addition, computational analysis of controversial literature proposals for a radical/electron transfer mechanism for ring-forming reactions of alkoxide allenes and amide allenes is reported and supports an anionic rather than a radical process.;Chapter Two highlights the ability of diketopiperazines 1-4 to promote the cross-coupling reactions of aryl halides 5-16 with benzene in the presence of potassium tert-butoxide 17 to form biaryls 18-24 via electron transfer [graphic of electron transfer process].;It also investigates the different outcomes of the reaction when a diketopiperazine is used or not, providing evidence for formation of a benzyne intermediate which can lead to both the coupling product with benzene (when aryl iodides are used) and to tert-butoxybenzenes.;Chapter Three explores electron transfer reactions that lead to alkyl aryl ether deprotection. It highlights that tert-butyllithium 25 performs this deprotection and shows the series of reactions that led to evidence of an anionic addition of phenyllithium 26 to benzene and also of tert-butyllithium 25 to benzene [graphic of base-induced process and additions to Benzene with oxidative termination].;Chapter Four focuses on a 4-DMAP-derived organic electron donor 32, commonly referred to as 'DMAP donor', that reduces nitrobenzene 34 and azobenzene 36, amongst others, under UV activation or thermal conditions, via successive single electron transfers. This chapter also discusses the unlikely possibility of an electron transfer from the DMAP donor 32 to the 1,2-diphenylhydrazine dianion 38 leading to the formation of aniline dianion 39. More rational mechanistic considerations involving the reduced diphenylhydrazine and dication 33 will be described to explain the formation of aniline 35 [graphic of DMAP electron donor].;Chapter Five is a computational study of the 5-endo-trig cyclisation of alkoxideallenes and amide-allenes, discussing the process involved (electron transfer or direct intramolecular anionic cyclisation) and comparing it with the, non-experimentally observed, 4-exo-dig cyclisation [DMSO graphic].;Chapter Six provides the detailed experimental procedures and data for the compounds that were synthesised and reported in this thesis.Electron transfer reactions using organic donors have been and are still successfully applied in the Murphy group to perform reductions usually requiring heavy metals. This thesis focuses on several organic electron donors used to: (i) promote the cross-coupling reaction between aryl halides and benzene, which was also studied with computational experiments, (ii) cleave carbon-oxygen bonds and (iii) reduce nitrobenzenes and azobenzenes.;In addition, computational analysis of controversial literature proposals for a radical/electron transfer mechanism for ring-forming reactions of alkoxide allenes and amide allenes is reported and supports an anionic rather than a radical process.;Chapter Two highlights the ability of diketopiperazines 1-4 to promote the cross-coupling reactions of aryl halides 5-16 with benzene in the presence of potassium tert-butoxide 17 to form biaryls 18-24 via electron transfer [graphic of electron transfer process].;It also investigates the different outcomes of the reaction when a diketopiperazine is used or not, providing evidence for formation of a benzyne intermediate which can lead to both the coupling product with benzene (when aryl iodides are used) and to tert-butoxybenzenes.;Chapter Three explores electron transfer reactions that lead to alkyl aryl ether deprotection. It highlights that tert-butyllithium 25 performs this deprotection and shows the series of reactions that led to evidence of an anionic addition of phenyllithium 26 to benzene and also of tert-butyllithium 25 to benzene [graphic of base-induced process and additions to Benzene with oxidative termination].;Chapter Four focuses on a 4-DMAP-derived organic electron donor 32, commonly referred to as 'DMAP donor', that reduces nitrobenzene 34 and azobenzene 36, amongst others, under UV activation or thermal conditions, via successive single electron transfers. This chapter also discusses the unlikely possibility of an electron transfer from the DMAP donor 32 to the 1,2-diphenylhydrazine dianion 38 leading to the formation of aniline dianion 39. More rational mechanistic considerations involving the reduced diphenylhydrazine and dication 33 will be described to explain the formation of aniline 35 [graphic of DMAP electron donor].;Chapter Five is a computational study of the 5-endo-trig cyclisation of alkoxideallenes and amide-allenes, discussing the process involved (electron transfer or direct intramolecular anionic cyclisation) and comparing it with the, non-experimentally observed, 4-exo-dig cyclisation [DMSO graphic].;Chapter Six provides the detailed experimental procedures and data for the compounds that were synthesised and reported in this thesis
Directing the self-assembly of short peptide derivatives
No full textSelf-assembly of molecular building blocks has attracted increasing interest as an effective bottom-up approach for the design of functional nanomaterials. Amongst the variety of known molecular building blocks, very short (di- and tri-) peptides and their derivatives are of particular relevance in this context due to their chemical simplicity, low cost and remarkable properties. In this thesis, we first investigate the behaviour of the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) in a predominantly aqueous environment. We demonstrate that these molecules can form metastable hydrogels upon a combination of solvent switching and sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel. Thanks to the highlyhydrophobic nature of the fibres formed, the gels can be employed as selective scavengers for small hydrophobic molecules. Combining biocatalysis and molecular self-assembly provides an effective approach for processing of self-assembled materials, directing the assembly kinetics by means of catalysis which results in the controlled formation of hierarchical nanostructures. Herein, we investigate the possibility to achieve localised self-assembly of peptide derivatives exploiting different strategies to immobilize enzymes, thereby adding spatial control over the self-assembly process. We functionalised surfaces with bioinspired polydopamine and polyphenol coatings to study the effects of enzyme surface localisation and surface release on the self-assembly process. We demonstrate how these coatings could be conveniently used to release protease enzyme thermolysin into a pre-gelator (Fmoc-T and F-NH2) solution for bulk gelation as well as to irreversibly immobilize the enzyme for localizing the self-assembly to the surface. Enzyme-(magnetic)nanoparticle conjugates were employed to trigger the self-assembly and gelation of peptide derivatives in two different systems, an equilibrium system and a far from equilibrium one. For both systems, the self-assembly results in the formation of stable hydrogels. We were able to visualise the self-assembled nanostructures at the site of enzyme immobilization by electron microscopy. Moreover, employing magnetic nanoparticles allows for an additional level of control on the properties of the hydrogels, which can be manipulated with an external magnetic field. Finally, we employed a soft-lithographic technique (microcontact printing) to transfer a pattern of enzymes onto a modified substrate. The surfaces with the patterned thermolysin were used to trigger the localized formation of the gelator Fmoc-TF-NH2 through direct condensation of two non-assembling precursors Fmoc-T and F-NH2. Fluorescence microscopy was employed to confirm the localized formation of self-assembled structure by staining the β-sheet fibres with Thioflavin T. The thesis concludes with a number of overall conclusions that can be drawn from the work presented, as well as some possible directions for future work.Self-assembly of molecular building blocks has attracted increasing interest as an effective bottom-up approach for the design of functional nanomaterials. Amongst the variety of known molecular building blocks, very short (di- and tri-) peptides and their derivatives are of particular relevance in this context due to their chemical simplicity, low cost and remarkable properties. In this thesis, we first investigate the behaviour of the well-known self-assembling dipeptide diphenylalanine (FF) and its amidated derivative (FF-NH2) in a predominantly aqueous environment. We demonstrate that these molecules can form metastable hydrogels upon a combination of solvent switching and sonication of the dipeptide solutions. The hydrogels show instantaneous syneresis upon mechanical contact resulting in rapid expulsion of water and collapse into a semi-solid gel. Thanks to the highlyhydrophobic nature of the fibres formed, the gels can be employed as selective scavengers for small hydrophobic molecules. Combining biocatalysis and molecular self-assembly provides an effective approach for processing of self-assembled materials, directing the assembly kinetics by means of catalysis which results in the controlled formation of hierarchical nanostructures. Herein, we investigate the possibility to achieve localised self-assembly of peptide derivatives exploiting different strategies to immobilize enzymes, thereby adding spatial control over the self-assembly process. We functionalised surfaces with bioinspired polydopamine and polyphenol coatings to study the effects of enzyme surface localisation and surface release on the self-assembly process. We demonstrate how these coatings could be conveniently used to release protease enzyme thermolysin into a pre-gelator (Fmoc-T and F-NH2) solution for bulk gelation as well as to irreversibly immobilize the enzyme for localizing the self-assembly to the surface. Enzyme-(magnetic)nanoparticle conjugates were employed to trigger the self-assembly and gelation of peptide derivatives in two different systems, an equilibrium system and a far from equilibrium one. For both systems, the self-assembly results in the formation of stable hydrogels. We were able to visualise the self-assembled nanostructures at the site of enzyme immobilization by electron microscopy. Moreover, employing magnetic nanoparticles allows for an additional level of control on the properties of the hydrogels, which can be manipulated with an external magnetic field. Finally, we employed a soft-lithographic technique (microcontact printing) to transfer a pattern of enzymes onto a modified substrate. The surfaces with the patterned thermolysin were used to trigger the localized formation of the gelator Fmoc-TF-NH2 through direct condensation of two non-assembling precursors Fmoc-T and F-NH2. Fluorescence microscopy was employed to confirm the localized formation of self-assembled structure by staining the β-sheet fibres with Thioflavin T. The thesis concludes with a number of overall conclusions that can be drawn from the work presented, as well as some possible directions for future work
Using forensic science in major crimes investigation : a preliminary review of limiting factors
Get PDFThe utilization of forensic science in the investigation of criminal activities has been shown to have increased over the years especially with the discovery of DNA profiling and the creation of various databases such as the NDNAD and CODIS. Notable advancements in science and technology have contributed to the way forensic science aids criminal investigations. In spite of the increased potential of the use of forensic science in criminal investigations, certain factors such as insufficient forensic training, knowledge and resources appear to limit its effective and efficient use.Major crimes investigations receive more attention in terms of investigative resources due to their severity and the effect they have on the public. These characteristics result in the prioritisation of allocation of resources compared to volume crime investigations. Previous research on the effective and efficient use of forensic science in volume crime investigations identified recurring themes that appeared to hinder the use of forensic science. This research considers these themes and others in relation to major crime investigation. It was found that in addition to themes previously identified in volume crime investigations; information management in major crime investigation appears to impact on the effective and efficient use of forensic science.The CJS is made up of actors such as the police, the courts and other agencies such as the Home Office in the United Kingdom. During investigation of criminal activities especially in major crimes, these actors communicate and collaborate in the bid to achieve effective justice outcomes. However, certain factors seem to hinder effective and efficient communication and collaboration such as organisational cultures and behavioural economics. These factors are explored in terms of their impact on the use of forensic science in major crimes investigations.The utilization of forensic science in the investigation of criminal activities has been shown to have increased over the years especially with the discovery of DNA profiling and the creation of various databases such as the NDNAD and CODIS. Notable advancements in science and technology have contributed to the way forensic science aids criminal investigations. In spite of the increased potential of the use of forensic science in criminal investigations, certain factors such as insufficient forensic training, knowledge and resources appear to limit its effective and efficient use.Major crimes investigations receive more attention in terms of investigative resources due to their severity and the effect they have on the public. These characteristics result in the prioritisation of allocation of resources compared to volume crime investigations. Previous research on the effective and efficient use of forensic science in volume crime investigations identified recurring themes that appeared to hinder the use of forensic science. This research considers these themes and others in relation to major crime investigation. It was found that in addition to themes previously identified in volume crime investigations; information management in major crime investigation appears to impact on the effective and efficient use of forensic science.The CJS is made up of actors such as the police, the courts and other agencies such as the Home Office in the United Kingdom. During investigation of criminal activities especially in major crimes, these actors communicate and collaborate in the bid to achieve effective justice outcomes. However, certain factors seem to hinder effective and efficient communication and collaboration such as organisational cultures and behavioural economics. These factors are explored in terms of their impact on the use of forensic science in major crimes investigations
Development of a vascular cell laden construct : towards an artificial artery
No full textPreviously held under moratorium from 23 May 2018 until 16 February 2022Development of readily available vasculature and small diameter vessels remains a keychallenge in tissue engineering. In recent years, a range of 3D biofabrication methods havebeen developed to create tubular cell-laden hydrogel structures that attempt to mimic keyfeatures of native mammalian vessels. The technique of rapid casting via subtractive methodsis a particularly promising approach, as it enables the easy fabrication of such constructswithout the need for the use of complex equipment. However, this method remains to be fullycharacterised before its potential for use in the development of tissue-engineered vasculaturecan be assessed.In this study various combinations of alginate and gelatin concentrations were explored inorder to fabricate tubular constructs that mimic vessels via the rapid casting fabricationmethod. The dimensions of the resultant constructs were measured to provide an indication ofthe repeatability of the fabrication method and to identify the optimal fabrication conditions.The impact of immersion in physiological solution on these dimensions was then assessed.Finally, those scaffolds that were shown to be stable, and which could support flow within an invitro perfusion system, were taken forward for assessment for preliminary investigation of theirmechanical properties and their biocompatibility with endothelial cells.The rapid casting fabrication method was shown to be capable of producing artery mimics ofconsistent length with a range of lumen sizes (0.7 – 4.36mm). Using the same method, it wasachievable to decrease the wall thickness of vessels by reducing the gel dipping from 3 sec to 1sec. Although tubular structures could be produced, the gels showed a low capacity to maintaincell viability in comparison to a conventional tissue culture method.The study results indicate that alginate-gelatin tubular constructs with controllable dimensionsand stability can be reliably produced via a simple rapid casting method. With furtheroptimization, this technique may represent a useful alternative to more complex methods forfabrication of artificial arteries.Development of readily available vasculature and small diameter vessels remains a keychallenge in tissue engineering. In recent years, a range of 3D biofabrication methods havebeen developed to create tubular cell-laden hydrogel structures that attempt to mimic keyfeatures of native mammalian vessels. The technique of rapid casting via subtractive methodsis a particularly promising approach, as it enables the easy fabrication of such constructswithout the need for the use of complex equipment. However, this method remains to be fullycharacterised before its potential for use in the development of tissue-engineered vasculaturecan be assessed.In this study various combinations of alginate and gelatin concentrations were explored inorder to fabricate tubular constructs that mimic vessels via the rapid casting fabricationmethod. The dimensions of the resultant constructs were measured to provide an indication ofthe repeatability of the fabrication method and to identify the optimal fabrication conditions.The impact of immersion in physiological solution on these dimensions was then assessed.Finally, those scaffolds that were shown to be stable, and which could support flow within an invitro perfusion system, were taken forward for assessment for preliminary investigation of theirmechanical properties and their biocompatibility with endothelial cells.The rapid casting fabrication method was shown to be capable of producing artery mimics ofconsistent length with a range of lumen sizes (0.7 – 4.36mm). Using the same method, it wasachievable to decrease the wall thickness of vessels by reducing the gel dipping from 3 sec to 1sec. Although tubular structures could be produced, the gels showed a low capacity to maintaincell viability in comparison to a conventional tissue culture method.The study results indicate that alginate-gelatin tubular constructs with controllable dimensionsand stability can be reliably produced via a simple rapid casting method. With furtheroptimization, this technique may represent a useful alternative to more complex methods forfabrication of artificial arteries
Detection of safety signals in randomised controlled trials
Get PDFThe occurrence, severity, and duration of patient adverse events are routinely recorded during randomised clinical trials. This data is used by a trial's Data Monitoring Committee to make decisions regarding the safety of a treatment and may lead to the alteration or discontinuation of a trial if real safety issues are detected. There are many different types of adverse event and the statistical analysis of this data, particularly with regard to hypothesis testing, must take into account potential multiple comparison issues.;Unadjusted hypothesis tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative. In addition, the anticipated effect sizes of adverse events in clinical trials are generally small and consequently the power to detect such effects is low.;A number of recent classical and Bayesian methods, which use groupings of adverse events, have been proposed to address this problem. We illustrate and compare a number of these approaches, and investigate if their use of a common underlying model, which involves groupings of adverse events by body-system or System Organ Class, is useful in detecting adverse events associated with treatments.;For data where this type of grouped approach is appropriate, the methods considered are shown to correctly flag more adverse event effects than standard approaches, while maintaining control of the overall error rate.;While controlling for multiple types of adverse event, these proposed methods do not take into account event timings or patient exposure time, and are more suited to end of trial analysis. In order to address the desire for the early detection of safety issues in clinical trials a number of Bayesian methods are introduced to analyse the accumulation of adverse events as the trial progresses, taking into account event timing, patient time in study, and body-system.;These methods are suitable for use at interim trial safety analyses. The models which performed best were those that had a common body-system dependence over the duration of the trial.The occurrence, severity, and duration of patient adverse events are routinely recorded during randomised clinical trials. This data is used by a trial's Data Monitoring Committee to make decisions regarding the safety of a treatment and may lead to the alteration or discontinuation of a trial if real safety issues are detected. There are many different types of adverse event and the statistical analysis of this data, particularly with regard to hypothesis testing, must take into account potential multiple comparison issues.;Unadjusted hypothesis tests may lead to large numbers of false positive results, but simple adjustments are generally too conservative. In addition, the anticipated effect sizes of adverse events in clinical trials are generally small and consequently the power to detect such effects is low.;A number of recent classical and Bayesian methods, which use groupings of adverse events, have been proposed to address this problem. We illustrate and compare a number of these approaches, and investigate if their use of a common underlying model, which involves groupings of adverse events by body-system or System Organ Class, is useful in detecting adverse events associated with treatments.;For data where this type of grouped approach is appropriate, the methods considered are shown to correctly flag more adverse event effects than standard approaches, while maintaining control of the overall error rate.;While controlling for multiple types of adverse event, these proposed methods do not take into account event timings or patient exposure time, and are more suited to end of trial analysis. In order to address the desire for the early detection of safety issues in clinical trials a number of Bayesian methods are introduced to analyse the accumulation of adverse events as the trial progresses, taking into account event timing, patient time in study, and body-system.;These methods are suitable for use at interim trial safety analyses. The models which performed best were those that had a common body-system dependence over the duration of the trial
Characterisation of metal-organic frameworks with inherent functionalisation for carbon capture methods
Get PDFCarbon Capture offers potential remediation for greenhouse gases from industrial point sources, and physical sorbents are an economically viable option, but one that requires optimisation. Here, materials were investigated to assess the effect of incorporation of functionalised ligands, which utilise a Lewis basic character, on the potential of such materials for Carbon Capture applications. Materials were investigated for their structural and adsorptive properties, allowing analysis and evaluation of the selective capture of carbon dioxide. Characterisation included single crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and elemental analysis. Adsorption properties were evaluated using volumetric nitrogen adsorption at 77 K, which showed all three materials experienced activated diffusion, and gravimetric carbon dioxide adsorption at 273 K. Further gravimetric adsorption analysis was performed at various temperatures using carbon dioxide, methane, and nitrogen gases, to analyse the performance of these materials under simulated conditions for carbon capture processes. Thermodynamic and kinetic properties were determined in order to provide an indication of the underlying processes governing diffusion and equilibration of adsorption.Three materials were investigated; Cu(bpetha)2SiF6 (bpetha = 1,2-bis(4-pyridyl)ethane), [Cu(TPT)]BF4.0.75H2O and [Cu(TPT)]NO3.MeOH (TPT = 1,3,5-tris(4-pyridyl)-2,4,6-triazine). Cu(bpetha)2SiF6 showed promising results for carbon dioxide adsorption (0.6 mmol g−1 at 100 kPa and 333 K), having kinetically selective behaviour for nitrogen and methane at timescales that are suitable for pressure swing adsorption processing (90 %/5 % of equilibrium uptake for carbon dioxide vs. nitrogen in under 3 min). The material also showed enhanced adsorption interactions towards carbonvdioxide as a consequence of electronegative fluorine atoms within the structure, and also exhibited flexibility of the framework towards carbon dioxide. [Cu(TPT)]BF4.0.75H2O showed poor adsorption capabilities for carbon dioxide (0.15 mmol g−1 at 100kPa and 333 K), which is ascribed to pore blocking effects of the anion within the structure. [Cu(TPT)]NO3.MeOH showed moderate uptakes for CO2 at low temperatures (1.96 mmol g−1 maximum capacity at 273 K), but demonstrated better adsorption capabilities for methane at higher temperatures (1.54 mmol g−1 at 100 kPa and 333 K). The framework experienced a large structural change upon adsorption, which was probed using methane at different temperatures.The results of this study showed that materials synthesised with inherent functionalisation could be developed to enhance carbon dioxide adsorption for Carbon Capture applications. However, other structural effects of the materials must be considered as the complexity of Metal-Organic Framework structures can influence the adsorption properties via a variety of mechanisms.Carbon Capture offers potential remediation for greenhouse gases from industrial point sources, and physical sorbents are an economically viable option, but one that requires optimisation. Here, materials were investigated to assess the effect of incorporation of functionalised ligands, which utilise a Lewis basic character, on the potential of such materials for Carbon Capture applications. Materials were investigated for their structural and adsorptive properties, allowing analysis and evaluation of the selective capture of carbon dioxide. Characterisation included single crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, thermogravimetric analysis, and elemental analysis. Adsorption properties were evaluated using volumetric nitrogen adsorption at 77 K, which showed all three materials experienced activated diffusion, and gravimetric carbon dioxide adsorption at 273 K. Further gravimetric adsorption analysis was performed at various temperatures using carbon dioxide, methane, and nitrogen gases, to analyse the performance of these materials under simulated conditions for carbon capture processes. Thermodynamic and kinetic properties were determined in order to provide an indication of the underlying processes governing diffusion and equilibration of adsorption.Three materials were investigated; Cu(bpetha)2SiF6 (bpetha = 1,2-bis(4-pyridyl)ethane), [Cu(TPT)]BF4.0.75H2O and [Cu(TPT)]NO3.MeOH (TPT = 1,3,5-tris(4-pyridyl)-2,4,6-triazine). Cu(bpetha)2SiF6 showed promising results for carbon dioxide adsorption (0.6 mmol g−1 at 100 kPa and 333 K), having kinetically selective behaviour for nitrogen and methane at timescales that are suitable for pressure swing adsorption processing (90 %/5 % of equilibrium uptake for carbon dioxide vs. nitrogen in under 3 min). The material also showed enhanced adsorption interactions towards carbonvdioxide as a consequence of electronegative fluorine atoms within the structure, and also exhibited flexibility of the framework towards carbon dioxide. [Cu(TPT)]BF4.0.75H2O showed poor adsorption capabilities for carbon dioxide (0.15 mmol g−1 at 100kPa and 333 K), which is ascribed to pore blocking effects of the anion within the structure. [Cu(TPT)]NO3.MeOH showed moderate uptakes for CO2 at low temperatures (1.96 mmol g−1 maximum capacity at 273 K), but demonstrated better adsorption capabilities for methane at higher temperatures (1.54 mmol g−1 at 100 kPa and 333 K). The framework experienced a large structural change upon adsorption, which was probed using methane at different temperatures.The results of this study showed that materials synthesised with inherent functionalisation could be developed to enhance carbon dioxide adsorption for Carbon Capture applications. However, other structural effects of the materials must be considered as the complexity of Metal-Organic Framework structures can influence the adsorption properties via a variety of mechanisms
A quantitative scale for directing group power in ruthenium(II)-catalysed ortho-directed C-H arylation reactions
Get PDFPreviously held under moratorium from 19 October 2017 until 24 February 2022Directed ruthenium-catalysed C-H functionalisation of heteroarenes, such as 2-phenylpyridineor 1-phenylpyrazole, has emerged as an efficient and environmentally benign alternative totraditional cross-coupling chemistry. Using readily available and inexpensive aryl halides, themechanisms of these transformations are beginning to be understood. However, there has beenno work completed towards understanding the different directing group power of thesesubstrates. Many of the literature examples consider only the behaviour of substrates with onefunctional group, and the behaviour of more densely functionalised substrates remainsunpredictable.In this work we have presented a quantitative reactivity scale of directing group power for aseries of ruthenium(II)-catalysed ortho-directed intermolecular C-H arylation reactions acrossa range of substrates. The scale of directing group power has been determined using sets ofcompetition reactions that were analysed by calibrated GC-FID. Using least squaresminimisation, relative reaction rates were obtained for each substrate delivering the firstquantifiable assessment of directing group power.These results have found that, in our series, 2-phenylpyridine >> 2-phenylpyrazole > Nmethyl-2-phenyl-imidazole > 2-phenyloxazoline >> N-(1-phenylethylidene)aniline. Theseresults cover a synthetically useful reactivity range of 10²and allow a quantitative predictionof site selectivity under the conditions examined.Additionally, we have presented initial experimental findings that support the intermolecularquantitative predictions within an intramolecular substrate. This sets the scene for predictionof regioselectivity in more densely functionalised molecules, on an inter- and intramolecularsetting.Directed ruthenium-catalysed C-H functionalisation of heteroarenes, such as 2-phenylpyridineor 1-phenylpyrazole, has emerged as an efficient and environmentally benign alternative totraditional cross-coupling chemistry. Using readily available and inexpensive aryl halides, themechanisms of these transformations are beginning to be understood. However, there has beenno work completed towards understanding the different directing group power of thesesubstrates. Many of the literature examples consider only the behaviour of substrates with onefunctional group, and the behaviour of more densely functionalised substrates remainsunpredictable.In this work we have presented a quantitative reactivity scale of directing group power for aseries of ruthenium(II)-catalysed ortho-directed intermolecular C-H arylation reactions acrossa range of substrates. The scale of directing group power has been determined using sets ofcompetition reactions that were analysed by calibrated GC-FID. Using least squaresminimisation, relative reaction rates were obtained for each substrate delivering the firstquantifiable assessment of directing group power.These results have found that, in our series, 2-phenylpyridine >> 2-phenylpyrazole > Nmethyl-2-phenyl-imidazole > 2-phenyloxazoline >> N-(1-phenylethylidene)aniline. Theseresults cover a synthetically useful reactivity range of 10²and allow a quantitative predictionof site selectivity under the conditions examined.Additionally, we have presented initial experimental findings that support the intermolecularquantitative predictions within an intramolecular substrate. This sets the scene for predictionof regioselectivity in more densely functionalised molecules, on an inter- and intramolecularsetting
Bacterial ion effects and their relation to salt tolerance
Get PDFPreviously held under moratorium from 25 June 2018 until 24 February 2022Extremophiles are organisms that are able to tolerate conditions that would otherwise inhibit or even kill non-extremophilic organisms – such extremes include acidity, high salt concentrations, high temperatures and high pressure. Specifically, halophiles are organisms that have a requirement for high concentrations of salt for growth. These organisms have been found to use either of two adaptation strategies, known as ‘salt-in’ (accumulation of inorganic ions) and ‘salt-out’ (removal of inorganic ions and accumulation of neutral molecules). In the current study, the relationship between the level of salt tolerance of an organism and its ion metabolism was investigated in order to gain insight into halo-adaptation and mechanisms of bacterial salt tolerance. This was accomplished by analysing the effects of a variety of salts (21 different combinations) on a halophile (Salinibacter ruber), non-halophile (Escherchiacoli) and halotolerant (Echinicola vietnamensis) organism, which was achieved via an analysis of the effects of salts on bacterial growth, intracellular cation accumulation, enzymatic activity and and bioinformatics analysis. It was found that cation preferences were directly related to the level of salt tolerance of the organism, which is hypothesised to be a product of proteome acidity as well as the presence of specific membrane cation transporters. Specifically, the preference of S. ruber for the higher charge density Na+ over K+ may be rationalised based on the Hofmeister effect –i.e. this cation may provide better stabilisation of intracellular enzymes at the optimal salt concentrations for growth of S. ruber, but may be destabilising if accumulated at higher concentrations, and for non-salt adapted organisms. The ability of E. vietnamensis to tolerate and utilise many non-physiological ions supports this theory. Additionally, E. vietnamensis was postulated to use a ‘hybrid’ osmotic adaptation strategy – this organism may have industrial applications due to its large salt concentration tolerance range and high tolerance for non-physiological cations. Crucially, it was also found that E. vietnamensis and S. ruber contained membrane cation transporters that may be essential for their salt tolerance, giving insight into the essential nature of these proteins for the possession of salt resistance, which may have potential to be utilised for the transfer of salt-tolerance to commercially important organisms. Finally, one specific salt combination tested, equimolar LiCl + KBr proved to totally inhibit bacterial growth and may show promise as an antimicrobial agent, for which a patent application has been initiated. The results of the current study can have various applications, including those within industry, medicine and astrobiology.Extremophiles are organisms that are able to tolerate conditions that would otherwise inhibit or even kill non-extremophilic organisms – such extremes include acidity, high salt concentrations, high temperatures and high pressure. Specifically, halophiles are organisms that have a requirement for high concentrations of salt for growth. These organisms have been found to use either of two adaptation strategies, known as ‘salt-in’ (accumulation of inorganic ions) and ‘salt-out’ (removal of inorganic ions and accumulation of neutral molecules). In the current study, the relationship between the level of salt tolerance of an organism and its ion metabolism was investigated in order to gain insight into halo-adaptation and mechanisms of bacterial salt tolerance. This was accomplished by analysing the effects of a variety of salts (21 different combinations) on a halophile (Salinibacter ruber), non-halophile (Escherchiacoli) and halotolerant (Echinicola vietnamensis) organism, which was achieved via an analysis of the effects of salts on bacterial growth, intracellular cation accumulation, enzymatic activity and and bioinformatics analysis. It was found that cation preferences were directly related to the level of salt tolerance of the organism, which is hypothesised to be a product of proteome acidity as well as the presence of specific membrane cation transporters. Specifically, the preference of S. ruber for the higher charge density Na+ over K+ may be rationalised based on the Hofmeister effect –i.e. this cation may provide better stabilisation of intracellular enzymes at the optimal salt concentrations for growth of S. ruber, but may be destabilising if accumulated at higher concentrations, and for non-salt adapted organisms. The ability of E. vietnamensis to tolerate and utilise many non-physiological ions supports this theory. Additionally, E. vietnamensis was postulated to use a ‘hybrid’ osmotic adaptation strategy – this organism may have industrial applications due to its large salt concentration tolerance range and high tolerance for non-physiological cations. Crucially, it was also found that E. vietnamensis and S. ruber contained membrane cation transporters that may be essential for their salt tolerance, giving insight into the essential nature of these proteins for the possession of salt resistance, which may have potential to be utilised for the transfer of salt-tolerance to commercially important organisms. Finally, one specific salt combination tested, equimolar LiCl + KBr proved to totally inhibit bacterial growth and may show promise as an antimicrobial agent, for which a patent application has been initiated. The results of the current study can have various applications, including those within industry, medicine and astrobiology
Computational fluid dynamics study of erosion processes
Get PDFPreviously held under moratorium from 7 December 2017 until 24 February 2022A very large number of papers have been published on erosion for over 50 years. For thefirst time, a series of geometry independent tools and methodologies have been developed to calculate erosion and its associated mesh deformation in any three dimensionaldomain. The software used for development is verified first against the literature andAnsys Fluent. An error was found in the implementation of the Lagrangian phase inFluent which was corrected in a later version. It is suspected that the error affects alarge number of CFD publications in which the Discrete Phase Model was used. Anexperimental methodology and test-rig that is able to erode samples at mass concentrations ranging from 1% to 7% were developed and repeatability confirmed throughtesting. Despite not being able to use the test-rig due to technical issues, erosion associated deformation was validated from the literature, confirming the appearance ofa new stagnation area as the wear scar deepens in the Jet Impingement Test. Thealgorithm was also applied to centrifugal slurry pumps in combination with state ofthe art erosion modeling and its results validated through visual inspection of erodedmodels.A very large number of papers have been published on erosion for over 50 years. For thefirst time, a series of geometry independent tools and methodologies have been developed to calculate erosion and its associated mesh deformation in any three dimensionaldomain. The software used for development is verified first against the literature andAnsys Fluent. An error was found in the implementation of the Lagrangian phase inFluent which was corrected in a later version. It is suspected that the error affects alarge number of CFD publications in which the Discrete Phase Model was used. Anexperimental methodology and test-rig that is able to erode samples at mass concentrations ranging from 1% to 7% were developed and repeatability confirmed throughtesting. Despite not being able to use the test-rig due to technical issues, erosion associated deformation was validated from the literature, confirming the appearance ofa new stagnation area as the wear scar deepens in the Jet Impingement Test. Thealgorithm was also applied to centrifugal slurry pumps in combination with state ofthe art erosion modeling and its results validated through visual inspection of erodedmodels
Social identity in Shakespeare's plays : a quantitative study
Get PDFThis thesis takes three major claims made by literary scholars about Shakespeare's use of language regarding issues of social identity. Each chapter introduces a critical perception of Shakespeare's language - madness (Neely 1991), whorishness (Stanton 2000, Stallybrass 1986, Newman 1986) and questions of race, ethnicity and nationality (Loomba 2000, Hall 1992) - and applies a quantitative approach to the claims they raise. In doing so, I illustrate how digital resources such as the Historical Thesaurus of the Oxford English Dictionary (Kay et al 2015), the Folger Digital Texts (Mowat, Werstine, Niles and Poston 2014) and corpus analysis software including AntConc (Anthony 2014) and Ubiqu+ity can be applied to a closed-set collection of plays understood to be written by Shakespeare (Wells and Taylor 1987, 109-134) to test claims laid out by literary critics. This thesis therefore shows how quantitative evidence can lead to a more complex and robust analysis of Shakespeare's language than qualitative evidence is able to.This thesis takes three major claims made by literary scholars about Shakespeare's use of language regarding issues of social identity. Each chapter introduces a critical perception of Shakespeare's language - madness (Neely 1991), whorishness (Stanton 2000, Stallybrass 1986, Newman 1986) and questions of race, ethnicity and nationality (Loomba 2000, Hall 1992) - and applies a quantitative approach to the claims they raise. In doing so, I illustrate how digital resources such as the Historical Thesaurus of the Oxford English Dictionary (Kay et al 2015), the Folger Digital Texts (Mowat, Werstine, Niles and Poston 2014) and corpus analysis software including AntConc (Anthony 2014) and Ubiqu+ity can be applied to a closed-set collection of plays understood to be written by Shakespeare (Wells and Taylor 1987, 109-134) to test claims laid out by literary critics. This thesis therefore shows how quantitative evidence can lead to a more complex and robust analysis of Shakespeare's language than qualitative evidence is able to
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