Novel polymers and dendrimers of intrinsic microporosity derived from triptycene and other monomers of high internal free volume

The research described in this thesis is largely focused on monomers derived from the triptycene moiety, and their potential to form polymers of intrinsic microporosity (PIMs), organic molecules of intrinsic microporosity (OMIMs) and dendrimers of intrinsic microporosity (DIMs). Triptycene is of particular interest here due to its high internal molecular free volume (IMFV) and previously reported success in the formation of microporous materials - triptycene is in fact the basis of the most microporous PIM reported to date, and the basis of the only reported example of an amorphous molecular microporous material. The work later extends to incorporate other presumed high IMFV moieties based on spirobifluorene and propellane. The research begins by focusing on the synthesis of potentially soluble polymers. They are of interest due to their processability, which when coupled with microporosity, can potentially yield permeable membranes suitable for selective gas separation. There has been much research into PIMs and their corresponding membranes, with particular interest surrounding PIM-1, a polymer formed between a spirobisindane based monomer, and 2,3,5,6-tetrafluoroterephthalonitrile.1 The same nucleophilic aromatic substitution reaction (SNAr) as is used to make PIM-1 is employed throughout this thesis for the formation of final products. The second section of this project focused on the synthesis of network polymers based around triptycene, introducing bitriptycenes, triptycene side groups, and unsymmetrical triptycenes with new functional groups, the main focus on increased surface area. Although highly microporous materials were prepared, no enhancement over previously obtained triptycene polymers was obtained. The third section of the thesis focuses on the synthesis of novel microporous materials termed Organic Molecules of Intrinsic Microporosity (OMIMs) and Dendrimers of Intrinsic Microporosity (DIMs). These are discrete molecules lacking any long range order that cannot pack space efficiently due to their rigid structures, composed of monomer subunits with high IMFV. All materials were analysed for their apparent BET surface areas (N2 adsorption at 77 K), which were in the range 0-700 m2 g"1.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Polymer Membranes for the Separation of Complex Natural Hydrocarbon Feeds

Polymer Membranes for the Separation of Complex Natural Hydrocarbon Feeds Ronita Mathias 231 Pages Directed by Dr. Ryan P. Lively The separation of complex liquid mixtures, which are mixtures without a clear singular solvent, is an emerging area of membrane science. Crude oil is one such complex industrial mixture that is comprised of several tens of thousands of hydrocarbon molecules but is typically fractionated via energy-intensive thermal processes. In this work, specific light fractions of crude oil were separated via novel spirocyclic polymer membranes, with the potential for bypassing significant energy expenditure associated with distillation. Polymeric materials are of interest for membrane fabrication as they are easily processable, inexpensive, and can be easily functionalized for stability. However, for membrane-based fractionation of crude oil to compete with current distillation processes on an industrial scale, multi-stage cascades containing several high-throughput membranes must be optimized. The capability to predict multi-molecule transport in target materials can accelerate the screening and design of materials for cascades that would otherwise require lengthy R&D timelines. Thus, advanced models were also utilized in this work to predict complex mixture permeation in polymeric membranes based only on pure molecule sorption and diffusion inputs. These simplifying hypotheses could enable an extension of predictive capabilities to N-component mixtures of hydrocarbons, of which there are many industrially relevant streams, not limited to crude oil. One of the limitations to the industrial implementation of this type of membrane-based process is whether the polymer membranes can be fabricated in a scalable manner. Therefore, a roll-to-roll dip-coating process was used to demonstrate the continuous fabrication of thin film composite hollow fiber membranes. In this precursive work, a more established spirocyclic polymer, PIM-1, was coated on a commercial polymer support to investigate the feasibility of this process for the novel spirocyclic polymers identified for crude oil separations. Upon successful demonstration, the learnings could be used to develop large-scale polymeric membranes capable of excellent separation performance in complex mixtures coupled with fast transport rates.Ph.D

Novel polymers and dendrimers of intrinsic microporosity derived from triptycene and other monomers of high internal free volume

The research described in this thesis is largely focused on monomers derived from the triptycene moiety, and their potential to form polymers of intrinsic microporosity (PIMs), organic molecules of intrinsic microporosity (OMIMs) and dendrimers of intrinsic microporosity (DIMs). Triptycene is of particular interest here due to its high internal molecular free volume (IMFV) and previously reported success in the formation of microporous materials - triptycene is in fact the basis of the most microporous PIM reported to date, and the basis of the only reported example of an amorphous molecular microporous material. The work later extends to incorporate other presumed high IMFV moieties based on spirobifluorene and propellane. The research begins by focusing on the synthesis of potentially soluble polymers. They are of interest due to their processability, which when coupled with microporosity, can potentially yield permeable membranes suitable for selective gas separation. There has been much research into PIMs and their corresponding membranes, with particular interest surrounding PIM-1, a polymer formed between a spirobisindane based monomer, and 2,3,5,6-tetrafluoroterephthalonitrile.1 The same nucleophilic aromatic substitution reaction (SNAr) as is used to make PIM-1 is employed throughout this thesis for the formation of final products. The second section of this project focused on the synthesis of network polymers based around triptycene, introducing bitriptycenes, triptycene side groups, and unsymmetrical triptycenes with new functional groups, the main focus on increased surface area. Although highly microporous materials were prepared, no enhancement over previously obtained triptycene polymers was obtained. The third section of the thesis focuses on the synthesis of novel microporous materials termed Organic Molecules of Intrinsic Microporosity (OMIMs) and Dendrimers of Intrinsic Microporosity (DIMs). These are discrete molecules lacking any long range order that cannot pack space efficiently due to their rigid structures, composed of monomer subunits with high IMFV. All materials were analysed for their apparent BET surface areas (N2 adsorption at 77 K), which were in the range 0-700 m2 g"1

Structure analysis of biologically important prokaryotic glycopolymers

Of the many post-translational modifications organisms can undertake, glycosylation is the most prevalent and the most diverse. The research in this thesis focuses on the structural characterisation of glycosylation in two classes of glycopolymer (lipopolysaccharide (LPS) and glycoprotein) in two domains of life (bacteria and archaea). The common theme linking these subprojects is the development and application of high sensitivity analytical techniques, primarily mass spectrometry (MS), for studying prokaryotic glycosylation. Many prokaryotes produce glycan arrangements with extraordinary variety in composition and structure. A further challenge is posed by additional functionalities such as lipids whose characterisation is not always straightforward. Glycosylation in prokaryotes has a variety of different biological functions, including their important roles in the mediation of interactions between pathogens and hosts. Thus enhanced knowledge of bacterial glycosylation may be of therapeutic value, whilst a better understanding of archaeal protein glycosylation will provide further targets for industrial applications, as well as insight into this post- translational modification across evolution and protein processing under extreme conditions. The first sub-project focused on the S-layer glycoprotein of the halophilic archeaon Haloferax volcanii, which has been reported to be modified by both glycans and lipids. Glycoproteomic and associated MS technologies were employed to characterise the N- and O-linked glycosylation and to explore putative lipid modifications. Approximately 90% of the S-layer was mapped and N-glycans were identified at all the mapped consensus sites, decorated with a pentasaccharide consisting of two hexoses, two hexuronic acids and a methylated hexuronic acid. The O-glycans are homogeneously identified as a disaccharide consisting of galactose and glucose. Unexpectedly it was found that membrane-derived lipids were present in the S- layer samples despite extensive purification, calling into question the predicted presence of covalently linked lipid. The H. volcanii N-glycosylation is mediated by the products of the agl gene cluster and the functional characterisation of members of the agl gene cluster was investigated by MS analysis of agl-mutant strains of the S-layer. Burkholderia pseudomallei is the causative agent of melioidosis, a serious and often fatal disease in humans which is endemic in South-East Asia and other equatorial regions. Its LPS is vital for serum resistance and the O-antigen repeat structures are of interest as vaccine targets. B. pseudomallei is reported to produce several polysaccharides, amongst which the already characterised ‘typical’ O-antigen of K96243 represents 97% of the strains. The serologically distinct ‘atypical’ strain 576 produces a different LPS, whose characterisation is the subject of this research project. MS strategies coupled with various hydrolytic and chemical derivatisation methodologies were employed to define the composition and potential sequences of the O-antigen repeat unit. These MS strategies were complemented by a novel NMR technique involving embedding of the LPS into micelles. Taken together the MS and NMR data have revealed a highly unusual O-antigen structure for atypical LPS which is remarkably different from the typical O-antigen. The development of structural analysis tools in MS and NMR applicable to the illustrated types of glycosylation in these prokaryotes will give a more consistent approach to sugar characterisation and their modifications thus providing more informative results for pathogenicity and immunological studies as well as pathway comparisons.Open Acces

Preparation and properties of polybenzodioxane PIM-1 and its copolymers with poly(ethylene glycol)

This thesis describes the synthesis of soluble Polymer of Intrinsic Microporosity (PIM-1), fluoro-endcapped PIM-1 (F-PIM-1) and copolymers of F-PIM-1 with poly(ethylene glycol) monomethyl ether (MeOPEG). The main aim of the project was to alter the porosity of microporous PIM-1 in three ways: (a) synthesis of copolymers of F-PIM-1 with MeOPEG (b) blending of PIM-1 with MeOPEG in various proportions; and (c) adsorption of MeOPEG from aqueous solution byPIM-1. PIM-1 and F-PIM-1 were synthesized by step growth polymerization of tetrafluoroterephthalonitrile (TFTPN) with 5,5',6,6'-tetrahydroxy-3,3,3',3'-tetramethyl-1,1'-spirobisindane (THSB), using the conventional method and a newly reported high shear mixing method. F-PIM-1 oligomers were then coupled to poly(ethylene glycol) monomethyl ether (MeOPEG). The products were analyzed by NMR, IR, MALDI ToF MSS, TGA and polystyrene based GPC as well as multidetector GPC techniques. The high shear technique generally produced high molar mass products and yields. This method was also more successful for copolymerization.Blending of PIM-1 and MeOPEG in different proportions resulted in macrophase separation. Copolymer products were used to facilitate mixing of blends (as compatibilizers), however only 5% of MeOPEG could be solubilised into a PIM-1 phase. The effect of compatibilizer was found to be affected by interaction between PIM-1 and copolymer. However, N2 adsorption studies showed that after thermal removal of MeOPEG, PIM-1 regained stable porosity with significant BET surface area.Fluorescence studies were aimed at applications of PIM-1 and copolymers in sensors. PIM-1 and copolymers, spin-coated on the polyester-based substrate Melinex, were studied with and without methanol treatment in an environment of different solvent vapours. The effect of time and volume on wavelength shift and change in intensity was studied. Polar solvents tended to cause a red shift with decrease in intensity while less polar solvents behaved otherwise. Based on fluorescence experiments, solvent profiles for PIM-1 and copolymers were established.EThOS - Electronic Theses Online ServiceHigher Education Commission, Government of PakistanGBUnited Kingdo

Molecular Simulation of Gas Permeation and Separation in Polymer Membranes

Ph.DDOCTOR OF PHILOSOPH

Development of a quantum dot-encoded microsphere suspension assay for the genotyping of single nucleotide polymorphisms

This thesis describes the investigation of quantum dot-doped particle fluorescent technology commercially available for its application to analyte profiling in suspension. The first part of the thesis described the characterisation of the quantum dot-encoded microspheres, QDEMs, developed by Crystalplex (PA, USA). The multiple fluorescence signatures of QDEMs were analysed using microscopy and flow cytometry technology which provided high-content measurements with a single excitation sources and multiple emission wavelength detectors. The sensitivity and stability of the materials was evaluated under typical biomedical conditions encounter in multiple analyte suspension assays. Novel analytical parameters were defined to study QDEM stability and confocal microscopy detection system was used to provide structural and fluorescent imagines of the fluorescent microspheres under various conditions. Composition of the aqueous environment, temperature and physical forces applied to QDEM induced changes in their fluorescent codes and structural properties. Optimal conditions were then defined for the application of the material to biomedical assays. In a second stage, a conjugation method was developed to produce optimised QDEM bioconjugates for the detection of single strand DNA in suspension. The impact of the conjugation buffer, the concentration and the structure of oligonucleotides was evaluated to optimise QDEM bioconjugates. Then, a novel approach was investigated to optimise the hybridisation of ssDNA to QDEM bioconjugates. Experimental design with response surface methodology determined optimum conditions for the hybridisation of oligonucleotides to QDEM surface in suspension array. Finally, the specific hybridisation of ssDNA to QDEM bioconjugates in a small liquid format adapted to single nucleotide polymorphism detection was demonstrated. The work presented here shows the potential of QDEM bioconjugates for suspension array technology and DNA genotyping. Further, this report highlights the challenges that remain for QDEM fluorescent technology to be reliable for biomedical and suspension array applications.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Glycoproteomic research using mass spectrometry

The development of problem-specific mass spectrometric (MS) glycoproteomic strategies has allowed the discovery of previously unknown protein glycosylation in both eukaryotic and prokaryotic organisms. The research in this thesis focuses on the identification and structural characterisation of novel glycan structures in ADAMTS13 and Clostridium difficile. ADAMTS13 is a large multi-domain protein which regulates thrombogenesis by cleavage of the adhesive blood glycoprotein, VWF, so generating smaller less thrombogenic fragments. Glycoproteomic strategies were employed to investigate a secretion-enhancing mutant by comparing the O-glycome of wild type (WT) with synonymous substitution, P118P, and a non-synonymous control, P118F. Identical post-translational modifications (PTMs) but several novel PTMs were discovered in ADAMTS13 including TSR1 O-glycosylation, C-mannosylation of W387 and DiSialyl Core-1 O-glycosylation of S1170. Clostridium difficile is one of the main organisms responsible for morbidity in hospitalised patients, and is the etiological agent of antibiotic-associated diarrhoea and pseudomembranous colitis. The C.difficile cell wall is surrounded by an S-layer composed of two proteins, high molecular weight (HMW) and low molecular weight (LMW) SLPs. 12 slpA gene cassettes have been recently described and cassette-11 carries an insert containing 19 ORFs. Combining different biochemical and ES- and MALDI-MS approaches, including the ETD technique, with genetic experiments, it was demonstrated that LMW SLP in strain Ox247 is glycosylated with a surprisingly large linear pentose-branched oligosaccharide of more than forty sugar residues, and a collaborative NMR study suggests a Phospho- and Acetyl- substituted non-reducing terminal rhamnose. Analysing different C.difficile hypervirulent strains, novel flagellar sulphonated peptidylamido-glycan structures not previously observed in sugar or amino acid chemistry were identified. High resolution mass measurement and negative-ion nanospray MS/MS of cone-voltage-induced fragment ions were crucial in allowing the discovery of a unique terminal Taurine (aminoethyl-sulphonic acid) peptidylamidoglycan unit which could provide a novel strategy to escape the immune system, by the C.difficile becoming more virulent.Open Acces