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Sulfonated poly(arylene ether sulfone)s as ion conductive copolymers have numerous potential applications. Membranes cast from these copolymers are desirable due to their good chemical and thermal stability, excellent mechanical strength, satisfactory conductivity, and excellent transport properties of water and ions. These copolymers can be used in a variety of topologies. Structure-property-performance relationships of these membranes as candidates for electrolysis of water for hydrogen production and for purification of water from dissolved ions have been studied. Linear and multiblock sulfonated poly(arylene ether sulfone)s are potential alternative candidates to Nafion membranes for hydrogen gas production via electrolysis of water. In this investigation, these copolymers were prepared from the direct polymerization of di-sulfonated and non-sulfonated comonomers with bisphenol monomers. In systematic investigations, a series of copolymers with modified properties were synthesized and characterized by changing the ratio of the sulfonated/non-sulfonated comonomers in each reaction. These copolymers were investigated in terms of mechanical stability, proton conductivity and H2 gas permeability at a range of temperatures and under fully hydrated conditions. A multiblock copolymer was synthesized and evaluated for its potential as membranes for electrolysis of water and for fuel cell applications. The multiblock copolymer contained some fluorinated repeat units in the hydrophobic blocks, and these were coupled with a fully disulfonated hydrophilic block prepared from 3,3'-disulfonate-4,4'-dichlorodiphenyl sulfone and biphenol. After annealing, the multiblock copolymer showed enhanced proton conductivity and a more ordered morphology in comparison to the random copolymer counterparts. At 90 oC and under fully hydrated conditions, improved proton conductivity and controlled H2 gas permeability was observed. Finally, the performance of the multiblock copolymer, which was measured as the ratio of proton conductivity to H2 gas permeability, was improved when compared to the state-of-the-art membrane, Nafion 212, by a factor of 3. In another systematic study, two series of random copolymers were synthesized and characterized, and then cast into membranes to evaluate for electrolysis of water. One series contained solely hydroquinone as the phenolic monomer, while the second series contained a mixture of resorcinol and hydroquinone as phenolic comonomers. The polymers that contained only the hydroquinone monomer showed exceptionally good mechanical properties due to the para-substituted comonomer in the composition of the polymer. In the resorcinol-hydroquinone series, gas permeability was constrained due to the presence of 25% of the meta-substituted comonomer incorporated into its structure. Low gas permeability and high proton conductivity at elevated temperatures were obtained for both the linear random and multiblock copolymers. Performance of these copolymers was superior to Nafion at elevated temperatures (80-95°C). In order to enhance the durability of these materials in their hydrated states at elevated temperatures, the surfaces of these copolymer films were treated with fluorine gas. In comparison with pristine non-fluorinated membranes, the modified membranes showed decreased water uptake and longer durability in Fenton's reagent. A series of linear and crosslinked copolymers were investigated with respect to their potential for use as membranes for desalination of water by electrodialysis and reverse osmosis. The crosslinked membranes were prepared by reacting controlled molecular weight, disulfonated oligomers that were terminated with meta-aminophenol with an epoxy reagent. The oligomers had systematically varied degrees of disulfonation and either 5000 or 10,000 Da controlled molecular weights. Membrane casting conditions were established to fabricate highly crosslinked systems with greater than 90% gel fractions. At such a high gel fraction, the water uptake of the crosslinked membranes was lower than that of the linear biphenol-based, disulfonated random copolymer with a similar IEC. Among these series of copolymers, it was shown that the crosslinked membranes cast from the oligomers with 50% degree of disulfonation and a molecular weight of 10,000 Da had the lowest salt permeability of 10-8 cm2/sec. For desalination applications, a comonomer was synthesized with one sulfonate substituent on 4,4'-dichlorodiphenyl sulfone. This new monosulfonated comonomer allows for even distribution of the ions on the linear copolymer backbone, and this may be important for controlling ion transport. Mechanical tests were conducted on the membranes while they were submerged in a water bath. The ultimate strength of a fully hydrated copolymer with an IEC of 1.36 meq/g was approximately 60 MPa with an elongation at break of 160%. Moreover, in a monovalent/divalent mixed salt solution, the monosulfonated linear copolymer exhibited a constant Na+ passage of less than 1.0%. / Ph. D.

Tuberculosis affects millions of people worldwide every year. The current treatment for TB is divided into a regimen of both first- and second-line drugs, where first-line treatments are more tolerated and require shorter treatment lengths. With rising levels of resistance, alternative treatment regimes are urgently needed to fight this disease. Ethionamide, a second-line drug is administered as a prodrug which is activated in vivo by the enzyme EthA, which is in turn regulated by EthR. The disruption of the action of EthR could lead to novel therapeutics which could enhance the efficacy of ethionamide, and raise it to a first-line treatment. The work reported in this thesis examines the elaboration of three chemical scaffolds using fragment-based approaches to develop novel inhibitors capable of disrupting the EthR-DNA interaction. The first scaffold, 5-(furan-2-yl)isoxazole was investigated by fragment-merging approaches and produced compounds with the best of these having a KD of 7.4 uM. The second scaffold, an aryl sulfone was elaborated using fragment-merging strategies. This led to several modifications of the fragment, leading to several variants with KDs around 20 uM. With both of these series the affinity could not be improved below 10 uM and due to the synthetic complexity a further scaffold was prioritised. The third scaffold was explored was a 4-(4-(trifluoromethyl)phenyl)piperazine using fragmentgrowing from the NH of the piperazine to probe deeper into the EthR binding pocket. In addition to this, SAR around the 4-(trifluoromethyl)phenyl group was assessed to explore the interactions with EthR. These modifications led to compounds with nanomolar IC50s. A range of compounds were then screened by REMAssay to determine the boosting effect on ethionamide, and this identified compounds with up to 30 times boosting in the ethionamide MIC. The final chapter examines a concept where compounds were designed to exploit the dimeric nature of EthR by linking two chemical warheads with a flexible linker. These compounds are examined using mass spectrometry to investigate the stoichiometry of the interaction to provide insight into the binding of these extended compounds and exploring an alternative strategy to inhibit EthR. The work in this thesis demonstrated the successful use of fragment-based approaches for development of novel EthR inhibitors which showed significant ethionamide boosting effects.

Charles University in Prague, Faculty of Science Department of Organic Chemistry Ing. Yana Chernykh Sulfur-Based Reagents for Nucleophilic and Radical Introduction of Tetrafluoroethyl and Tetrafluoroethylene Groups Ph.D. Thesis Prague 2014 ABSTRACT This project was aimed at developing new methodologies for selective introduction of tetrafluoroethyl and tetrafluoroethylene groups into organic molecules. The study was focused on reactivities of fluorinated sulfones and sulfides as tetrafluoroalkylation reagents. In the Introduction part of the thesis, main aspects of organofluorine chemistry are outlined, illustrating beneficial effects of fluorine atoms on physical, chemical and biological properties of organic compounds. General synthetic methods for the selective introduction of fluorine atoms and fluoroalkyl groups to organic molecules are described. Particular attention is given to reactivity and applications of CF2CF2-containing compounds, indicating challenges in synthetic approaches toward tetrafluoroalkylation. The Results and discussion part describes reactivities of four new fluorinated organosulfur reagents as tetrafluoroethyl and tetrafluoroethylene building blocks. The application of these reagents as various carbanionic or radical synthons proved to be effective for the incorporation of CF2CF2...

The results described in this dissertation focus on the synthesis and utilization of several disulfonated poly(arylene ether) random copolymer membranes in fuel cell and reverse osmosis applications. Poly(arylene ether)s were prepared by direct step copolymerization using a third monomer 3,3–-disulfonated 4,4–-dichlorodiphenylsulfone. The membrane properties of a 4,4–-biphenol-based disulfonated poly (arylene ether sulfone) random copolymer (BPS-35), optionally blended with various fluorine containing polymers or unsulfonated biphenol-based poly (arylene ether sulfone)s (Radel R) were investigated for fuel cell applications. Fluorine containing copolymers used included with 2,2–-hexafluoroisopropylidene 4,4–-biphenol based unsulfonated (6F-00) or disulfonated (6FS-35 and 6FS-60) PAES, hexafluoroisopropylidene biphenol based 4,4–-difluoro phenyl phosphine oxide) (6FPPO), and poly(vinylidene fluoride) (Kynar®). Tapping mode atomic force microscopy (TM-AFM) images of the membranes with 10 wt% of fluorinated copolymers showed macroscopic phase separation. Good miscibility between the copolymers at low concentrations was also confirmed by the observation of only one glass transition temperature. Compared to the benchmark Nafion 1135, the 10wt% blends of the fluorinated copolymers afforded a considerable reduction in the methanol permeabilities, which is important for direct methanol fuel cells (DMFC). The best DMFC performance with 0.5 M methanol fuel was illustrated with blends containing 10 wt% 6FS-00. At higher methanol concentrations (up to 2.0 M) BPS-35/6FS-00 (90/10) membranes outperformed both Nafion membranes. Blends of BPS-35 blends with 6FS-35 or Radel R were also used as RO membranes. The highest salt rejections of 97.2 and 98.0% were obtained from BPS35/Radel R (90:10) and BPS-35/6FS-35 (95:5) blends, respectively in the salt form. A systematic study of the preparation of BPS-20 random copolymer skin-core asymmetric membranes by diffusion induced phase separation (DIPS) from various polar aprotic solvent or cosolvent systems is reported. The best aprotic solvents to generate an asymmetric structure were NMP and DMAc whereas tetrahydrofuran (THF)/ formamide (FAm) (80/20 v/v) mixtures proved to be the best co-solvent systems. Acetone was the best non-solvent to prepare asymmetric membranes from both aprotic solvents and co-solvent mixtures. Overall, asymmetric membranes prepared from THF/FAm co-solvent mixtures illustrated the most stable phase separated morphology that was free of macrovoids. However, thicker skins (~5 μM) were formed due to the high volatility of THF. Therefore, ultra-thin skin thin film composites (TFC) based on BPS-20 in diethylene glycol (Di(EG) were prepared. Thermal treatment of these TFC was conducted at 90 °C and the addition of 20 wt% glycerin to the casting formulation helped to prevent pore collapse in the porous Udel polysulfone. A minimum of three coats was required to obtain a dense, smooth, and pinhole free skin layer. The generation of three dimensional (ternary) solubility parameter phase diagrams based on experimental data was formulated and a region of solubility based on the solubility parameters of the aprotic solvents and the different co-solvent systems was established for BPS-20. / Ph. D.

This thesis focuses on the synthesis and characterization of various poly(arylene ether)s to improve the efficiency of gas separation and water desalination membranes. This class of polymers includes polymers such as poly(arylene ether sulfone), poly(arylene ether ketone) and poly(phenylene oxide) which offer excellent thermal and mechanical stability and usually have high enough rigidity to support gas separation and water desalination operations. Besides the plethora of properties offered by the homopolymers, these polymers can also be post-modified to cater to specific needs. For example, the polyphenylene oxides have been brominated to increase the permeability for gas separation applications. Blending is another viable method to impart desirable properties to polymers. Bisphenol A based poly(arylene ether ketone) (BPAPAEK) has been blended with commercially available poly(2,6-dimethylphenylene oxide)s (PPO) of different molecular weights in a fixed ratio (66/34 wt/wt) and in various ratios of a 22000 g/mol PPO. All the blends were UV crosslinked to minimize plasticization by condensable gases and analyzed for gel fractions, whereas, only the 22,000 g/mol blends were tested for transport properties since they yielded the highest gel fractions and exhibited the best mechanical properties. The crosslinking reduced the free volume and improved the selectivity with some drop in permeability. The blends with 90% of the 22000 g/mol PPO by weight was plotted closest to the upperbound. A phosphine oxide based poly(arylene ether ketone) (POPAEK) was blended with the various PPOs in a similar manner. The results were compared to the BPAPAEK based blends in terms of miscibility behavior and transport properties. It was found that the POPAEK based blends had higher permeability due to the higher fractional free volumes of the POPAEK. The POPAEK was more compatible with the PPOs than BPAPAEK as seen by analyzing various blend permeability models, mechanical properties and scanning electron microscope images. Moreover, blends with both the PAEKs displayed only a small drop in mechanical properties, such as the Young's modulus and the yield strength in comparison to the parent polymers. Hydroquinone based poly(arylene ether sulfone) oligomers were synthesized, post-sulfonated and chemically crosslinked to determine the effect of water uptake, fixed charge concentration and block length of oligomers on the salt permeability and the hydrated mechanical properties of the networks. The sulfonic acid groups were placed strategically and quantitatively on the hydroquinone units. The strategic placement of the acid groups may help in maintaining high rejection of monovalent ions in the presence of divalent ions, as shown in unpublished work by our group. It was found that the water uptake and fixed charge density had the opposite effects on the salt permeability. Also, the salt permeability varied differently for 5000g/mol and 10000g/mol block based networks. Another polymer that was investigated in this thesis was poly(2-ethyl-2-oxazoline) (PEtOx). An elaborate account of synthesis of monofunctional, heterobifunctional and telechelic poly(2-ethyl-2-oxazoline)s using different initiators including methyl triflate, activated alkyl halides (e.g., benzyl halides), and non-activated alkyl halides has been presented in this thesis. Endgroup functionalities and molecular weight distributions were studied by SEC, 1H NMR and titrations. The oligomers initiated with the benzyl or xylyl chloride had a PDI of 1.3-1.4 which is broader than expected for a living cationic ring opened polymer. This was attributed to the participation of covalent species which propagated slowly in the activated halide reactions. These oligomers were quantitatively terminated as proven by NMR and titrations. Due to the molecular weight distributions and quantitative termination these oligomers were deemed to be desirable for drug delivery applications. / PHD