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No description available.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Abstract not available

Semi-synthetic β-lactam antibiotics are the most prescribed class of antibiotics in the world. Chemical coupling of a β-lactam moiety with an acyl side chain has dominated the industrial production of semi-synthetic β-lactam antibiotics since their discovery in the early 1960s. Enzymatic coupling of a β-lactam moiety with an acyl side chain can be accomplished in a process that is much more environmentally benign but also results in a much lower yield. The goal of the research presented in this dissertation is to improve the enzymatic synthesis of β-lactam antibiotics via reaction engineering, medium engineering and data-drive protein engineering. Reaction engineering was employed to demonstrate that the hydrolysis of penicillin G to produce the β-lactam nucleus 6-aminopenicillanic acid (6-APA), and the synthesis of ampicillin from 6-APA and (R)-phenylglycine methyl ester ((R)-PGME), can be combined in a cascade conversion. In this work, penicillin G acylase (PGA) was utilized to catalyze the hydrolysis step, and PGA and α-amino ester hydrolase (AEH) were both studied to catalyze the synthesis step. Two different reaction configurations and various relative enzyme loadings were studied. Both configurations present a promising alternative to the current two-pot set-up which requires intermittent isolation of the intermediate, 6-APA. Medium engineering is primarily of interest in β-lactam antibiotic synthesis as a means to suppress the undesired primary and secondary hydrolysis reactions. The synthesis of ampicillin from 6-APA and (R)-PGME in the presence of ethylene glycol was chosen for study after a review of the literature. It was discovered that the transesterification product of (R)-PGME and ethylene glycol, (R)-phenylglycine hydroxyethyl ester, is transiently formed during the synthesis reactions. This never reported side reaction has the ability to positively affect yield by re-directing a portion of the consumption of (R)-PGME to an intermediate that could be used to synthesize ampicillin, rather than to an unusable hydrolysis product. Protein engineering was utilized to alter the selectivity of wild-type PGA with respect to the substituent on the alpha carbon of its substrates. Four residues were identified that had altered selectivity toward the desired product, (R)-ampicillin. Furthermore, the (R)-selective variants improved the yield from pure (R)-PGME up to 2-fold and significantly decreased the amount of secondary hydrolysis present in the reactions. Overall, we have expanded the applicability of PGA and AEH for the synthesis of semi-synthetic β-lactam antibiotics. We have shown the two enzymes can be combined in a novel one-pot cascade, which has the potential to eliminate an isolation step in the current manufacturing process. Furthermore, we have shown that the previously reported ex-situ mixed donor synthesis of ampicillin for PGA can also occur in-situ in the presence of a suitable side chain acyl donor and co-solvent. Finally, we have made significant progress towards obtaining a selective PGA that is capable of synthesizing diastereomerically pure semi-synthetic β-lactam antibiotics from racemic substrates.

The implementation of sustainable solvents and processes is critical to new developments in reducing environmental impact, improving net efficiency, and securing economic profitability in the chemical and pharmaceutical industries. In order to address the challenge of sustainability, researchers have used switchable solvents for both reaction and separation by utilizing a built-in switch to undergo a step change in chemical and physical properties. This allows us to facilitate reactions in the solvent then activate the switch to enable separation and facile product recovery. Subsequently, we can recover the solvent for reuse and avoid energy- or waste-intensive separation processes; thus we are developing and using these switchable solvents as sustainable and environmentally benign alternatives to traditional processes. In this research, we enable the sustainable scale-up of a switchable solvent - piperylene sulfone - a "volatile" and recyclable DMSO replacement. In the development of this process, we improved the reaction performances and developed a green purification method. Furthermore, we enable and demonstrate the implementation of a Meerwein-Ponndorf-Verley (MPV) reduction, a pharmaceutically relevant reaction, into a continuous flow platform. The innovation of continuous flow processes can replace traditional batch reaction technology, and is indeed a key research area that has been acknowledged by the pharmaceutical industry. Additionally, we utilize the switchable sulfone solvents, piperylene and butadiene sulfone, for reaction and separation of HMF produced from monosaccharides as an alternative to a process which has been limited by an inefficient separation step.

Cross-linked polyethylene has higher upper use temperature than normal polyethylene and is used as an insulating material for electricity carrying cables and hot water pipes. The most common method of inducing crosslinks is by reaction with silanes. After incorporation of silanes into polyethylene and upon hydrolysis with ambient moisture or with hot water, Si-O-Si crosslinks are formed between the various linear polyethylene chains. Industrially, this reaction is performed routinely. However, the efficiency of this reaction with respect to the silane is low and control of product distribution is difficult. A precise fundamental understanding is necessary to be able to manipulate the reactions and thus, allow for the facile processing of the polymers. Hydrocarbon models of polymers - heptane, dodecane - are being used to study this reaction in the laboratory. For the reaction, vinyltrimethoxysilane is used as the grafting agent along with di-tert-butyl peroxide as the radical initiator. MALDI, a mass spectrometric technique is used for the analysis of the product distribution after work-up. Advanced NMR techniques (COSY, HSQC, DEPT, APT, HMBC) are being conducted on the grafted hydrocarbon compounds to gain an in-depth understanding of the mechanism and regiochemistry of the grafting reaction. Scalable and cost effective methods to capture CO2 are important to counterbalance some of the global impact of the combustion of fossil fuels on climate change. The main options available now include absorption, adsorption and membrane technology. Amines, especially monoethanolamine, have been the most commercialized technology. However, it is not without disadvantages. House et al have investigated the energy penalty involved in the post-combustion CO2 capture and storage from coal-fired power plants and found that 15-20% reduction in the overall electricity usage is necessary to offset the penalty from capturing and storing 80% of United States coal fleet's CO2 emssions1. Novel non-aqueous amine solvents, developed by the Eckert Liotta group, react with CO2 to form ionic liquids. The ionic liquids readily desorb CO2 upon heating, regenerating the reactive amines and this cycle can be carried out multiple times. An iterative procedure is being adopted to develop amine solvents for CO2 capture. Thermodynamic information like reversal temperature and boiling point of the solvents are collected; they are then used to formulate structure property relationships which allow for new molecules to be engineered. On reaction with CO2, there is a sharp increase in viscosity which is unfavorable from a processing standpoint. Many approaches to mitigate and control viscosity are being studied as well. 1House et al, Energy Environ Sci, 2009, 2, 193-205

Thesis (Ph. D.)--Chemistry and Biochemistry, Georgia Institute of Technology, 2009. / Committee Chair: Ragauskas, Arthur; Committee Member: Bunz, Uwe; Committee Member: Cairney, John; Committee Member: Collard, David; Committee Member: Singh, Preet. Part of the SMARTech Electronic Thesis and Dissertation Collection.

An increasing demand for electricity in modem society has resulted in the burning of large quantities of coal and ultimately the production of large quantities of fly ash. The petrochemical industry, if based on coal in a country such as South Africa, also produce large quantities of fly ash. In a semi-arid country like South Africa, there is a need to recover water. Processes currently in use for the recovery of wastewater produce large quantities of brines. These brines are stored in waste dams, which are not only expensive to maintain, but also pose a potential threat to the environment. The process of geosynthesis led to the development of a new type of material, namely geopolymers. Geopolymers can best be viewed as a polymeric silicon-oxygen¬aluminium framework with alternating silicon and aluminium tetrahedra joined together in three directions by sharing all the oxygen atoms. Cations such as Na+, K+, Ca2+ and H3O+ must be present in the framework cavities to balance the negative charge generated by the Al3+ in IV-fold co-ordination. It was attempted in this study to manufacture a geopolymeric binder, supplying most of the ingredients through waste materials. In the first set of experiments, matrices containing different amounts of fly ash, kaolinite, sodium hydroxide, sodium silicate and brine or water were synthesised by mixing and heating at 50°C for 24 hours. Compressive strength measurements showed a maximum strength of 4.05 MPa after 28 days. Leaching tests indicated that sodium was the best stabilised showing a stabilisation of between 30 and 40% (70 to 60% of the sodium initially added leached out again). The anions were stabilised to a lesser extent. Infrared spectra obtained confirmed an aluminosilicate structure. The second set of experiments was done to obtain the optimum curing conditions. Matrices containing the same amounts of fly ash, kaolinite, sodium hydroxide, sodium silicate and brine or water were cured at different temperatures and for different time periods. The matrices containing water showed a maximum compressive strength of 7.25 MPa after 28 days when cured at 60°C for 48 hours, while their brine-containing counterparts showed a maximum compressive strength of 7.76 MPa after 28 days when cured at 70°C for 72 hours. Infrared spectra obtained confirmed an aluminosilicate structure while X-ray diffraction patterns obtained indicated a largely amorphous product. In the third set of experiments matrices containing different amounts of fly ash, metakaolinite, sodium hydroxide, sodium silicate and brine or water were synthesised by mixing and heating at the optimum conditions determined previously. Compressive strength measurements indicated a maximum strength of 1.45 MPa after 28 days. Leaching tests indicated a higher stabilisation of the cations than in the first set of experiments. Potassium was the best stabilised, showing a stabilisation of above 80%. The anions were again stabilised to a lesser extent. Infrared spectra obtained confirmed an aluminosilicate structure while X-ray diffraction patterns obtained indicated a largely amorphous material. / Dissertation (MSc (Chemistry))--University of Pretoria, 2007. / Chemistry / unrestricted

The construction industry is increasingly turning to the use of environmentally friendly materials in order to meet the sustainable aspect required by modern infrastructures. Consequently, for the last two decades, the expansion of this concept, and the increasing global warming have raised concerns on the extensive use of Portland cement due to the high amount of carbon dioxide gas associated with its production. The development of geopolymer concretes offers promising signs for a change in the way of producing concrete. However, to seriously consider geopolymer binders as an alternative to ordinary Portland cement, the durability of this new material should be evaluated in any comparative analysis. The main purpose of this study was to evaluate the durability characteristics of low calcium fly ash-based geopolymer concretes subjected to the marine environment, compared to ordinary Portland cement concrete with similar exposure. To achieve this goal, 8 molar geopolymer, 14 molar geopolymer and ordinary Portland cement concrete mixes were prepared and tested for exposure in seawater. Compressive strengths in the range of 2900 to 8700 psi (20-60 MPa) were obtained. The corrosion resistance performance of steel-reinforced concrete beams, made of these mixes, was also studied, using an accelerated electrochemical method, with submergence in salt water. The test results indicated that the geopolymer concrete showed excellent resistance to chloride attack, with longer time to corrosion cracking, compared to ordinary Portland cement concrete. / by Jean-Baptiste Edouard. / Thesis (M.S.C.S.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.