A dissertation submitted In fulfilment of the degree Doctor of Philosophy (Chemistry) In the Faculty of Science School of Chemistry University of the Witwatersrand. Johannesburg 2015. / According to the World Health Organization (WHO), cancer is a leading cause of death worldwide and has accounted for 7.6 million deaths (13% of all deaths) in 2008. The number of effective drugs available has been reduced by chemo resistant malignant tumors. Similarly, bacterial infections are one of the world’s most pressing public health problem. The major challenge in anti-bacterial treatment is due to the development of bacteria strains that are resistant to antibiotics. Each year more than 11 million people die from major infections such as MDR tuberculosis. In 2013, 9 million people fell ill with TB and 1.5 million died from the disease (WHO). Therefore there is a need for novel therapeutic alternatives such as the discovery of new anti-cancer and anti-bacterial agents. Benzofurans have attracted much attention due to their broad spectrum of pharmacological activities such as anti-cancer and anti-bacterial activities and one classical example is usnic acid. Most of the published synthesis of the benzofuran moiety involved the formation of annellated furan ring by intramolecular cyclisation of benzene, and these procedures involved a multi-step, rigorous reaction conditions and expensive catalyst. This research investigated the novel synthesis of benzofurans through the application of biocatalysis, where the reactions involved the use of the oxidative enzyme laccase to generate carbon-carbon bonds, carbon-oxygen and carbonnitrogen bonds between aromatic compounds. The substrates used were o-diols from catechols 1, p-quinone 2 from naphthoquinones and naphthohydroquinone 3, which, when activated by the enzyme action, could be reacted with 1,3-diketones 4, 5 or coumarins 6 (Figure 1). The aim of synthesising different classes of compounds was to vary the functional groups and to increase the number of rings, so as to possibly increase the biological activities.

Thesis advisor: Lawrence T. Scott / Thermal cyclodehydrogenation is the key step in the total synthesis of fullerene C60 and represents an important family of carbon-carbon bond-forming reactions. My research focuses on understanding the mechanism of C-C bond formation in the high temperature cyclodehydrogenations of PAHs using appropriate test cases to form 5- or 6-membered rings. My goal was to understand more about molecular reactions under extreme conditions and thereby realize new synthetic pathways for new molecules. This dissertation describes the synthesis of several substrates and studies of their thermal cyclodehydrogenations. Chapter 1 presents the cyclodehydrogenations of [5]helicene and benzo[5]helicene to form 6-membered rings under flash vacuum pyrolysis (FVP) conditions. An observed rate difference established that an electrocyclic mechanism is favored in this case and disproved the radical cyclization and 1,2-hydrogen shift/carbene insertion mechanisms. Chapter 2 describes the cyclodehydrogenations of phenyl-substituted phenanthrenes to form 6-membered rings under FVP conditions. The radical mechanism is ruled out because of the rate difference. Chapter 3 shows the synthesis of 7-(9H-fluoren-9-ylidene)-7H-benzo[c]fluorene and its thermal cyclodehydrogenation to form 6-membered rings under FVP conditions. In chapter 4, the cyclodehydrogenations of phenyl-substituted anthracenes and phenanthrenes to form 5-membered rings under FVP conditions are presented. The unexpected dominance of phenyl loss suggests that radical mechanisms are occurring during the cyclodehydrogenations. Chapter 5 describes the cyclodehydrogenations of [4]helicene and benzo[4]helicene to form 5-membered rings under FVP conditions. The results point to a carbene cyclization mechanism, in competition with the radical mechanism. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Dissertation submitted for the qualification Master of Science in Molecular and Cell biology (full time) University of Witwatersrand 01 February 2016 / Ambergris is a large lump excreted by whales, when exposed to sunlight, air and sea water, it oxidatively decomposed through inorganic reactions to form different compounds including (-) ambrafuran. (-) Ambrafuran is a highly fragrant compound and it is considered to be a stronger perfume ingredient than other constituents in ambergris. It is used as a fixative agent to stabilize perfumes by reducing the rate of evaporation of volatile substances. A two-step process for production of (-) ambrafuran starting from sclareol was developed at CSIR for an industrial partner, Teubes cc. The current commercial production of (-) ambrafuran entails a chemical process consisting of at least 8 steps and require very harsh chemicals and elevated temperatures. In the current study, relevant technologies for the optimization of a process for commercial production of (-) ambrafuran were investigated. The project objective has been to optimize fermentation conditions on laboratory scale for the conversion of sclareol to an intermediate diol using the microorganism Hyphozyma roseoniger and to subsequently test different zeolites for conversion of diol to (-) ambrafuran. Production of ambradiol was achieved in potato dextrose broth media in 13 days compared to a patented method which took 16 days. The method was also scaled-up in a 2 L fermentation bioreactor and the yield of 93% was achieved after 24 hours of reaction. Following the initial use of the zeolite CBV320, two new zeolites (CFG-1 and ZD0614) were identified which have the potential to convert ambradiol to (-) ambrafuran without undergoing an activation process. Zeolite CFG-1 have been recognized to be highly effective for converting the intermediate ambradiol to the resulting (-) ambrafuran. One of the greatest outcomes of this research project is that the amount of zeolite required per substrate has been reduced from between 1:6 and 1:9 to 1:2. The substrate concentration has been increased from 5 mg/mL to 100 mg/mL which also resulted in the reduction of the volume of solvent required for the cyclodehydration step. The study allowed for scale-up and following further optimisation on larger scale should result in a process on commercial scale.

Polycyclic aromatic hydrocarbons (PAHs) are an important class of persistent organic pollutants (POPs) that are commonly found in the environment at low concentrations. POPs are long-lived organic compounds and originate almost entirely from anthropogenic activities such as chemical industries, combustion and agriculture activities. Owing to their potential carcinogenicity, mutagenicity and teratogenicity, PAHs have been determined in several matrices, particularly water, soil and sediment. Hazards associated with these compounds are owing to their hydrophobic character, persistence and bioaccumulation properties of several individual PAHs. Hence the primary goal of this research was to identify and determine PAHs in water and sediment samples, from rivers and dams in greater Johannesburg area, South Africa. In this work, three extraction techniques have been optimized for the extraction of PAHs in various samples. The extraction techniques based on hollow fiber liquid phase microextraction (HF-LPME) and solid phase extraction (SPE) were optimized for aqueous samples. Microwave assisted extraction technique (MAE) was optimized for solid samples. The optimized methods were applied to real water and sediment samples in and around Johannesburg area. HF-LPME and SPE techniques were compared with each other, while MAE was compared with Soxhlet (SE) in terms of their extraction efficiencies, enrichment factors, detection limits, relative standard deviations and concentrations of PAHs found in real samples. HF-LPME technique involved extraction of PAHs from a 20 mL sample containing 20% acetonitrile as a modifier. The PAHs were extracted into a 5 cm hollow fibre filled with heptane as organic solvent. At a stirring speed and extraction time of 600 rpm and 30 minutes, respectively, the acceptor solvent was collected to be analysed by GC-MS. The obtained enrichment factors ranged from 40 to 95 and the recoveries ranged from 3-8% depending on individual PAHs. The detection limits ranged from 23.0-95.0 ng L-1 while relative standard deviations for the recoveries were less than 5%, (n=3). The concentrations obtained in real water samples ranged from 30.3-213.8 ng L-1 and the relative standard deviations were between 0.8-11.9%, (n=3). SPE technique involved extraction of PAHs from a 100 mL sample containing 10% methanol as a modifier. The PAHs were extracted using C18 cartridges with 40% methanol in water as conditioning solvents and 3 mL acetone: THF (1:1) as eluting solvents. After eluting, the analyte is reduced to 1 mL under nitrogen and then analysed using GC-MS. The obtained enrichment factors ranged from 78-135 depending on the individual PAH. The detection limits ranged from 20.0-52.0 ng L-1. The relative standard deviations for the obtained enrichment factors were less than 6%. The obtained concentrations from real water samples ranged from 21.4-615.7 ng L-1 and the relative standard deviations were between 1.9-13.0%, (n=3). In MAE technique, the extraction was carried out with 20 mL of hexane: acetone (1:1, v/v) mixture with 1 g sample at 250 W for 20 minutes. After extraction, the extract was cleaned and reduced to 1 mL under nitrogen and then injected into an HPLC-Fluoresence system. The obtained recoveries ranged from 61-98% depending on the individual PAHs. The detection limits obtained ranged from 0.03-0.5 μg L-1 for HPLC-Fluorescence. The relative standard deviations were less than 6% for the obtained enrichment factors. The obtained concentrations in the sediments ranged from 61-45281μg kg-1 and the relative standard deviations ranged from 2.1-10.8%, (n=3). The possible major sources of PAHs pollution in rivers and dams in great Johannesburg area was suspected to be due to poor wastewater and solid waste management in informal settlements and a large oil spill accident that happened. This is supported by the large concentrations of PAHs found in sediments from Jukskei River which passes through one of the largest informal settlements. The pH in this river is also basic with large conductivity suggesting the presence of anions. The recipient dam of this river had also problems of algae and weeds growing in it. The influence of oil spill that happened is supported by decreasing concentrations of PAHs in the sediments with distance away from the accident area in the Blaauwpan dam. Other possible sources of PAHs are vehicle emission since studies have shown that from about 2005, the number of these in high ways in the city have been increasing by about 15-20% per year.

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Graduation date: 1999

The catalytic hydrogenation of an aromatic sulfonyl chloride was investigated in continuous and semi-batch mode processes using a Robinson-Mahoney stationary basket reactor. A complete experimental unit was designed and built. The operating and analytical procedures have been developed and the methodologies to gather the kinetic data have been described. Hydrogenation reactions were conducted at a reaction pressure of 364.7 psia, at three different reaction temperatures: 85 °C, 97 °C and 110 °C, at five different residence times: 0.6 (only at 110 °C), 1.0, 1.5, 2.0, 3.1 hr, with the hydrogen to the aromatic sulfonyl chloride molar ratio: 8.0 mol/mol and hydrogen to argon molar ratio: 3.0 mol/mol. Intrinsic reaction rates of the reacting species were obtained on the surface of a commercial 1 wt% palladium on charcoal catalyst. The conversion and molar yield profiles of the reacting species with respect to process time suggest a deactivation of the 1 wt % palladium on charcoal catalyst. Kinetic data collected in a continuous process mode show that the catalyst is deactivated during an experiment when the process time equal to two to three times the residence time of the liquid within the reactor. XRD analysis shows that the active sites are blocked and an amorphous layer was formed on the surface of the palladium catalyst. Semi-Batch mode experimental data were obtained at 110 °C after 8 hours of reaction time for several aromatic sulfonyl chlorides. A kinetic model has been developed, which includes adsorption of individual components and surface reactions as well as rate equations of the Hougen-Watson type. A hyperbolic deactivation function expressed in term of process time is implemented in the Hougen-Watson equation rates. The mathematical model consists of non-linear and simultaneous differential equations with multiple variables. The kinetic parameters were estimated from the minimization of a multi-response objective function by means of a sequential quadratic program, which includes a quasi-Newton algorithm. The statistical analysis was based on the t- and F-tests and the simulated results were compared to the experimental data.

Thesis (Ph. D.)--University of Missouri-Columbia, 2000. / Typescript. Vita. Includes bibliographical references. Also available on the Internet.