published_or_final_version / Chemistry / Doctoral / Doctor of Philosophy

This project is focused on the synthesis and biological activity of aloin and derivatives. Aloin is a C-glucoside anthrone that is found in Aloe marlothii, a common Southern African plant used in traditional medicine. Aloin was isolated from A. marlothii, employing a selective chelation isolation procedure. This compound is known to have numerous biologically active properties, and can be used as a laxative, an anti-bacterial agent, an anti-oxidant, and as a cytotoxic drug against breast and ovarian tumour cell lines. More relevant to this research investigation, was the reported anti-inflammatory activity of aloin. Specifically, the inhibitory activity of aloin on matrix metalloproteinases, which when excessively secreted, can lead to the development of osteoarthritis and cancer metastasis. Aloin has also been reported to have antiplasmodial activity, which was also investigated. Aloin was synthetically transformed into several derivatives, which could be potentially useful medicinal compounds. The choice of derivatives to be made was based upon (i) known biologically active compounds (e.g. aloe-emodin) and (ii) interesting biologically active functional groups (e.g. amines). These aloin derivatives include aloe-emodin, rheinal, rhein and three amine derivatives. Homonataloin, an aloin-analogue, which was also isolated from A. marlothii, was synthetically transformed into nataloe-emodin. These two compounds serve as aloin structural analogues for the biological testing. Aloin and derivatives were characterised using NMR, HR-MS, UV and IR, which allowed for their unambiguous structural elucidation. Aloin and derivatives were all tested for (i) possible inhibition towards MMP-2 and MMP-9, which are the two most common MMPs in the blood, and (ii) antiplasmodial activity against chloroquine sensitive Plasmodium falciparum parasites. Doxycycline, a clinical tetracycline drug, was used as a reference compound for the biological assays, since it shares many common structural features with aloin and derivatives. 11-(Piperidin-1-yl)chrysophanol and 11-(morpholin-1-yl)chrysophanol proved to be the most potent selective MMP-2 inhibitors. 11-(Piperidin-1-yl)chrysophanol was also found to be the most potent against P. falciparum parasite, along with 11-(pyrrolidin-1-yl)chrysophanol. Aloin has been shown to be a cheap, easily obtainable lead compound that could facilitate the production of a range of powerful medicinal drugs. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2008.

The use of supported catalysts to essentially combine the positive traits offered by both homogeneous and heterogeneous catalysis has become a competitive field of research. In particular, hydrotalcite-like catalysts (HTIc) has proven to be valuable for this purpose. Various osmium - containing catalysts were synthesized according to the co-precipitation method viz. Os-Cu-HTIc, Os-Ni-HTlc and the Os-Co-HTlc. Techniques such as SEM, IR, EDS, XRD, ICP, BET and XPS were exploited during catalyst characterisation and these essentially confirm that the hydrotalcite (HT) structure has been obtained. Various olefin substrates, ranging from simple straight-chained alkenes to cyclic, allylic and halogenated olefins, were tested. The results are promising and suggest that the diols are produced both with high selectivity and in good yield. Further experiments suggest: 1) Ofthe various co-oxidants tested, N-methylmorpholine-N-oxide is most suitable 2) The reaction proceeds faster at 60 °C than at room temperature 3) The addition of water to the reaction mixture increases the rate of the reaction for most substrates and 4) The catalyst is thermally stable and produces better results when calcined at 200 0 C prior to use This thesis reports that a new heterogeneous catalytic system for the efficient and selective cisdihydroxylation of olefins has been developed - one which suggests no leaching of metal into the reaction solution and no over-oxidation products. / Thesis (M.Sc.)-University of KwaZulu Natal, 2004.

The study involves the investigation of the chemical composition of some marine organisms. This entails collecting the organism, extracting compounds from it and separation, characterization and identification of these compounds. Marine chemistry has been ignored by many scientists in the past and it is for this reason that these organisms have been investigated, with the aim of discovering their chemistry and also finding new compounds which might be of value in our society. Such value may be the medicinal benefit and/or the understanding of some toxicological effect of some species. This study was conducted on Codium extricatum, Palythoa natalensis, Zoanthus sansibaricus and Zoanthus durbanensis all of which were collected from reefs situated at the southern part of Durban in KwaZulu-Natal (KZN). Carpobrotus edulis was another organism that was used in this work. The plant normally occurs on sand dunes. This, however, was collected from the terrestrial environment within the premises of University of Natal (Durban). Sterols, i.e., compound l, 2 and compound 4 were obtained from both the Codium and Zoanthus genera. Zoanthus also gave compounds which are derivatives of genetic material and these include inosine nucleoside, adenine nucleoside and guanine nucleoside. Zoanthus further gave a compound which is aromatic in nature i.e., compound 5 and this belongs to a class of compounds known as the tyramines. Cinnamic acid was found from Carpobrotus edulis. The structures of all compounds were elucidated by conducting a number of experiments using spectroscopic methods. These included nuclear magnetic resonance spectroscopy (n.m.r), mass and infrared spectroscopy. / Thesis (M.Sc.)-University of Natal, Durban, 2000.

Diarylheptanoids are a family of plant metabolites with a characteristic structure of two hydroxylated aromatic rings attached by a linear seven-carbon chain. Diarylheptanoids have mostly been isolated from plants belonging to the Zingiberaceae family. The South African medicinal plant Siphonochilus aethiopicus, more commonly known as ‘wild ginger’, also belongs to the Zingiberaceae family. One of the compounds isolated from this plant it a novel diarylheptanoid. In this study, the synthesis of this novel diarylheptanoid will be investigated. The targeted diarylheptanoid has two substituted phenyl rings attached by a seven-carbon aliphatic chain with two sterogenic centers and a carbon-carbon double bond. Osmiumcatalysed asymmetric dihydroxylation was used to generate the two stereogenic centres. The Horner Wadsworth-Emmons (HWE) reaction was investigated, in order to generate the trans-double bond on the seven carbon aliphatic chain. HWE reaction is a transselective reaction leading to the formation of only the desired isomer. The synthetic strategy used for the synthesis of the targeted diarylheptanoid is the C2-moiety + C5-moiety strategy. The C2-moiety is the phosphonate ester and the C5-moiety is the aldehyde for the HWE reaction. In this investigation we were able to successfully synthesis the required C2-moiety and the C5-moiety. Both the precursors were synthesised from commercially available starting materials, utilising functional group transformation reactions. However, modifications to the C5-moiety were made due to its instability under the HWE reaction conditions. When the C5-moiety was an aldehyde, decomposition was seen under HWE reaction conditions. Thus the C5-moiety was converted to the corresponding lactol and then subjected to the HWE reaction. Nevertheless, this reaction was not successful, thus we were not able to couple the two precursors to form the desired seven-carbon aliphatic chain. Even though the targeted diarylheptanoid was not successfully synthesised, the synthetic route developed in this investigation is not only viable to the target compound but is also versatile enough to allow the synthesis of its analogues. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

(1). An improved method for synthesizing bicyclo (2,2,1) hepta-2,5-diene-7-spiro-1'-cyclopentane (5) has been developed. Thermal reaction of compound (5) with neat iron pentacarbonyl under nitrogen atmosphere affords the corresponding cage dimer (6). Some aspects of the syntheses, spectra, and chemistry of compound (5) and (6) are discussed. (2). A structure isomer of decamethyldodecahedrane (C₃₀H₄₀), molecule (11), is expected to be synthesized via thermal reaction of iron carbonyl complexes with compound (10). An intermediate in this synthesis, 2,2- tetramethylene-1,4-dibromobutane (9) was efficiently synthesized starting from cyclopentanone. Some aspects of the syntheses, spectra, and chemistry of compound (1) to (9) will be discussed.

The synthesis and insecticidal activity of a series of 2,2-dicyano cyclopropane carboxylic acids, (3-phenoxyphenyl)- methyl esters were investigated. Synthesis of the compounds was accomplished by reaction of a dimethyl sulfonium carbethoxy ylide with propanedinitrile alkylidene compounds. Final products were formed in one step by use of the (3-phenoxyphenyl)-methyl ester of the ylide. Insecticidal activity was determined at 500 ppm application with Permethrin as the standard against houseflies, mexican bean beetles, and southern army worms.

Ph.D. / This work presents a detailed study of the synthesis of carbon nanotubes and nanospheres by nebulised spray pyrolysis. This method has been used by other workers mainly for preparation of sub-micron particles and the deposition of thin films on various substrates. The effect of various synthesis parameters including the temperature, choice of the carbon source and the metal precursor as well as the carrier gas flow rate on the selectivity of the reaction and the properties of the carbon nanotubes produced was investigated. A major part of this work was devoted to a study of the effects of the addition of small quantities of oxygencontaining compounds (alcohols, esters and aldehydes) to the reaction mixture. The products were analysed using various methods including TEM, SEM, Laser- Raman spectroscopy and HRTEM. Furthermore, the possible use of carbon nanotubes and carbon nanospheres as supports for palladium in the hydrogenation of ethylene was investigated. Nebulised spray pyrolysis proved to be a suitable technique for the synthesis of well graphitized carbon nanotubes and carbon nanospheres with uniform diameters and it was demonstrated that good control of the carbon nanotube properties could be achieved by controlling the synthesis parameters. Better graphitization of the carbon nanotubes was observed at higher temperatures. Ferrocene, iron pentacarbonyl, nickelocene and cobaltocene were successfully used in carbon nanotube synthesis with the last two producing carbon nanotubes with diameters close to those on single-walled carbon nanotubes. Toluene (with and without acetylene as a supplementary carbon source), benzene, mesitylene, xylene and nhexane were successfully used to produce carbon nanotubes with a high degree of alignment while no success was achieved with ethanol. The poor yields obtained with ethanol appear to be a consequence of chemical changes in the ethanol induced by exposure to ultrasound irradiation. On the other hand, low concentrations of methyl acetate and ethyl acetate appear to enhance the production of carbon nanotubes. It was demonstrated that carbon nanotubes and nanospheres are suitable for use as supports for palladium in the hydrogenation of ethylene. Pd particles of uniform size were obtained and the conversion rates were slightly higher when the carbon nanotubes were pre-treated with a mixture of sulphuric acid and nitric acid.

Within solid-state chemistry, coordination polymers have gained interest for use in various applications such as sensing, catalysis, display technology, hydrogen storage, etc. The use of lanthanide ions in these materials provides a mean of exploring how structure may affect luminescence efficiency. In this study, the photophysics of several lanthanide benzenecarboxylates was studied. This data combined with data from other coordination polymers created in our lab indicate that the established guidelines for producing highly efficient materials may not correlate directly from solution to the solid state and that structure may also play a role. / by Jessica Montressa Clark. / Thesis (M.S.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Cheung, Chi Wai. / "December 2010." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references. / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract also in Chinese.