This work is an account of investigations into the chemistry of members of the Amaryllidaceae and Hyacinthaceae families. The plants of the family Amaryllidaceae are a large group comprising over sixty genera and more than a thousand species. They are widely distributed, but are found more richly in the tropics, with a particularly high density in South Africa, with smaller centers of diversity in Andean South America and the Mediterranean. Amaryllidaceae plants have been extensively used by local traditional healers and have been reported to have numerous pharmacological uses. The alkaloids isolated from this family are a group of isoquinoline alkaloids found exclusively in this family. Plants belonging to two Amaryllidaceae genera were investigated phytochemically, one from each of the sub-tribes Crinineae and Amaryllidineae were investigated phytochemically. Brunsvigia natalensis is used in local traditional medicine to "straighten bones of children", treat barrenness in women and ease childbirth. This is the first phytochemical investigation of Brunsvigia natalensis, and yielded two new alkaloids, a new ceramide type compound and a known flavanoid. A comparative phytochemical investigation was carried out on the bulbs and seeds of Crinum stuhlmanni, which resulted in a number of different alkaloids being isolated from the seeds and bulbs of this plant. The southern African Hyacinthaceae is a large and chemically morphologically diverse group of plants. This family comprises approximately sixty-seven genera and nine hundred species worldwide, of which twenty-seven genera and three hundred and sixty - eight species are found locally. There are five sub-families of which three occur in southern Africa. The chemical constituents of this family can be divided into four classes, namely homoisoflavanones, steroidal compounds, bufadienolides and miscellaneous compounds. These plants are used in local traditional medicine for treating ailments such as hangovers, rheumatic fever, sprains and even cancer. The phytochemistry of three Hyacinthaceae plants was studied. The phytochemical investigation of Drimia macrocentra and Urginea riparia yielded a novel bufadienolide glycoside. These glycosides are quite unusual with the glycone attached to the aglycone at C-2 and C-3 and this has only been reported only once before in this family. The phytochemical investigation of Ledebouria revoluta yielded a number of homoisoflavanones. These homoisoflavanones have been shown to have anti-inflammatory activity and all of the compounds isolated in this work have been screened for this activity. Structural elucidation was carried out using spectroscopic methods such as NMR, MS, UV and IR. / Thesis (Ph.D.)-University of KwaZulu-Natal, Durban, 2004.

The Mkuze Wetland System, situated in northern KwaZulu-Natal, is South Africa’s largest freshwater wetland area. The system plays a vital role in the functioning of the local landscape and has been identified as an important site for the retention of a number of solutes. The mechanisms through which this retention occurs were investigated through analysis of sediment, groundwater and porewater samples collected from the lower floodplain. Sample analysis was achieved through the use of several techniques, including Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), X-ray Diffraction (XRD), X-ray Fluorescence (XRF), electron microscopy and sequential extraction. / Thesis (Ph.D)-University of KwaZulu-Natal, Westville, 2008.

Part A of this thesis is an account of the extractives isolated from one member of the Melianthaceae and two members of the Meliaceae. Plants belonging to these families are known to produce compounds with medicinal applications. Crude extracts from these plants are known to be widely used in traditional medicine. Structural elucidation was facilitated by the use of infrared, mass and nuclear magnetic resonance spectroscopic techniques. Three 20(29)-lupene type compounds (two known and one knew) were isolated from the bark of Bersama swinnyi (Melianthaceae); oleanolic acid was isolated from the leaves. The Meliaceae family is only represented b~ one species, Dysoxylum spectabile, in New Zealand. Two diterpenoids and two limonoids were isolated from the bark. The extracts of the rootbark and stembark of the hitherto uninvestigated species Turraea holstii (Gurke), supplied by Professor H. S. Rajab, Moi University, Kenya, were examined. Eight limonoids and a protolimonoid were isolated from the rootbark. A limonoid and a protolimonoid were isolated from the stembark. Some of the compounds isolated were found in both extracts. Four of the eight limonoids isolated were of the neotrichilenone type. The spectra for the compounds discussed in this text are presented in a separate book. / Thesis (Ph.D.)-University of Natal, 1997.

The thesis involves a study of the thermodynamics of ternary liquid mixtures involving carboxylic acids with nitriles, hydrocarbons including cycloalkanes, and water. Carboxylic acids are an important class of compounds with a great number of industrial uses and applications. In many parts ofthe world the separation of carboxylic acids (in particular acetic and propanoic acid) is an important and desirable task. In South Africa, these carboxylic acids together with many other oxygenates and hydrocarbons are produced by SASOL using the Fischer - Tropsch process. The separation of these acids from hydrocarbons and from water is a commercially lucrative consideration, and is the raison d' etre for this study. The work focussed on the use of nitriles in effecting separation by solvent extraction and not by the more common method of distillation. The nitrile compounds were chosen because of their high polarity. The carboxylic acids used in this study always refer to: acetic acid, propanoic acid, butanoic acid, 2-methylpropanoic acid, pentanoic acid and 3-methylbutanoic acid. The first part of the experimental programme is devoted to the determination of excess molar volumes of mixtures of (a carboxylic acid + nitrile compound), where the nitrile refers to acetonitrile, butanenitrile or benzonitrile, respectively. Densimetry was used to determine the excess molar volumes. The work was done in order to get some idea of the interactions involved between a carboxylic acid and a nitrile. The second part of the experimental study is concerned with the determination of excess molar enthalpies of mixtures of( a carboxylic acid + nitrile compound), where the nitrile refers to acetonitrile, butanenitrile or benzonitrile, respectively. The excess molar enthalpies were determined using flow microcalorimetry Again, this work was done in order to gain some insight into the interactions involved between a carboxylic acid and a nitrile. The third part of the experimental work consists ofternary liquid-liquid equilibria of mixtures of (acetonitrile + a carboxylic acid + heptane or cyclohexane), (benzonitrile + a carboxylic acid + water); and (butanenitrile + a carboxylic acid + water), at 298.15 K. The purpose was to investigate the use of nitriles as solvent extractors in separating carboxylic acids from hydrocarbons and also carboxylic acids from water. Ternary liquid-liquid equilibrium data are essential for the design and selection of solvents used in the liquid-liquid extraction process. The final section deals with the fitting of models of liquid mixtures to the experimental data collected in this work. The NRTL (Non-random, two liquid), UNIQUAC (Universal quasichemical), and FBT (Flory-Benson-Treszczanowicz) models were used. The modelling work served three purposes: • to summarise the experimental data • to test theories of liquid mixtures • prediction of related thermodynamic properties / Thesis (Ph.D.)-University of Natal,Durban, 2003.

The oxidation reaction mechanisms of water soluble textile dyes amaranth (an azo dye), brilliant blue-R (a triaryl dye) and safranine-O (an azine dye) with oxidants- hypochlorite and chlorine dioxide, were investigated. The detailed kinetics of the reactions of the three dyes was studied under excess concentrations of the oxidant and other reagents. The depletion of concentration of the chosen dye, taken at low concentration was monitored using a Hi-Tech SF-61 DX2 double mixing micro volume stopped-flow apparatus. The hypochlorite initiated oxidations were investigated as function of varying concentration of oxidant and hydrogen ion, ionic strength and temperature. For the chosen dyes and reaction conditions, the depletion of dye followed pseudo first-order kinetics and the rate constants were estimated using KinetAsystTM software. All the three reactions had first-order dependence on the oxidant concentration, and the reaction rates increased by varied extent with increase in [H+]0. The role of acid in their reaction mechanisms was established. The kinetic data was analysed to evaluate the rate constants for the competitive pathways initiated by hypochlorite ion and hypochlorous acid. The overall second-order rate coefficients for the OCl- and HOCl initiated reactions were estimated for all the three reactions. Major oxidation products for the reactions were separated and characterized by 1H NMR and 13C NMR and GC-MS techniques and the stoichiometry was established. The energy parameters inclusive of Arrhenius factor, enthalpy, entropy and energy of activations for the oxidation of three dyes both by OCl- and HOCl species were estimated. Based on the experimental findings, the probable rate laws, mechanisms and reaction schemes were described. Simulations studies were conducted to validate the proposed mechanisms using SIMKINE2 computer programme. The rate of oxidation of safranine-O is greater than that of amaranth and brilliant blue-R with OCl- / HOCl reaction. Following similar protocol, the oxidations of the chosen dyes with chlorine dioxide were investigated by monitoring the depletion kinetics of dye as function of varying concentration of ClO2 and OH- ion, ionic strength and temperature. All the three dyes, exhibited pseudo first-order kinetics and the rate constants were estimated using KinetAsystTM software. All the three reactions had first-order dependence on the oxidant concentration at pH conditions 7.0, 8.0 and 9.0 suggesting that reaction mechanism remains unaltered with pH variation. The effect of hydroxide ion on the reaction rate revealed that it acts as catalyst. All the three reactions had first-order dependence on [OH-]0, when its concentration was low; but the order with respect to [OH-] decreased as [OH-] increased stoichiometry proportion to reactants. The catalytic constant for hydroxide catalysed reaction was estimated for all the three reactions. Kinetic salt effect experiments were conducted to identify the possible reaction species involved in the reactions. The major reaction products were characterized by 1H NMR, 13C NMR and GC-MS techniques. The stoichiometry ratios were established and energy parameters were estimated. The rate laws and probable reaction mechanisms were proposed and appropriate reaction schemes for all the reactions were described. The elucidated mechanisms were confirmed by simulation studies using SIMKINE2 software. At neutral pH the rate of oxidation of amaranth is greater than safranine-O and brilliant blue-R, and brilliant blue R being the slowest. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2010.

The emergence of multi-drug resistance (MDR) to antimalarial and anticancer drugs has stimulated a search for novel MDR inhibitors/reversers. Bisbenzylisoquinoline alkaloids (BBIQ) are potential agents for reversing MDR, especially when used as synergistic enhancers of anticancer and antimalarial drugs with improved therapeutic efficacy. Despite numerous useful biological activities reported for BBIQ’s, the various syntheses of individual members remained cumbersome and the overall yields are low. In addition, published methods are nonstereospecific and produced racemates. The aim of this project was to develop a synthetic pathway for the preparation of cycleanine, a natural BBIQ with a symmetrical structure. The protocols developed for the synthesis of cycleanine will serve as a template for the synthesis of other BBIQ’s with more complex structures. The only published total synthesis of cycleanine did not address regioselectivity and stereoselectivity, furthermore, key steps suffered from extremely low yields of the products. Our synthetic pathway is a chiral auxiliary-based asymmetric synthesis that generates enantioselectively a 1,2,3,4-tetrahydroisoquinolines (THIQ) monomers. Cheap, commerciallyavailable starting materials were used to prepare monomers in a regioselective as well as stereoselective manner in good yields. The key feature of this method entails coupling of a chiral β-phenethylamine and halophenylacetaldehyde using the Pictet-Spengler reaction. Due to the difficulties encountered during the course of the preparation of monomers, different methods were tried and formation of unanticipated products rationalised. Dimeric BBIQ’s are constituted of monomeric THIQ’s which are reported to have array of biological properties including MDR reversing activities, therefore, the total synthesis of cycleanine will serve two purposes. In this investigation, the THIQ monomers were synthesised by a pathway that avoid harsh reaction conditions. Major reactions employed include nucleophilic aromatic substitutiton, Wittig reaction, hydroboration and IBX oxidation. Some of the steps were attempted on model compounds to optimise the conditions prior to attempting the reaction on cycleanine precursors. Two major contributions toward the synthesis of BBIQ’s were made in this study. The reaction conditions to control the regioselectivity and enantioselectivity of the Pictet- Spengler reaction for the preparation of THIQ moiety were developed. A major drawback of the published syntheses of BBIQ’s is the harsh conditions and low yields associated with the Ullmann reaction, which is used in the formation of the diaryl ether bonds. We have shown that the microwave-assisted nucleophilic aromatic substitution of aryl fluorides provide a much superior method for the formation of the key diaryl ether bond. Although we failed to form the final diaryl ether bond, the pitfalls encountered in the synthetic pathway are discussed and potential solutions are presented. The developed synthetic pathways are of general applicability and therefore can also be employed in the synthesis of other macrocyclic natural products containing diaryl ethers. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2011.

The phytochemistry of Ochna serrulata (Hochst.) Walp. was investigated for the first time; two new dimeric chalcones (5-deoxyurundeuvine C and serrulone A) and two new biflavonoid derivatives (4,4’,7-tri-O-methylisocampylospermone A and 4”’-de-Omethylafzelone A) were isolated. These compounds were isolated along with the known compounds lophirone A, afzelone B, campylospermone A, isocampylospermone A, ochnaflavone, 2”,3”-dihydroochnaflavone, lophirone C, psilosin, 3’-O-methylpsilosin, a cyanoglucoside, epicatechin, (2’,4’- dihydroxyphenyl)acetic acid, methyl (2’,4’-dihydroxyphenyl)acetate, irisolone 4’- methyl ether, iriskumaonin 3’-methyl ether, 3',4'-dimethoxy-6,7-methylenedioxyisoflavone, lophirone L, syringaresinol and 16α,17-dihydroxy-entkauran-19-oic acid. The growth inhibitory effect of these compounds was evaluated against three cancer cell line panel of TK 10 (renal), UACC62 (melanoma) and MCF7 (breast) using a sulforhodamine B (SRB) assay. Ochnaflavone and 3’-methoxypsilosin demonstrated selectivity and only inhibited the growth of melanoma cancer cells. However, ochnaflavone showed higher activity by totally inhibiting the growth of melanoma cancer cells at 12.91 μM, whereas, 3’-O-methylpsilosin has this effect at a concentration of 14.11 μM. Lophirone C, a dimeric chalcone, demonstrated the highest cytotoxic activity amongst all isolated compounds against renal, melanoma and breast cancer cells with TGI at 35.63 μM, 11.67 μM and 30.35 μM, respectively. Lophirone A, a rearranged biflavonoid, showed TGI against these cancer cells at 58.96 μM, 26.23 μM and 40.01 μM, respectively. The rest of the compounds showed no significant cytotoxicity against the three cancer cells. The new biflavonoid, 4,4’,7-tri-O-methylisocampylospermone A demonstrated the highest antimalarial activity against chloroquine-resistant strains of Plasmodium falciparum (FCR-3) with IC50 of 11.46 μM, followed by ochnaflavone (17.25 μM). iv Serrulone A (26.52 μM), lophirone A (29.78 μM), 5-deoxyurundeuvine C (31.07 μM), lophirone C (35.31 μM), 4”’-de-O-methylafzelone A (38.43 μM), afzelone B (39.54 μM), irisolone 4’-methyl ether (40.72 μM) and syringaresinol (42.66 μM) were moderately active. The following compounds exhibited the lowest antimalarial activity, 2”,3”-dihydroochnaflavone (61.86 μM), iriskumaonin 3’-O-methyl ether (93.69 μM),3’- O-methylpsilosin (106.35 μM) and16α,17-dihydroxy-ent-kauran-19-oic acid (106.48 μM). Owing to the observed and reported biological/pharmacological activity, ochnaflavone (an ether-linked biflavone consisting of apigenin and luteolin moieties) was selected for synthetic studies. An older method, nucleophilic aromatic substitution (SNAr) was successfully applied in the construction of the diary ether. Oxidative ring cyclization of the ether-linked dimeric chalcone was achieved by using heated pyridine and iodine. The two methods can be extended further in the synthesis of other novel biflavones with ether linkage. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

The main objective of this work is to propose a mechanism for the transfer of impurities into the sucrose crystal. To this end the transfer of impurities into the sucrose crystal was investigated, under crystallisation conditions similar to those found industrially. Most of the impurities, namely, colour bodies, potassium, calcium and starch, were selected on the basis of their industrial importance, but some exotic species, namely lithium and nickel, were chosen to represent other mono- and di-valent ions respectively, and dyes, such as methylene blue, which have been used in work with single crystal sucrose crystallisation, were included to make the results more general. A parameter to measure the rate at which impurities are transferred into the sucrose crystal was proposed. Experiments, carried out in a pilot plant evaporative crystalliser, were performed to establish the effect of selected factors on both the concentrations of impurities found in the sucrose crystal, and on the rate at which these impurities are incorporated into the crystal. All the factors selected, namely the rate of crystallisation, the temperature, the concentration and type of impurity, the diffusivity of the impurity in concentrated sucrose solutions, and the crystal dimensions, are shown to influence the rate of impurity transfer. Only the concentration in the feed and type of impurity, however, affect the final concentration of the impurity in the crystal. Concepts involving partition coefficients and adsorption isotherms were also investigated. The experimental data did not fit the adsorption isotherm models well, but the values obtained for the partition coefficients were similar to those quoted in the literature when exchange types of reactions are operative. Activation energies have been measured, both for the rate of crystallisation of sucrose, and for the rates of impurity transfer. The values obtained, particularly for the rate of impurity transfer, indicate that a transport mechanism is effective. The experimental results have been used to investigate the relevance of two models, one involving a two-step approach and the other an interfacial process, for the incorporation of the impurity into the sucrose crystal. The results obtained indicate that the interfacial breakdown model describes the transfer of all the impurities studied here, except for starch. / Thesis (Ph.D.)-University of Natal, Durban, 1998.

This work is an account of the phytochemical analysis of two genera, Vernonia and Vepris which are used as remedies for illness by the Kalenjin community of Kenya. Species of Vernonia are known to yield sesquiterpene lactones, which typify the genus whereas Vepris is rich in alkaloids and limonoids which have a wide range of biological activities. The species studied in this work were Vernonia auriculifera, Vernonia urticifolia, Vepris glomerata and Vepris uguenensis. Phytochemical studies revealed a range of compounds being present in the four species. From Vernonia, triterpenoids, a sesquiterpene amine, a carotenoid and a polyene were isolated. This was the first account of a sesquiterpene amine from a plant species and the first account of the novel polyene. The triterpenoids showed moderate antibacterial activity, with b-amyrin acetate and oleanolic acid being effective at decreasing adhesion of selected gram-negative and gram-positive bacteria. Lutein and urticifolene showed good antibacterial activity against Enterococcus feacium and Pseudomonas aeruginosa. In Vepris, a range of compounds were isolated, belonging to the furoquinoline alkaloids, coumarins, flavonoids, cinnamic acid derivatives, lignins, cinnamaldehydes, triterpenoids and limonoids. Five new compounds; a cinnamaldehyde derivative (glomeral), two flavonoids (veprisinol, uguenenprenol) and two A, D-seco-limonoids (uguenensene and uguenensone) were amongst the compounds isolated. Antibacterial studies showed that glomeral inhibited the growth of Staphylococcus aureus and Shigella dysentrieae at low concentrations (MIC of 2 μg mLˉ¹ and 0.4 μg mLˉ¹ respectively). Antioxidant assays of several compounds revealed that, veprisinol, isohaplopine-3,3’-dimethylallyl ether, uguenenprenol and 7-O-methylaromadenrin are good antioxidant agents. The limonoids isolated from Vepris uguenensis also make up an interesting biogenetic relationship. Structural elucidation was carried out by 1D and 2D NMR spectroscopy in conjuction with mass spectrometry, infrared, ultraviolet and circular dichroism analysis where applicable. Biological assays were carried out using standard methods at laboratories in the University of KwaZulu-Natal and Kenya Medical Research Institute (KEMRI-Nairobi). / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2012.

Unable to copy abstract. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2011.