Chemistry

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A detailed kinetic and mechanistic investigation into the rate of chloride substitution from chloro terpyridine platinum (II) and analogous complexes by a series of azole nucleophiles.
(2010) Gillham, Kate J.; Reddy, Desigan.; Jaganyi, Deogratius.
Structural and synthetic studies of sesquiterpenoids and flavonoids isolated from Helichrysum species
(2008) Lourens, Anna C. U.
The genus Helichrysum (Asteraceae) consists of approximately 500 species worldwide, with 245 indigenous to South Africa. As a result of the large number of species, the chemistry and biological activity of several species have not yet been investigated. The aim of this project was to investigate the phytochemistry of three species and propose a synthetic route to one of the antibacterial compounds isolated. An extensive literature review regarding the widespread traditional uses, biological activity and phytochemistry of the South African Helichrysum species is provided. From Helichrysum splendidum, a plant used traditionally to treat rheumatism, two monomeric guaianolides and a dimeric guaianolide, helisplendidilactone, were isolated. The stereochemistry of these known compounds was confirmed and the NMR assignments for certain peaks of helisplendidilactone were corrected. An X-ray structure for helisplendidilactone was obtained for the first time. The phytochemistry of Helichrysum montanum was investigated for the first time and new diastereoisomers of known guaianolides were isolated. The phytochemistry of H. splendidum and H. montanum is remarkably similar and supports their morphological classification in the same taxonomic group. The chloroform:methanol extract of H. montanum yielded a new dimeric guaianolide, 13’-epihelisplendidilactone, which is related to helisplendidilactone, as well as three monomeric guaianolides (of which one is a new diastereomer of a known compound). The extract also yielded spathulenol (a sesquiterpene), umbelliferone (a coumarin) and 4’,5,7-trihydroxy-3,3’,8-trimethoxyflavone (a flavonoid). Thirty-five Helichrysum species were screened for antimicrobial activity against six microorganisms and a preliminary cytotoxic assay, which included the use of “normal” and cancer cell lines, was performed. H. excisum was selected for further study based on the fact that it exhibited promising antimicrobial activity and relative low toxicity. Furthermore, with the exception of the essential oil, the phytochemistry of this species has not been investigated. From the aerial parts of H. excisum, five flavonoids, identified as pinocembrin, gnaphaliin, lepidissipyrone, 5-hydroxy-7,8-dimethoxyflavone and isoscutellarein 7-O-b-glucoside were isolated. Four of these flavonoids have an unsubstituted B-ring, a phenomenon often observed in flavonoids isolated from Helichrysum species. The active antimicrobial component of H. excisum has been identified as lepidissipyrone. Owing to the interesting biological activities reported for phloroglucinol a-pyrones and the synthetic challenges associated with these molecules, lepidissipyrone was selected for a synthetic study. Both the flavanone and pyrone moieties present in lepidissipyrone have been successfully synthesised. A successful strategy towards the CH2 linker between the two units has been illustrated. The strategy could be used to synthesise similar phloroglucinol-derived pyrones.
Progress towards the synthesis of Indolizidine alkaloid 223AB
(2008) Janse van Rensburg, Caryl Kerith Alice.
It has been shown that alkaloids from various sources are vital as lead compounds in medicinal research and thus also the efficient synthesis of these. With the goal of developing a general synthetic route that can potentially access pyrrolizidine, indolizidine, quinolizidine and possibly lehmizidine alkaloid skeletons, a modified route that has been shown to produce pyrrolizidines was employed towards the synthesis of indolizidine alkaloid 223AB. Within this synthesis, a 6-endo-dig hydroamination-cyclization step was attempted for construction of the bicyclic system. For this purpose, a selection of titanium-based catalysts were synthesized in order to determine their regiochemical outcome. For the purpose of investigating ab initio the mechanism of regioselective hydroamination, the skills and methods involved in computational chemistry were acquired through a study into amide rotational barriers: A range of novel 2-oxo-2H-chromen-7-yl dimethylcarbamates were synthesised containing either an oxygen or sulphur in the α-position to the carbonyl or thiocarbonyl group of the amide moiety. Microwave synthesis was essential for the successful synthesis of some of the sulphur containing carbamates. The barriers to internal rotation of each of these compounds were investigated as follows. Variable Temperature and Exchange Spectroscopy NMR was performed on these compounds and the barrier to free amide rotation was calculated. Each of these compounds were also modeled ab initio and the gas phase barrier to rotation calculated. These three sets of data were compared and the influence of the α-heteroatom on rotation for amides and thioamides evaluated.
Structural and Physical Studies of Co(III) Salen Derivatives.
(2007) Govender, Santham.
A number of ligands that belong to the salen-type family were synthesized in this thesis. These ligands were synthesized from salicylaldehyde and 1,2-phenylenediamine, 1,3- diamino-2-hydroxypropane, 1,2-diamino-ethane, N-(3-aminopropyl)-1,3-propanediamine, diethylenetriamine, diaminomaleonitrile, 2,2-dimethyl-1,3-propanediamine and 1,3- diaminopropane. From this range of ligands, H2salophen was chosen as the ligand for further studies. This work is aimed primarily at elucidating the structures and spectroscopic properties of [Co(salophen)(amine)2](OAc) derivatives, where salophen is N,N’-disalicylidene-1,2- phenylenediamine and the amines used were butylamine, benzylamine, a- methylbenzylamine, dibutylamine, N-methylpiperazine and piperidine. Three novel crystal structures of [CoIII(salophen)L2]Cl derivatives, where L = butylamine, benzylamine, and piperidine, with Co-N distances that range from 1.901 Å to 2.024 Å, have been reported in this thesis. The novel crystal structure of [Co(salophen)(N-MePipz)(OAc)] is also reported in this thesis. These cobalt complexes have been analysed by 1H, 13C and 59Co NMR as well as electronic and IR spectroscopy. A 59Co NMR spectrum was obtained for the [Co(salophen)(BuNH2)2]CH2Cl2×Cl complex. The spectrum exhibits a single line at 8504 ppm. The binding constants of all [Co(salophen)(amine)2](OAc) complexes, where amine = butylamine, benzylamine, a-methylbenzylamine, dibutylamine, N-methylpiperazine and piperidine, were determined by spectroscopic titrations. The titrations were carried out at various concentrations of the amine and at temperatures ranging from 25°C to 45°C. It was found that the primary amines had much larger values of K1 and K2 compared to the secondary amines. Typical values of K1 and K2 were 8000 M-1 and 63.6 M-1 respectively at 25°C, for a-methylbenzylamine. Of the primary amines, it was found that a- methylbenzylamine had the largest value of K1 and K2 compared to the other two amines. For the secondary amines, it was found that N-methylpiperazine had the bigger value of K1 compared to that of dibutylamine.
Approaches to the total synthesis of a novel diarylheptanoid
(2008) Vela, Nomandla Magnificent
The total synthesis of a novel diarylheptanoid isolated from a South African medicinal plant, Siphonochilus aethiopicus, was investigated. S. aethiopicus (Indungulu in Zulu) is the only South African species of the Zingiberaceae plant family and is widely used in traditional medicine. One of the compounds isolated from this plant is a novel diarylheptanoid. Diarylheptanoids constitute a distinct group of natural plant metabolites characterized by two aromatic rings linked by a linear seven-carbon aliphatic chain, with varying functional groups on the aryl and the aliphatic chain. The target molecule for our synthesis contains two highly oxygenated aryl rings linked by an aliphatic chain with two stereogenic centres and a trans-alkene. In this study we present our investigation of different strategies to a viable synthetic method that could provide material to supplement the relatively small quantity of product that can be isolated from the plant extract. The major challenges of this synthesis were to develop procedures for the preparation of the homobenzylic trans-alkene, the stereogenic centres and to attach the electron-rich aromatic rings to the aliphatic chain. In this thesis the following aspects are described: • Various types of olefination reactions (including Wittig, Julia and organometalic-mediated type of olefination reactions) • Various types of alkylation reactions (including Grignard, Friedel-Crafts and organometalic-mediated type of alkylation reactions) • Incorporation of the stereogenic centres (including asymmetric hydroxylation and use of chiral starting materials) The synthesis will not only give a viable synthetic route to the target compound but is also versatile enough to allow the preparation of analogues.
Elemental distribution in selected edible nuts and the impact of soil quality on the chemical characteristics of macadamia (Macadamia integrifolia) nuts
(2007) Moodley, Roshila.
Environmental and nutritional imperatives make it necessary to carry out regular and reliable
Synthesis of novel pentacyclo-undecane chiral ligands for application in asymmetric catalysis
(2008) Naicker, Tricia.
There is enormous interest in the design and development of efficient chiral ligands for asymmetric catalysis, as a result, this field has become one of the most popular areas of research in organic chemistry. This project involved the investigation of the novel chiral pentacyclo-undecane (PCU) diol 54a, PCU bisimine 87 and PCU bis(oxazoline) 100 type ligands. The PCU diol ligand was synthesized, but proved to be difficult to obtain enantiomerically pure which hindered further investigation into this type of ligand. The PCU bisimine ligand 87 was synthesized. However due to its instability it was not further pursued. Synthesis of the PCU bis(oxazoline) ligand 100 was successful. This ligand was complexed to various metal salts and its efficiency as a chiral Lewis acid catalyst was evaluated on the asymmetric Diels-Alder reaction between 3-acryloyloxazolidin- 2-one 52 and cyclopentadiene 33. The anhydrous magnesium perchlorate ligand complex emerged as the best catalyst providing the endo-cycloadduct product 53 in 81 % enantiomeric excess at -40 oC. Optimizations of the possible conformations of the magnesium complex of ligand 100 with the substrate 52 were performed using Density Functional Theory (DFT) calculations. The more energetically favoured complex conformation was established. The Re-face of the dienophile which was less hindered produced the product consistent with the experimentally observed product 16. Based on the calculated bond lengths from the computational model binding of the ether oxygen on the PCU moiety to magnesium was observed. All the novel compounds were fully characterized using NMR, IR and mass spectroscopy as the main tools.
N-butane activation over ruthenium and iron promoted VPO catalysts.
(2009) Masilo, Neoentle.; Friedrich, Holger Bernhard.
The Fe- and Ru-promoted vanadium phosphorus oxide (VPO) catalysts were synthesized via the organic route in iso-butanol to form the VPO precursor, VOHPO4·0.5H2O. The resulting precursor was then activated in a stream of nitrogen to form an amorphous (VO)2P2O7, which crystallized after conditioning in the reactor in the presence of n-butane. The promoted catalysts were synthesized at 0.1%, 0.3% and 1% loading, pelletized and sieved to give a 300-600 μm pellet size. The catalysts were tested in a fixed-bed continuous flow micro-reactor and the products were analyzed by GC’s equipped with a flame ionization detector (FID) to monitor maleic anhydride and n-butane and a thermal conductivity detector (TCD) to monitor the carbon oxides. A range of characterization techniques were employed to determine the influence of the promoting elements on a VPO catalyst and to associate the composition of the catalysts obtained from such techniques with their performance. The characterization techniques used include X-ray diffraction (XRD), BET-surface area, ICP-OES, EDS, 31PNMR, TPR, redox titrations, ATR and SEM to determine the phase composition of the catalysts, the surface area of the promoted catalysts relative to the un-promoted VPO, elemental mole ratios, the reducibility of the catalysts, average vanadium oxidation state, determination of the anions present in the surface of the catalysts and the variations in the morphology of the catalysts, respectively. Optimization of the system involved variation of the GHSV, the reactor temperature and the promoter loading. (Activation of a 0.75% n-butane in air mixture was performed at an optimum temperature of 400oC while varying the gas hourly space velocity to establish a range of feed conversions and subsequently determine the activity of each catalyst with respect to n-butane conversion). The promoted catalysts modified the morphology of the catalysts as evidenced by the scanning electron microscopy and the X-ray diffraction patterns. Furthermore an improved conversion was obtained with these catalysts. However, only the 0.1% iron-promoted catalyst improved maleic anhydride yield leading to ca. 10% maleic anhydride yield increment. Yields of 46% and 55% were obtained at GHSVs of 2573 and 1450 per hour respectively and a temperature of 400oC. Electronic and structural modifications were encountered leading to an improved catalytic performance. The performance of this catalyst is associated with a vanadyl pyrophosphate phase (XRD), and a limited and controlled amount of V5+ species as illustrated in the TPR, and solid state 31P NMR data. Moreover, this modification can be considered both structural and electronic in nature as observed in the SEM images and FTIR spectra of this catalyst. Furthermore, this improved performance is possible at higher conversions 80 to 90% conversion.
Sedimentation and chemical processes on the Lower Mkuze floodplain : implications for wetland structure and function
(2008) Humphries, Marc
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.
An investigation into the antimalarial activity of metal chelators
(2008) Pareskevopoulos, Jason Nicholas.; Maguire, Glenn Eamonn Mitchel.; Kruger, Hendrik Gerhardus.
Malaria remains one of the greatest problems facing developing nations, especially in sub-Saharan Africa. Part of the problem stems from increased resistance to current treatments hence there is a large drive to develop novel antimalarial compounds. Several chelating compounds, including 8-hydroxyquinoline (8-HQ), 1,10- phenanthroline (1,10-phen) and 2,2.6,2-terpyridine (terpy), have disputed activities (8-HQ and 1,10-phen) or are untested (terpy). Furthermore the mechanism(s) by which these ligands and/or their complexes with metal ions exhibit their toxic effect is unknown. In order to resolve these issues, a study of the antimalarial activities of the free ligands, the ligands complexed with metal ions (Au 3+, Cu 2+, Fe 3+, Pd 2+ and Pt 2+), and the ligands with free metals in solution were measured. The ligands, complexes and metals were also tested for their ability to inhibit β-haematin formation, the mode of action ascribed to the most widely used antimalarial, chloroquine. The background toxicity levels of the various metal ions (previously unreported) were also measured and are reported here. None of the ligands were found to have particularly high activity (all approximately 1μM). In general the metals in were found to have no beneficial effect on activity whether complexed or freely available in solution. None of the ligands were found to inhibit β-haematin formation. The complexes however, with the exception of those of Cu 2+, all inhibited β-haematin formation. Upon further investigation it was found that the each of the metal ions with the exception of Cu 2+ had an innate ability to inhibit β-haematin formation. Thus the mode of action of the ligands and the complexes is likely to be via different mechanisms. In an attempt to enhance the activities of the ligands they were modified by covalently linking them to nutrients essential to the malaria parasite (adenosine and pantothenic acid). These six novel compounds however, showed no improvement in action.
Studies on ozone initiated inactivation of pathogenic bacteria in aqueous systems
(2008) Zuma, Favourite N.
The effect of ozone on the inactivation of two Gram-negative strains (Escherichia coli and Pseudomonas aeruginosa) and one Gram-positive endospore (Bacillus subtilis) bacteria, often present in water and the cause of some waterborne diseases was investigated as a function of ozone concentration and ozonation duration. Ozone was generated in situ using corona discharge methods where the ozone concentration ranged from 0.906 - 4.724 mg/L and the inactivation of the three microbes followed pseudo-first order kinetics with respect to the microbes. Three microbes were cultured and the influence of temperature and pH of the aqueous systems on the ozone initiated inactivation rate of the three microbes was also investigated. This study reports that molecular ozone is more effective than hydroxyl radicals initiated by the ozone chain reactions. Two suggested mechanisms for the antimicrobial effectiveness of ozone in water systems from the literature is discussed. The study also found that ozonation significantly decreased the Biological Oxygen Demand (BOD) value of natural water.
Synthesis of polycyclic hydantoin derivitaves and peptides.
(2008) Albasheer, Mohamed Saadaldin Altaib.; Govender, Thavendran.; Kruger, Hendrik Gerhardus.
Cyclic cage compounds have attracted much attention in pharmaceutical studies. The lipophilic nature of these compounds plays an important role in facilitating the crossing of the cellular membranes, including the blood brain barrier (BBB) and the central nervous system (CNS). Several adamantane and pentacyclo[5.4.0.02,6.03,10.05,9]undecane (PCU) derivatives have shown great potential as antiviral, antibacterial and neuroprotective compounds. The aim of this study includes the synthesis of hydantoin derivatives of adamantane and PCU as anticonvulsant compounds. Fosphentoin sodium (Cerebyx) 48 is a commercial anticonvulsant drug. Structurally, compound 51 and 52 are similar to Cerebyx 48, where the two phenyl groups have been replaced with PCU or adamantane skeleton respectively. The cage skeleton should increase the lipophilic character of the drug whilst the phosphate group should retain the water solubility of the substrate. The attempted synthesis of these compounds is described in Chapter 2. The PCU hydantoin is readily converted to the PCU amino acid. The synthesis of the PCU amino acid 41 and its Fmoc derivative 106 is described in Chapter 3. This compound was incorporated into small peptides, namely Ala-Ala-Ala-PCU-Ala-Ala-Ala-Fmoc and Ala-Val- PCU-Ile for future testing as a potential anti-cancer agent. NMR studies of these peptides are also reported.
Supramolecular resorcin [4] arene-capped porphyrins : ligands towards homogeneous catalysis
(2008) McKay, Michael.
The synthesis of cavitand-capped porphyrin ligands, with a view towards their potential as ligands in homogeneous catalysis, is described. The ligand apertures, one of which is outlined in the figure below, are focal with the aim of synthesising a ligand which can control access to the active site of the porphyrin via these apertures Synthesis of the target ligand (where R' = CH2 in the figure presented) was attempted via two pathways. Synthesis commenced by using an in situ protocol, which used successive functionalisation of the cavitand structure towards the required aldehyde precursor for porphyrin formation. It was found that subsequent in situ cyclisation and porphyrin formation was hindered by steric factors, arising directly from the short -CH2O- bridges used to link the cavitand to the porphyrin. Ligand synthesis was thus unsuccessful. In a second approach, the porphyrin was synthesised in isolation before being coupled with the cavitand in a direct capping protocol, which gave more promising results. In the case of R = C11H23 (in the figure above), preliminary UV-Vis analysis indicated a successful synthesis. Subsequent analysis of the reaction product by NMR techniques and mass spectrometry could not conclusively confirm the synthesis of the target ligand. The synthesis could therefore not be deemed a success; conceivably the short bridge length being the decisive factor once more. Computational chemistry was used to investigate synthetic results, and therefore the viability of using the -CH2O- bridges to afford limited access to the porphyrin active site. By using molecular mechanics, -CH2O- bridges were found to be too short, giving an aperture of insufficient size to enable only the terminus of a linear paraffin to gain access to the inner cavity of the ligand. Further investigation using molecular dynamics indicated that a ligand bearing bridges four or five atoms in length would afford an aperture of the desired size to accommodate the terminus of a paraffin exclusively. Consequently, synthesis was redesigned towards the preparation of two new ligands, bearing - O(CH2)2O- (four atom, R' = O(CH2)2 in the figure above) and -O(CH2)3O- (five atom, R' = O(CH2)3 in the figure above) bridges. Using 2-phenylethyl feet (R = CH2CH2C6H5 in the figure presented) and adopting the in situ synthetic protocol, both ligands were successfully synthesised. Characterisation using UV-Vis and NMR spectroscopic techniques, as well as mass spectrometry confirmed that both ligands had been obtained pure. Additionally, the in situ cyclisation (in both ligands) was performed via the use of microwave heating, a technique hitherto unreported. A viable synthetic route was thus established for the preparation of two new cavitand-capped porphyrin ligands towards their use in size-selective catalysis. In addition, a number of crystal structures of synthetic intermediates are described, five of which are newly reported. These illustrated notable structural features regarding resorcin[4]arene cavitands and their abilities as host molecules. In particular, the structure of the aldehyde precursor to capped porphyrin formation following the (initial) in situ synthetic protocol was significant in illustrating the reason as to why in situ cyclisation was unsuccessful for the synthesis involving -CH2O- bridges.
Synthesis and incorporation of a Trishomocubane Amino Acid into short Peptides
(2006) Jali, Samuel.
Cage compounds have attracted pharmaceutical and biological interest amongst others as anti-Parkinson agents. The serendipitous observation of the activity of 1-aminoadamantane 1 in Parkinsonian patients against selected viruses i.e. Herpes simplex Type I & II and Influenza A2-Asian viruses/Taiwan has increased the interest in cage compounds. This study involves the synthesis of the cage amino acid 14. Due to the insolubility of pentacyclo-[6.3.0.02,6.03,10.05,9]-undecane (trishomocubane) amino acid 14 in both polar and nonpolar solvents, including DMSO (d6), the synthesis of Fmoc-tris amino acid 50 was required for analysis. The Fmoc derivative of trishomocubane amino acid was also useful for controlled* coupling of the cage amino acid 14 to short peptides. The synthesis of the Fmoc-tris amino acid fluoride derivative is described as well as that of the tri-peptide (Ala-Ala-Ala). The incorporation of the Fmoc-tris amino acid fluoride in a tetra-peptide Ala-Ala-Ala-tris and in a hepta-peptide Ala-Ala-Ala-tris-Ala-Ala-Ala will also be presented. A computational chemistry project was undertaken using density functional theory (B3LYP) at the 6-31+G(d) level of theory, so as to enhance the understanding of the mechanism of esterification. Methanol, acetyl chloride and acetic acid were used in the model for simplicity. Four membered ring transition states were obtained with both acetyl chloride and acetic acid. A six membered ring transition state is facilitated by the selective use of one methanol molecule from the solvent. Both a concerted and step-wise mechanism are presented.
Structure and synthesis of Phloroglucinol derivatives from Hypericum roeperianum
(2010) Smith, Kerry-Ann
The research presented in this study combines natural product chemistry with organic
Application of analytical chemistry and waste minimisation techniques in a paint drier plant.
(2009) Rasalanavho, Muvhango
Environmental sustainability, strict Municipal bylaws, ever-increasing waste disposal
Thermal transformation of organoboranes : applicability of ¹¹B NMR spectroscopy and supporting molecular modelling.
(2008) Mzinyati, Andile Bulelani.; Jaganyi, Deogratius.
The high temperature transformations of trialkylboranes were investigated in the range: 50- 200 ºC. The extent of dealkylation was found to be linked to temperature with ca. 10% octene liberation from tri-n-octylborane at 150 ºC in the absence of bulk solvent. Analysis of the oxidised samples from the dealkylation investigation shows that, whereas the control experiment shows no back-isomerisation of tri-n-octylborane at 150 ºC, the addition of 10 mol% of DMF, DMSO, HMPA and trimethoxyphosphate results in back-isomerisation of the alkyl chain. In general, the addition of Lewis base catalyst was found to enhance the extent of dealkylation. In a supporting 11B NMR spectroscopy study to understand the interaction of trialkylboranes and Lewis bases, the interactions of a series of oxygen and phosphorous donor Lewis bases with tri-n-butylborane were found to be favourable, as indicated by large negative binding enthalpy ( HBIND) and entropy ( SBIND) values. Only the trialkylamine Lewis bases were found to have unfavourable interactions with tri-nbutylborane, as indicated by positive HBIND and SBIND values. The results also show that the chemical shift of the adduct at infinite dilution ( 11 B = ) is not as reliable a measure of the interaction between the two species and that correlation of binding constant (logKBIND) at 25.0 ºC to GBIND defines a linear trend that orders the Lewis bases according to spontaneity of the interaction with the strength of the dative bond formed. The applicability of 11B NMR spectroscopy to the study of the reactions of boranes and alkylboranes was extended to the investigation of the reduction of nitriles by BH3.SMe2 in dichloromethane (15-30 ºC). Results from the kinetic study indicate that the overall reduction with BH3.SMe2 is associative ( Sactivation = -71 ± 10 J K-1 mol-1), with the dependence of kobs data on SMe2 concentration highlighting the importance of the dissociation of the SMe2 from BH3 to the reduction process. The lack of reaction with propionitrile and benzonitrile at 25 ºC can be attributed to lack of stability of their adducts with BH3 as demonstrated by the small equilibrium constants for the formation of their adducts with borane; as determined by 1H NMR spectroscopy and further illustrated by computational calculation of their energies at the B3LYP/6-31G* level of theory.
Bioactive sesquiterpenoids from dicoma anomala subsp. gerrardii
(2008) Van der Merwe, Marina Mikhailovna.; Van Heerden, Fanie Retief.; Parkinson, Chris.
Through South Africa’s first collaborative project between a large scientific organisation, the Council for Scientific and Indust rial Research (CSIR), and the Traditional Healer’s Committee, Dicoma anomala was identified as a plant containing potent anticancer and antimalarial compo unds. In the process of evaluation, extracted plant material with reported or anecdotal use for the treatment of respiratory problems was found to have significant anticancer activity in vitro in a 3-cell line preliminary screen . The extract was further shown to have potent anticancer activity against the 60-cell line panel at the National Cancer Institute (NCI) in the USA. Bioassay-guided fractio nation, initially utilising an in vitro anticancer assay, and structural elucidation resul ted in two potent compounds with sesquiterpenoid skeletons (C-15 and C-30). The crystal structure of the C-15 compound, not published previously, was obtained. B oth compounds were further screened in an antiplasmodial assay during the cour se of the National Drug Development Platform (RSA: CSIR, MRC and UCT) proje ct, and were found to have potent activity against Plasmodium falciparum (a malaria protozoon). Although the C-15 compound had a selectivity index (SI) of 10, suggesting that it was suitable for subsequent development, the dimer was highly toxic (SI index of 1), limiting opportunities for future development. A further study of the structure- activity relationship (SAR), which was initiated fo r the C-15 compound, showed that removal of each unsaturated structural compone nt decreased activity 10–fold in both bioassays. Additional investigations were c arried out into amino-acid Michael adducts with the exocyclic double bond of t he C-15 sesquiterpenoids, and the products were characterised by NMR spectroscopy and mass spectrometry. A similar investigation, involving the conjugate addi tion of simple amines, was undertaken in an attempt to enhance the bioavailabi lity of the parent sesquiterpenoid. Three diethylamine derivatives wer e prepared and characterised. A general 10-fold drop in the bioactivity of these “pro-drug” derivatives in both assays was observed. Finally, the C-15 compound was tested in vivo in the Plasmodium berghei murine malaria model and was found to have some eff ect on the survival rates of the laboratory animals when c ompared with the control. A possible mode of action is suggested based on the e xperimental and published bioactivity data. Further studies to improve the bi oactivity and alternative design of future in vivo studies are also proposed.
Rhodium-catalyzed and uncatalyzed synthesis of boronate esters and their subsequent utility in the Suzuki realm.
(2008) Hadebe, Siphamandla Wiseman.
This study has shown that alkythioboranes 1,3,2-dithiaborolane and 1,3,2-dithiaborinane, disproportionated significantly during their synthesis. Their interaction with 1-octene has been investigated, and the rate constants, enthalpies and entropies of the hydroboration process, have been determined. The thermodynamic and kinetic parameters obtained have shown that the hydroboration reaction is sluggish and proceeded via an associative mechanism.
Isolation and characterisation of antibacterial agents produced by soil bacterium V3.
(2006) Khumalo, Lindiwe Lucia.
Actinomycetes are bacteria belonging to the order of Actinomyceteles and are

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