Recent work in our laboratory has led to a new synthesis of the 2-oxo-a8'&-hexahydroquinoline ring system. This involved the condensation of B-alkylaminopropanoates with 2-methylcyclohexanone. Further reactions of B-aminopropanoates with other cyclic ketones and acyclic ketones have been investigated and are now reported. These reactions are found to be sensitive to steric effects, the stability of the ketone and the presence of molecular sieves and have led not only to the synthesis of the quinolone ring system but also to the inden-7-one and pyridone ring systems. A new one pot synthesis of the bicyclo[2.2.2]octan-5-one ring system from acyclic precursors has recently been reported. Reaction of" two equivalents of phenyl vinyl ketone with one equivalent of N-2-butylidenebenzylamine has lead to the synthesis of 2-benzoyl-4-methyl-l-phenylbicyclo[2.2.2]octan-5one as a mixture of two isomers. This reaction has now been extended to N-2-(4-phenylbutylidene)propylamine and ethyl N-propyl-4-iminopentanoate and our findings are reported. / Thesis (M.Sc.)-University of Natal, Durban, 1993.

The initial aim of this research project was to oxidise Cr C4 alcohols to their respective aldehydes. However, isolation of these aldehydes was impossible due to their low boiling points. Another problem was the proximity of the boiling points of these aldehydes with the boiling points of solvents used in reactions. As a result, the alcohols investigated in this project were changed to C4-C6 alcohols. Different oxidising reagents are known that oxidise oxidise primary alcohols to aldehydes. Of these, chromium (VI) has been used the most. In this project, Chromium (VI) supported on different inert: inorganic supports was chosen as the oxidising reagent. The first task was therefore to synthesise these supported oxidants. The synthesis of some of these oxidants was lengthy. This is advantage the preparation of supported oxidants. Unsupported oxidants like PCC and chromium trioxide were only used as a basis of comparison to emphasise the usefulness of supported oxidants. Pyridinium chlorochromate was used to oxidise primary alcohols to aldehydes in moderate yields. The reaction was found to be moisture sensitive. The yield and the duration of the reaction was found to be better with the use of molecular sieves. Silica gel-supported pyridinium chromate was also used to oxidise alcohols to aldehydes in good yields. Poly[vinyl(pyridinium chlorochromate)] was used to oxidise I-hexanol and I-pentanol to their respective aldehydes also in good yields. The duration of these reactions ranged from 30 min. to 3 days. During the oxidation of alcohols using silica gel-supported chromium trioxide and diethyI ether/chromium trioxide it was found that the reaction conditions can be changed so that either aldehydes or symmetrical esters were the products. This was achieved by varying the duration of the reaction. Silica gel-supported chromium trioxide resulted in both the aldehydes and esters in good yields while the diethyl iii Aluminium-supported chromium trioxide, kieselguhr-supported chromic acid, alumium silicate-supported chromic acid and alumina-supported pyridinium chlorochromate were used to oxidise primary alcohols to symmetrical and unsymmetrical esters in good to excellent yields. The duration of these reactions varied from 1 hour to 48 hours depending on the conditions employed and the chain length of the reagents. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1998.

A variety of hazardous organic compounds are present in leachate from landfill sites that accept medical and industrial chemical waste. Most of these compounds find their way into nearby streams, rivers and dams, posing a threat to the ecosystem. In the present work two hazardous organic compounds, namely, m-xylene and 2-chloroethanol were chosen to react with ozone gas at different experimental conditions. The ozone initiated oxidation of m-xylene and 2-chloroethanol in solvent free conditions were investigated as a function of time. Gas chromatographic analysis of ozonated m-xylene, showed an increase in the conversion of substrate from about 1 % after 3 hours to about 14 % after 24 hours. Some of the ozonation products identified were formic acid, acetic acid, 3-methylbenzylalcohol, 3-methylbenzaldehyde and 3-methylbenzoic acid. The presence of acetic acid, ethyl acetate or acetone during ozonation significantly improved the percent conversion of m-xylene relative to similar products obtained under solvent free conditions. The presence of activated charcoal during ozonation of m-xylene showed marginal improvement in percent conversion compared to solvent free ozonation. The oxidation of 2-chloroethanol was followed by monitoring the consumption of the halogenated organic substrate which showed an increase in conversion from about 2 % after 3 hours to about 46 % after 12 hours. Ozonated products contained a mixture of acetaldehyde and acetic acid. It was also found that the ozonation of 2-chloroethanol yielded quantitative amounts of chloride ions. The percent conversion of 2-chloroethanol in the presence of acetic acid and ethyl acetate were higher than those under solvent free conditions. The use of activated charcoal during ozonolysis of 2-chloroethanol showed a significant increase in percent conversion of the substrate. Since 2-chloroethanol has a higher solubility in water than m-xylene the effects of solution pH, activated charcoal and hydrogen peroxide on ozone initiated reactions were studied. Solutions of 2-chloroethanol maintained at pH level 4 and 7 showed marginal changes in percent conversion compared to ozonation alone, however percent conversion improved significantly when the pH of the solution was increased to 10. The ozonation of 2-chloroethanol in the presence of 5 % hydrogen peroxide in water at pH levels 4 and 7 showed marginal changes in percent conversion compared to ozonation alone, however, percent conversion and product yields improved significantly, when the pH of the solution was increased to 10. Increasing the strength of the hydrogen peroxide in the reaction mixture from 5 % to 10 % had very little effect in the percent conversion of 2-chloroethanol and product formation. Based on the experimental findings the overall reaction mechanism for the reaction of both m-xylene and 2-chloroethanol with ozone is described. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

Germanium can be extracted from aqueous solutions by KELEX 100 dissolved in an appropriate diluent. KELEX 100 is a commercially available chelating extractant containing the active constituent 7-(4ethyl-l-methyloctyl)-8-hydroxyquinoline. Previous work in the solvent extraction of germanium with this reagent has shown that germanium is extracted most efficiently at low pH. When the germanium is present in sulphuric acid solutions at pH less than 2, the extracted complex is GeL3+HS04-,however at pH 3 to 8, the metal is extracted as GeL2(OH)2 (where HL = KELEX 100). In this work, the extraction kinetics and equilibrium extraction of germanium in the GeKELEX 100 solvent extraction system is examined by AKUFVE and shaking assemblies, which both employ rapid mixing of the organic and aqueous phases, and by a quiescent interface Lewis Cell. The AKUFVE is a Swedish designed apparatus for solvent extraction, its performance and suitability for solvent extraction studies is evaluated using the extraction experiments carried out on the GeKELEX 100 solvent extraction system. Experiments conducted using an experimental set-up with a large interfacial area to phase volume ratio reveal that the extraction of germanium occurs in two distinct kinetic regimes. The first regime occurs in the first few minutes of an extraction experiment and is fast relative to the second kinetic regime which follows this fast initial extraction period and occurs until the extraction of germanium attains the equilibrium value. In this work an extraction mechanism involving interfacial reaction of germanium and extractant is proposed to explain this kinetic behaviour. An increase in ionic strength is shown to reduce the rate of germanium extraction in the Ge-KELEX 100 solvent extraction system. Modifiers, such as organic alcohols, are shown to greatly improve extraction kinetics. / Thesis (M.Sc.)-University of Natal, Durban, 1990.

The interfacial behaviour of two amphiphillic poly iso-butenyl succinic anhydride (PIBSA)-derived surfactants and the effect of their interaction with various nitrate salts on the stability of a water-in-oil type emulsion has been investigated. The adsorption of the esterification product of PIBSA and coco-diethanolamide (PICDEA) and of Experse-70 (E-70) at the equilibrated aqueous-fuel oil interface was investigated via the measurement of interfacial tension using the ring detachment method.The interfacial pressure of PICDEA decreased in the presence of excess unreacted coco-diethanolamide (CDE) and for both PICDEA and E-70 interfacial pressure decreased with an increase in the length of the poly iso-butenyl (PIB) hydrocarbon tail. Interfacial tension-concentration curves and the Gibbs Equation were used to determine surfactant surface excess concentration and the packing efficiency of the surfactant in the interphase. The double hydrocarbon PICDEA molecule was found to occupy a larger interfacial area than the single hydrocarbon E-70 molecule. The pH of the aqueous phase effects the interfacial activity and nature of, PICDEA and E-70 at the interface. PICDEA is protonated at pH values less than 4.6 and deprotonated at higher pH values. E-70 is neutral at low pH and deprotonated at pH values greater than approximately 2.The effect of sodium, calcium and ferric nitrate salts on the interfacial free energy of the surfactant saturated interface was also determined. The interfacial tension at the E-70 aqueous nitrate interface was dependent on ionic strength alone with a general decrease in interfacial free energy as nitrate concentration was increased. In the case of PICDEA, however, a surfactant-cation orientation effect was observed. The divalent Ca2+ cation attracts two adjacent PICDEA anions resulting in the adverse interaction of hydrocarbon tails in the interphase. This produces an interface with a higher than expected interfacial free energy. The Na+ cation produces an interface with a more energetically stable orientation. PICDEA in the presence of a ferric nitrate solution (pH 1 to 2) is protonated and therefore the univalent nitrate anion forms the counterion layer at the positively charged surfactant interface. Stability studies were carried out on aqueous nitrate salt in diesel emulsions using PICDEA as the stabilizing surfactant. Droplet coalescence rates were determined from droplet size distribution data in the presence of varying concentrations of sodium, calcium and ferric nitrate salts. Droplets were sized microscopically at progressive time intervals and the rate of coalescence determined from the change in droplet concentration with time. Coalescence was found to follow two or more consecutive first order reactions. After an initial period of rapid droplet coalescence, involving small droplets with diameters of 5~m and less, a droplet distribution is attained conducive to a more stable emulsion which then undergoes a slower rate of coalescence involving larger droplets. The effect of the nitrate salt type on the initial droplet coalescence rate (in order of increasing rate) is as follows: Ca2+< Na+< Fe3+. The opposite trend was observed for the slower long term rate of coalescence, i.e. Fe3+< Na+< Ca2+. These trends are explained in terms of the surfactant cation orientation effect, the effect of the droplet's radius of curvature on the potential energy barrier against coalescence and the effect of the droplet distribution of the emulsion system. / Thesis (M.Sc.)-University of Natal, Durban, 1990.

Ultraviolet (UV) radiation is a potent DNA-damaging agent and a known inducer of mutations and skin cancer. The increasing incidence of skin cancer has emphasised the importance of understanding the mechanistic processes involved in the interaction of UV radiation with DNA. One of the most significant photoproducts, induced by UV light, in the DNA molecule is the cis-syn cyclobutane pyrimidine dimer. These dimers, particularly the cytosinecontaining dimers, have been implicated in the mutagenic and carcinogenic effects of sunlight. Dimerisation of contiguous pyrimidine residues in DNA can result from direct irradiation (A = 295-310 nm) or photosensitised irradiation (A > 300 nm) by endogenous photosensitisers. Direct irradiation of DNA produces a wide range of photoproducts, whereas triplet photosensitisation of DNA by acetone produces only thymine, cytosine and cytosinethymine dimers. Thus, acetone photosensitisation of DNA can be used in the elucidation of the mechanistic processes involved in the formation of photoproducts from the direct irradiation of DNA. Calf thymus DNA was irradiated in the presence of acetone at wavelengths greater than 300 nm, using a high pressure mercury lamp. Experimental conditions investigated were irradiation time, acetone concentration and DNA concentration. Irradiated DNA samples were degraded by hot acid hydrolysis to excise the dimers. The yields of thymine and cytosine-thymine dimers were able to be quantitated by reverse phase high performance liquid chromatography with DV detection.Independent kinetic mechanisms were proposed for thymine and cytosine-thymine dimerisation in calf thymus DNA. Rate constants were assigned from experimentally determined values, values cited in literature and values calculated from Stern-Volmer steady state analysis of the proposed mechanisms. Verification of the proposed kinetic mechanisms was achieved by the comparison of experimental dimer yields with those calculated from the computer simulation of the proposed kinetic mechanism. The computer program CAKE (Computer Analysis of Kinetic Equations) was used to obtain the simulated data. Good agreement between the experimental and simulated data was taken as corroboration of the proposed kinetic mechanism. A section of this work was concerned with the application of spectroradiometry to determine the amount of light intensity absorbed by irradiated solutions. The modification, calibration and operation of a Macam SR 9010 spectroradiometer to achieve this aim is discussed. / Thesis (M.Sc.)-University of Natal, Durban, 1992.

All over Africa, traditional healers use medicinal plants to prepare medicines to treat a wide range of illnesses. One of these illnesses is sickle cell anaemia or drepanocytosis or sicklemia. This disease is particularly common among sub-Saharan Africans with a clear predominance in equatorial Africa. However, it also exists in North Africa, Greece, Turkey, Saudi Arabia and India. An estimated 50 million people are affected worldwide. A literature review on sickle cell anaemia revealed that a number of plants have anti-drepanocytosic activity. The availability and frequency of ethnobotanic use of plants were taken into account when selecting the plants investigated in this study. Cajanus cajan, Callistemon viminalis, Melaleuca bracteata var. Revolution Gold and Syzygium guineense (from DRC and South Africa) were selected for study. The selected plants were subjected to modern phytochemical analysis. A total of 8 compounds were isolated from the plants’ extracts and their structures determined by modern spectroscopic techniques (1D and 2D NMR, FT-IR and MS). S. guineense from DRC (Democratic Republic of Congo) yielded flavanonoid glycoside (A) as its major chemical constituent. The South African S. guineense afforded 4 compounds namely betulinic acid (B), sitosterol (C), friedelan-3-one (D) and a betulinic acid derivative (E). Cajanus cajan showed the presence of fatty acids, one of them was characterized as an unsaturated fatty acid (I). Callistemon viminalis afforded one compound, betulic acid (F) and Melaleuca bracteata afforded two compounds which were characterized as betulinic acid acetate (G) and ursolic acid acetate (H). CH3-(CH2)n-CH2-CH=CH-CH2-CH=CH-(CH2)n-CH2-CH2-COOH The investigation of the anti-drepanocytosis activities of the extractives and their crude extracts showed in vitro antisickling activity. Ethyl acetate crude extracts of Callistemon viminalis and Melaleuca bracteata; hexane, dichloromethane and ethyl acetate crude extracts of Syzygium guineense of DRC, betulinic acid, betulinic acid acetate and maslinic acid showed a high antisickling activity, more than 70% of normalization. The compound BF4, a fatty acid, from Melaleuca bracteata was found to have a medium activity, between 50 and 70% of normalization and oleanolic acid showed the weakest activity, between 10 and 50 % of normalization. Maslinic acid and oleanolic acid which were used for anti-sickling bioassay were isolated and characterized from Syzygium cordatum by my supervisor, Professor Shode. Others crude extracts and pure isolated compounds were found to be non-active antisickling agents. These included crude hexane and methanol extracts of Cajanus cajan; crude dichloromethane extract of Callistemon viminalis; crude dichloromethane, methanol and 80% aqueous methanol extracts of Melaleuca bracteata; crude hexane, dichloromethane, ethyl acetate, and methanol extracts of Syzygium guineense (South Africa); ursolic acid from Melaleuca bracteata and flavanone glycoside from Syzygium guineense of DRC. This is the first report of the in vitro anti-sickling activity of betunilic acid, betulinic acid acetate, oleanolic acid, and maslinic acid. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

No abstract available. / Thesis (M.Sc.)-University of Natal, Pietermaritzburg, 1996.

The substitution kinetics of the complexes: [Pt(terpy)Cl]Cl?2H2O (PtL1), [Pt(tBu3terpy)Cl]ClO4 (PtL2), [Pt{4?-(2???-CH3-Ph)terpy}Cl]BF4 (PtL3), [Pt{4?-(2???-CF3-Ph)terpy}Cl]CF3SO4 (PtL4), [Pt{4?-(2???-CF3-Ph)-6-Ph-bipy}Cl] (PtL5) and [Pt{4?-(2???-CH3-Ph)-6-2??-pyrazinyl-2,2?-bipy}Cl]CF3SO3 (PtL6) with the nucleophiles: imidazole (Im), 1-methylimdazole (MIm), 1,2-dimethylimidazole (DIm), pyrazole (pyz) and 1,2,4-triazole (Trz) were investigated in a methanolic solution of constant ionic strength. Substitution of the chloride ligand from the metal complexes by the nucleophiles was investigated as a function of nucleophile concentration and temperature under pseudo first-order condition using UV/Visible and stopped-flow spectrophotometric techniques. The results obtained indicate that by either changing the substituents on the terpy backbone or by slight modification of the chelate itself leads to changes in the ?-acceptor ability of the chelate. This in turn controls the electrophilicity of the metal centre and hence its reactivity. In the case of PtL3 and PtL4, the ortho substituent on the phenyl ring at the 4?-position on the terpy backbone is either electron-donating or electron-withdrawing respectively. For an electron-donating group (CH3, PtL3) the reactivity of the metal centre is decreased whilst an electron-withdrawing group (CF3, PtL4) lead to a moderate increase in reactivity. Electron-donating groups attached directly to the terpy moiety (tBu3, PtL2) also leads to a decrease in the rate of chloride substitution. Placing a strong ?-donor cis to the leaving group (PtL5) greatly decreases the reactivity of a complex while the addition of a good ?-acceptor group (PtL6) significantly enhances the reactivity. The results obtained for PtL5 and PtL6 indicate that the group present in the cis position activates the metal centre in a different manner than when in the trans position. The experimental results obtained were supported by DFT calculations at the B3LYP/LACVP+** level of theory, with the NBO charges showing a less electrophilic Pt(II) centre when a strong ?-donor cis to the leaving group was present such as in PtL5 and a more electrophilic centre for complexes with good ?-acceptor groups such as with PtL6. Surprisingly, the results indicate that in the case of PtL5, when the metal centre was less electrophilic it also appears to be less selective. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2010.

The aims of this work were first to synthesize and fully characterize compounds that may function as bleomycin analogues and, second, to test their anticancer activity in vitro. Three novel tetradentate O,N,N,O Schiff base ligands, H₃L¹, H₂L³ and H₂L³ were synthesized by condensation of three different 1,3-diaminoalkane bridging units with two equivalents of (2,4-dihydroxy–phenyl)-(phenyl)methanone. These ligands contain two neutral imine nitrogen donors and two anionic phenolate oxygen donors for the coordination of metal ions. The choice of ligand was guided by the fact that Cu(II) bleomycin analogues with ligands employing O,N,N,O donor atom sets are able to cleave double-stranded DNA via oxygen radical formation. Using these ligands, six novel metal complexes of copper(II), nickel(II) and zinc(II) were synthesized and fully characterised. Two novel ligand crystal structures and six novel metal complex crystal structures are reported in this work. The X-ray structures of the two structurally characterized nickel(II) complexes [Ni(L²)] and [Ni(L³)] adopted the same nominally square planar coordination geometry, with the metal ion bound by the pairs of imine nitrogen and ortho-phenolic oxygen atoms of the ligand’s tetradentate donor atom set. The Ni–N and Ni–O distances averaged 1.892(3) Å and 1.845(2) Å, respectively. However, when reacted with Cu(II) and Zn(II), the ligands favored the formation of multinuclear complexes as a result of metal ion bridging by ionized oxygen donor atoms (either the phenolic oxygen atoms or an alkoxide oxygen atom of the 2-hydroxy substituted alkane bridge in the case of H₃L¹) of the polyfunctional ligands. For the di- and trinuclear copper(II) complexes, the mean Cu–N and Cu–O distances averaged 1.953(3) Å and 2.082(3) Å, respectively. For the dinuclear zinc(II) complex, the mean Zn–N and Zn–O distances averaged 2.074(3) Å and 2.042(3) Å, respectively. Electron spin resonance (ESR) measurements on the paramagnetic trinuclear copper(II) complexes confirmed that the trinuclear solid state structures remain intact in fluid solution (DMF) and that two of the three copper(II) ions are antiferromagnetically coupled, leaving the third as an S = ½ center with a hyperfine coupling constant to the I = 3/2 Cu nucleus of 14.80 G. Super-hyperfine coupling (15.13 G) to two N atoms was also evident, consistent with one of the terminal copper(II) centers (O,N,N,O donor atom set) being the site of the unpaired spin density in the molecule. Density functional theory (DFT) simulations were used to determine the electronic structures of the diamagnetic mononuclear nickel(II) complexes. The simulations reproduced the structures of [Ni(L²)] and [Ni(L³)] accurately with similarity coefficients for the two complexes of 0.982 and 0.990, respectively. The simulated electronic spectra (TD-DFT) of the nickel(II) complexes showed reasonably good agreement with the experimental spectra and were useful for the assignment of the low-lying MLCT state (near 400 nm) for the complexes as well as the higher-lying π-π* transitions between 300–350 nm. All of the metal complexes and one ligand were sent to MINTEK¹ (Project AuTEK) for anticancer screening. The copper(II) complexes (bleomycin analogues capable of generating hydroxyl radicals in vivo) showed significant cytotoxicity against the human cancer cell lines A549, DU145, HT-29, and U21. The trinuclear complexes were the most cytotoxic with mean IC₅₀ values of 6(2) and 7(1) μM for [Cu₃(L²)₂Cl₂(DMF)₂] and [Cu₃(L³)₂(H₂O)₂]Cl₂, respectively. The nickel(II) complexes [Ni(L²)] and [Ni(L³)] were comparatively inactive with mean IC₅₀ values of >50 and 35(16) μM, respectively, consistent with the fact that they do not readily generate reactive oxygen species in a cellular environment. / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2013.