Masters Degrees (Chemistry and Polymer Science)

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    Investigating mechanical responses to structural changes in crystalline materials
    (Stellenbosch : Stellenbosch University, 2023-11) van Rijn, Raymond Michael; Barbour, Leonard James; Loots, Leigh-Anne; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: Previous work has established that the compound 2,7-dimethylocta-3,5-diyne-2,7-diol crystallizes to produce a range of inclusion compounds – the crystals of which exhibit elastic flexibility. In an attempt to tailor the Young’s modulus of the system, substitution of guest species, using both polar and apolar compounds, was carried out. Ultimately, little difference in elasticity was observed, regardless of the included guest species. Analysis of crystal structures revealed that little interaction takes place between guest molecules, or between host and guest. Thus, hydrogen bonding in the host framework is concluded to be the determining factor in crystal flexibility. Several other elastically flexible crystals were subsequently investigated to determine how their elastic moduli would change when temperature was varied. A relationship was identified between the change in elasticity and thermal expansion of the crystals. As the bending axis of a crystal expands in length, the Young’s modulus decreases. Thus, for crystals exhibiting positive thermal expansion, elasticity is reduced as temperature is decreased. Conversely, for a material displaying negative thermal expansion, decrease in temperature was found to produce an increase in elasticity. Greater intermolecular spacing likely allows for a greater degree of molecular reorientation that must occur to facilitate mechanical bending of crystals. Two of the compounds subjected to variable-temperature flexibility studies, Pd(acac)2 and Cu(acac)2, are isostructural and isomorphous, yet exhibit opposite thermal expansion characteristics along their crystallographic b axes. As such, they were identified as promising candidates to form solid solutions, whose thermal expansion behaviours could be tuned. A mixed crystal displaying near-zero thermal expansion was successfully produced, demonstrating the applicability of solid solutions in tailoring the thermal properties of molecular compounds. A reaction between 2,7-dimethylocta-3,5-diyne-2,7-diol and iodine was observed to produce a novel cumulene-type compound in high yield. It was established that light is required for the reaction to proceed, and can also be used to isomerize the cumulene in a cis to trans manner. Several other diyne compounds were found to react in analogous ways under the novel reaction conditions, provided they featured hydroxyl functional groups. Thus, it is proposed that formation of hydrogen-bonded adducts is responsible for halting the halogenation reaction upon formation of a cumulene.
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    Crystallisation of multicomponent crystals by sublimation: effect of experimental conditions
    (Stellenbosch : Stellenbosch University, 2023-10) Volkwyn, Alexandra Lemisha; Haynes, Delia Ann; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: This thesis aimed to develop a greater understanding of important principles behind the technique of sublimation and demonstrate how we can gain control over the technique to selectively form multicomponent crystal forms, such as hydrates, co-crystals, and salts. This aim was attained by carrying out two studies. The first study focused on investigating whether hydrates of oxalic acid (1), isonicotinamide (2), theophylline (3), caffeine (4), and 1,4-diazabicyclo[2.2.2]octane (5) can be grown by sublimation. Compounds 1-5 were sublimed in the presence and absence of water. An increase in the quantity of water added to the sublimation vessel resulted in an increase in the water content of sublimed crystals. Hydrates of 1 and 5 were easily crystallised from the gas phase in the presence of water. Competition experiments were carried out by co- subliming an anhydrous material and a hydrate, and water transfer took place from the hydrate to the anhydrous material. This study has shown that materials which have the most favourable interactions between the molecule in question and water within the hydrate crystal structure are more likely to crystallise as the hydrate from sublimation with water. The second study focused on investigating the effect of sublimation time, vacuum pressure, temperature, separation apparatus, mass scale, additives, and co-former polymorph on the co-sublimation of two systems: system 1 = succinic acid + hexamethylenetetramine and system 2 = oxalic acid + 4,4'-bipyridine. A salt formed under higher temperature and lower pressure conditions, and co-crystal was favoured under a reduced temperature and higher pressure. Separating the acid and base components prior to sublimation allowed for more control over the concentration of components in the gas phase. Sublimation conditions under which the concentration of acid and base component in the gas phase is maximised are more likely to result in salt formation. In the presence of additives, co-crystal formation was favoured during co-sublimations of system 1. In system 2, salt formation was favoured in the presence of methanol. Results suggest that the type and quantity of additive added to the sublimation vessel can be used to control the outcome of co-sublimations. These studies have shown that simple experimental conditions can be used to gain control over the method of sublimation, and can be used tomanipulate the concentration of components in the gas phase to selectively form salts or co-crystals. The effect of polymorph used during the co-sublimation of system 1 was studied. Sublimation with the β polymorph of succinic acid favoured the formation of co-crystal. It is clear that the use of a specific co-former polymorph can be used to direct the co-sublimation outcome. Overall, this thesis has provided a good foundational understanding of the important principles of the technique of sublimation, and has successfully demonstrated the importance of simple experimental conditions in multicomponent crystal growth from the gas phase. We believe that this simple approach towards gaining control over a crystallisation technique to form a desired product has broadened the scope of sublimation as a whole and will aid the development and design of new materials.
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    Direct visible light initiated SMAnh (Styrene-Maleic anhydride) RAFT mediated copolymerisation
    (Stellenbosch : Stellenbosch University, 2023-03) Brits, Anya; Klumerman, Bert; Pfukwa, Rueben; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: The work contained herein pertains to the practical investigation of light-initiated polymerisation mediated by a RAFT agent, termed Pi-RAFT. Through direct irradiation of a vessel containing the reaction mixture, successful Pi-RAFT was achieved and formed low molecular weight copolymer oligomers. By utilising 1H-NMR spectroscopy, in kinetics studies, the progress of the formation of these oligomers was monitored and gave new insights into precisely where proton signals occur in 1HNMR spectra as monomer insert. Finally, Pi-RAFT was combined with the SUMI technique to help elucidate more exact rate of monomer conversions as well as helping to confirm that selective insertion is possible with Pi-RAFT.
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    Development of new antimalarial ferrocenyl-artesunate complexes
    (Stellenbosch : Stellenbosch University, 2023-03) Munnik, Brandon Liam; Chellan, Prinessa; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: Despite declining numbers over the past 20 years, malaria, which is caused by the parasite Plasmodium falciparum, remains a serious issue in many parts of the world, especially in Africa. This problem is further exacerbated by the arrival of the COVID-19 pandemic, which led to difficulties in service delivery to third-world countries. The World Health Organization shifted to the use of artemisinin-based combination therapy in order to counteract increasing resistance to chloroquine. However, as of 2004, resistance to artemisinin-based combination therapy has been on the rise. Organometallic drugs have shown promise in combatting malaria strains that are resistant to chloroquine, a previously used quinoline based drug. Ferroquine is a ferrocene containing chloroquine hybrid, which has made it to phase II clinical trials and is a prime example of improving activity through metal conjugation. Artesunate (Ars), a derivative of artemisinin, is a semisynthetic antimalarial drug and forms part of the artemisinin-based combination therapy arsenal. The drug functions mainly by activation of its endoperoxide bridge leading to increased oxidative stress in malaria parasites. The goal of this project was to prepare four ferrocenyl containing artesunate derivatives to explore the effects of combining the two moieties. The complexes were all obtained in moderate yields with high purity and characterized by 1H and 13C{ 1H} NMR spectroscopy as well as electrospray ionisation mass spectrometry and the redox profiles were examined using cyclic voltammetry. All the complexes demonstrated good activity against the model Apicomplexa Toxoplasma gondii (T. gondii) with IC50 values in the low micromolar range (0.28-1.2 µM). T. gondii was further used to investigate a potential mode of action (MoA). It was determined that the mode of action for the MoA of the organometallic conjugates was through the generation of reactive oxygen species, the same as that of the parent drug, artesunate. However, in the case of the artesunate-ferrocenyl ethyl amide (C3) a novel mechanism of death to the parasite was observed using immunofluorescence microscopy. All complexes showed good to excellent antimalarial Stellenbosch University https://scholar.sun.ac.za iii activity against the chloroquine sensitive strain of Plasmodium falciparum (P. falciparum, NF54), with IC50 values ranging from 12 to 4858 nM. The complexes all showed low cytotoxicity towards the two healthy cell lines tested – Human embryonic kidney (HEK293) and Human prostatic cells (PNT1A) – and high selectivity for T. gondii over healthy cells. Future work will involve testing the complexes as potential anticancer agents and further looking into the novel mechanism of action demonstrated by the artesunate-ferrocenyl ethyl amide (C3). This could potentially be done by attaching a fluorescent probe to the drug and monitoring where the drug accumulates.
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    Synthesis of ferrocenyl conjugates of sulfa drugs and study as antimicrobial agents
    (Stellenbosch : Stellenbosch University, 2023-03) Setlaba, Katleho; Prinessa, Chellan; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: As humans have spread across the globe so have infectious diseases. Malaria and tuberculosis are among the most widespread infectious diseases, after Covid-19, affecting millions of people annually. Despite the effectiveness of the currently used antimalarial and anti-TB drugs, the emergence of drug resistance in the malaria parasite, Plasmodium falciparum, as well as multidrug resistant and extremely drug resistant forms of Mycobacterium tuberculosis is a growing problem and calls for the urgent need of new antimicrobial agents. In efforts to decrease the morbidity/mortality rates related to these diseases, it is important for these new antimicrobial drugs to target the resistant strains. A unique strategy in drug discovery today is drug repositioning, which involves the modification of known clinical drugs to rapidly identity new ones to treat other diseases. Looking at the current economic situation, this strategy could speed up the process of drug development to save costs. This study investigated the synthesis, characterisation, electrochemical and biological properties of new ferrocenyl amido sulfonamide complexes prepared from known sulfa drugs. The new ferrocenyl organometallic complexes were prepared by the reaction of the primary amine functional group of sulfonamide compounds with ferrocenoyl chloride. All complexes were characterised using various spectroscopic and analytical techniques, such as 1H and 13C { 1H} nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, electrospray ionisation-mass spectrometry (ESI-MS), cyclic voltammetry (CV), and reversedphase high performance liquid chromatography (RP-HPLC). The new complexes were tested for antiplasmodial activity against the chloroquine-sensitive NF54 strain of Plasmodium falciparum. Upon the introduction of the ferrocenyl moiety, the activity of selected sulfonamides was significantly enhanced, with some of the complexes being more active than their respective sulfa drugs. Complex C2 displayed the best activity of all the complexes with an IC50 value of 3.714 µM followed by C5 (IC50 = 5.822 µM). Thereafter, the complexes and their respective sulfa drugs were tested for antimycobacterial activity against the non-pathogenic Mc2 155 and the pathogenic H37Rv strains of Mycobacterium tuberculosis. The complexes displayed better activities when tested against the strain H37Rv compared to results obtained for the Mc2 155 strain. The complexes also displayed to be more potent than isoniazid against both strains. Stellenbosch University https://scholar.sun.ac.za v In addition, the complexes were further screened for their cytotoxicity against the human embryonic kidney (HEK) and immortalised prostatic (PNT1A) cell lines and were found to be non-cytotoxic.