Masters Degrees (Chemistry and Polymer Science)


Recent Submissions

Now showing 1 - 5 of 326
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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 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 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.
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    The incorporation of thiazyl radicals into metal-organic compounds
    (Stellenbosch : Stellenbosch University, 2023-03) Zitha, Marvin; Haynes, Delia; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: In this study, the incorporation of thiazyl radicals into metal-organic compounds was investigated. Previously in our group, a novel coordination polymer was isolated from the reaction of cobalt(II) meso-tetraphenylporphyrin (CoTPP) and 4-(4'-pyridyl)- 1,2,3,5-dithiadiazolyl (p-PyrDTDA). Our initial aim was to expand this study by synthesizing and investigating the coordination of other thiazyl radicals to various metalloporphyrins. 5-Methylbenzodithiazolyl (MBDTA) radical was synthesized and investigated first. A series of crystallization reactions were carried out between the MBDTA and four metalloporphyrins; CoTPP, CuTPP, NiTPP, and ZnTPP (TPP=tetraphenylporphyrin). Unfortunately, this did not yield any crystals. However, the ultraviolet-visible (UV-Vis) spectroscopic analysis of the reaction solutions, and the solid materials isolated from these reactions, revealed that coordination only occurs between CoTPP and MBDTA. Electron paramagnetic resonance (EPR) studies between CoTPP and the MBDTA also confirmed spin-pairing between the cobalt ion unpaired electron and the radical. The study was then extended to investigate the coordination of other 1,2,3,5- dithiadiazolyl radicals to metalloporphyrins. Attempts were made to synthesize and isolate zinc porphyrin-dithiadiazolyl complexes first observed by van Laeren during UV-Vis spectrophotometric titration of ZnTPP with PhDTDA or pPyrDTDA in dimethyl sulfoxide:dichloromethane. However, it was found that the coordination observed during the UV-Vis studies was caused by the formation of a zinc porphyrin-dimethyl sulfoxide complex in solution. Coordination between all four investigated 1,2,3,5-dithiadiazolyl radicals, p-PyrDTDA,4-phenyl-1,2,3,5-dithiadiazolyl (PhDTDA), 4-(3ʹ-cyanophenyl)-1,2,3,5-dithiadiazolyl (m-NCPDTDA), and 4-(4ʹcyanophenyl)-1,2,3,5-dithiadiazolyl (p-NCPhDTDA) with ZnTPP in the absence of dimethyl sulfoxide showed no evidence of coordination. However, CoTPPdithiadiazolyl associations were observed for all four dithiadiazolyl radicals. EPR titration studies between CoTPP and the dithiadiazolyl radicals also confirm a spinpairing between the spin-active materials. The last part of this study focused on investigating the inclusion of PhDTDA into cobaltcontaining MOFs. The crystal structure of an inclusion compound containing monomeric PhDTDA inside the cavity of [Co2(bpep)(obc)2], where bpeb=1,4-bis[2-(4-pyrdyl)ethenyl]benzene and obc=4,4'-oxybisbenzoate, was determined by single crystal X-ray diffraction. Thermogravimetric studies of this inclusion compound confirmed the presence of one PhDTDA molecule per unit of MOF. Overall, this study contributes to the understanding of the coordination chemistry of thiazyl radicals and metalated tetraphenylporphyrins. The inclusion of PhDTDA radical into a [Co2(bpep)(obc)2] showed promising results with the possibility of further investigations.
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    The synthesis and study of novel ferrocenyl-benzimidazole derivatives as antiplasmodial agents
    (Stellenbosch : Stellenbosch University, 2023-03) Ndlovu, Malcolm Thabo; Prinessa, Chellan; Stellenbosch University. Faculty of Science. Dept. of Chemistry and Polymer Science.
    ENGLISH ABSTRACT: Malaria continues to be a major health concern despite efforts being made to curb the disease. This is evident from the latest world malaria report published by the World Health Organisation, pointing at a drastic increase in malaria cases and deaths in 2020 compared to 2019. This was attributed mainly to the disruption of malaria services as the world faced the COVID-19 pandemic, but there are also concerns over the continued increase in resistance of malaria towards currently available frontline treatments. Due to its various biological activities, the privileged benzimidazole scaffold has been explored in research based on the development of novel, effective antiplasmodial compounds, with overcoming malaria resistance in mind. The hybridisation of organic compounds with organometallic fragments in the search of highly effective biologically active compounds has become popular. The ferrocenyl moiety is one such organometallic fragment which has been explored, resulting in the potent antiplasmodial compound ferroquine, through hybridisation of chloroquine with ferrocene. In this study, a small library of four ferrocenyl benzimidazole compounds was successfully synthesised and obtained with high purity. The compounds were characterised by 1H NMR, 13C NMR and FTIR spectroscopy. The compounds were further analysed by mass spectrometry. Once synthesised, the stability and reactivity of the compounds under physiological conditions was investigated. To probe their possible mode of action the ferrocenyl benzimidazole derivatives were evaluated against Toxoplasma gondii, a model apicomplexan parasite. Two of the synthesised compounds (TC2 and TC3) were found to be moderately active. The active compounds were found to trigger the production of reactive oxygen species (ROS) within the parasite, making ROS production one of their modes of action. The antiplasmodial activity of the synthesised compounds was investigated against the chloroquine sensitive NF54 strain of Plasmodium falciparum, where one of the target compounds (TC1) was found to be moderately active. Evaluation for cytotoxicity against two human cell lines of healthy cells showed the synthesised compounds were relatively non-toxic.