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Carbonylation of cyclohexene with carbon dioxide (CO2) using transition metals as heterogeneous and homogeneous catalysts

  • Authors: Sekaleli, Bafokeng Thabelo
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464565 , vital:76522
  • Description: From a green chemistry perspective, carbon dioxide (CO2) emerges as an appealing C1 synthon, given its abundance in the atmosphere and cost-effectiveness. Many essential chemicals for daily life are derived from fossilized carbon sources like coal, petroleum, and natural gas. However, the by-product of these processes, CO2, poses environmental risks when excessively emitted as a greenhouse gas. Achieving a balance between carbon emissions and removal is crucial to address environmental concerns surrounding CO2. Utilizing CO2 as a C1 source in organic synthesis holds promise for mitigating this balance in the long term. Combining CO2 with other underutilized fine chemicals, such as alkanes, alkenes, and alkynes, to produce more valuable platform chemicals presents an economically viable strategy due to carbon dioxide’s abundance, low cost, and recyclability. Despite its simplicity, CO2's high thermodynamic stability and low kinetic reactivity, owing to its highly oxidized state, pose challenges to its use as a feedstock. Overcoming these hurdles requires catalysts to enhance CO2 reactivity. Our work focuses on developing and employing catalytic systems capable of activating CO2 as a C1 synthon in reactions with cyclohexene and a reducing agent to yield carboxylic acids or esters. In one approach, we have developed heterogeneous catalyst systems comprising transition metals (Au, Fe, Ni, Ru) supported on metal oxide (TiO2). Characterization techniques such as TEM, EDX, UV-Vis, BET, and XRD were used to study the properties of these materials. The catalysts were evaluated in a reaction involving cyclohexene, CO2, and H2O. In another approach, we explored the use of cyclo-tris(tetracarbonylruthenium) [Ru3(CO)12] as a homogeneous catalyst in a reaction involving cyclohexene, methanol, and CO2 in the presence of an ionic liquid, 1-Butyl-3-methylimidazolium chloride ([BMIM]+Cl-). 1H NMR and ATR-FT-IR were utilized to characterize [BMIM]+Cl-. The reaction product was characterised utilizing GC-MS. Upon seeing that Ru3(CO)12 changes color from orange to black when exposed to heat, an investigation was undertaken on the kind of transformations that the catalyst undergoes. This investigation was carried out with the hopes of finding the structures that could be resulting from Ru3(CO)12 during the reaction and their significance to it. The orange and black Ru complexes were characterized utilizing DSC, TGA, ATR-FT-IR and PXRD. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Co-crystal formation of pharmaceutical and veterinary tranquilizer molecules

  • Authors: Mngwengwe, Bongeka Naledi Precious
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464532 , vital:76519
  • Description: Midazolam, a 1,4-benzodiazepine derivative is commonly used to treat anxiety, insomnia and may be used as a sedative in anaesthesia as it has calming, anti-convulsant and muscle relaxant properties. Midazolam has a rapid onset but a short duration of action resulting in fewer adverse effects. Midazolam also has the potential to form insoluble crystalline precipitates in pharmaceutical dosage forms such as syrups and solutions, which is a challenge in formulation and process development activities. The primary goal of this research was to prepare multicomponent crystals of midazolam free base, specifically targeting interactions with coformers structurally similar to methyl paraben. Key preparation techniques included neat grinding, liquid-assisted grinding, and slow evaporation. The resulting solid forms were characterized using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction (PXRD). In addition, Single-Crystal X-Ray Diffraction (SCXRD) was used to elucidate detailed structural information on the novel multicomponent crystals formed. Successful preparation of midazolam free base from the hydrochloride salt was confirmed through FTIR, DSC, and PXRD analysis. Different co-crystals and salts of midazolam with coformers such as salicylic acid (SA), benzoic acid (BA), 3-hydroxybenzoic acid (3-HBA) and p-aminobenzoic acid (PABA) were synthesized and characterized. The structure of the single crystal obtained from a veterinary tranquilizer solution was solved and found to be a salt that had formed between midazolam free base, midazolam HCl, and methyl paraben. This finding inspired further investigation of similar multicomponent crystals of midazolam and methyl paraben analogues. This study demonstrated the effectiveness of both mechanochemical and slow evaporation methods for the preparation of multicomponent crystals. PXRD and DSC provided insights into the stability and purity of the crystals that had formed and the differences in melting points and PXRD patterns were particularly important in this regard. Differences in FTIR spectra were used to distinguish between different solid forms and to confirm the successful formation of new solid forms. Extensive searches in the Cambridge Structural Database (CSD) confirmed that the multicomponent crystals of midazolam, such as MDZ‧SA, MDZ‧BA, MDZ‧3-HBA, and MDZ‧PABA, had not previously been reported, highlighting the novelty of these findings. The research successfully isolated and characterized several novel multicomponent crystals of midazolam, demonstrating the potential of mechanochemistry and solvent evaporation techniques in the development of pharmaceutical and veterinary medicinal applications. These findings contribute to the understanding of cocrystal formation and provide a foundation for future studies in which the stability and efficacy of midazolam-based formulations can be evaluated. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Cocrystals, salts and eutectics of anti-tuberculosis medicines

  • Authors: Matlapeng, Tsebang Alice
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464521 , vital:76518
  • Description: Tuberculosis remains as a prominent cause of death worldwide. This infectious disease is treated with first and second line drugs. However, challenges of multi drug resistant tuberculosis and adverse side effects such as depletion of essential B group vitamins in the body by first line drugs, as well as poor physicochemical properties of second line drugs persist. Cocrystallisation of anti-tubercular drugs with various coformers has therefore been used as an alternative method to improve the physicochemical properties of active pharmaceutical ingredients (API) while maintaining their efficacy. The main objective of this study was to carry out cocrystal screening of anti-tubercular API and vitamin B coformers to make drug-drug or drug-vitamin multicomponent complexes. Preparation of the multicomponent complexes was carried out by mechanochemical grinding (neat grinding (NG), liquid assisted grinding (LAG) and slow evaporation. All complexes were characterised using Fourier-transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and crystal structures were elucidated using single-crystal X-ray diffraction (SCXRD). The cocrystal screening resulted in the formation of various solid forms, which included cocrystals, salts and eutectic products. Two cocrystals of 4-aminosalicylic acid (PAS) were isolated and characterised. The cocrystal of PAS with isoniazid (INH) demonstrated similar characteristics for both the bulk crystalline material and milled materials. The cocrystal of PAS and pyrazinamide (PYR) prepared using mechanochemical synthesis was met with challenges, while difficulties were also encountered in obtaining suitable crystals for SCXRD analysis. The ground and recrystallised samples of the PAS and pyrazinecarboxylic acid (PCBA) showed distinct differences in their thermal behaviour, with SCXRD revealing the decomposition product phenolammonium-pyrazinecarboxylate salt ‘sans’ the CO2 moiety. Salt formation involving pyridoxine (PN) yielded a salt hydrate with PAS (PN-PAS) and an anhydrous salt with PCBA (PN-PCBA). Both salts exhibited very complex packing arrangements with equally complex thermal behaviour depending on the solvent used during preparation, and the method of preparation. Three eutectic systems involving INH with PYR, PN and pyridoxine hydrochloride (PNꞏHCl) were identified, and their phase diagrams were constructed from DSC data. The eutectic compositions obtained were 1:1 for INH:PYR, 1:1 for INH:PN and 6:4 for INH:PNꞏHCl. Finally, a total of eight multicomponent complexes were prepared using selected API and vitamin B6 components. The results presented here provide motivation for further investigation and evaluation of the pharmacochemical properties of these API. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Fluorescence-doped silica nanoparticles for ultrasensitive detection of prostate specific antigen

  • Authors: Msutu, Tumelo
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464543 , vital:76520
  • Description: Restricted access. Expected release in 2026. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Investigating optoelectronic and thermal properties of perylene tetracarboxylic bisimide derivatives-and-cellulose nanocomposites for possible solar energy applications

  • Authors: Ndwandwe, Bongeka Lethukukhanya
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464554 , vital:76521
  • Description: Restricted access. Expected release in 2026. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Photodynamic anticancer and antimicrobial activities of novel bacteriochlorins

  • Authors: Tauyakhale, Kaisano Goodness
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464587 , vital:76524
  • Description: The World Health Organization cautioned that the major contributing factors of cancer amongst people are the excessive usage of alcohol, smoking, lack of exercise and low intake of fruits, vegetables, and high-fibre foods. Furthermore, cancer by far is reported to be the most common and leading cause of death worldwide (1 in 6 deaths is due to cancer). Moreover, it is reported that cancer kills more people than tuberculosis, malaria and AIDS combined every year. Chemotherapy has been utilised as a mode of rehabilitation for complete being used in conjunction with surgery or to improve the state of well-being of patients until their point of death. However, it is well known for its adverse effects, such as loss of hair, altered gastric metabolism, vomiting and nausea, dehydration, weight loss, and loss of appetite. For this reason, photodynamic therapy (PDT) was developed as an alternative. A molecular dye (photosensitiser/PS) and light of a specific wavelength produce cytotoxic singlet oxygen species, which induce cell death. The aim of this project is to prepare novel structurally modified porphyrin-type dyes that absorb far into the near-infrared region. Identifying suitable dyes that absorb significantly in the 700−800 nm region is particularly important from an African perspective, since melanin significantly limits the penetration of laser light into human tissue in the 600−700 nm region, where first- and second-generation photosensitiser dyes usually absorb. The porphyrin analogues that will be investigated in this regard are bacteriochlorins (BChls), which are known to have suitable optical properties that are potentially suitable in this regard. The first step of the study would be to synthesise tetraarylporphyrins with electron- withdrawing meso-aryl rings because their reduction to BChls is more readily attainable than is the case with electron-donating rings. However, these contrasting properties can be combined to tailor the BChls for effective photodynamic therapy, so the type of porphyrins synthesised will be tetraarylBChls with different meso-aryl groups to first analyze the induction of different chemical properties in this case, the impact of introducing electron donating (4- and 3-quinoline substituents) or electron-withdrawing (pentafluorophenyl substituents) groups on the meso-positions of the dyes and more specifically whether the position of the quinoline nitrogen atom relative to the core of the BChl has any significant impact on the reactivity of the dye (the 4- or 3-position of the quinoline). The next factor to be considered is the induction of the heavy atom effect by introducing a metal in the centre of the dye in order to try to increase the singlet oxygen quantum yields for high production of reactive oxygen species and singlet oxygen and further red shift the lowest energy absorption band of the BChls in the therapeutic window for deep tissue penetration for effective. Lastly, the goal will be to explore whether the delivery of bacteriochlorin photosensitisers to cancer cells can be enhanced by introducing quaternised nitrogen atoms to the meso-aryl ligands. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Synthesis and biological evaluation of simple carboxylated chalcone and aurone derivatives

  • Authors: Shauri, Thierry Lwanzo
  • Date: 2024-10-11
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464576 , vital:76523
  • Description: Restricted access. Expected release in 2026. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

The effect of an alkyl chain and β-diketonato-metal moiety on the photochromic behaviour of azobenzene compounds as materials for solar thermal fuels

  • Authors: Bokhe, Witness Londi
  • Date: 2024-10-11
  • Subjects: Photochemistry , Isomerization , Solar thermal energy , Solar thermal fuel , Liquid crystals , Optical materials
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/464510 , vital:76517
  • Description: Scientists have been studying the development of renewable energy technologies in detail to create a sustainable energy supply. Among many new advanced material classes being researched recently are photo functional and photo responsive materials. These classes include azobenzene derivatives which are characterized by azo linkage (N=N) sandwiched by two phenyl rings. The trans-to-cis isomerization of azobenzene is a highly efficient and reversible process, making it an ideal candidate for solar thermal energy storage. This research investigates the impact of alkyl chain modifications and the incorporation of a β-diketonato-copper(II) complex on azobenzene derivatives, aiming to optimize their performance as efficient components in solar thermal fuel cells (STFs). The study focuses on a comprehensive analysis of these materials' ability to capture, convert, store, and release solar energy for enhanced sustainability in renewable energy applications. Experimental methodologies include synthesis of azobenzene derivatives with varying alkyl chain length, n (where n =8 & 10) and coordination of these compounds with a β-diketonato-copper(II) complex. Standard analytical techniques such as Nuclear Magnetic Resonance (1H and 13C NMR), Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet/visible spectroscopy (UV/vis) were employed for chemical analysis of the synthesized material. Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), and Polarised Optical Microscope (POM) were used to study the thermal properties and morphology. The photostationery states were determined using NMR spectroscopy and the kinetic parameters of the cis-to-trans relaxation process determined by a UV spectroscopy study. The cis-to-trans isomerisation had a longer half-life than the trans-to-cis isomerisation. The band gap of the isomers is within the range of semiconducting inorganic materials. DSC and POM thermograms showed that the compounds are liquid crystalline. Finally, the study reports that the synthesised azobenzene derivatives show potential as material for solar thermal fuel cells because of their photo-isomerization ability. Furthermore, the synthesised compounds contribute to the advancement of sustainable and efficient solar energy utilization technologies, addressing the growing demand for clean energy solutions in the face of global environmental challenges. Because solar energy may be stored and used without causing direct emissions or pollution, they are considered clean energy. If solar thermal fuels fulfil sustainability standards, they may qualify as green energy. This entails minimising adverse effects on the environment, using non-toxic chemicals and procedures. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-10-11

Graphene derivatives and electrocatalysts as composite electrodes for selective detection of catecholamine neurotransmitters

  • Authors: Luhana, Charles Benjamin
  • Date: 2024-04-05
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/435907 , vital:73211 , DOI 10.21504/10962/435907
  • Description: In this thesis, we investigated the development of electrochemical sensing electrodes based on graphene derivatives and the electrocatalyst composites of metallophthalocyanines and metal oxides towards the selective and sensitive detection of catecholamine neurotransmitters (NTs). The graphene and its derivatives offer excellent electron conductivity and hence their use as base electrode materials. Metallophthalocyanines are N4-macrocyclic metal organic complexes that have structural modification flexible and 18-π electrons with excellent electrocatalytic properties. They can incorporate transition metal ions at the centre of the macrocycle ring, and this further enhances their electrocatalytic activity. Transition metal oxides are of interest as these also offer excellent redox properties and pH sensitivity. A pH sensitive electrochemical sensor based on aminated graphene quantum dots (AmGQDs) and cobalt tetra carboxyphenoxy phthalocyanine (CoTCPhOPc) covalent conjugates onto the pre-grafted isophthalic acid (IPA) gold electrode was fabricated. It displayed excellent analytical performance towards the detection of dopamine (DA), norepinephrine (NOR) and epinephrine (EP). The electrochemical sensor exhibited good ability to suppress the background current due to ascorbic acid (AA), a major interference in the detection catecholamine NTs. The carboxylic acid functional group of cobalt phthalocyanine induced the pH sensitivity of the thin film and electrostatic repulsion of the negatively charged ascorbate (AA-) anion at physiological pH. In addition, the electrode could screen-off biological molecules in the newborn calf serum as a representative of a real sample. An electrochemically reduced graphene oxide–based cobalt phthalocyanine polymer (polyCoTAPc) composite electrochemical sensor was fabricated on glassy carbon electrode, GCE-ERGO/polyCoTAPc. The GCE-ERGO/polyCoTAPc could detect dopamine and paracetamol simultaneously as co-existing analytes in buffer and synthetic urine samples. We observed, (i) very strong absorption of the materials, (ii) increase in the electrode surface area, (iii) excellent conductivity, and (iv) electrocatalytic activity of the ERGO/polyCoTAPc composite surface. Furthermore, a simple ultrasensitive electrochemical sensor based on nickel hydroxide thin film electrodeposited onto reduced graphene oxide-molybdenum disulfide (RGO/MoS2) composite resulted in the electrochemical sensor that can selectively and simultaneously detect ascorbic acid, dopamine, and uric acid. A distinct peak potential separation was observed with excellent electrocatalytic oxidation currents. The electrochemical sensors developed in this work exhibited high sensitivity, selectivity, stability, and low detection limits suitable for the detection and determination of catecholamine NTs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-04-05

Phthalocyanine-based bio-functional conjugates: photodynamic therapy and photoantimicrobial chemotherapeutic efficacy evaluation in-vitro

  • Authors: Magadla, Aviwe
  • Date: 2024-04-05
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/435918 , vital:73212 , DOI 10.21504/10962/435918
  • Description: This thesis reports on the syntheses and characterisation of symmetrical and asymmetrical phthalocyanines (Pcs) with different ring substituents derived to form either cationic styryl pyridine, cationic styryl pyridine triphenylphosphonium (TPP+)-based, benzothiazole, cationic pyridyl-dihydrothiazole and other closely related groups. The starting Pc complex of the synthesised Pc derivatives was typically obtained through the cyclotetramerisation of a substituted phthalonitrile. Then, depending on the desired final complex, the desired complexes were synthesised through the Knoevenagel condensation, alkylation reaction, and Schiff base reaction. Furthermore, silica nanoparticles (SiNPs) were also used to encapsulate Pcs. Following aminopropyl triethoxysilane amino (APTES) functionalisation of the surface of the Pc@SiNPs-APTES, biomolecules such as gallic acid, folic acid, and ampicillin were covalently attached to the surface. Additionally, Pc@SiNPs-APTES is protonated with 1,3-propanesultone. The pair of synthesised asymmetric Pcs is attached to ciprofloxacin (CIP) via an amide bond. Different analytical methods were used to characterise the Pcs and their conjugates. The photophysics and photochemistry of the Pcs both by themselves and in their conjugate form when doped with SiNPs. The cationic Pcs were able to produce sufficient singlet oxygen on their own in most cases. This is explained by the Pcs greater solubility in water. Since singlet oxygen is produced from the triplet state, singlet oxygen quantum yield (Δ) values complement triplet quantum yield (T) values. Low Δ values could be attributed to ineffective energy transfer; screening effects may have prevented the excited triplet state of the Pcs from interacting with the ground state molecular oxygen, lowering the Δ values. In other instances, the Pcs' protection by the SiNPs could be credited with extending the triplet lifetime. The direct connection of Pcs with CIP increased the formation of T and Δ in ABSTRACT comparison to Pcs alone. Both in planktonic and biofilm form, the cationic Pcs and conjugates showed enhanced bacterial elimination. The Pcs and conjugates demonstrated significant activity in photodynamic therapy treatment (PDT) experiments at the tested doses. In both PDT and photodynamic antimicrobial chemotherapy (PACT) treatment, the cationic Pcs outperformed the neutral Pc in terms of biological activity. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-04-05

Aptamer-based biosensor for prostate specific antigen detection using cobalt phthalocyanine-exfoliated graphite composites

  • Authors: Benise, Emihle
  • Date: 2024-04-04
  • Subjects: Aptamer , Exfoliated graphite nano-platelets , Phthalocyanines , Impedance spectroscopy , Prostate-specific antigen
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/434850 , vital:73110
  • Description: The work focuses on the development of biosensors and their use for the detection of prostate specific antigen (PSA). Four cobalt phthalocyanines (CoPcs) complexes: (1) cobalt tetra pyridyloxy phthalocyanine, (2) cobalt tetra acetamidophenoxy phthalocyanine, (3) cobalt tris(acetamidophenoxy) mono benzoic acid phthalocyanine, and (4) cobalt tris(acetamidophenoxy) mono propionic acid phthalocyanine, an exfoliated graphite (EG), and aptamer are used to make probes for PSA detection. Each complex is π-π stacked onto the EG to form EG-CoPc(π-π) hybrid which was used to modify a glassy carbon electrode (GCE). EG and CoPc were also used to modify the GCE sequential (seq) with CoPc on top to give GCE-EG-CoPc(seq). For the detection PSA, PSA specific aptamer was either sequential added or covalently linked to complexes 3 and 4 on the modified electrodes and was only sequentially added onto complexes 1 and 2 modified electrodes. Electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV) were the techniques used for the detection of PSA. The electrodes were found to be selective in bovine serum albumin, glucose and cysteine and stable when 50 DPV scans were run. Electrodes gave good % recovery when human serum was spiked with different PSA concentrations. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-04-04

Insights: elucidation of squalene monooxygenase inhibitors for lowering cholesterol in cardiovascular diseases

  • Authors: Leoma, Mofeli Benedict
  • Date: 2024-04-04
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/434861 , vital:73111
  • Description: Statins have been used to lower high cholesterol levels in the past few decades. However, several studies have shown that some people taking statins experience side effects over time, especially elderly patients, women of childbirth possibility, and children. Several studies have shown that the majority of people with underlying cardiovascular complications caused by high cholesterol are at a greater risk of fatality due to COVID-19, regardless of age and sex. The literature suggests that antimycotic squalene monooxygenase inhibitors, terbinafine and its derivatives, and anticholesterolemic squalene monooxygenase (SM) inhibitors could be another option and a safer remedy for lowering cholesterol in mammals. Molecular docking calculations, molecular dynamics (MD) simulations, molecular mechanics generalized born surface area (MM-GBSA) calculations, quantum mechanics/molecular mechanics calculations (QM/MM), and density functional theory (DFT) calculations were used in this study. An early stage in drug discovery, in which small molecular hits from high- throughput screening (HTS) are evaluated and undergo limited optimization to identify promising lead compounds, is referred to as lead generation. To address the first step of lead generation, the number of compounds to be tested was narrowed down, and the hit compounds that could be taken for further tests were obtained. Thus, the molecular docking technique was taken advantage of, which assisted us in identifying the antimycotic ligand SDZ 18, which had a good binding affinity of about -8,4 kcal mol−1. Another widely employed strategy, the molecular mechanics-generalized born surface area (MM-GBSA), was used to investigate the binding free energies of the protein-ligand complexes to validate the binding affinities obtained from molecular docking. Despite the excellent docking results, it must be emphasized that the stability of the ligand in the binding pocket must be investigated. To address this, the protein-ligand complexes were then taken through molecular dynamics for 100 ns simulations calculations which showed that the inhibitors stayed in the binding pocket with the RMSD values below 3.5 Å for most systems. This provided insight into a realistic model because the docked complexes were placed in conditions closer to the physiological environment at 300 K and 1.01325 bar, and in an explicitly solvated dynamic environment. Density functional theory (DFT) at the B3LPY level of theory using the standard 6-31G(d,p) basis set was used to assess the reactivity and other properties of the SM inhibitors. ONIOM calculations were performed to explain what was happening at the microscopic level by calculating the total energy of the complex. The aim of this project was to efficiently uncover the non-physical aspects of SM inhibitors with the help of computational techniques to identify new drugs that can lower high cholesterol levels. From a theoretical perspective, the results obtained from docking indicated that the antimycotic ligands SDZ SBA 586 18 and TNSA 84 (trisnor-squalene alcohol ) have good binding affinities, and the MM-GBSA method provided free energy calculations. MD results indicated that the stability of the ligand in the binding pocket was achieved during the 100 ns simulations. The HOMO-LUMO energy gaps obtained from DFT calculations provided information on the reactivity of the ligands. Other insights into the protein-ligand complexes were obtained from a hybrid ONIOM QM/MM study. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
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  • Date Issued: 2024-04-04

Asymmetrical zinc(II) phthalocyanines conjugated to nanomaterials for degradation of organic pollutants and inactivation of Staphylococcus aureus bacteria

  • Authors: Mgidlana, Sithi
  • Date: 2023-10-13
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/431859 , vital:72809 , DOI 10.21504/10962/431860
  • Description: This thesis reports on the syntheses and characterization of asymmetrical phthalocyanines (Pcs) with different ring substituents (tert-butyl, ester, diimide, trimethoxy, acetophenone, heptanoylphenoxy, perfluorophenoxy, dimethoxy, propanoic acid, acetic acid, carboxylic acid, aminophenoxy, acrylic acid). Several nanoparticles including metal tungstate, capped with glutathione and 1-mercaptohexanol are prepared and characterized using analytical techniques. The synthesized Pcs are covalently linked to various nanoparticles (NPs) through ester and amide bonds to form Pc-NP conjugates, in order to improve their catalytic properties. The Pcs and their conjugates are characterized using different analytical techniques. The photophysics and photochemistry of the MPcs and conjugates are studied. The conjugates T). The complexes and the conjugates with nanomaterials are evaluated for singlet oxygen-generating ability. Conjugates generate higher singlet oxygen in comparison to Pc complexes alone. The photocatalytic activity of the conjugates of ZnPc complexes with NiWO4, Ag2WO4, Bi2WO6, CoWO4, and Ag-Fe3O4-based nanoparticles is evaluated based on photodegradation of methylene blue, tetracycline, and dibenzothiophene. The photocatalytic efficiencies of the synthesized phthalocyanine complexes increased in the presence of nanoparticles. This work also reports on the photodynamic antimicrobial chemotherapy activity of these materials against Staphylococcus aureus (S. aureus) bacteria in DMSO. The results indicated that silver-based nanoconjugates exhibit high antimicrobial activity with high log reductions compared to NiWO4, CoWO4, and Ag-Fe3O4-based materials. The z-scan technique is employed to experimentally test the nonlinear optical response of complexes and nanoconjugates in solution. The nonlinear absorption coefficient, third-order optical susceptibility and optical limiting threshold of the materials are obtained from the Z-scan aperture data. The nonlinear absorption parameters improved in the presence of semiconductor quantum dots, with 1-ethanoic-CdTe/ZnSeS/ZnO giving the best results due to the presence of electron-donating substituents. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Enhancement of the electrocatalytic activity of phthalocyanines through the reduction in symmetry and conjugation to detonation nanodiamonds

  • Authors: Ncwane, Lunathi
  • Date: 2023-10-13
  • Subjects: Phthalocyanines , Electrocatalysis , Nanodiamonds , Hydrazine
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/424541 , vital:72162
  • Description: This thesis reports on the synthesis of novel phthalocynines tetrakis[(benzo[d]thiazol-2ylthio)phthalocyaninato]cobalt(II)chloride (complex 1) and tris(2-(ethylthio)benzo[d]thiazole)2-(phthalocyanine-9-ylthio)propionate cobalt(II) chloride (complex 2). The complexes are combined with DNDs via different techniques such as π-π stacking, covalent linkage and sequential modification on glassy carbon electrode. The synthesized MPcs and conjugates were characterized using UV-visible, mass, Fourier transform infrared, and Raman spectroscopies as well as transmission electron microscopy and dynamic light scattering. Combining MPcs with DNDs sought to improve electrooxidation of hydrazine. The electrochemical studies were conducted using cyclic voltammetry, chronocoloumetry, electrochemical impedance spectroscopy and chronoamperometry. Hydrazine was utilized as an analyte of interest, due to its mutagenic and carcinogenic effects. Glassy carbon electrodes (GCE) were modified using drop and dry method. The conjugation via covalent linkage proved to be the best way of enhancing electrocatalytic properties. Since it performed better in terms of limit of detection (0.33 μM), even though catalytic rate and sensitivity are not the highest. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Enhancing the electrocatalytic activity of phthalocyanines through finding the ideal combination of substituents in push-pull phthalocyanine-based systems

  • Authors: Nkhahle, Reitumetse Precious
  • Date: 2023-10-13
  • Subjects: Phthalocyanines , Electrocatalysis , Hydrazine , Nitrites , Activating group , Deactivating group
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/432578 , vital:72882 , DOI 10.21504/10962/432578
  • Description: Phthalocyanines (Pcs) are a class of synthetic pigments with a similar structure to porphyrins. The work presented in this thesis is centred around these electron-rich macrocycles and their use in electrocatalysis. This body of work provides a more rigorous analysis on asymmetric Pcs, focusing on finding the “ideal” combination of substituents in the synthesis of A3B-type Pcs and how these asymmetric structures compare with their symmetric counterparts (A4) in the electrocatalysis of hydrazine and nitrite. The choice in substituents in the syntheses of the Pcs was such that there is both electron-donating and electron-withdrawing groups to induce a push-pull effect. In the studies involving the electrocatalysis of hydrazine, asymmetric cobalt Pcs (CoPcs) possessing alkyl groups as the primary substituents, with variations in the acid-containing group, along with their symmetric counterparts, probes with potential for further improvement were identified. Using voltammetric and amperometric techniques, the analyte-electrode kinetics, mechanism in which the electrochemical reaction proceeds along with the limits of detection (LoD) were determined. In the general sense, the pentadecylphenoxy-derived CoPcs performed better than those containing the tert-butyl substituent as the dominant substituent with the asymmetric CoPcs producing more favourable results than their symmetric analogues. With respect to the probes designed for nitrite, a multi-dimensional approach was undertaken in that acetaminophen was chosen as the primary substituent whilst multiple changes in the asymmetric component were made. In addition to varying the carboxylic acid-containing substituent, alkyne- and amine-based substituents were also explored in which the alkyne-containing Pc was anchored onto the electrode surface through click chemistry while the amine-bearing Pc was covalently linked (and π-stacked) to nitrogen-doped graphene quantum dots (NGQDs). Another component that was altered was the central metal where CoPcs were compared to manganese Pcs (MnPcs). The most desirable peak oxidation potential for nitrite was observed in the MnPcs as it was the lowest with adsorption sometimes being a better suited method of electrode modification relative to clicking. The inclusion of NGQDs was found to be beneficial when combined with the symmetric CoPc whilst in the presence of an asymmetric Pc complex, less desirable results were observed. Overall, there were variations in the results with the symmetric CoPc sometimes being better than some of the asymmetric CoPcs demonstrating that a blanket-approach in terms of synthesizing and applying asymmetric Pcs is not always viable. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Fabrication of nanocatalysts as nanozymes-based biosensors for the detection of glucose and ascorbic acid

  • Authors: Chavalala, Ridge Nhlamulo
  • Date: 2023-10-13
  • Subjects: Uncatalogued
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/424501 , vital:72159
  • Description: Embargoed. Expected release in 2025. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

From more sustainable isocyanide-based multicomponent reactions to spiro-heterocyclic compound syntheses

  • Authors: Salami, Sodeeq Aderotimi
  • Date: 2023-10-13
  • Subjects: Passerini reaction , Isocyanides , Isothiocyanate , Mechanical chemistry , Organic reaction
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/432229 , vital:72853 , DOI 10.21504/10962/432229
  • Description: The global pharmaceutical industry has undergone profound transformations in the past two decades in the search for new drugs. For this reason, most pharmaceutical companies made significant investments not only in the development of new drugs but new methodologies. Modern drug development is confronted with the challenge of developing chemical reactions that are highly capable of providing most of the elements of structural complexity and diversity with the fewest possible synthetic steps for the specific target with the most intriguing properties. The discovery of more sustainable, environmentally friendly reactions capable of forming multiple bonds in a single step has been a challenge in organic synthesis over the years. Many organic chemists have recently started focusing on creative ways of reducing environmental pollution. The use of hazardous solvents has been reduced or eliminated in research to limit harm to both people and the environment. The pursuit of this goal has drawn many organic chemists to the study of various sustainable synthetic techniques including catalysis, aqueous organic reactions and mechanochemistry. The scope of this thesis was to apply sustainable techniques to design multicomponent synthetic protocols for the Passerini reaction and further apply these new protocols to construct spiro-heterocyclic compounds, all based on green chemistry principles. There is a need to develop rapid, efficient, and versatile strategies for the synthesis of bioactive molecules via multicomponent reactions. This project tried to avoid some of the pitfalls of traditional approaches, such as toxicity, low yield, long reaction times, harsh conditions, experimental complexity, and limited functionalization scope. This was achieved by focussing on the use of isonitriles and isothiocyanates as key reactive intermediates, and making extensive use of aqueous reaction conditions, mechanochemistry and microwave activation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Halogenated Aza-BODIPY dyes for photodynamic anticancer and antimicrobial activity studies

  • Authors: Magwaza, Temlandvo Matshidiso
  • Date: 2023-10-13
  • Subjects: BODIPY , Dyes and dyeing Chemistry , Active oxygen , Photosensitizing compounds , Photochemotherapy , Time-dependent density functional theory , Anti-infective agents
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/424514 , vital:72160
  • Description: This thesis reports on the synthesis and characterisation of differently substituted aza-BODIPY dyes for use in photodynamic antimicrobial chemotherapy (PACT) and photodynamic therapy (PDT) activity studies. The aza-BODIPY dyes were synthesised by adding phenyl and naphthyl rings at the 3,5-positions of the aza-BODIPY core, with methylthiolphenyl (9a and 9b, respectively) or thien-2-yl rings (9c and 9d, respectively) at the 1,7-positions. 9a-c were iodinated at the 2-position to form 10a-c, respectively, while 9d was diiodinated at the 2,6-positions to form 10d. The methylthiolphenyl-substituted dyes (10a and 10b) were successfully conjugated to gold nanoparticles (AuNPs) to form nanoparticles conjugates (10a-AuNPs and 10b-AuNPs), while attempts to conjugate the thien-2-yl-substituted dyes were unsuccessful. The photophysicochemical properties of 9a-d, 10a-d and nanoconjugates 10a-AuNPs and 10b-AuNPs were investigated to determine their suitability for use in the applications. Adding heavy atoms such as iodine at the 2,6-positions of the aza-BODIPY led to enhanced singlet oxygen generation since these dyes displayed moderate to high singlet oxygen quantum yields. None of the dyes exhibited any fluorescence. The PACT activity studies for 9c-d, 10a-d, and the 10a-AuNPs and 10b-AuNPs were carried out against Staphylococcus aureus and Escherichia coli with a Thorlabs M660L3 light-emitting diode (LED) with an irradiance of 280 mW/cm2 for all dyes other than 10d. A Thorlabs M730L4 LED with an irradiance of 160 mW/cm2 was used for 10d. Time dependence studies were only carried out against Staphylococcus aureus, so very low log reductions were observed against Escherichia coli in initial concentration studies. The 10a-AuNP and 10b-AuNP nanoconjugates exhibited high antimicrobial activity with a log reduction of 9.41 and 0.00% viable colonies, while the iodinated aza-BODIPY had a log reduction of 8.94. The in vitro photodynamic therapy activities and dark cytotoxicity were investigated against human MCF-7 breast cancer cells for dyes 9c-d and 10c-d with a Thorlabs M660L3 LED (280 mW/cm2) for all dyes. The dark cytotoxicity was minimal in each case with IC50 > 50. Iodinated dyes 10c and 10d had IC50 values of 11.6 and 8.2 μM, respectively, and non-iodinated dyes 9c and 9d had IC50 values of 12.5 and 19.2 μM. The heavy atom effect associated with the iodine atoms increases the singlet oxygen quantum yield and enhances the suitability of the dyes for photodynamic therapy. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Liposomal formulations of metallophthalocyanines-nanoparticle conjugates for hypoxic photodynamic therapy and photoelectrocatalysis

  • Authors: Nwahara, Nnamdi Ugochinyere
  • Date: 2023-10-13
  • Subjects: Liposomes , Photochemotherapy , Phthalocyanines , Photoelectrochemistry , Cancer Treatment
  • Language: English
  • Type: Academic theses , Doctoral theses , text
  • Identifier: http://hdl.handle.net/10962/432159 , vital:72847 , DOI 10.21504/10962/432159
  • Description: This thesis investigates new strategies to enhance the efficacy of photodynamic therapy (PDT) under hypoxic conditions using in-vitro cancer cell models. Phthalocyanines are chosen as viable photosensitizer complexes owing to the favourable absorption properties. To this end, this thesis reports on the synthesis and photophysicochemical properties of various zinc and silicon phthalocyanines (Pcs). To afford better photophysicochemical properties, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. All the studied Pcs showed relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The various mechanisms for hypoxic response include (i) Type I PDT, (ii) PDT coupled with oxygen-independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles which serve to supplement in-vitro oxygen concentrations using MPcs or MPc-NPs conjugates. The mechanisms were assessed using electrochemical, computational techniques and catalase mimicking experiments. The as-synthesised Pcs or Pc-NPs were subjected to liposomal loading before PDT studies which led to enhanced biocompatibility and aqueous dispersity. The in-vitro dark cytotoxicity tests and photodynamic therapy activities of the fabricated Pc-liposomes and Pc-NPs-liposomes on either Henrietta Lacks (HeLa) or Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are presented herein. This work further showed that folic acid (FA) functionalization of liposomes could be exploited for active drug delivery and herein led to an almost 3-fold increase in drug uptake vs non-FA functionalised liposomes in accordance with folate receptor (FR) expression levels between HeLa and MCF-7 cells. The in-vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates were accessed using MCF-7 and HeLa cell lines. The various mechanisms; (i) Type I PDT, (ii) PDT coupled with oxygen -independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles were shown to adequately compensate for the otherwise attenuation of PDT activity under hypoxia. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13

Octa carboxy metal (II) phthalocyanine covalent films as pH sensitive electrochemical sensor for neurotransmitters

  • Authors: Moyo, Iphithuli
  • Date: 2023-10-13
  • Subjects: Phthalocyanines , Thin films , Neurotransmitters , Carboxylic acids
  • Language: English
  • Type: Academic theses , Master's theses , text
  • Identifier: http://hdl.handle.net/10962/424525 , vital:72161
  • Description: Octa acyl chloride metallophthalocyanines of cobalt (CoOAClPc) and iron (FeOAClPc) were synthesized and characterized using spectroscopic and electrochemical techniques. The metallophthalocyanines were fabricated as thin films onto phenylethylamine (PEA) pre-grafted Au electrode following a covalent amide reaction. The spectroscopic and electrochemical characterization confirmed the modification of the bare Au with PEA monolayer thin film (Au-PEA) and the covalent immobilization of MOAClPc to yield Au-PEA-MOAClPc (where M is Co and Fe). The acyl chloride functional groups were hydrolyzed forming pH sensitive thin films of terminal carboxylic acid (-COOH) functional groups (Au-PEA-MOCAPc). The Au-PEA-MOCAPc electrode exhibited pH selectivity and sensitivity properties towards the negatively charged [Fe(CN)6]3-/4- and positively charged [Ru(NH3)6]2+/3+ redox probes. The Au-PEA-MOCAPc electrodes were studied for their electrocatalytic and electroanalytical properties towards the detection of catecholamine neurotransmitters; dopamine (DA), epinephrine (EP) and norepinephrine (NOR). The electrodes were further investigated in the screening of ascorbic and uric acids by means of pH sensitive functional groups. The modification process exhibited good reproducibility. Excellent electrocatalytic and electroanalytical properties were observed. The limits of detection (LOD) determined using 3σ/m was found to be 64 nM, 0.22 μM and 0.17 μM for DA, EP and NOR respectively using Au-PEA-CoOCAPc. For Au-PEA-FeOCAPc, the LOD was found to 0.24 μM, 0.45 μM and 0.34 μM for DA, EP and NOR respectively. The Au-PEA-MOCAPc electrodes screened off the strong interferents, ascorbic and uric acid. The Au-PEA-FeOCAPc electrode was evaluated for its potential application in real sample analysis using new born calf serum, and it showed excellent percentage recoveries. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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  • Date Issued: 2023-10-13
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