List of Titles

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

- Luhana, Charles Benjamin

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

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

- Magadla, Aviwe

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

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

- Benise, Emihle

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

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

- Leoma, Mofeli Benedict

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

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

- Mgidlana, Sithi

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

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

- Ncwane, Lunathi

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

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

- Nkhahle, Reitumetse Precious

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

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

- Salami, Sodeeq Aderotimi

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

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

- Magwaza, Temlandvo Matshidiso

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

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

- Nwahara, Nnamdi Ugochinyere

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

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

- Moyo, Iphithuli

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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Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments

- Soy, Rodah Cheruto

Authors: Soy, Rodah Cheruto
Date: 2023-10-13
Subjects: Uncatalogued
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/432252 , vital:72855 , DOI 10.21504/10962/432252
Description: The search for alternative therapies and non-toxic photosensitizer drugs that can efficiently generate cytotoxic reactive oxygen species for biomedical applications, such as in alternative photodynamic therapy (PDT) for cancer treatment and photodynamic antimicrobial chemotherapy (PACT) for drug-resistant bacteria treatment is on the rise. Nevertheless, the lack of photosensitizer dyes that absorb light strongly within the therapeutic window (620−850 nm) that can locally target the tumor and bacterial cells and generate singlet oxygen efficiently are some of the main challenges in PDT and PACT treatment. This study sought to address the challenges that impede PDT and PACT from realizing their full potential by synthesizing a series of meso-aryltetrapyrrolic photosensitizer dyes that absorb light within the therapeutic window. These include meso-tetraarylporphyrin (Por), A3-type meso-triarylcorrole (Cor), meso-tetraarylchlorin (Chl), and N-confused meso-tetraarylporphyrin (NCP) dyes with 4-thiomethylphenyl (1), thien-3-yl (2), thien-2-yl (3), 5-bromo-thien-2-yl (4), 4-methoxyphenyl (5), 3-methoxyphenyl (6), 4-hydroxyphenyl (7) and 4-hydroxy-3-methoxyphenyl (8) meso-aryl rings. Por, Cor, Chl and NCP dyes and and their Ga(III), P(V), In(III) and/or Sn(IV) complexes with 1-8, 1-4, 5-8 and 5 meso-aryl rings were studied, along with two A2B-type Ga(III) meso-triarylcorroles with pentafluorophenyl rings at the A2 positions and 3,6-di-t-butyl-9H-carbazole (9) or N-butyl-4-carbazole (10) rings at the B position that were prepared in the laboratory of Prof. Xu Liang of Jiangsu University in the People’s Republic of China. The carbazole nitrogen of 10-GaCor was quaternized at Rhodes University with ethyl iodide to form a cationic species (10-GaCor-Q) for PDT and PACT activity studies. The structures of the synthesized dyes were confirmed using UV-visible absorption and 1H NMR spectroscopy, and MALDI-TOF-mass spectrometry. 1-4-InPor In(III) porphyrins, 1-4-PVCor, 1-4-GaCor A3 PV and GaIII corrole dyes were also conjugated to gold nanoparticles (AuNPs) and silver nanoparticles (AgNPs) via sulfur-gold and sulfur-silver affinities. The successful conjugation of the dyes onto the nanoparticles to form dye-AuNP or dye-AgNP nanoassemblies was confirmed using transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray powered diffraction (XRD), and (X-ray photon spectroscopy) XPS. The photophysicochemical, photostability, and lipophilicity properties of the dyes and their PDT and PACT activities were investigated, and the structure-property relationships were analyzed. This was accomplished by analyzing the changes in the properties of the dyes due to the meso-aryl substituents, central ions, molecular symmetry, and heavy atom effects. Time-dependent-density functional theory (TD-DFT) calculations were also used to further probe the electronic and optical spectroscopic properties of the dyes. The analysis of the photophysicochemical, photostability, and lipophilicity data for the synthesized dyes demonstrated that there are inherent structure-property relationships for the dyes studied. The TD-DFT calculations also assisted in rationalizing the observed optical spectroscopic data for the dyes. The introduction of different meso-aryl substituents resulted in minor absorption spectral changes on the parent structures of the dyes due to their inductive and mesomeric effects, while the insertion of Ga(III), In(III), and Sn(IV) electropositive metal centers resulted in marked red shifts of the B bands due to favorable interactions with the porphyrin or porphyrinoid ligand core. The lower symmetries of the corrole, chlorin, and N-confused porphyrin dyes resulted in enhanced absorption properties within the therapeutic window relative to porphyrins. The heavy atom effect from the Ga(III), In(III), and Sn(IV) central ions, the meso-aryl groups, and the external heavy atom effect from the AuNPs and AgNPs significantly reduced the fluorescence quantum yield values of the dyes resulting in high singlet oxygen quantum yields. The dye complexes also exhibited properly balanced lipophilic properties and high photostabilities. The P(V) ion of the A3 PV corrole dyes reduced the aggregation effects, enhanced cellular uptake, and lowered the lipophilicity values relative to the A3 GaIII corrole dyes. The porphyrin and porphyrinoid complexes studied exhibited relatively low in vitro dark cytotoxicity toward MCF-7 cancer cells, which is enhanced for AuNP nanoconjugates of 1-InPor, 1-3-PVCor, and 1-3-GaCor. The dyes also have low in vitro dark cytotoxicity toward planktonic and biofilm cells of S. aureus and E. coli. The complexes also exhibited favorable PDT and PACT activities toward MCF-7 cancer cells, and planktonic and biofilm S. aureus and E. coli bacteria due to their high singlet oxygen quantum yields. AuNP and AgNP nanoconjugates of 1-4-InPor, 1-4-PVCor, and 1-4-GaCor exhibited enhanced PDT and PACT activities due to the favorable synergistic effects of nanoparticles. The PDT and PACT activities of A3 PV corrole dyes and the nanoconjugates of 1-4-PVCor are slightly higher than those of A3-type GaIII corroles and their nanoconjugates due to decreased aggregation effects and enhanced PS drug uptake. The cationic 10-GaCor-Q species also exhibit favorable PDT and PACT activities in contrast to the neutral 9-10-GaCor dyes due to enhanced PS drug penetration into the tumor or bacteria cells. The complexes also exhibited high Log10 reduction values for planktonic S. aureus suggesting that the dyes are highly efficient PS dyes. The activities of the complexes toward planktonic E. coli bacteria are moderate except for 10-GaCor-Q, 2-4-PVCor-AgNPs, and 5-8-SnChl chlorins exhibiting relatively favorable activity with > 3 Log10 CFU.mL−1 values. The dyes also exhibit moderate activities toward the S. aureus and E. coli biofilm cells, which are lower than for the planktonic cells, as shown by their lower Log10 reduction values. The data demonstrate that the low symmetry corrole, chlorin, and N-confused porphyrin complexes that absorb light strongly within the therapeutic window have significantly enhanced PDT and PACT activities relative to their porphyrin analogs. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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Date Issued: 2023-10-13

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The electrocatalytic activity of metallophthalocyanines and their conjugates with carbon nanomaterials and metal tungstate nanoparticles

- Ndebele, Nobuhle

Authors: Ndebele, Nobuhle
Date: 2023-10-13
Subjects: Phthalocyanines , Electrocatalysis , Nitrites , Dopamine , Catechol , Detection limit
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/431934 , vital:72816 , DOI 10.21504/10962/431933
Description: In this dissertation, seventeen phthalocyanine complexes were synthesised. Of these, only four are known and have been published. These complexes were synthesised using the conventional statistical condensation method that involves refluxing the phthalonitrile(s) (4-((1,3-bis(dimethylamino)propan-2-yl)oxy)phthalonitrile, 4-(4-carboxyphenoxy)phthalonitrile, 4-(4-acetylphenoxy)phthalonitrile, dimethyl 5-(3,4-dicyanophenoxy)-isophthalate, 4-(4-(tert-butyl)phenoxy)phthalonitrile, 5-phenoxylpicolinic acid phthalonitrile 4-(4-formylphenoxy) phthalonitrile, and 4-(4-(3-oxo-3-phenylprop-1-enyl) phenoxy) phthalonitrile) with the metal salt and 1,8-diazabicyclo[5.4.0]undecane as a catalyst in a high-temperature solvent. And thereafter (when necessary), isolation and purification of the target compounds were achieved through the use of silica column chromatography. These compounds were characterised using various analytical techniques such as; ultraviolet-visible absorption, mass spectroscopy, and Fourier transform infrared spectra and elemental analysis. These techniques proved that the complexes were successfully synthesised and isolated as pure compounds. Carbon-based (graphene quantum dots and nitrogen-doped graphene quantum dots) and metal oxide (bismuth tungsten oxide and nickel tungsten oxide) nanomaterials were synthesised. Together with the purchased single-walled carbon nanotubes, these nanomaterials were conjugated to some of the MPc complexes via non-covalent (carbon-based nanomaterials) and covalent (metal oxides) linkage forming hybrid materials. These nanomaterials and hybrids were characterised using various analytical methods (ultraviolet-visible absorption, X-ray diffraction, Raman spectroscopy, thermographic analysis, and dynamic light scattering). Nanomaterials were utilised herein to determine their effect on the properties of MPc complexes and provide a synergistic effect in the hope of enhancing these properties. All complexes synthesised in this work (MPcs, nanomaterials and hybrids) were employed as electrocatalysts in electrochemical sensing. These electrocatalysts were embedded onto the glassy carbon electrode via an adsorption method known as drop-casting. The modified electrode surfaces were characterised using cyclic voltammetry, electrochemical impedance spectroscopy and scanning electrochemical microscopy to determine various electrochemical parameters. These electrocatalysts were used in the detection of either nitrite, catechol and/or dopamine. The detection limits, sensitivities, kinetics and catalytic constants were among other parameters determined for each electrocatalyst. These electrocatalysts proved to be stable electrocatalysts that could potentially be used for practical applications. The determined parameters were comparable and sometimes better than those obtained in literature. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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Date Issued: 2023-10-13

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The photodynamic therapeutic activities and optical limiting properties of metalated asymmetric porphyrins and corroles

- Burgess, Kristen Paige

Authors: Burgess, Kristen Paige
Date: 2023-10-13
Subjects: Porphyrins , Corrole , Photochemotherapy , Anti-infective agents , Nonlinear optics , Z-scan technique , Active oxygen , Time-dependent density functional theory , Chemical synthesis
Language: English
Type: Academic theses , Master's theses , text
Identifier: http://hdl.handle.net/10962/424490 , vital:72158
Description: Cancer is a devastating disease that is a leading cause of death worldwide. Despite the available cancer treatments, there is a significant need to improve the therapeutic approach towards this disease. Photodynamic therapy (PDT) is an alternative approach for treating cancer, which requires a photosensitiser, molecular oxygen and light. Although some porphyrin-based derivatives have been approved by the United States Food and Drug Administration (FDA) and other similar agencies elsewhere for photodynamic therapy, their relatively poor photophysicochemical properties mean that there is an ongoing need for new photosensitiser dyes. Singlet oxygen photosensitiser dyes can also be used to treat bacteria that develop antimicrobial resistance in the context of photodynamic antimicrobial chemotherapy (PACT). The main aim of this study was to synthesise and characterise a series of porphyrin dyes with 4-quinolinyl, thien-2-yl and 4-bromo-thien-2-yl meso-aryl groups and their Sn(IV) and In(III) complexes, as well as their corrole analogues. Corroles are contracted macrocycles that have interesting optical properties. The corroles selected for study were found to be difficult to synthesise and purify and had unfavourable photophysicochemical properties and were thus omitted from the PDT and PACT biological applications within this thesis. High- and low-symmetry A4 and ABAB type meso-tetraarylporphyrins porphyrins were synthesised to improve the photophysicochemical properties of the photosensitisers; the utility of these dyes as photosensitisers was studied against the MCF-7 breast cancer cell line for PDT and against Staphylococcus aureus and Escherichia coli for PACT. The thienyl-2-yl rings were introduced to red shift the lowest energy Q band towards the phototherapeutic window, while quaternisation of the nitrogen and sulfur atoms of the 4-quinolinyl and thien-2-yl rings to introduce a cationic nature was explored to improve the bioavailability of the drugs and uptake into the target cell walls for improved efficacy. Heavy Sn(IV) and In(III) central metal ions were introduced to enhance the singlet oxygen quantum yields and limit aggregation through axial ligation. The bromine atoms of the 4-bromo-thien-2-yl meso-aryl rings were also introduced to enhance the singlet oxygen quantum yields of the dyes. Furthermore, the utility of the porphyrin and corrole molecules for optical limiting properties to limit laser radiation to protect optical devices, including eyes, was explored by the z-scan technique. One of the dyes studied, Sn(IV) tetrathien-2-ylporphyrin, that exhibited the most favourable reverse saturable absorbance (RSA) response was embedded into a poly(bisphenol carbonate A) polymer thin film to further explore its suitability for practical applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
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Date Issued: 2023-10-13

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Rapid Synthesis of Thiol-Co-Capped CdTe/CdSe/ZnSe Multi-Core-Shell QDs and Their Encapsulation in Liposomes and Chitosan Nanoparticles; Comparative Bio-compatibility Studies Using Hela and Vero Cells

- Daramola, Olamide Abiodun

Authors: Daramola, Olamide Abiodun
Date: 2023-03-31
Subjects: Chitosan , Chitosan nanoparticles , Quantum dots , Liposomes , Toxicity , Cadmium telluride , Cadmium selenide , Zinc selenide
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/422617 , vital:71962 , DOI 10.21504/10962/422617
Description: The common method that has been used to reduce the toxicity posed to living cells by CdTe Quantum Dots (QDs) is through the synthesis of CdTe multi-core-shells nanoparticles. In this process, the surface of CdTe QDs is usually coated by less toxic ZnS or ZnSe shells. This heterostructure compound does not only reduce the toxicity of CdTe QDs but can also be used in applications such as deep tissue imaging. The heterostructures can be in numerous forms such as CdTe/CdSe/ZnSe or CdTe/CdSe/ZnS or CdTe/CdS/ZnS multi-core-shell QDs. However, the drawbacks attributed to the fabrication of these compounds is long synthesis times (6- 24 h) in achieving the highest wavelength emission maxima. Others are the use of toxic reagents and poor reproducibility of synthesized materials. An additional problem is that the ZnSe or ZnS coating is insufficient to completely protect the highly toxic Cd metal from escaping into immediate solution. This limits their use in biochemistry and with living systems. Liposomes and biopolymers such as chitosan are known to be environmentally friendly compounds that have been used in various studies as delivery systems for QDs and model drugs for drug delivery applications. They are generally non-toxic and highly bio-compatible. In this study, the rapid synthesis of thiol-co-capped CdTe/CdSe/ZnSe multi-core-shell QDs with a maximum reaction time of 35 mins, gave reliable QDs with emission maxima at 625 nm. The multi-core-shell QDs were encapsulated in two different bio-compatible environments, namely liposome and chitosan nanoparticles (CNP) at 14 different formulations (F) for liposome and 12 different formulations for CNP. Cytotoxicity and florescence imaging studies using HeLa and Vero cells, were used to investigate the improved bio-compatibility. Various characterization techniques were used to elucidate the optical properties, morphology and physico-chemical properties of the QDs and nanocomposites. Two of the best formulations, QD-liposome vesicles (LVs)-F12 and QD-CNP-F9 (with chitosan), demonstrated high loading efficiencies of 42 ± 6 % and 59 ± 5 %, respectively. While the plain CdTe QDs showed high toxicity, some of the encapsulated materials, QD-LVs-F1 and F12, depicted no-toxicity against the cells (IC50 > 0.5 mg/ml). The QDs also retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus, indicating the successful internalization of the QDs in the cytosol. These results shows that encapsulation of CdTe multi-core-shell QDs in liposomes produce better bio-compatibility compared to multi-core-shell QDs and better than CNP coating. These particles therefore show good promise in cell-labelling, drug delivery studies. Their core-shell nanoparticles have also shown good behavior in enhancing the memory of a device which is based on some recent collaborated works. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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Date Issued: 2023-03-31

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The development of ionic zinc(II) phthalocyanines for sono-photodynamic combination therapy of cervical and breast cancer

- Nene, Lindokuhle Cindy

Authors: Nene, Lindokuhle Cindy
Date: 2023-03-31
Subjects: Phthalocyanines , Sonochemistry , Photochemotherapy , Cancer Treatment
Language: English
Type: Academic theses , Doctoral theses , text
Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
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Date Issued: 2023-03-31

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