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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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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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: Uncatalogued
- 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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Liposomal formulations of metallophthalocyanines-nanoparticle conjugates for hypoxic photodynamic therapy and photoelectrocatalysis
- Authors: Nwahara, Nnamdi Ugochinyere
- Date: 2023-10-13
- Subjects: Uncatalogued
- 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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Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments
- 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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The electrocatalytic activity of metallophthalocyanines and their conjugates with carbon nanomaterials and metal tungstate nanoparticles
- Authors: Ndebele, Nobuhle
- Date: 2023-10-13
- Subjects: Uncatalogued
- 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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The development of ionic zinc(II) phthalocyanines for sono-photodynamic combination therapy of cervical and breast cancer
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Uncatalogued
- 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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