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
Evaluation of the antibacterial activity of gallic acid anchored phthalocyanine-doped silica nanoparticles towards Escherichia coli and Staphylococcus aureus biofilms and planktonic cells
- Authors: Magadla, Aviwe , Openda, Yolande Ikala , Mpeta, Lekhetho S , Nyokong, Tebello
- Date: 2023
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/360424 , vital:65087 , xlink:href="https://doi.org/10.1016/j.pdpdt.2023.103520"
- Description: In this work, we have described the synthesis of phthalocyanine complexes Zn(II) tetrakis 4-(5-formylpyridin-2-yl)oxy) phthalocyanine (2), Zn(II) tetrakis-1 butyl 4-(2-(6- (tetra-phenoxy)pyridin-3-yl) vinyl)pyridin-1-ium phthalocyanine (3) and Zn(II) tetrakis 1 butyl 5-(2-(1-butylpyridin-1-ium-4-yl)vinyl)-2-(tetra-phenoxy)pyridin-1-ium phthalocyanine (4). The effect of a varying number of charges when the Pc complexes are alone or grafted in gallic acid (GA) tagged silica nanoparticles on photodynamic antimicrobial chemotherapy (PACT) is investigated toward Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli) in both planktonic and biofilm forms. Complex 4, bearing a total of 8 cationic charges, displayed the highest activity with log CFU (colony forming units) values of 8.60 and 6.42 against E.coli and S.aureus biofilms, respectively. The surface stability of E.coli and S.aureus biofilms in the presence of 4 and its conjugate was analyzed using cyclic voltammetry. Scanning electron microscopy (SEM) and Raman spectra are also used to study the conformational and biochemical changes within biofilm upon subjecting them to PACT.
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- Date Issued: 2023
Enhanced mitochondria destruction on MCF-7 and HeLa cell lines in vitro using triphenyl-phosphonium-labelled phthalocyanines in ultrasound-assisted photodynamic therapy activity
- Authors: Nene, Lindokuhle Cindy , Magadla, Aviwe , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295766 , vital:57376 , xlink:href="https://doi.org/10.1016/j.jphotobiol.2022.112553"
- Description: This work reports on the reactive oxygen species (ROS) generation and the therapeutic activities of new triphenyl-phosphonium-labelled phthalocyanines (Pcs), the 2,9,16,23-tetrakis(N-(N-butyl-4-triphenyl-phosphonium)- pyridine-4-yloxy) Zn(II) Pc (3) and 2,9,16,23-tetrakis-(N-(N-butyl-4-triphenyl-phosphonium)-morpholino) Zn(II) Pc (4) upon exposure to light, ultrasound and the combination of light and ultrasound. Two types of ROS were detected: the singlet oxygen (1O2) and hydroxyl radicals. For light irradiations, only the 1O2 was detected. An increase in the ROS generation was observed for samples treated with the combination of light and ultrasound compared to the light and ultrasound mono-treatments. The in vitro anticancer activity through photodynamic (PDT) and sonodynamic (SDT) therapy for the Pcs were also determined and compared to the photo-sonodynamic combination therapy (PSDT). The two cancer cell lines used for the in vitro studies included the Michigan Cancer Foundation-7 (MCF-7) breast cancer and Henrietta Lacks (HeLa) cervical cancer cell lines. The SDT treatments showed improved therapeutic efficacy on the cancer cells for both the Pcs compared to PDT. PSDT showed better therapeutic efficacy compared to both the PDT and SDT mono-treatments.
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- Date Issued: 2022
The implications of ortho-, meta-and para-directors on the in-vitro photodynamic antimicrobial chemotherapy activity of cationic pyridyl-dihydrothiazole phthalocyanines
- Authors: Magadla, Aviwe , Openda, Yolande Ikala , Nyokong, Tebello
- Date: 2022
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/295875 , vital:57386 , xlink:href="https://doi.org/10.1016/j.pdpdt.2022.103029"
- Description: Cationic Zn phthalocyanine complexes were derived by alkylation reaction of tetra-(pyridinyloxy) phthalocyanines (Pcs) at the ortho, meta, and para positions to form Zn (II) tetrakis 3-(4-(2-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (2), Zn (II) tetrakis 3-(4-(3-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (4) and Zn (II) tetrakis 3-(4-(4-pyridin-1-ium-1-yl) butyl)-2-mercapto-4,5-dihydrothiazol-3-ium phthalocyanine (6). The photophysicochemical behaviors of the Pc complexes were assessed. The meta and para-substituted complexes gave high singlet oxygen quantum yields. The cationic Pcs demonstrated good planktonic antibacterial activity against Staphylococcus aureus and Escherichia coli with the high log reduction values of 9.29 and 8.55, respectively. The cationic complexes also showed a significant decrease in the viability of in vitro biofilms after photo-antimicrobial chemotherapy at 100 µM for both Staphylococcus aureus and Escherichia coli biofilms.
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- Date Issued: 2022
Positively charged styryl pyridine substituted Zn (II) Phthalocyanines for Photodynamic Therapy and Photoantimicrobial Chemotherapy
- Authors: Magadla, Aviwe , Babu, Balaji , Mack, John , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/190600 , vital:45009 , xlink:href="https://doi.org/10.1039/D1DT01047F"
- Description: Cationic Zn phthalocyanine complexes were synthesized using Knoevenagel reaction starting from a Zn(II) tetrakis(2-formylphenoxy)phthalocyanine (1) to form Zn(II) tetrakis(1-butyl-4-(4-(tetraphenoxy)styryl)pyridin-1-ium) phthalocyanine (2) and Zn(II) tetrakis(4-(4-(tetraphenoxy)styryl)-1-(4-(triphenylphosphonio)butyl)pyridin-1-ium)phthalocyanine (3). The photophysicochemical behaviours of the Pc complexes were assessed. The cationic complexes display high water-solubility and gave moderate singlet oxygen quantum yield in water. The cationic Pcs demonstrate good cellular uptake and photodynamic activity against MCF-7 cells with IC50 values of 8.2 and 4.9 μM for 2 and 3, respectively. The cationic Pcs also demonstrate high photoantimicrobial activity against Escherichia coli with log reductions of 5.3 and 6.0 for 2 and 3, respectively.
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- Date Issued: 2021
The photophysicochemical properties and photodynamic therapy activity of Schiff base substituted phthalocyanines doped into silica nanoparticles and conjugated to folic acid
- Authors: Magadla, Aviwe , Babu, Balaji , Sen, Pinar , Nyokong, Tebello
- Date: 2021
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/185407 , vital:44384 , xlink:href="https://doi.org/10.1016/j.poly.2021.115227"
- Description: This work explores the synthesis, photophysicochemical properties and photodynamic activity (PDT) of tetrakis [N,N’–bis (4-(diethylamino)benzylidene) amino)propan-2-yl)oxy) phthalocyaninato] Zn (II) (3) and tetra-phenoxy N,N-dimethyl-4-((methylimino) Zn (II) (4) when the encapsulated into silica nanoparticles (SiNPs) followed by conjugation of folic acid (FA). The synthesised complexes and their doped analogues are examined for their PDT activity using MCF-7 cells. All the complexes showed dark toxicity that is >80%. The folic acid conjugates, MPc@SiNPs-FA showed greater photocytoxicity against MCF-7 cells upon irradiation with laser light.
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- Date Issued: 2021
Effect of the nature of nanoparticles on the photophysicochemical properties and photodynamic antimicrobial chemotherapy of phthalocyanines
- Authors: Magadla, Aviwe
- Date: 2020
- Subjects: Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/123107 , vital:35406
- Description: In this work, the syntheses and characterisation of Zn monocaffeic acid tri–tert–butyl phthalocyanine (1), Zn monocarboxyphenoxy tri– tert–butylphenoxyl phthalocyanine (2), tetrakis phenoxy N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (3) and tetrakis N,N-dimethyl-4-(methylimino) phthalocyanine indium (III) chloride (5) are presented. Complexes 3 and 5 were further quartenised with 1,3- propanesultone to form corresponding complexes (4) and (6), respectively. Complexes 1 and 2 were covalently linked to amino functionalised nanoparticles (NPs). Complexes 3, 4, 5 and 6 where linked to oleic acid/oleylamine capped (OLA/OLM) silver-iron dimers (Ag-Fe3O4 OLA/OLM) and silver-iron core shell (Ag@Fe3O4 OLA/OLM) NPs via interaction between the nanoparticles and the imino group on the phthalocyanines. The phthalocyanine-NP conjugates afforded an increase in triplet quantum yields with a corresponding decrease in fluorescence quantum yield as compared to the phthalocyanine complexes alone. Complexes 3, 4 and their conjugates were then used for photodynamic antimicrobial chemotherapy on E. coli. The zwitterionic photosensitiser 4 and its conjugates showed better efficiency for photodynamic antimicrobial chemotherapy compared to their neutral counterparts.
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- Date Issued: 2020
Enhanced photodynamic antimicrobial activity of surface modified SiNPs doped with zinc (II) phthalocyanines: The effect of antimicrobial ampicillin and extra charges from a sultone
- Authors: Magadla, Aviwe , Nyokong, Tebello
- Date: 2020
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/186034 , vital:44457 , xlink:href="https://doi.org/10.1016/j.pdpdt.2020.101996"
- Description: 1-(2-Methoxyethyl) piperidine sustituted Zn phthalocyanine complex (2) is synthesised and quartenised (3). These complexes are loaded into silica nanoparticles (SiNPs) that are futher surface modified with ampicillin and 1.3-propanesultone. The photophysical and photochemical properties of the complexes and their doped conjugates were investigated in dimethylsulfoxide. The cationic complex (3) is used for photodynamic antimicrobial activity. Log reduction values of above 9 are obtained towards the photoiactivation of Staphyloccocus aureus.
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- Date Issued: 2020
Enhanced photodynamic antimicrobial activity of surface modified SiNPs doped with zinc (II) phthalocyanines: the effect of antimicrobial ampicillin and extra charges from a sultone
- Authors: Magadla, Aviwe , Nyokong, Tebello
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/160511 , vital:40452 , https://doi.org/10.1016/j.pdpdt.2020.101996
- Description: 1-(2-Methoxyethyl)piperidine sustituted Zn phthalocyanine complex (2) is synthesised and quartenised (3). These complexes are loaded into silica nanoparticles (SiNPs) that are futher surface modified with ampicillin and 1.3-propanesultone. The photophysical and photochemical properties of the complexes and their doped conjugates were investigated in dimethylsulfoxide. The cationic complex (3) is used for photodynamic antimicrobial activity. Log reduction values of above 9 are obtained towards the photoiactivation of Staphyloccocus aureus.
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- Date Issued: 2020
Physicochemical and antimicrobial photodynamic chemotherapy (against E. coli) by indium phthalocyanines in the presence of silver–iron bimetallic nanoparticles
- Authors: Magadla, Aviwe , Oluwole, David O , Managa, Muthumuni , Nyokong, Tebello
- Date: 2019
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/187091 , vital:44564 , xlink:href="https://doi.org/10.1016/j.poly.2019.01.032"
- Description: In this work, Schiff base indium phthalocyanines: In–Cl tetrakis N,N-dimethyl-4-(methylimino) phthalocyanine (complex 1b) and In–Cl tetrakis phenoxy N,N-dimethyl-4-(methylimino) phthalocyanine (complex 2b) are synthesized from tetra amino and tetra phenoxy amino phthalocyanines, respectively. These complexes were further quartenised with 1,3-propanesultone to form zwitterionic complexes 1 and 2, respectively. Silver–iron dimers (Ag–Fe3O4) and silver-iron core shell (Ag@Fe3O4) nanoparticles (NPs) were linked to the synthesised complexes. The photophysical and photochemical behaviour of the complexes and their conjugates with NPs were investigated in dimethyl sulfoxide. Complexes 2 and 2b and their conjugates were then used for photodynamic antimicrobial chemotherapy on Escherichia coli. The zwitter ionic photosensitiser 2 and its conjugates showed better efficiency for photodynamic antimicrobial chemotherapy compared to their neutral counterparts.
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- Date Issued: 2019
Effect of nature of nanoparticles on the photophysicochemical properties of asymmetrically substituted Zn phthalocyanines
- Authors: Magadla, Aviwe , Oluwole, David O , Britton, Jonathan , Nyokong, Tebello
- Date: 2018
- Subjects: To be catalogued
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/234539 , vital:50206 , xlink:href="https://doi.org/10.1016/j.ica.2018.06.043"
- Description: In this work, low symmetry Zn mono caffeic acid tri-tert butyl (1) and Zn monocarboxyphenoxy tri-(tert-butylphenoxyl) (2) phthalocyanines (Pcs) were covalently linked to amino (using glutathione, GSH, or 3-aminopropyl)triethoxysilane, APTES) functionalised nanoparticles. The nanoparticles are represented as: AgNPs-GSH, SiNPs-APTES, Fe3O4-Ag-SiNPs-APTES and Fe3O4-AgNPs-GSH). The photophysical and photochemical behaviour of the complexes 1 and 2 and their conjugates with nanoparticles were investigated in dimethyl sulfoxide. The conjugates of the Pc complexes with the NPs afforded increase in triplet quantum yields with corresponding decrease in fluorescence quantum yield compared to the Pc complexes alone. The conjugates of 1-AgNPs-GSH, 2-SiNPs-APTES and 2-Fe3O4-Ag-SiNPs-APTES showed higher singlet oxygen quantum yield values as compared to the Pc complexes alone.
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- Date Issued: 2018