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
- Full Text:
- Date Issued: 2023-10-13
- 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
- Full Text:
- Date Issued: 2023-10-13
Liposomal formulations of metallophthalocyanines-nanoparticle conjugates for hypoxic photodynamic therapy and photoelectrocatalysis
- Authors: Nwahara, Nnamdi Ugochinyere
- Date: 2023-10-13
- Subjects: Liposomes , Photochemotherapy , Phthalocyanines , Photoelectrochemistry , Cancer Treatment
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/432159 , vital:72847 , DOI 10.21504/10962/432159
- Description: This thesis investigates new strategies to enhance the efficacy of photodynamic therapy (PDT) under hypoxic conditions using in-vitro cancer cell models. Phthalocyanines are chosen as viable photosensitizer complexes owing to the favourable absorption properties. To this end, this thesis reports on the synthesis and photophysicochemical properties of various zinc and silicon phthalocyanines (Pcs). To afford better photophysicochemical properties, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. All the studied Pcs showed relatively high triplet and singlet oxygen quantum yields corresponding to their low fluorescence quantum yields. The various mechanisms for hypoxic response include (i) Type I PDT, (ii) PDT coupled with oxygen-independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles which serve to supplement in-vitro oxygen concentrations using MPcs or MPc-NPs conjugates. The mechanisms were assessed using electrochemical, computational techniques and catalase mimicking experiments. The as-synthesised Pcs or Pc-NPs were subjected to liposomal loading before PDT studies which led to enhanced biocompatibility and aqueous dispersity. The in-vitro dark cytotoxicity tests and photodynamic therapy activities of the fabricated Pc-liposomes and Pc-NPs-liposomes on either Henrietta Lacks (HeLa) or Michigan Cancer Foundation-7 (MCF-7) breast cancer cells are presented herein. This work further showed that folic acid (FA) functionalization of liposomes could be exploited for active drug delivery and herein led to an almost 3-fold increase in drug uptake vs non-FA functionalised liposomes in accordance with folate receptor (FR) expression levels between HeLa and MCF-7 cells. The in-vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates were accessed using MCF-7 and HeLa cell lines. The various mechanisms; (i) Type I PDT, (ii) PDT coupled with oxygen -independent therapy and (iii) in-situ oxygen generation using catalase-mimicking nanoparticles were shown to adequately compensate for the otherwise attenuation of PDT activity under hypoxia. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- 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
- Full Text:
- Date Issued: 2023-10-13
The photodynamic therapeutic activities and optical limiting properties of metalated asymmetric porphyrins and corroles
- 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
- Full Text:
- Date Issued: 2023-10-13
- 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
- Full Text:
- Date Issued: 2023-10-13
Photodynamic anticancer and antimicrobial activities of π-extended BODIPY dyes and cationic mitochondria-targeted porphyrins
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
The synthesis and characterisation of Sn(IV) porphyrin derivatives and their potential application in anti-cancer and antimicrobial photodynamic therapy
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , vital:44791
- Description: In photodynamic therapy (PDT), the activation of light-sensitive drugs in tumour cells produces reactive singlet oxygen species, which cause tumour destruction through a cascade of biochemical reactions. Over the years, the wavelength of activation has been shown to be a critical factor in the penetration of light. Hence the properties of photosensitiser dyes in this context shape their ability to treat deep-seated tumours. In this study, the synthesis, structural characterisation and photophysicochemical properties of a series of Sn(IV) porphyrins with meso-methylthiophenyl rings that have been prepared to study their PDT and photodynamic antimicrobial chemotherapy (PACT) activity properties are reported. The series of Sn(IV) complexes is comprised of a porphyrin (1-Sn), a corrole (2-Sn), a chlorin (3-Sn) and an N-confused porphyrin (4-Sn). Herein, the low symmetry Sn(IV) porphyrin derivatives are shown to have excellent singlet oxygen generation capabilities, and lifetimes of the triplet excited states were in the microsecond range. For example, 4-Sn had a singlet oxygen quantum yield (ФΔ) and an excited triplet state lifetime (τT) of 0.88 and 27 μs, respectively. The complexes were studied using UV-visible and magnetic circular dichroism (MCD) spectroscopies. Interestingly, the positive-to-negative sign sequences of the Faraday B0 terms of 2-Sn and 3-Sn reveal that the structural modifications involved break the degeneracy of the MOs derived from the 1eg* LUMO of the porphyrin 1-Sn. In contrast, a conventional negative-to-positive sign sequence is observed for 4-Sn, since the confusion of a pyrrole moiety also results in a large separation of the 1a1u and 1a2u MOs of the porphyrin 1-Sn that are derived from the HOMO of a C16H162−parent hydrocarbon perimeter. The trends in the electronic structures of the Sn(IV) complexes were further investigated through a series of time-dependent density functional theory calculations, so that the suitability of the different types of complex for use in singlet oxygen applications could be further explored. During in vitro photodynamic antimicrobial chemotherapy (PACT) studies, chlorin derivative 3-Sn had the highest activity towards S. aureus and E. coli with log10 reductions of 10.5 and 8.74, respectively. The unusually high activity of 3-Sn against E.coli suggests that the interaction of neutral photosensitisers with gram-negativebacteria is more complex than previously understood. Anti-cancer PDT studies demonstrated that the photosensitisers had negligible dark cytotoxicity. Upon photoirradiation, the Sn(IV) complexes consistently exhibited IC50 values lower than 15 μM against MCF-7 adenocarcinoma cells. An IC50 value of 1.4 μM for 4-Sn after activation at the deep-red region of the spectrum demonstrates that complexes of this type merit further in-depth investigation. The results provide evidence that the low-symmetry Sn(IV) chlorins and N-confused porphyrins merit further in-depth study for use in singlet oxygen applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Dingiswayo, Somila
- Date: 2021-10
- Subjects: Porphyrins , Photochemotherapy , Cancer Photochemotherapy , Active oxygen Physiological effect , Aromaticity (Chemistry) , Tetrapyrroles , Magnetic circular dichroism , Corroles , Chlorins , Photodynamic antimicrobial chemotherapy (PACT)
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188843 , vital:44791
- Description: In photodynamic therapy (PDT), the activation of light-sensitive drugs in tumour cells produces reactive singlet oxygen species, which cause tumour destruction through a cascade of biochemical reactions. Over the years, the wavelength of activation has been shown to be a critical factor in the penetration of light. Hence the properties of photosensitiser dyes in this context shape their ability to treat deep-seated tumours. In this study, the synthesis, structural characterisation and photophysicochemical properties of a series of Sn(IV) porphyrins with meso-methylthiophenyl rings that have been prepared to study their PDT and photodynamic antimicrobial chemotherapy (PACT) activity properties are reported. The series of Sn(IV) complexes is comprised of a porphyrin (1-Sn), a corrole (2-Sn), a chlorin (3-Sn) and an N-confused porphyrin (4-Sn). Herein, the low symmetry Sn(IV) porphyrin derivatives are shown to have excellent singlet oxygen generation capabilities, and lifetimes of the triplet excited states were in the microsecond range. For example, 4-Sn had a singlet oxygen quantum yield (ФΔ) and an excited triplet state lifetime (τT) of 0.88 and 27 μs, respectively. The complexes were studied using UV-visible and magnetic circular dichroism (MCD) spectroscopies. Interestingly, the positive-to-negative sign sequences of the Faraday B0 terms of 2-Sn and 3-Sn reveal that the structural modifications involved break the degeneracy of the MOs derived from the 1eg* LUMO of the porphyrin 1-Sn. In contrast, a conventional negative-to-positive sign sequence is observed for 4-Sn, since the confusion of a pyrrole moiety also results in a large separation of the 1a1u and 1a2u MOs of the porphyrin 1-Sn that are derived from the HOMO of a C16H162−parent hydrocarbon perimeter. The trends in the electronic structures of the Sn(IV) complexes were further investigated through a series of time-dependent density functional theory calculations, so that the suitability of the different types of complex for use in singlet oxygen applications could be further explored. During in vitro photodynamic antimicrobial chemotherapy (PACT) studies, chlorin derivative 3-Sn had the highest activity towards S. aureus and E. coli with log10 reductions of 10.5 and 8.74, respectively. The unusually high activity of 3-Sn against E.coli suggests that the interaction of neutral photosensitisers with gram-negativebacteria is more complex than previously understood. Anti-cancer PDT studies demonstrated that the photosensitisers had negligible dark cytotoxicity. Upon photoirradiation, the Sn(IV) complexes consistently exhibited IC50 values lower than 15 μM against MCF-7 adenocarcinoma cells. An IC50 value of 1.4 μM for 4-Sn after activation at the deep-red region of the spectrum demonstrates that complexes of this type merit further in-depth investigation. The results provide evidence that the low-symmetry Sn(IV) chlorins and N-confused porphyrins merit further in-depth study for use in singlet oxygen applications. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
In vitro susceptibility of Staphylococcus aureus to porphyrin-silver mediated photodynamic antimicrobial chemotherapy
- Authors: Shabangu, Samuel Malewa
- Date: 2020
- Subjects: Porphyrins , Nanoparticles , Photochemotherapy , Drug resistance in microorganisms , Staphylococcus aureus
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167476 , vital:41484
- Description: This work reports on the syntheses and characterization of symmetrical and unsymmetrical porphyrin complexes namely, 5,10,15,20-tetra(4-pyridyl)-porphyrinato zinc(II) (1), 5,10,15,20-tetrathienyl porphyrinato zinc(II) (2), 5-(4-hydroxyphenyl)-10, 15, 20-tris(2-thienyl) porphyrinato zinc(II) (3), 5-(4-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)- porphyrinato zinc(II) (4), 5-(4-carboxyphenyl)-10,15,20-triphenyl-porphyrinato zinc(II) (5) and 5-(4-carboxyphenyl)-10, 15, 20-tris(2-thienyl)-porphyrinato zinc(II) (6). The synthesis of silver nanoparticles (AgNPs) was also undertaken in this research work. Complexes 1, 2, 3 and 6 were linked to oleic acid/oleylamine functionalized nanoparticles via self-assembly and 4-6 were linked via covalent interaction through an amide bond to glutathione capped AgNPs. The effect of nature of bond along with symmetry were investigated, of interest were the five membered thienyl substituents. The photophysical and photochemical behaviour of the complexes and their conjugates with AgNPs were investigated in dimethylformamide. The porphyrin and AgNPs conjugates afforded an increase in singlet oxygen quantum yield. Complexes 1-6 and their conjugates were used for photodynamic antimicrobial chemotherapy of Staphylococcus aureus. The antimicrobial studies were done in two different concentrations of 0.36 and 2.0 μg/mL. The thienyl substituted porphyrin complexes and their conjugates gave better photodynamic activity as compared to phenyl analogues
- Full Text:
- Date Issued: 2020
- Authors: Shabangu, Samuel Malewa
- Date: 2020
- Subjects: Porphyrins , Nanoparticles , Photochemotherapy , Drug resistance in microorganisms , Staphylococcus aureus
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/167476 , vital:41484
- Description: This work reports on the syntheses and characterization of symmetrical and unsymmetrical porphyrin complexes namely, 5,10,15,20-tetra(4-pyridyl)-porphyrinato zinc(II) (1), 5,10,15,20-tetrathienyl porphyrinato zinc(II) (2), 5-(4-hydroxyphenyl)-10, 15, 20-tris(2-thienyl) porphyrinato zinc(II) (3), 5-(4-carboxyphenyl)-10,15,20-tris(pentafluorophenyl)- porphyrinato zinc(II) (4), 5-(4-carboxyphenyl)-10,15,20-triphenyl-porphyrinato zinc(II) (5) and 5-(4-carboxyphenyl)-10, 15, 20-tris(2-thienyl)-porphyrinato zinc(II) (6). The synthesis of silver nanoparticles (AgNPs) was also undertaken in this research work. Complexes 1, 2, 3 and 6 were linked to oleic acid/oleylamine functionalized nanoparticles via self-assembly and 4-6 were linked via covalent interaction through an amide bond to glutathione capped AgNPs. The effect of nature of bond along with symmetry were investigated, of interest were the five membered thienyl substituents. The photophysical and photochemical behaviour of the complexes and their conjugates with AgNPs were investigated in dimethylformamide. The porphyrin and AgNPs conjugates afforded an increase in singlet oxygen quantum yield. Complexes 1-6 and their conjugates were used for photodynamic antimicrobial chemotherapy of Staphylococcus aureus. The antimicrobial studies were done in two different concentrations of 0.36 and 2.0 μg/mL. The thienyl substituted porphyrin complexes and their conjugates gave better photodynamic activity as compared to phenyl analogues
- Full Text:
- Date Issued: 2020
Metallophthalocyanines linked to metal nanoparticles and folic acid for use in photodynamic therapy of cancer and photoinactivation of bacterial microorganisms.
- Authors: Matlou, Gauta Gold
- Date: 2020
- Subjects: Cancer -- Photochemotherapy , Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166540 , vital:41377
- Description: This thesis presents on the synthesis and characterization of novel asymmetric and symmetrical metallophthalocyanines (MPcs) substituted with carboxylic acid functional groups and centrally metallated with zinc and indium. The MPcs are further covalently linked to cysteine capped silver nanoparticles (cys-AgNPs), amino functionalized magnetic nanoparticles (AMNPs) and folic acid (FA) through an amide bond between the carboxylic group of MPcs and the amino group of FA, cys-AgNPs or AMNPs. The covalent linkage of MPcs to FA improved the water solubility of MPcs and allowed for singlet oxygen quantum yield determination in water. Asymmetric MPcs and their conjugates were found to have improved photochemical and photophysical properties compared to symmetrical MPcs and their conjugates. The heavy atom effect of AMNPs and AgNPs improved the triplet and singlet oxygen quantum yields of MPcs. MPcs and their conjugates (MPc-FA, MPc-AMNPs, MPc-AgNPs) were found to have lower in vitro dark cytotoxicity and higher photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. The water soluble MPc-FA had better PDT activity when compared to MPc-AMNPs due to the active targeting of folic acid-folate binding on cancer cell surface. MPcs and MPc-AgNPs conjugates also showed excellent in vitro cytotoxicity on S. aureus under light irradiation compared to dark cytotoxicity. The photosensitizing properties of MPcs and their conjugates are demonstrated for the first time in this thesis, both on breast cancer cells (MCF-7) through photodynamic therapy and on microorganisms (S. aureus) through photodynamic antimicrobial chemotherapy.
- Full Text:
- Date Issued: 2020
- Authors: Matlou, Gauta Gold
- Date: 2020
- Subjects: Cancer -- Photochemotherapy , Nanoparticles , Phthalocyanines , Anti-infective agents -- Therapeutic use , Photochemotherapy , Photochemistry
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166540 , vital:41377
- Description: This thesis presents on the synthesis and characterization of novel asymmetric and symmetrical metallophthalocyanines (MPcs) substituted with carboxylic acid functional groups and centrally metallated with zinc and indium. The MPcs are further covalently linked to cysteine capped silver nanoparticles (cys-AgNPs), amino functionalized magnetic nanoparticles (AMNPs) and folic acid (FA) through an amide bond between the carboxylic group of MPcs and the amino group of FA, cys-AgNPs or AMNPs. The covalent linkage of MPcs to FA improved the water solubility of MPcs and allowed for singlet oxygen quantum yield determination in water. Asymmetric MPcs and their conjugates were found to have improved photochemical and photophysical properties compared to symmetrical MPcs and their conjugates. The heavy atom effect of AMNPs and AgNPs improved the triplet and singlet oxygen quantum yields of MPcs. MPcs and their conjugates (MPc-FA, MPc-AMNPs, MPc-AgNPs) were found to have lower in vitro dark cytotoxicity and higher photodynamic therapy (PDT) activity on MCF-7 breast cancer cells. The water soluble MPc-FA had better PDT activity when compared to MPc-AMNPs due to the active targeting of folic acid-folate binding on cancer cell surface. MPcs and MPc-AgNPs conjugates also showed excellent in vitro cytotoxicity on S. aureus under light irradiation compared to dark cytotoxicity. The photosensitizing properties of MPcs and their conjugates are demonstrated for the first time in this thesis, both on breast cancer cells (MCF-7) through photodynamic therapy and on microorganisms (S. aureus) through photodynamic antimicrobial chemotherapy.
- Full Text:
- Date Issued: 2020
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