Photodynamic anticancer and antimicrobial activities of aza-BODIPY and porphyrinbased photosensitisers and their non-linear properties
- Authors: Molupe, Nthabeleng Regina
- Date: 2024-10-11
- Subjects: Photochemotherapy , Anti-infective agents , Nonlinear optics , Cancer Treatment , BODIPY , Porphyrins
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466603 , vital:76758 , DOI https://doi.org/10.21504/10962/466603
- Description: New aza-BODIPY dyes and porphyrins were synthesised and characterised so that photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity studies could be performed. Several strategies were explored to achieve targeted nanoplatforms or biocompatible nanoplatforms to enhance the suitability of these compounds for use in PDT. Following earlier MSc research on the encapsulation of halogenated boron dipyrromethene (BODIPY) dyes into Pluronic® micelles, similar nanomicelles were prepared to encapsulate halogenated boron aza-dipyrromethene (aza-BODPY) dyes to enhance their aqueous solubility. However, the 1,7-dimethylthiophenyl- 2,6-diiodo-3,5-diphenyl (1) and 1,7-di-methylthiophenyl-2,6-diiodo- 3,5-dithien-3-yl (2) aza-BODIPY dyes that were prepared in this context were found to degrade when encapsulated. A different strategy was then followed in which gold nanoparticles (AuNPs) were conjugated to 1 and 2 via Au-S interactions to form biocompatible aza-BODIPY-AuNP conjugates (1-AuNP and 2-AuNP). This strategy was successful, and favourable IC50 values of 3.60 and 10.0 μM for 1-AuNP and 2- AuNP were obtained during in vitro PDT activity studies against MCF-7 human breast cancer cells, respectively, while values of 11.0 and 12.8 μM were obtained for 1 and 2. To further explore the preparation of better-targeted aza-BODIPY photosensitiser dyes, folic acid (FA) was conjugated to 1,7-dihydroxyphenyl-2,6-diiodo-3,5-di-4- bromophenyl (3) and 1,7-di-4-bromo-2,6-diiodo-3,5-dihydroxyphenylphenyl (4) aza- BODIPYs via ester bonds. Not only was the conjugation to form 3-FA and 4-FA successful, but the conjugated dyes are water-soluble, which is advantageous for drug transport in the context of PDT. These conjugates were applied in vitro against MCF-7 cancer cells and were found to have relatively high activities with IC50 values of 0.91 and 7.48 μM for 3-FA and 4-FA, respectively, while values of 11.3 and 13.0 μM were obtained for the non-conjugated 3 and 4 dyes. In a similar manner, tin (IV) and indium (III) tetrapyridylporphyrins (5 and 6) were axially conjugated to folic acid via ester bonds (5-FA and 6-FA). The conjugation was successful and enhanced the PDT activities of the dyes MCF-7 cancer cells in vitro from 48.2 to 29.6 μM for 5 and 5-FA, and from 43.9 to 13.3 μM for 6 and 6-FA. Relatively high dark toxicity was observed for 6-FA of 26.1 μM. When the nitrogen atoms of the meso-pyridyl rings were quaternized (5-FAQ and 6-FAQ) to further enhance the aqueous solubility of the complexes, it was not possible to calculate an IC50 value. When octanol-water partition coefficients (Log P) were calculated by the shake flask method, values of −0.70 and −1.70 were obtained for 5-FAQ and 6-FAQ, respectively. This provides evidence that the dyes are too water-soluble and not sufficiently lipophilic. The PACT activity properties of the synthesised diiodinated aza-BODIPYs were studied against Staphylococcus aureus (S. aureus) through photoirradiation for 60 min with Thorlabs M660L4 (280 mW.cm−2) and M730L4 (160 mW.cm−2) light emitting diodes (LEDs) mounted on the illumination chamber of Modulight® 7710-680 medical laser system providing doses at the well-plate of 100 and 57 J.cm−2.min−1. Aza- BODIPYs 2, 3 and 4 all inhibited the growth of S. aureus but with relatively low Log10 reductions of 1.37, 1.20 and 0.20. In contrast, aza-BODIPY 1 was found to have a Log10 reduction of 7.82. The PACT activities of free base and Sn(IV) 5-[4-(3- bromoethylcarboxyamidyl)phenyl]-10,15,20-triphenylporphyrins (7 and 8) prepared by Dr Balaji Babu (New Journal of Chemistry 2022, 46, 5288-5295) were tested against S. aureus to determine whether adding a triphenylphosphonium moiety to form free base and Sn(IV) 5-[4-(triphenylphosphonium)ethylcarboxyamidyl)phenyl]-10,15,20- triphenylporphyrin (18 and 19) enhances the photo-induced antibacterial activity, in addition to optimising the PDT properties due to its mitochondria-targeting properties. The PACT activities obtained against S. aureus were not favourable, but 18 exhibited enhanced activity across the studied concentration range. The potential utility of aza-BODIPY dyes 1-4 and their non-iodinated analogues (1a- 4a) for optical limiting applications was analysed by carrying out a series of Z-scan measurements, since dyes of this type have large ground state dipole moments, and this can enhance the non-linear optical limiting response. All the aza-BODIPY dyes under investigation exhibited intense non-linear absorption (NLA) behaviour with Zscan profiles that contain significant reverse saturable absorption (RSA) responses. Aza-BODIPYs 1, 2a, 2, 3, 4a, and 4 decreased the transmitted intensity of the strong laser beam to less than 50% of the linear response in organic solutions with a fixed absorbance of 1.8 for the main aza-BODIPY spectral band and a laser pulse input energy of 42 μJ. Higher second-order hyperpolarizability (γ) values were obtained for iodinated dyes 1, 2, 3 and 4. The highest value of 3.15×10−29 esu was obtained for 1. A comparative study involving the four non-iodinated dyes 1, 2, 3 and 4 and seven 1,3,5,7-tetraaryl aza-BODIPY dyes reported previously in the PhD thesis of Gugu Kubheka at Rhodes University demonstrated that there was no clear trend correlation between the γ values calculated from the Z-scan measurements and calculated dipole moments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Authors: Molupe, Nthabeleng Regina
- Date: 2024-10-11
- Subjects: Photochemotherapy , Anti-infective agents , Nonlinear optics , Cancer Treatment , BODIPY , Porphyrins
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/466603 , vital:76758 , DOI https://doi.org/10.21504/10962/466603
- Description: New aza-BODIPY dyes and porphyrins were synthesised and characterised so that photodynamic therapy (PDT) and photodynamic antimicrobial chemotherapy (PACT) activity studies could be performed. Several strategies were explored to achieve targeted nanoplatforms or biocompatible nanoplatforms to enhance the suitability of these compounds for use in PDT. Following earlier MSc research on the encapsulation of halogenated boron dipyrromethene (BODIPY) dyes into Pluronic® micelles, similar nanomicelles were prepared to encapsulate halogenated boron aza-dipyrromethene (aza-BODPY) dyes to enhance their aqueous solubility. However, the 1,7-dimethylthiophenyl- 2,6-diiodo-3,5-diphenyl (1) and 1,7-di-methylthiophenyl-2,6-diiodo- 3,5-dithien-3-yl (2) aza-BODIPY dyes that were prepared in this context were found to degrade when encapsulated. A different strategy was then followed in which gold nanoparticles (AuNPs) were conjugated to 1 and 2 via Au-S interactions to form biocompatible aza-BODIPY-AuNP conjugates (1-AuNP and 2-AuNP). This strategy was successful, and favourable IC50 values of 3.60 and 10.0 μM for 1-AuNP and 2- AuNP were obtained during in vitro PDT activity studies against MCF-7 human breast cancer cells, respectively, while values of 11.0 and 12.8 μM were obtained for 1 and 2. To further explore the preparation of better-targeted aza-BODIPY photosensitiser dyes, folic acid (FA) was conjugated to 1,7-dihydroxyphenyl-2,6-diiodo-3,5-di-4- bromophenyl (3) and 1,7-di-4-bromo-2,6-diiodo-3,5-dihydroxyphenylphenyl (4) aza- BODIPYs via ester bonds. Not only was the conjugation to form 3-FA and 4-FA successful, but the conjugated dyes are water-soluble, which is advantageous for drug transport in the context of PDT. These conjugates were applied in vitro against MCF-7 cancer cells and were found to have relatively high activities with IC50 values of 0.91 and 7.48 μM for 3-FA and 4-FA, respectively, while values of 11.3 and 13.0 μM were obtained for the non-conjugated 3 and 4 dyes. In a similar manner, tin (IV) and indium (III) tetrapyridylporphyrins (5 and 6) were axially conjugated to folic acid via ester bonds (5-FA and 6-FA). The conjugation was successful and enhanced the PDT activities of the dyes MCF-7 cancer cells in vitro from 48.2 to 29.6 μM for 5 and 5-FA, and from 43.9 to 13.3 μM for 6 and 6-FA. Relatively high dark toxicity was observed for 6-FA of 26.1 μM. When the nitrogen atoms of the meso-pyridyl rings were quaternized (5-FAQ and 6-FAQ) to further enhance the aqueous solubility of the complexes, it was not possible to calculate an IC50 value. When octanol-water partition coefficients (Log P) were calculated by the shake flask method, values of −0.70 and −1.70 were obtained for 5-FAQ and 6-FAQ, respectively. This provides evidence that the dyes are too water-soluble and not sufficiently lipophilic. The PACT activity properties of the synthesised diiodinated aza-BODIPYs were studied against Staphylococcus aureus (S. aureus) through photoirradiation for 60 min with Thorlabs M660L4 (280 mW.cm−2) and M730L4 (160 mW.cm−2) light emitting diodes (LEDs) mounted on the illumination chamber of Modulight® 7710-680 medical laser system providing doses at the well-plate of 100 and 57 J.cm−2.min−1. Aza- BODIPYs 2, 3 and 4 all inhibited the growth of S. aureus but with relatively low Log10 reductions of 1.37, 1.20 and 0.20. In contrast, aza-BODIPY 1 was found to have a Log10 reduction of 7.82. The PACT activities of free base and Sn(IV) 5-[4-(3- bromoethylcarboxyamidyl)phenyl]-10,15,20-triphenylporphyrins (7 and 8) prepared by Dr Balaji Babu (New Journal of Chemistry 2022, 46, 5288-5295) were tested against S. aureus to determine whether adding a triphenylphosphonium moiety to form free base and Sn(IV) 5-[4-(triphenylphosphonium)ethylcarboxyamidyl)phenyl]-10,15,20- triphenylporphyrin (18 and 19) enhances the photo-induced antibacterial activity, in addition to optimising the PDT properties due to its mitochondria-targeting properties. The PACT activities obtained against S. aureus were not favourable, but 18 exhibited enhanced activity across the studied concentration range. The potential utility of aza-BODIPY dyes 1-4 and their non-iodinated analogues (1a- 4a) for optical limiting applications was analysed by carrying out a series of Z-scan measurements, since dyes of this type have large ground state dipole moments, and this can enhance the non-linear optical limiting response. All the aza-BODIPY dyes under investigation exhibited intense non-linear absorption (NLA) behaviour with Zscan profiles that contain significant reverse saturable absorption (RSA) responses. Aza-BODIPYs 1, 2a, 2, 3, 4a, and 4 decreased the transmitted intensity of the strong laser beam to less than 50% of the linear response in organic solutions with a fixed absorbance of 1.8 for the main aza-BODIPY spectral band and a laser pulse input energy of 42 μJ. Higher second-order hyperpolarizability (γ) values were obtained for iodinated dyes 1, 2, 3 and 4. The highest value of 3.15×10−29 esu was obtained for 1. A comparative study involving the four non-iodinated dyes 1, 2, 3 and 4 and seven 1,3,5,7-tetraaryl aza-BODIPY dyes reported previously in the PhD thesis of Gugu Kubheka at Rhodes University demonstrated that there was no clear trend correlation between the γ values calculated from the Z-scan measurements and calculated dipole moments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
Photodynamic anticancer and antimicrobial activities of novel bacteriochlorins
- Tauyakhale, Kaisano Goodness
- Authors: Tauyakhale, Kaisano Goodness
- Date: 2024-10-11
- Subjects: Bacteriochlorin , Porphyrins , Photochemotherapy , Photophysics , Molecules Models , Active oxygen
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464587 , vital:76524
- Description: The World Health Organization cautioned that the major contributing factors of cancer amongst people are the excessive usage of alcohol, smoking, lack of exercise and low intake of fruits, vegetables, and high-fibre foods. Furthermore, cancer by far is reported to be the most common and leading cause of death worldwide (1 in 6 deaths is due to cancer). Moreover, it is reported that cancer kills more people than tuberculosis, malaria and AIDS combined every year. Chemotherapy has been utilised as a mode of rehabilitation for complete being used in conjunction with surgery or to improve the state of well-being of patients until their point of death. However, it is well known for its adverse effects, such as loss of hair, altered gastric metabolism, vomiting and nausea, dehydration, weight loss, and loss of appetite. For this reason, photodynamic therapy (PDT) was developed as an alternative. A molecular dye (photosensitiser/PS) and light of a specific wavelength produce cytotoxic singlet oxygen species, which induce cell death. The aim of this project is to prepare novel structurally modified porphyrin-type dyes that absorb far into the near-infrared region. Identifying suitable dyes that absorb significantly in the 700−800 nm region is particularly important from an African perspective, since melanin significantly limits the penetration of laser light into human tissue in the 600−700 nm region, where first- and second-generation photosensitiser dyes usually absorb. The porphyrin analogues that will be investigated in this regard are bacteriochlorins (BChls), which are known to have suitable optical properties that are potentially suitable in this regard. The first step of the study would be to synthesise tetraarylporphyrins with electron- withdrawing meso-aryl rings because their reduction to BChls is more readily attainable than is the case with electron-donating rings. However, these contrasting properties can be combined to tailor the BChls for effective photodynamic therapy, so the type of porphyrins synthesised will be tetraarylBChls with different meso-aryl groups to first analyze the induction of different chemical properties in this case, the impact of introducing electron donating (4- and 3-quinoline substituents) or electron-withdrawing (pentafluorophenyl substituents) groups on the meso-positions of the dyes and more specifically whether the position of the quinoline nitrogen atom relative to the core of the BChl has any significant impact on the reactivity of the dye (the 4- or 3-position of the quinoline). The next factor to be considered is the induction of the heavy atom effect by introducing a metal in the centre of the dye in order to try to increase the singlet oxygen quantum yields for high production of reactive oxygen species and singlet oxygen and further red shift the lowest energy absorption band of the BChls in the therapeutic window for deep tissue penetration for effective. Lastly, the goal will be to explore whether the delivery of bacteriochlorin photosensitisers to cancer cells can be enhanced by introducing quaternised nitrogen atoms to the meso-aryl ligands. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Authors: Tauyakhale, Kaisano Goodness
- Date: 2024-10-11
- Subjects: Bacteriochlorin , Porphyrins , Photochemotherapy , Photophysics , Molecules Models , Active oxygen
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/464587 , vital:76524
- Description: The World Health Organization cautioned that the major contributing factors of cancer amongst people are the excessive usage of alcohol, smoking, lack of exercise and low intake of fruits, vegetables, and high-fibre foods. Furthermore, cancer by far is reported to be the most common and leading cause of death worldwide (1 in 6 deaths is due to cancer). Moreover, it is reported that cancer kills more people than tuberculosis, malaria and AIDS combined every year. Chemotherapy has been utilised as a mode of rehabilitation for complete being used in conjunction with surgery or to improve the state of well-being of patients until their point of death. However, it is well known for its adverse effects, such as loss of hair, altered gastric metabolism, vomiting and nausea, dehydration, weight loss, and loss of appetite. For this reason, photodynamic therapy (PDT) was developed as an alternative. A molecular dye (photosensitiser/PS) and light of a specific wavelength produce cytotoxic singlet oxygen species, which induce cell death. The aim of this project is to prepare novel structurally modified porphyrin-type dyes that absorb far into the near-infrared region. Identifying suitable dyes that absorb significantly in the 700−800 nm region is particularly important from an African perspective, since melanin significantly limits the penetration of laser light into human tissue in the 600−700 nm region, where first- and second-generation photosensitiser dyes usually absorb. The porphyrin analogues that will be investigated in this regard are bacteriochlorins (BChls), which are known to have suitable optical properties that are potentially suitable in this regard. The first step of the study would be to synthesise tetraarylporphyrins with electron- withdrawing meso-aryl rings because their reduction to BChls is more readily attainable than is the case with electron-donating rings. However, these contrasting properties can be combined to tailor the BChls for effective photodynamic therapy, so the type of porphyrins synthesised will be tetraarylBChls with different meso-aryl groups to first analyze the induction of different chemical properties in this case, the impact of introducing electron donating (4- and 3-quinoline substituents) or electron-withdrawing (pentafluorophenyl substituents) groups on the meso-positions of the dyes and more specifically whether the position of the quinoline nitrogen atom relative to the core of the BChl has any significant impact on the reactivity of the dye (the 4- or 3-position of the quinoline). The next factor to be considered is the induction of the heavy atom effect by introducing a metal in the centre of the dye in order to try to increase the singlet oxygen quantum yields for high production of reactive oxygen species and singlet oxygen and further red shift the lowest energy absorption band of the BChls in the therapeutic window for deep tissue penetration for effective. Lastly, the goal will be to explore whether the delivery of bacteriochlorin photosensitisers to cancer cells can be enhanced by introducing quaternised nitrogen atoms to the meso-aryl ligands. , Thesis (MSc) -- Faculty of Science, Chemistry, 2024
- Full Text:
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:
- 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:
Porphyrinoid dyes for photodynamic anticancer and antimicrobial therapy treatments
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- 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
- Full Text:
- Authors: Soy, Rodah Cheruto
- Date: 2023-10-13
- Subjects: Porphyrins , Corrole , Chlorin , Photochemotherapy , Active oxygen , Photophysics , Photosensitizing compounds
- 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
- Full Text:
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:
- 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:
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:
- 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:
Singlet oxygen and optical limiting applications of BODIPYs and other molecular dyes
- Authors: May, Aviwe Khanya
- Date: 2022-04-08
- Subjects: Dyes and dyeing Chemistry , Phthalocyanines , Photochemotherapy , Active oxygen , Nonlinear optics , Time-dependent density functional theory , Photochemistry
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294618 , vital:57238 , DOI 10.21504/10962/294620
- Description: A series of structurally diverse novel and previously synthesized BODIPY core dyes are synthesized and characterized in this thesis. These BODIPYs were synthesized using 2-methylpyrrole, 2-ethylpyrrole, 2,4-dimethylpyrrole and 3-ethyl-2,4-dimethylpyrrole as the starting pyrroles. The combination of different pyrroles with the same aldehyde results in BODIPY core dyes that are structural analogues. These core dyes were used as precursors to synthesise halogenated BODIPYs and novel styrylBODIPY dyes, which were successfully characterized using FT-IR and 1H NMR spectroscopy. The halogenated BODIPY core dyes and the styrylBODIPY dyes were also characterized using MALDI-TOF mass spectrometry. The introduction of heavy atoms on the BODIPY core leads to a red shift of the main spectral. In the presence of styryl groups, the main spectral band red shifts to the far red end of the visible region. As expected, the halogenated BODIPY core dyes also had moderate singlet oxygen quantum yields. These halogenated core dyes were found to be suitable as photosensitizers as all the dyes reduced bacterial viability to below 50% during photodynamic antimicrobial chemotherapy (PACT) studies against Staphylococcus aureus. The structure-property relationships studied demonstrate that the presence of protons rather than methyls at the 1,7-positions or iodines at the 2,6-positions results in more favorable PACT activity. This is likely to be related to the greater ability of the meso-aryl to rotate into the plane of the dipyrromethene ligand and suggests that there should be a stronger focus on dyes of this type in future studies in this field. During nonlinear optical (NLO) studies, all the styrylBODIPYs exhibited favorable reverse saturable absorption (RSA) responses. In the absence of methyl groups at the 1,7-positions, the meso-aryl ring lies closer to the π-system of the BODIPY core, enhancing donor (D)–π–acceptor (A) properties and resulting in slightly enhanced optical limiting (OL) parameters. Additionally, there is no evidence that the introduction of heavy atoms at the 2,6-positions significantly enhances OL properties. In a similar manner, alkyl substituents at these positions also do not significantly enhance OL properties; this was studied for the first time using 15 with ethyl groups at the 2,6-positions. The combination of z-scan data and transient spectroscopy for 16 demonstrated that the main mechanism responsible for the NLO properties of nonhalogenated BODIPY dyes is one-photon absorption from the ground state followed by ESA in the singlet manifold. From the NLO studies of 25, OL parameters of 1,3,5-tristyrylBODIPY dyes were found to be similar in magnitude to properties of distyrylBODIPY dyes, but to have less favorable optical properties for OL applications. The OL properties of scandium phthalocyanines were assessed for the first time, since the Sc(III) ion, unusually for a first row transition metal ion, is known to readily form sandwich complexes. The presence of a Sc(III) ion does not significantly enhance the OL properties of phthalocyanines relative to those of rare earth metal ions that also form complexes of this type. Because BODIPYs and phthalocyanines typically absorb significantly in the visible region, transparent PBC polymer thin films of disilane-bridged compounds with minimal absorption in this region were studied and exhibited an excellent RSA response. These compounds may be useful in the design of OL materials that can protect the human eye. The optimized geometries and spectroscopic properties of selected BODIPYs were studied. As expected, the presence of bromine, iodine, ethyl and styryl groups at different positions of the BODIPY core leads to a narrowing of the HOMO–LUMO band gap, which results in a red-shift of the main spectral band. Partial atomic charges have also been calculated for some of the styrylBODIPY dyes studied for application in OL, and electrostatic potential energy maps were also visualized to better assess how the dipole moment of BODIPY dyes can be modulated since this can affect the OL properties. For all the BODIPYs studied, the electronegativity of the atoms present influences charge distribution on the BODIPY structure. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Authors: May, Aviwe Khanya
- Date: 2022-04-08
- Subjects: Dyes and dyeing Chemistry , Phthalocyanines , Photochemotherapy , Active oxygen , Nonlinear optics , Time-dependent density functional theory , Photochemistry
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294618 , vital:57238 , DOI 10.21504/10962/294620
- Description: A series of structurally diverse novel and previously synthesized BODIPY core dyes are synthesized and characterized in this thesis. These BODIPYs were synthesized using 2-methylpyrrole, 2-ethylpyrrole, 2,4-dimethylpyrrole and 3-ethyl-2,4-dimethylpyrrole as the starting pyrroles. The combination of different pyrroles with the same aldehyde results in BODIPY core dyes that are structural analogues. These core dyes were used as precursors to synthesise halogenated BODIPYs and novel styrylBODIPY dyes, which were successfully characterized using FT-IR and 1H NMR spectroscopy. The halogenated BODIPY core dyes and the styrylBODIPY dyes were also characterized using MALDI-TOF mass spectrometry. The introduction of heavy atoms on the BODIPY core leads to a red shift of the main spectral. In the presence of styryl groups, the main spectral band red shifts to the far red end of the visible region. As expected, the halogenated BODIPY core dyes also had moderate singlet oxygen quantum yields. These halogenated core dyes were found to be suitable as photosensitizers as all the dyes reduced bacterial viability to below 50% during photodynamic antimicrobial chemotherapy (PACT) studies against Staphylococcus aureus. The structure-property relationships studied demonstrate that the presence of protons rather than methyls at the 1,7-positions or iodines at the 2,6-positions results in more favorable PACT activity. This is likely to be related to the greater ability of the meso-aryl to rotate into the plane of the dipyrromethene ligand and suggests that there should be a stronger focus on dyes of this type in future studies in this field. During nonlinear optical (NLO) studies, all the styrylBODIPYs exhibited favorable reverse saturable absorption (RSA) responses. In the absence of methyl groups at the 1,7-positions, the meso-aryl ring lies closer to the π-system of the BODIPY core, enhancing donor (D)–π–acceptor (A) properties and resulting in slightly enhanced optical limiting (OL) parameters. Additionally, there is no evidence that the introduction of heavy atoms at the 2,6-positions significantly enhances OL properties. In a similar manner, alkyl substituents at these positions also do not significantly enhance OL properties; this was studied for the first time using 15 with ethyl groups at the 2,6-positions. The combination of z-scan data and transient spectroscopy for 16 demonstrated that the main mechanism responsible for the NLO properties of nonhalogenated BODIPY dyes is one-photon absorption from the ground state followed by ESA in the singlet manifold. From the NLO studies of 25, OL parameters of 1,3,5-tristyrylBODIPY dyes were found to be similar in magnitude to properties of distyrylBODIPY dyes, but to have less favorable optical properties for OL applications. The OL properties of scandium phthalocyanines were assessed for the first time, since the Sc(III) ion, unusually for a first row transition metal ion, is known to readily form sandwich complexes. The presence of a Sc(III) ion does not significantly enhance the OL properties of phthalocyanines relative to those of rare earth metal ions that also form complexes of this type. Because BODIPYs and phthalocyanines typically absorb significantly in the visible region, transparent PBC polymer thin films of disilane-bridged compounds with minimal absorption in this region were studied and exhibited an excellent RSA response. These compounds may be useful in the design of OL materials that can protect the human eye. The optimized geometries and spectroscopic properties of selected BODIPYs were studied. As expected, the presence of bromine, iodine, ethyl and styryl groups at different positions of the BODIPY core leads to a narrowing of the HOMO–LUMO band gap, which results in a red-shift of the main spectral band. Partial atomic charges have also been calculated for some of the styrylBODIPY dyes studied for application in OL, and electrostatic potential energy maps were also visualized to better assess how the dipole moment of BODIPY dyes can be modulated since this can affect the OL properties. For all the BODIPYs studied, the electronegativity of the atoms present influences charge distribution on the BODIPY structure. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
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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:
- 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
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