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
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Phthalocyanine-based bio-functional conjugates: photodynamic therapy and photoantimicrobial chemotherapeutic efficacy evaluation in-vitro
- Authors: Magadla, Aviwe
- Date: 2024-04-05
- Subjects: Photochemotherapy , Anti-infective agents , Biofilms , Active oxygen , Quantum yield , Phthalocyanines
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/435918 , vital:73212 , DOI 10.21504/10962/435918
- Description: This thesis reports on the syntheses and characterisation of symmetrical and asymmetrical phthalocyanines (Pcs) with different ring substituents derived to form either cationic styryl pyridine, cationic styryl pyridine triphenylphosphonium (TPP+)-based, benzothiazole, cationic pyridyl-dihydrothiazole and other closely related groups. The starting Pc complex of the synthesised Pc derivatives was typically obtained through the cyclotetramerisation of a substituted phthalonitrile. Then, depending on the desired final complex, the desired complexes were synthesised through the Knoevenagel condensation, alkylation reaction, and Schiff base reaction. Furthermore, silica nanoparticles (SiNPs) were also used to encapsulate Pcs. Following aminopropyl triethoxysilane amino (APTES) functionalisation of the surface of the Pc@SiNPs-APTES, biomolecules such as gallic acid, folic acid, and ampicillin were covalently attached to the surface. Additionally, Pc@SiNPs-APTES is protonated with 1,3-propanesultone. The pair of synthesised asymmetric Pcs is attached to ciprofloxacin (CIP) via an amide bond. Different analytical methods were used to characterise the Pcs and their conjugates. The photophysics and photochemistry of the Pcs both by themselves and in their conjugate form when doped with SiNPs. The cationic Pcs were able to produce sufficient singlet oxygen on their own in most cases. This is explained by the Pcs greater solubility in water. Since singlet oxygen is produced from the triplet state, singlet oxygen quantum yield (Δ) values complement triplet quantum yield (T) values. Low Δ values could be attributed to ineffective energy transfer; screening effects may have prevented the excited triplet state of the Pcs from interacting with the ground state molecular oxygen, lowering the Δ values. In other instances, the Pcs' protection by the SiNPs could be credited with extending the triplet lifetime. The direct connection of Pcs with CIP increased the formation of T and Δ in ABSTRACT comparison to Pcs alone. Both in planktonic and biofilm form, the cationic Pcs and conjugates showed enhanced bacterial elimination. The Pcs and conjugates demonstrated significant activity in photodynamic therapy treatment (PDT) experiments at the tested doses. In both PDT and photodynamic antimicrobial chemotherapy (PACT) treatment, the cationic Pcs outperformed the neutral Pc in terms of biological activity. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
- Full Text:
- Authors: Magadla, Aviwe
- Date: 2024-04-05
- Subjects: Photochemotherapy , Anti-infective agents , Biofilms , Active oxygen , Quantum yield , Phthalocyanines
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/435918 , vital:73212 , DOI 10.21504/10962/435918
- Description: This thesis reports on the syntheses and characterisation of symmetrical and asymmetrical phthalocyanines (Pcs) with different ring substituents derived to form either cationic styryl pyridine, cationic styryl pyridine triphenylphosphonium (TPP+)-based, benzothiazole, cationic pyridyl-dihydrothiazole and other closely related groups. The starting Pc complex of the synthesised Pc derivatives was typically obtained through the cyclotetramerisation of a substituted phthalonitrile. Then, depending on the desired final complex, the desired complexes were synthesised through the Knoevenagel condensation, alkylation reaction, and Schiff base reaction. Furthermore, silica nanoparticles (SiNPs) were also used to encapsulate Pcs. Following aminopropyl triethoxysilane amino (APTES) functionalisation of the surface of the Pc@SiNPs-APTES, biomolecules such as gallic acid, folic acid, and ampicillin were covalently attached to the surface. Additionally, Pc@SiNPs-APTES is protonated with 1,3-propanesultone. The pair of synthesised asymmetric Pcs is attached to ciprofloxacin (CIP) via an amide bond. Different analytical methods were used to characterise the Pcs and their conjugates. The photophysics and photochemistry of the Pcs both by themselves and in their conjugate form when doped with SiNPs. The cationic Pcs were able to produce sufficient singlet oxygen on their own in most cases. This is explained by the Pcs greater solubility in water. Since singlet oxygen is produced from the triplet state, singlet oxygen quantum yield (Δ) values complement triplet quantum yield (T) values. Low Δ values could be attributed to ineffective energy transfer; screening effects may have prevented the excited triplet state of the Pcs from interacting with the ground state molecular oxygen, lowering the Δ values. In other instances, the Pcs' protection by the SiNPs could be credited with extending the triplet lifetime. The direct connection of Pcs with CIP increased the formation of T and Δ in ABSTRACT comparison to Pcs alone. Both in planktonic and biofilm form, the cationic Pcs and conjugates showed enhanced bacterial elimination. The Pcs and conjugates demonstrated significant activity in photodynamic therapy treatment (PDT) experiments at the tested doses. In both PDT and photodynamic antimicrobial chemotherapy (PACT) treatment, the cationic Pcs outperformed the neutral Pc in terms of biological activity. , Thesis (PhD) -- Faculty of Science, Chemistry, 2024
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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
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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
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Phthalocyanine-nanoparticle conjugates supported on inorganic nanofibers as photocatalysts for the treatment of biological and organic pollutants as well as for hydrogen generation
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
The de novo biosynthesis of biotin is required for the optimal growth of Salmonella enterica serovar Typhimurium in the intracellular environment
- Authors: McLaughlin, Claire
- Date: 2021-10-29
- Subjects: Salmonella , Biotin , Biosynthesis , Salmonella typhimurium , Antibacterial agents , Anti-infective agents , Pathogenic bacteria , Salmonella food poisoning
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192097 , vital:45195
- Description: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne pathogen infecting humans and animals, contributing to significant morbidity and mortality worldwide each year. The increase in antibiotic-resistant S. Typhimurium infections in recent years has highlighted the need for new antibacterial drugs and drug targets. S. Typhimurium can acquire biotin through de novo biosynthesis or via transport from its extracellular environment. The importance of the vitamin for bacterial survival, coupled with the absence of the biotin biosynthetic pathway in humans, makes the biotin biosynthetic enzymes attractive targets for drug discovery. The study's primary aim was to determine the relative importance of the biotin biosynthesis and transport pathways for the in vitro and ex vivo growth and survival of S. Typhimurium, with the goal of validating the pathways as valid targets for antimicrobial drug development. In order to achieve this aim, we generated S. Typhimurium mutant strains harbouring deletions in either the biotin biosynthetic gene, bioB, or putative high-affinity biotin transporter, yigM (ΔbioB and ΔyigM, respectively), as well as a double mutant in which the two mutations were combined (ΔbioB ΔyigM). Since the simultaneous disruption of biotin biosynthesis and transport in the double mutant may form a synthetic lethal combination, preventing further analysis of the strain, we also constructed a conditional mutant in which the promoter of the yigM gene was replaced by the arabinose-regulatable, PBAD promoter in the ΔbioB background (ΔbioB PBAD::yigM). Since the expression of the YigM in this strain is arabinose-regulatable, its role as a biotin transporter can be evaluated by altering the arabinose concentration in the growth media. Once the mutant strains were isolated and verified genetically, their growth and that of their genetically complemented counterparts were analysed in liquid and/or solid M9 minimal medium in the absence of biotin. Consistent with previous observations, the ΔbioB auxotrophic mutant's growth was severely compromised in minimal media in the absence of biotin. The growth of the strain could, however, be restored by supplementation with exogenous biotin or expression of the wild type bioB gene from an episomal plasmid. The ability of biotin to reverse the growth defect of the ΔbioB mutant strain was, however, dependent on the presence of a functional YigM, since biotin supplementation did not affect the growth of the ΔbioB ΔyigM double mutant strain. The introduction of a second copy of the yigM gene in the ΔbioB ΔyigM background, however, restored the growth of the strain in the presence, but not absence, of biotin. The dependence of the double mutant on both YigM and biotin for growth supports the idea that the protein functions as the sole or primary biotin transporter in S. Typhimurium, as it has recently been shown for E. coli (Ringsletter, 2010; Finkenwirth et al, 2013). The essentiality of YigM for biotin transport was subsequently verified by two independent means. Firstly, the growth of the ΔbioB PBAD::yigM promoter-replacement mutant was strictly dependent on the inclusion of arabinose in biotin-supplemented M9 minimal media supplemented, indicating that the expression of YigM from the PBAD promoter is essential for biotin transport. Secondly, following treatment with a known small-molecule inhibitor of the biotin biosynthesis, MAC-13772, exogenous biotin was capable of restoring the growth defect of the YigM+ wild type S. Typhimurium strain, but not the YigM− ΔyigM mutant. Taken together, these findings confirm that YigM serves as the biotin transporter for S. Typhimurium and that the corresponding ΔyigM mutant is, as a result, defective for biotin transport. Having confirmed the genotypes and phenotypes of the ΔbioB, ΔyigM, and ΔbioB ΔyigM mutants, we next analysed the importance of the biotin biosynthesis and transport pathways for the growth and survival of S. Typhimurium within the intracellular environment. To this end, we determined the proliferation of each of the mutant strains following infection of HeLa epithelial and RAW264.7 macrophage-like cell lines. Our results revealed that the de novo biosynthesis of biotin is required for the optimal growth of S. Typhimurium following infection of both epithelial and macrophage-like cell lines. Disruption of biotin transport, by contrast, had no significant effect on the intracellular proliferation of S. Typhimurium when a functional pathway for the biosynthesis of biotin was present. The simultaneous disruption of biotin biosynthesis and transport, however, resulted in significant attenuation of S. Typhimurium in epithelial cells, while bacterial survival in macrophages decreased to below the limit of detection. Overall, our results suggest the S. Typhimurium relies primarily on biotin produced by the de novo biosynthesis pathway to support its growth in the intracellular environment. While YigM-mediated biotin transport is essential for sustaining the viability of intracellular S. Typhimurium in the absence of de novo biosynthesis, it appears to play a relatively minor role in the acquisition of biotin during growth in the nutrient-limited Salmonella containing vacuole. Our findings suggest that inhibiting biotin biosynthesis may be a viable strategy for combating systemic infections caused by Salmonella, as has been recently proposed for other medically important bacterial pathogens (Carfrae et al., 2020). , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
- Authors: McLaughlin, Claire
- Date: 2021-10-29
- Subjects: Salmonella , Biotin , Biosynthesis , Salmonella typhimurium , Antibacterial agents , Anti-infective agents , Pathogenic bacteria , Salmonella food poisoning
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192097 , vital:45195
- Description: Salmonella enterica serovar Typhimurium (S. Typhimurium) is a foodborne pathogen infecting humans and animals, contributing to significant morbidity and mortality worldwide each year. The increase in antibiotic-resistant S. Typhimurium infections in recent years has highlighted the need for new antibacterial drugs and drug targets. S. Typhimurium can acquire biotin through de novo biosynthesis or via transport from its extracellular environment. The importance of the vitamin for bacterial survival, coupled with the absence of the biotin biosynthetic pathway in humans, makes the biotin biosynthetic enzymes attractive targets for drug discovery. The study's primary aim was to determine the relative importance of the biotin biosynthesis and transport pathways for the in vitro and ex vivo growth and survival of S. Typhimurium, with the goal of validating the pathways as valid targets for antimicrobial drug development. In order to achieve this aim, we generated S. Typhimurium mutant strains harbouring deletions in either the biotin biosynthetic gene, bioB, or putative high-affinity biotin transporter, yigM (ΔbioB and ΔyigM, respectively), as well as a double mutant in which the two mutations were combined (ΔbioB ΔyigM). Since the simultaneous disruption of biotin biosynthesis and transport in the double mutant may form a synthetic lethal combination, preventing further analysis of the strain, we also constructed a conditional mutant in which the promoter of the yigM gene was replaced by the arabinose-regulatable, PBAD promoter in the ΔbioB background (ΔbioB PBAD::yigM). Since the expression of the YigM in this strain is arabinose-regulatable, its role as a biotin transporter can be evaluated by altering the arabinose concentration in the growth media. Once the mutant strains were isolated and verified genetically, their growth and that of their genetically complemented counterparts were analysed in liquid and/or solid M9 minimal medium in the absence of biotin. Consistent with previous observations, the ΔbioB auxotrophic mutant's growth was severely compromised in minimal media in the absence of biotin. The growth of the strain could, however, be restored by supplementation with exogenous biotin or expression of the wild type bioB gene from an episomal plasmid. The ability of biotin to reverse the growth defect of the ΔbioB mutant strain was, however, dependent on the presence of a functional YigM, since biotin supplementation did not affect the growth of the ΔbioB ΔyigM double mutant strain. The introduction of a second copy of the yigM gene in the ΔbioB ΔyigM background, however, restored the growth of the strain in the presence, but not absence, of biotin. The dependence of the double mutant on both YigM and biotin for growth supports the idea that the protein functions as the sole or primary biotin transporter in S. Typhimurium, as it has recently been shown for E. coli (Ringsletter, 2010; Finkenwirth et al, 2013). The essentiality of YigM for biotin transport was subsequently verified by two independent means. Firstly, the growth of the ΔbioB PBAD::yigM promoter-replacement mutant was strictly dependent on the inclusion of arabinose in biotin-supplemented M9 minimal media supplemented, indicating that the expression of YigM from the PBAD promoter is essential for biotin transport. Secondly, following treatment with a known small-molecule inhibitor of the biotin biosynthesis, MAC-13772, exogenous biotin was capable of restoring the growth defect of the YigM+ wild type S. Typhimurium strain, but not the YigM− ΔyigM mutant. Taken together, these findings confirm that YigM serves as the biotin transporter for S. Typhimurium and that the corresponding ΔyigM mutant is, as a result, defective for biotin transport. Having confirmed the genotypes and phenotypes of the ΔbioB, ΔyigM, and ΔbioB ΔyigM mutants, we next analysed the importance of the biotin biosynthesis and transport pathways for the growth and survival of S. Typhimurium within the intracellular environment. To this end, we determined the proliferation of each of the mutant strains following infection of HeLa epithelial and RAW264.7 macrophage-like cell lines. Our results revealed that the de novo biosynthesis of biotin is required for the optimal growth of S. Typhimurium following infection of both epithelial and macrophage-like cell lines. Disruption of biotin transport, by contrast, had no significant effect on the intracellular proliferation of S. Typhimurium when a functional pathway for the biosynthesis of biotin was present. The simultaneous disruption of biotin biosynthesis and transport, however, resulted in significant attenuation of S. Typhimurium in epithelial cells, while bacterial survival in macrophages decreased to below the limit of detection. Overall, our results suggest the S. Typhimurium relies primarily on biotin produced by the de novo biosynthesis pathway to support its growth in the intracellular environment. While YigM-mediated biotin transport is essential for sustaining the viability of intracellular S. Typhimurium in the absence of de novo biosynthesis, it appears to play a relatively minor role in the acquisition of biotin during growth in the nutrient-limited Salmonella containing vacuole. Our findings suggest that inhibiting biotin biosynthesis may be a viable strategy for combating systemic infections caused by Salmonella, as has been recently proposed for other medically important bacterial pathogens (Carfrae et al., 2020). , Thesis (MSc) -- Faculty of Science, Biochemistry and Microbiology, 2021
- Full Text:
Azadipyrromethenes for applications in photodynamic antimicrobial chemotherapy, photodynamic therapy and optical limiting
- Authors: Dubazana, Nadine
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Staphylococcus aureus , Nonlinear optics , Azadipyrromethenes , BODIPY
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166150 , vital:41333
- Description: Azadipyrromethenes, azaBODIPYs and zinc azadipyrromethene complexes were prepared and characterised to examine the effect on their photophysical properties of incorporating phenyl groups at the 1,3,5,7-positions with electron-donating and withdrawing groups at the para-positions. To enhance their ability to generate singlet oxygen, appropriate structural modifications were made through the addition of a Zn(II) ion or halogenation at the 2,6 positions. In vitro photodynamic therapy (PDT) studies targeting MCF-7 human breast cancer cells were carried out. To evaluate and understand the effectiveness of the dyes as photosensitisers, cellular uptake, phototoxicity and the half-maximal inhibitory concentration (IC50) values were analysed. Photodynamic antimicrobial chemotherapy (PACT) studies were also carried out to study the effectiveness of the dyes against Staphylococcus aureus (S. aureus). Dyes with donor-π-acceptor (D-π-A) properties were synthesised and tested against the second harmonic of the Nd:YAG laser in optical limiting (OL) studies. The second-order hyperpolarisability, third-order susceptibility and nonlinear absorption coefficient values were determined. The results suggest that 1,3,5,7-azaBODIPY dyes may be less suitable for use in this context than analogous D-π-A 3,5-distyrylBODIPY dyes. Molecular modelling was carried out to identify the structure-property relationships of the synthesised dyes by analysing trends in the energies of the frontier molecular orbitals (MOs) and spectroscopic properties.
- Full Text:
- Authors: Dubazana, Nadine
- Date: 2020
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Staphylococcus aureus , Nonlinear optics , Azadipyrromethenes , BODIPY
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/166150 , vital:41333
- Description: Azadipyrromethenes, azaBODIPYs and zinc azadipyrromethene complexes were prepared and characterised to examine the effect on their photophysical properties of incorporating phenyl groups at the 1,3,5,7-positions with electron-donating and withdrawing groups at the para-positions. To enhance their ability to generate singlet oxygen, appropriate structural modifications were made through the addition of a Zn(II) ion or halogenation at the 2,6 positions. In vitro photodynamic therapy (PDT) studies targeting MCF-7 human breast cancer cells were carried out. To evaluate and understand the effectiveness of the dyes as photosensitisers, cellular uptake, phototoxicity and the half-maximal inhibitory concentration (IC50) values were analysed. Photodynamic antimicrobial chemotherapy (PACT) studies were also carried out to study the effectiveness of the dyes against Staphylococcus aureus (S. aureus). Dyes with donor-π-acceptor (D-π-A) properties were synthesised and tested against the second harmonic of the Nd:YAG laser in optical limiting (OL) studies. The second-order hyperpolarisability, third-order susceptibility and nonlinear absorption coefficient values were determined. The results suggest that 1,3,5,7-azaBODIPY dyes may be less suitable for use in this context than analogous D-π-A 3,5-distyrylBODIPY dyes. Molecular modelling was carried out to identify the structure-property relationships of the synthesised dyes by analysing trends in the energies of the frontier molecular orbitals (MOs) and spectroscopic properties.
- Full Text:
Composition and fate of triclosan in the sludge from wastewater treatment in Grahamstown, South Africa and Tiaret, Algeria
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
- Authors: Ncube, Mbonisi
- Date: 2017
- Subjects: Sewage sludge , Sewage Purification South Africa Grahamstown , Sewage Purification Algeria Tiaret , Sewage sludge as fertilizer , Anti-infective agents
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/65156 , vital:28697
- Description: Physicochemical properties such as pH, specific surface area (SSA), cationic exchange capacity (CEC), loss on ignition (LOI), pathogens, plant nutrients (nitrates, ammonium and phosphates), and heavy metals (manganese, copper, lead and cadmium) were determined for sewage sludge from Grahamstown and Tiaret. The values obtained were log transformed thereafter a t-test at 5 % level of significance was used to test for the difference in each parameter for both sludges. The pH of sludge was determined in 1:3 water, 16 water, 1:3 0.01 M calcium chloride and 1:3 1 M potassium chloride. The pH for Grahamstown and Tiaret sludge were in the ranges of 6.66-7.11 and 7.88-8.18 respectively. The SSA values for Grahamstown and Tiaret were 218 ± 108 and 261 ± 99.9 m2/g, and the CEC values were 119 ± 2.09 and 136 ± 6.03 mEq/100, respectively. The LOI values obtained were 1.33 ± 0.03 and 1.48 ± 0.11 % for Grahamstown and Tiaret, respectively. E. coll and heterotrophic bacteria were the pathogens determined, and were extracted from sludge using sterile saline and nutrient broth. The concentration of E. coll in Grahamstown and Tiaret sludge were 468 ± 7.63 and 7769 ± 1268 CFU/g d.w and for heterotrophic bacteria were 1.17x109 ± 7.42x108 and 1.43x109 ± 9.11 x108 CFU/g d.w. For Grahamstown sludge, the concentration of nitrates, ammonium and phosphates were 55.61 ± 55.20 mg/g d.w, 6.60 ± 2.36 mg/g d.w and 1.40 ± 0.30 mg/g d.w, respectively. For Tiaret sludge, the concentration of nitrates, ammonium and phosphates were 2.56 ± 2.90 mg/g d.w, 0.64 ± 0.45 mg/g d.w and 0.24 ± 0.19 mg/g d.w, respectively. The concentration of Mn, Cu, Pb and Cd in Grahamstown sludge were 423 ± 101, 353 ± 92, 40.2 ± 20 and 0.0 mg/kg d.w respectively, and for Tiaret sludge, the corresponding concentrations were 358± 295, 549±50, 1427± 1352 and 1.54 ± 0.61 mg/kg d.w. Sewage sludge was found to contain Triclosan, and solubility studies of the compound were conducted using sodium deoxycholate and sodium lithocholate. The apparent solubilities and rate constants indicated in brackets of TCS at 37 °C were 35.4 ± 1.21 mg/L (1.28 ± 0.36 Hr-) and 14.4 ± 0.34 mg/L (0.99 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. The apparent solubilities and rate constants indicated in brackets of TCS at 15 °C were 32.3 ± 0.88 mg/L (2.16 ± 0.80 Hr-) and 14.2 ± 0.39 mg/L (1.02 ± 0.17 Hr-) in sodium lithocholate and sodium deoxycholate, respectively. Triclosan was extracted from sludge using 1 g/L sodium deoxycholate and the determined concentration were 142 ± 33.5 gg/g d.w for Grahamstown sludge and 0-12 gg/g d.w for Tiaret sludge. Finally plant growth studies were conducted on radish and garden cress plants using Grahamstown sludge at 0, 20, 40, 80 and 100 % treatments. Statistical analysis (t-test and Kruskal-Wallis) at 5 % level of significance was done to compare growth parameters between control and different sludge treatments. For radish plants, the values for plant height, root length, number of leaves, leaf length and dry mass were 28.4-80-7 mm, 4.3-44.7 mm, 3.3-17.0 mm, 2.3-4.0 leaves and 6.3-15.3 %, respectively. For garden cress, the values for plant height, root length, number of leaves, leaf length and dry mass were 13.7-25.0 mm, 7.7-20.3 mm, 5.7-8.3 leaves, 3.0-8.3 mm and 8.8-15.0 %, respectively. Twenty percent (20 %) sludge treatment gave the best results in radish and garden cress plants with respect to plant height, root length, number of leaves and dry mass. Triclosan concentration in radish and garden cress plants was below the detection limit of 32.4 gg/g d.w. , Thesis (MSc) -- Faculty of Pharmacy, Pharmacy, 2017
- Full Text:
Synthesis and physicochemical evaluation of a series of boron dipyrromethene dye derivatives for potential utility in antimicrobial photodynamic therapy and nonlinear optics
- Authors: Kubheka, Gugu Patience
- Date: 2017
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Nonlinear optics , BODIPY
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4776 , vital:20723
- Description: A series of new BODIPY dye derivatives have been synthesized and characterized using various characterization tools such as 1H-NMR, MALDI-TOF mass spectrometry, FT-IR, UV-visible spectrophotometry and elemental analysis. The aniline-substituted BODIPY derivative was further coordinated with gold nanorods and the characterization was achieved by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS).In addition to this dye, quaternized BODIPY dyes were also synthesized and investigated for their potential utility as photosentitizers in antimicrobial photodynamic therapy (APDT).BODIPY dyes with pyrene substituted styryl groups were embedded in polymer thin film using poly(bisphenol A carbonate) (PBC) to study their optical limiting properties. The optical limiting values of these BODIPY dyes once embedded in thin films were found to be greatly improved and the limiting intensityof each film was well below the maximum threshold which is set to be 0.95 J.cm-². The physicochemical properties and NLO parameters of all of the synthesized dyes were investigated.
- Full Text:
- Authors: Kubheka, Gugu Patience
- Date: 2017
- Subjects: Dyes and dyeing -- Chemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Nonlinear optics , BODIPY
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/4776 , vital:20723
- Description: A series of new BODIPY dye derivatives have been synthesized and characterized using various characterization tools such as 1H-NMR, MALDI-TOF mass spectrometry, FT-IR, UV-visible spectrophotometry and elemental analysis. The aniline-substituted BODIPY derivative was further coordinated with gold nanorods and the characterization was achieved by transmission electron microscopy (TEM), X-ray diffractometry (XRD) and X-ray photoelectron spectroscopy (XPS).In addition to this dye, quaternized BODIPY dyes were also synthesized and investigated for their potential utility as photosentitizers in antimicrobial photodynamic therapy (APDT).BODIPY dyes with pyrene substituted styryl groups were embedded in polymer thin film using poly(bisphenol A carbonate) (PBC) to study their optical limiting properties. The optical limiting values of these BODIPY dyes once embedded in thin films were found to be greatly improved and the limiting intensityof each film was well below the maximum threshold which is set to be 0.95 J.cm-². The physicochemical properties and NLO parameters of all of the synthesized dyes were investigated.
- Full Text:
Photodynamic antimicrobial chemotherapy activities of porphyrin- and phthalocyanine-platinum nanoparticle conjugates
- Authors: Managa, Muthumuni Elizabeth
- Date: 2015
- Subjects: Photochemotherapy , Anti-infective agents , Porphyrins , Phthalocyanines , Platinum , Nanoparticles , Bioconjugates , Electrospinning
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4539 , http://hdl.handle.net/10962/d1017919
- Description: This work reports on the conjugation of differently shaped Pt nanoparticles (PtNPs) with ClGa(III) 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin (1) as well as chloro - (5,10,15,20-tetrakis (4- (4- carboxy phenycarbonoimidoyl) phenyl) porphyrinato) gallium(III) (2) The work also reports on platination of dihydroxosilicon octacarboxyphthalocyanine (OH)₂SiOCPc (3) to give dihydroxosilicontris(diaquaplatinum)octacarboxyphthalocyanine (OH)₂SiOCPc(Pt)₃ (4). The resulting conjugates were used for photodynamic antimicrobial chemotherapy against S. aureus, E. coli and C. albicans. The degree of photo-inactivation is dependent on concentration of the conjugates, light dose (fluence) and illumination time. The log reduction obtained for 1 when conjugated to cubic PtNPs was 4.64 log (which indicate 99.99 percent of the bacteria have been killed), which is much higher than 3.94 log unit for 1-hexagonal PtNPs and 3.31 log units for 1-unshaped PtNPs. Complex 2 conjugated to hexagonal PtNPs showed 18 nm red shift in the Soret band when compared to 2 alone. Complex 2 and 2-hexagonal PtNPs as well showed promising photodynamic antimicrobial chemotherapy (PACT) activity against S. aureus, E. coli and C. albicans in solution where the log reduction obtained was 4.92, 3.76, and 3.95 respectively for 2-hexagonal PtNPs. The singlet oxygen quantum yields obtained were higher at 0.56 for 2-hexagonl PtNPs in DMF while that of 2 was 0.52 in the same solvent. This resulted in improved PACT activity for 2-hexagonal PtNPs compared to 2. Complex 4 showed slight blue shifting of the absorption spectrum when compared to complex 3 The antimicrobial activity of 4 were promising as the highest log reduction value was observed when compared to the porphyrin conjugates.
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- Authors: Managa, Muthumuni Elizabeth
- Date: 2015
- Subjects: Photochemotherapy , Anti-infective agents , Porphyrins , Phthalocyanines , Platinum , Nanoparticles , Bioconjugates , Electrospinning
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4539 , http://hdl.handle.net/10962/d1017919
- Description: This work reports on the conjugation of differently shaped Pt nanoparticles (PtNPs) with ClGa(III) 5,10,15,20-tetrakis-(4-carboxyphenyl) porphyrin (1) as well as chloro - (5,10,15,20-tetrakis (4- (4- carboxy phenycarbonoimidoyl) phenyl) porphyrinato) gallium(III) (2) The work also reports on platination of dihydroxosilicon octacarboxyphthalocyanine (OH)₂SiOCPc (3) to give dihydroxosilicontris(diaquaplatinum)octacarboxyphthalocyanine (OH)₂SiOCPc(Pt)₃ (4). The resulting conjugates were used for photodynamic antimicrobial chemotherapy against S. aureus, E. coli and C. albicans. The degree of photo-inactivation is dependent on concentration of the conjugates, light dose (fluence) and illumination time. The log reduction obtained for 1 when conjugated to cubic PtNPs was 4.64 log (which indicate 99.99 percent of the bacteria have been killed), which is much higher than 3.94 log unit for 1-hexagonal PtNPs and 3.31 log units for 1-unshaped PtNPs. Complex 2 conjugated to hexagonal PtNPs showed 18 nm red shift in the Soret band when compared to 2 alone. Complex 2 and 2-hexagonal PtNPs as well showed promising photodynamic antimicrobial chemotherapy (PACT) activity against S. aureus, E. coli and C. albicans in solution where the log reduction obtained was 4.92, 3.76, and 3.95 respectively for 2-hexagonal PtNPs. The singlet oxygen quantum yields obtained were higher at 0.56 for 2-hexagonl PtNPs in DMF while that of 2 was 0.52 in the same solvent. This resulted in improved PACT activity for 2-hexagonal PtNPs compared to 2. Complex 4 showed slight blue shifting of the absorption spectrum when compared to complex 3 The antimicrobial activity of 4 were promising as the highest log reduction value was observed when compared to the porphyrin conjugates.
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The development of functionalized electrospun nanofibers for the control of pathogenic microorganisms in water.
- Authors: Kleyi, Phumelele Eldridge
- Date: 2014
- Subjects: Electrospinning , Nanofibers , Pathogenic microorganisms , Pathogenic microorganisms -- Detection , Drinking water -- Microbiology , Water quality -- Measurement , Imidazoles , Spectrum analysis , Anti-infective agents , Polymerization
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4497 , http://hdl.handle.net/10962/d1013134
- Description: The thesis presents the development of functionalized electrospun nylon 6 nanofibers for the eradication of pathogenic microorganisms in drinking water. Imidazole derivatives were synthesized as the antimicrobial agents and were characterized by means of NMR spectroscopy, IR spectroscopy, elemental analysis and X-ray crystallography. The first set of compounds (2-substituted N-alkylimidazoles) consisted of imidazole derivatives substituted with different alkyl groups (methyl, ethyl, propyl, butyl, heptyl, octyl, decyl and benzyl) at the 1-position and various functional groups [carboxaldehyde (CHO), alcohol (CH2OH) and carboxylic acid (COOH)] at the 2-position. It was observed that the antimicrobial activity of the compounds increased with increasing alkyl chain length and decreasing pKa of the 2-substituent. It was also observed that the antimicrobial activity was predominantly against a Gram-positive bacterial strains [Staphylococcus aureus (MIC = 5-160 μg/mL) and Bacillus subtilis subsp. spizizenii (MIC = 5-20 μg/mL)], with the latter being the more susceptible. However, the compounds displayed poor antimicrobial activity against Gram-negative bacterial strain, E. coli (MIC = 150- >2500 μg/mL) and did not show any activity against the yeast, C. albicans. The second set of compounds consisted of the silver(I) complexes containing 2-hydroxymethyl-N-alkylimidazoles. The complexes displayed a broad spectrum antimicrobial activity towards the microorganisms that were tested and their activity [E. coli (MIC = 5-40 μg/mL), S. aureus (MIC = 20-80 μg/mL), Bacillus subtilis subsp. spizizenii (MIC = 5-40 μg/mL) and C. albicans (MIC = 40-80 μg/mL)] increased with the alkyl chain length of the 2-hydroxymethyl-N-alkylimidazole. The third set of compounds consisted of the vinylimidazoles containing the vinyl group either at the 1-position or at the 4- or 5- position. The imidazoles with the vinyl group at the 4- or 5-position contained the alkyl group (decyl) at the 1-position. For the fabrication of the antimicrobial nanofibers, the first two sets of imidazole derivatives (2-substituted N-alkylimidazoles and silver(I) complexes) were incorporated into electrospun nylon 6 nanofibers while the third set (2-substituted vinylimidazoles) was immobilized onto electrospun nylon 6 nanofibers employing the graft polymerization method. The antimicrobial nylon nanofibers were characterized by IR spectroscopy and SEM-EDAX (EDS). The electrospun nylon 6 nanofibers incorporated with 2-substituted N-alkylimidazoles displayed moderate to excellent levels of growth reduction against S. aureus (73.2-99.8 percent). For the electrospun nylon 6 nanofibers incorporated with silver(I) complexes, the levels of growth reduction were >99.99 percent, after the antimicrobial activity evaluation using the shake flask method. Furthermore, the grafted electrospun nylon 6 nanofibers showed excellent levels of growth reduction for E. coli (99.94-99.99 percent) and S. aureus (99.93-99.99 percent). The reusability results indicated that the grafted electrospun nylon 6 nanofibers maintained the antibacterial activity until the third cycle of useage. The cytotoxicity studies showed that grafted electrospun nylon 6 nanofibers possess lower cytotoxic effects on Chang liver cells with IC50 values in the range 23.48-26.81 μg/mL. The thesis demonstrated that the development of antimicrobial electrospun nanofibers, with potential for the eradication of pathogenic microoganisms in water, could be accomplished by incorporation as well as immobilization strategies.
- Full Text:
- Authors: Kleyi, Phumelele Eldridge
- Date: 2014
- Subjects: Electrospinning , Nanofibers , Pathogenic microorganisms , Pathogenic microorganisms -- Detection , Drinking water -- Microbiology , Water quality -- Measurement , Imidazoles , Spectrum analysis , Anti-infective agents , Polymerization
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4497 , http://hdl.handle.net/10962/d1013134
- Description: The thesis presents the development of functionalized electrospun nylon 6 nanofibers for the eradication of pathogenic microorganisms in drinking water. Imidazole derivatives were synthesized as the antimicrobial agents and were characterized by means of NMR spectroscopy, IR spectroscopy, elemental analysis and X-ray crystallography. The first set of compounds (2-substituted N-alkylimidazoles) consisted of imidazole derivatives substituted with different alkyl groups (methyl, ethyl, propyl, butyl, heptyl, octyl, decyl and benzyl) at the 1-position and various functional groups [carboxaldehyde (CHO), alcohol (CH2OH) and carboxylic acid (COOH)] at the 2-position. It was observed that the antimicrobial activity of the compounds increased with increasing alkyl chain length and decreasing pKa of the 2-substituent. It was also observed that the antimicrobial activity was predominantly against a Gram-positive bacterial strains [Staphylococcus aureus (MIC = 5-160 μg/mL) and Bacillus subtilis subsp. spizizenii (MIC = 5-20 μg/mL)], with the latter being the more susceptible. However, the compounds displayed poor antimicrobial activity against Gram-negative bacterial strain, E. coli (MIC = 150- >2500 μg/mL) and did not show any activity against the yeast, C. albicans. The second set of compounds consisted of the silver(I) complexes containing 2-hydroxymethyl-N-alkylimidazoles. The complexes displayed a broad spectrum antimicrobial activity towards the microorganisms that were tested and their activity [E. coli (MIC = 5-40 μg/mL), S. aureus (MIC = 20-80 μg/mL), Bacillus subtilis subsp. spizizenii (MIC = 5-40 μg/mL) and C. albicans (MIC = 40-80 μg/mL)] increased with the alkyl chain length of the 2-hydroxymethyl-N-alkylimidazole. The third set of compounds consisted of the vinylimidazoles containing the vinyl group either at the 1-position or at the 4- or 5- position. The imidazoles with the vinyl group at the 4- or 5-position contained the alkyl group (decyl) at the 1-position. For the fabrication of the antimicrobial nanofibers, the first two sets of imidazole derivatives (2-substituted N-alkylimidazoles and silver(I) complexes) were incorporated into electrospun nylon 6 nanofibers while the third set (2-substituted vinylimidazoles) was immobilized onto electrospun nylon 6 nanofibers employing the graft polymerization method. The antimicrobial nylon nanofibers were characterized by IR spectroscopy and SEM-EDAX (EDS). The electrospun nylon 6 nanofibers incorporated with 2-substituted N-alkylimidazoles displayed moderate to excellent levels of growth reduction against S. aureus (73.2-99.8 percent). For the electrospun nylon 6 nanofibers incorporated with silver(I) complexes, the levels of growth reduction were >99.99 percent, after the antimicrobial activity evaluation using the shake flask method. Furthermore, the grafted electrospun nylon 6 nanofibers showed excellent levels of growth reduction for E. coli (99.94-99.99 percent) and S. aureus (99.93-99.99 percent). The reusability results indicated that the grafted electrospun nylon 6 nanofibers maintained the antibacterial activity until the third cycle of useage. The cytotoxicity studies showed that grafted electrospun nylon 6 nanofibers possess lower cytotoxic effects on Chang liver cells with IC50 values in the range 23.48-26.81 μg/mL. The thesis demonstrated that the development of antimicrobial electrospun nanofibers, with potential for the eradication of pathogenic microoganisms in water, could be accomplished by incorporation as well as immobilization strategies.
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Photophysicochemical and photodynamic antimicrobial chemotherapeutic studies of novel phthalocyanines conjugated to silver nanoparticles
- Authors: Rapulenyane, Nomasonto
- Date: 2013 , 2013-06-10
- Subjects: Phthalocyanines , Photochemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Escherichia coli , Nanoparticles , Silver , Zinc
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4291 , http://hdl.handle.net/10962/d1003912 , Phthalocyanines , Photochemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Escherichia coli , Nanoparticles , Silver , Zinc
- Description: This work reports on the synthesis, characterization and the physicochemical properties of novel unsymmetrically substituted zinc phthalocyanines: namely tris{11,19, 27-(1,2- diethylaminoethylthiol)-2-(captopril) phthalocyanine Zn ((ZnMCapPc (1.5)), hexakis{8,11,16,19,42,27-(octylthio)-1-(4-phenoxycarboxy) phthalocyanine} Zn (ZnMPCPc(1.7)) and Tris {11, 19, 27-(1,2-diethylaminoethylthiol)-1,2(caffeic acid) phthalocyanine} Zn ((ZnMCafPc (1.3)). Symmetrically substituted counterparts (tetrakis(diethylamino)zinc phthalocyaninato (3.8), octakis(octylthio)zinc phthalocyaninato (3.9) and tetrakis (carboxyphenoxy)zinc phthalocyaninato (3.10) complexes) were also synthesized for comparison of the photophysicochemical properties and to investigate the effect of the substituents on the low symmetry Pcs. The complexes were successfully characterized by IR, NMR, mass spectral and elemental analyses. All the complexes showed the ability to produce singlet oxygen, while the highest triplet quantum yields were obtained for 1.7, 1.5 and 3.9 (0.80, 0.65 and 0.62 respectively and the lowest were obtained for 1.3 and 3.10 (0.57 and 0.47 respectively). High triplet lifetimes (109-286 μs) were also obtained for all complexes, with 1.7 being the highest (286 μs) which also corresponds to its triplet and singlet quantum yields (0.80 and 0.77 respectively). The photosensitizing properties of low symmetry derivatives, ZnMCapPc and ZnMCafPc were investigated by conjugating glutathione (GSH) capped silver nanoparticles (AgNP). The formation of the amide bond was confirmed by IR and UV-Vis spectroscopies. The photophysicochemical behaviour of the novel phthalocyanine-GSH-AgNP conjugates and the simple mixture of the Ag NPs with low the symmetry phthalocyanines were investigated. It was observed that upon conjugation of the phthalocyanines to the GSH-AgNPs, a blue shift in the Q band was induced. The triplet lifetimes and quantum yields improved upon conjugation as compared to the phthalocyanines (Pc) alone. Complex 1.5 triplet lifetimes increased from 109 to 148 and triplet quantum yield from 0.65 to 0.86 upon conjugation. Fluorescence lifetimes and quantum yields decreased for the conjugates compared to the phthalocyanines alone, due to the quenching caused by the Ag NPs. The antimicrobial activity of the zinc phthalocyanines (complexes 1.3 and 1.5) and their conjugates against Escherichia coli was investigated. Only 1.3 and 1.5 complexes were investigated because of the availability of the sample. In general phthalocyanines showed increase in antibacterial activity with the increase in phthalocyanines concentration in the presence and absence of light. The Pc complexes and their Ag NP conjugates showed an increase in antibacterial activity, due to the synergistic effect afforded by Ag NP and Pcs. Improved antibacterial properties were obtained upon irradiation. 1.5-AgNPs had the highest antibacterial activity compared to 1.3-AgNPs conjugate; these results are in agreement with the photophysical behaviour. This work demonstrates improved photophysicochemical properties of low symm
- Full Text:
- Authors: Rapulenyane, Nomasonto
- Date: 2013 , 2013-06-10
- Subjects: Phthalocyanines , Photochemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Escherichia coli , Nanoparticles , Silver , Zinc
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4291 , http://hdl.handle.net/10962/d1003912 , Phthalocyanines , Photochemistry , Photochemotherapy , Cancer -- Photochemotherapy , Anti-infective agents , Escherichia coli , Nanoparticles , Silver , Zinc
- Description: This work reports on the synthesis, characterization and the physicochemical properties of novel unsymmetrically substituted zinc phthalocyanines: namely tris{11,19, 27-(1,2- diethylaminoethylthiol)-2-(captopril) phthalocyanine Zn ((ZnMCapPc (1.5)), hexakis{8,11,16,19,42,27-(octylthio)-1-(4-phenoxycarboxy) phthalocyanine} Zn (ZnMPCPc(1.7)) and Tris {11, 19, 27-(1,2-diethylaminoethylthiol)-1,2(caffeic acid) phthalocyanine} Zn ((ZnMCafPc (1.3)). Symmetrically substituted counterparts (tetrakis(diethylamino)zinc phthalocyaninato (3.8), octakis(octylthio)zinc phthalocyaninato (3.9) and tetrakis (carboxyphenoxy)zinc phthalocyaninato (3.10) complexes) were also synthesized for comparison of the photophysicochemical properties and to investigate the effect of the substituents on the low symmetry Pcs. The complexes were successfully characterized by IR, NMR, mass spectral and elemental analyses. All the complexes showed the ability to produce singlet oxygen, while the highest triplet quantum yields were obtained for 1.7, 1.5 and 3.9 (0.80, 0.65 and 0.62 respectively and the lowest were obtained for 1.3 and 3.10 (0.57 and 0.47 respectively). High triplet lifetimes (109-286 μs) were also obtained for all complexes, with 1.7 being the highest (286 μs) which also corresponds to its triplet and singlet quantum yields (0.80 and 0.77 respectively). The photosensitizing properties of low symmetry derivatives, ZnMCapPc and ZnMCafPc were investigated by conjugating glutathione (GSH) capped silver nanoparticles (AgNP). The formation of the amide bond was confirmed by IR and UV-Vis spectroscopies. The photophysicochemical behaviour of the novel phthalocyanine-GSH-AgNP conjugates and the simple mixture of the Ag NPs with low the symmetry phthalocyanines were investigated. It was observed that upon conjugation of the phthalocyanines to the GSH-AgNPs, a blue shift in the Q band was induced. The triplet lifetimes and quantum yields improved upon conjugation as compared to the phthalocyanines (Pc) alone. Complex 1.5 triplet lifetimes increased from 109 to 148 and triplet quantum yield from 0.65 to 0.86 upon conjugation. Fluorescence lifetimes and quantum yields decreased for the conjugates compared to the phthalocyanines alone, due to the quenching caused by the Ag NPs. The antimicrobial activity of the zinc phthalocyanines (complexes 1.3 and 1.5) and their conjugates against Escherichia coli was investigated. Only 1.3 and 1.5 complexes were investigated because of the availability of the sample. In general phthalocyanines showed increase in antibacterial activity with the increase in phthalocyanines concentration in the presence and absence of light. The Pc complexes and their Ag NP conjugates showed an increase in antibacterial activity, due to the synergistic effect afforded by Ag NP and Pcs. Improved antibacterial properties were obtained upon irradiation. 1.5-AgNPs had the highest antibacterial activity compared to 1.3-AgNPs conjugate; these results are in agreement with the photophysical behaviour. This work demonstrates improved photophysicochemical properties of low symm
- Full Text:
An investigation of the antimicrobial and antifouling properties of marine algal metabolites
- Authors: Mann, Maryssa Gudrun Ailsa
- Date: 2008 , 2013-07-11
- Subjects: Anti-infective agents , Marine metabolites -- Therapeutic use , Marine algae , Pharmacognosy , Fouling , Marine fouling organisms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3831 , http://hdl.handle.net/10962/d1007465 , Anti-infective agents , Marine metabolites -- Therapeutic use , Marine algae , Pharmacognosy , Fouling , Marine fouling organisms
- Description: Prevention of the accumulation of undesirable biological material i.e. biofouling upon a solid surface requires the use of antifouling systems. The solid surface may be a contact lens, an off shore oil rig or a living organism. When chemicals are employed as a mechanism of defense against biofouling, the agents involved are known as antifouling agents. Marine algae must protect themselves from fouling organisms and it is thought that one of the mechanisms used by these organisms is the production of secondary metabolites with an array of biological activities. In vitro studies have shown numerous compounds isolated from marine algae to possess antibacterial, antifungal and antimacrofouling activity. The aim of this study was to evaluate the secondary metabolite extracts of selected Southern African marine macro-algae as a potential source of compounds that inhibit biofilm formation and that could be used as antifouling agents. In this project, marine macro-algae were collected from various sites along the South African coastline. Their extracts were screened for antimicrobial activity against four ubiquitous microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium aurm and Candida albicans. Results of screening assays guided the fractionation of two Rhodophyta, Plocamium corallorhiza and Laurencia flexuosa. The algae were fractionated using silica gel column chromatography and compounds were isolated by semi-preparative normal phase HPLC. Compound characterization was performed using UV, IR and advanced one- and two-dimensional NMR (¹H, ¹³C NMR, COSY, HSQC, HMBC and NOESY) spectroscopy and mass spectrometry. Ten halogenated monoterpenes including four members of the small class of halogenated monoterpene aldehydes were isolated from extracts of P. corallorhiza. The compounds isolated included the known compounds 3,4,6,7-tetrachloro-3,7-dimethyl-1-octene; 4,6-dibromo-1, 1-dichloro-3,7 -dimethyl-2E,7 octadiene; 4,8-d ibromo-1,1,7 -trichloro-3, 7-dimethyl-2,5Eoctadiene;1 ,4,8-tribromo-3, 7 -dichloro-3,7-dimethyl-1 E,5E-octadiene; 8-bremo-6, 7-dichloro-3,7-dimethyl-octa-2E,4E-dienal; 4-Bromo-8-chloro-3,7-dimethyl-octa-2E,6E-dienal; 4,6- Dibromo-3,7-dimethyl-octa-2E,7-dienal; 2,4-dichloro-1-(2-chlorovinyl)-1-methyl-5-methylidene-cyclohexane and two new metabolites 4,8-chloro-3,7-dimethyl-2Z,4,6Z-octatrien-1-al and Compound 3.47. Methodology was developed for the chemical derivatization and mass spectrometric analysis of the aldehydic compounds, The aldehyde trapping reagent 0-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride was used to derivatize the molecules, stabilizing them and allowing for their complete characterization. From Laurencia flexuosa a new cuparene sesquiterpene 4-bremo-2-(5-hydroxy-1,2,2- trimethylcyclopent-3-enyl)-5-methylphenol was isolated along with two geometric isomers of the vinyl acetylene bromofucin , An halogenated monoterpene 3S*,4R*-1-bromo-3,4,8-trichloro-9-dichloromethyl-1-E,5-E,7-Z-octatriene was also isolated but was suspected to be a contaminant and an investigation into its biological source revealed that it originated from Plocamium suhrii. A third alga, Martensia elegans was extracted based on published reports of antimicrobial compounds in related species. A new a-alkyl malate derivative was isolated and characterized. Selected compounds isolated during the course of the study were employed in preliminary assays that tested their ability to inhibit biofilm formation by Pseudomonas aeruginosa. The halogenated monoterpenes isolated from the Plocamium species were the only active compounds. 3S*,4R*-1-bromo-3,4,S-trichloro-g-dichloromethyl-1-E,5-E,7-octatriene from P. suhrii inhibited biofilm formation through antibacterial activity on planktonic cells but could not prevent biofilm formation when employed as a film on the surface of microtitre plate wells. 1,4,8-tribromo-3,7-dichloro-3,7-dimethyl-1E,5E-octadiene and 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene inhibited biofilm formation when applied as a film to the microtitre plate wells but had no significant antibacterial activity. No potential antifouling agents were identified in this project but the antimicrobial activity exhibited by the crude algal extracts was highly encouraging and a number of new research areas have been identified. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
- Full Text:
- Authors: Mann, Maryssa Gudrun Ailsa
- Date: 2008 , 2013-07-11
- Subjects: Anti-infective agents , Marine metabolites -- Therapeutic use , Marine algae , Pharmacognosy , Fouling , Marine fouling organisms
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:3831 , http://hdl.handle.net/10962/d1007465 , Anti-infective agents , Marine metabolites -- Therapeutic use , Marine algae , Pharmacognosy , Fouling , Marine fouling organisms
- Description: Prevention of the accumulation of undesirable biological material i.e. biofouling upon a solid surface requires the use of antifouling systems. The solid surface may be a contact lens, an off shore oil rig or a living organism. When chemicals are employed as a mechanism of defense against biofouling, the agents involved are known as antifouling agents. Marine algae must protect themselves from fouling organisms and it is thought that one of the mechanisms used by these organisms is the production of secondary metabolites with an array of biological activities. In vitro studies have shown numerous compounds isolated from marine algae to possess antibacterial, antifungal and antimacrofouling activity. The aim of this study was to evaluate the secondary metabolite extracts of selected Southern African marine macro-algae as a potential source of compounds that inhibit biofilm formation and that could be used as antifouling agents. In this project, marine macro-algae were collected from various sites along the South African coastline. Their extracts were screened for antimicrobial activity against four ubiquitous microorganisms, Staphylococcus aureus, Klebsiella pneumoniae, Mycobacterium aurm and Candida albicans. Results of screening assays guided the fractionation of two Rhodophyta, Plocamium corallorhiza and Laurencia flexuosa. The algae were fractionated using silica gel column chromatography and compounds were isolated by semi-preparative normal phase HPLC. Compound characterization was performed using UV, IR and advanced one- and two-dimensional NMR (¹H, ¹³C NMR, COSY, HSQC, HMBC and NOESY) spectroscopy and mass spectrometry. Ten halogenated monoterpenes including four members of the small class of halogenated monoterpene aldehydes were isolated from extracts of P. corallorhiza. The compounds isolated included the known compounds 3,4,6,7-tetrachloro-3,7-dimethyl-1-octene; 4,6-dibromo-1, 1-dichloro-3,7 -dimethyl-2E,7 octadiene; 4,8-d ibromo-1,1,7 -trichloro-3, 7-dimethyl-2,5Eoctadiene;1 ,4,8-tribromo-3, 7 -dichloro-3,7-dimethyl-1 E,5E-octadiene; 8-bremo-6, 7-dichloro-3,7-dimethyl-octa-2E,4E-dienal; 4-Bromo-8-chloro-3,7-dimethyl-octa-2E,6E-dienal; 4,6- Dibromo-3,7-dimethyl-octa-2E,7-dienal; 2,4-dichloro-1-(2-chlorovinyl)-1-methyl-5-methylidene-cyclohexane and two new metabolites 4,8-chloro-3,7-dimethyl-2Z,4,6Z-octatrien-1-al and Compound 3.47. Methodology was developed for the chemical derivatization and mass spectrometric analysis of the aldehydic compounds, The aldehyde trapping reagent 0-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride was used to derivatize the molecules, stabilizing them and allowing for their complete characterization. From Laurencia flexuosa a new cuparene sesquiterpene 4-bremo-2-(5-hydroxy-1,2,2- trimethylcyclopent-3-enyl)-5-methylphenol was isolated along with two geometric isomers of the vinyl acetylene bromofucin , An halogenated monoterpene 3S*,4R*-1-bromo-3,4,8-trichloro-9-dichloromethyl-1-E,5-E,7-Z-octatriene was also isolated but was suspected to be a contaminant and an investigation into its biological source revealed that it originated from Plocamium suhrii. A third alga, Martensia elegans was extracted based on published reports of antimicrobial compounds in related species. A new a-alkyl malate derivative was isolated and characterized. Selected compounds isolated during the course of the study were employed in preliminary assays that tested their ability to inhibit biofilm formation by Pseudomonas aeruginosa. The halogenated monoterpenes isolated from the Plocamium species were the only active compounds. 3S*,4R*-1-bromo-3,4,S-trichloro-g-dichloromethyl-1-E,5-E,7-octatriene from P. suhrii inhibited biofilm formation through antibacterial activity on planktonic cells but could not prevent biofilm formation when employed as a film on the surface of microtitre plate wells. 1,4,8-tribromo-3,7-dichloro-3,7-dimethyl-1E,5E-octadiene and 4,6-dibromo-1,1-dichloro-3,7-dimethyl-2E,7-octadiene inhibited biofilm formation when applied as a film to the microtitre plate wells but had no significant antibacterial activity. No potential antifouling agents were identified in this project but the antimicrobial activity exhibited by the crude algal extracts was highly encouraging and a number of new research areas have been identified. , KMBT_363 , Adobe Acrobat 9.54 Paper Capture Plug-in
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