Quinolone-Pyrazinamide Derivatives: synthesis, characterisation, in silico ADME analysis and in vitro biological evaluation against Mycobacterium tuberculosis
- Authors: Rukweza, Kudakwashe Gerald
- Date: 2023-10-13
- Subjects: Quinolone antibacterial agents , Mycobacterium tuberculosis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/390901 , vital:68596
- Description: Tuberculosis is one of the leading causes of death worldwide caused by an infectious species, Mycobacterium tuberculosis (Mtb). Some of the factors that contribute to the prevalence of this disease include the complexity of diagnosis, prolonged period of therapy, side effects associated with current TB drugs, the prevalence of resistance against the current treatment options and a high incidence of co-infection with HIV/AIDS. Thus, there is a need for new alternative drugs to provide safer and shorter treatment therapy options that are not susceptible to the development of drug resistance. In this project, we focus our attention on the quinolone pharmacophore. Quinolones are currently used as alternative options in the treatment of resistant strains of Mtb. Previous work pertaining to quinolone-isoniazid hybrid compounds showed promising in vitro activity against the H37Rv strain of Mtb and served as the inspiration to pursue this project. The journey commenced with the synthesis of quinolone-pyrazinamide hybrid compounds (Figure 3.1). These compounds were synthesised, through the attachment of the quinolone and the pyrazinamide entity through a hydrazine linker. The synthesised compounds were purified, and their structural identity confirmed using common spectroscopic techniques including 1H and 13C NMR, infra-red (IR) and mass spectrometry. In vitro biological assays were performed by testing for the activity against the H37RvMA strain of Mtb. The bioassays were performed in triplicates to ensure the accuracy of the results. Moxifloxacin and isoniazid were tested as control compounds. Finally, the resultant compounds were profiled in silico for physicochemical and ADMET properties using open access software SwissADME. All the synthesised compounds 3.8a-f showed no activity against H37RvMA. In most cases, the resulting compounds showed minimal to no activity (MICs ≥ 57.3 μM) in all three media. During the in vitro studies, the compounds showed significant precipitation in the media over time suggesting poor aqueous solubility. The SwissADME analysis of these compounds indicated poor solubility in aqueous media, which is likely linked to their molecular size and complexity. Despite poor aqueous solubility, compounds 3.8a-f showed acceptable physicochemical properties and ADME parameters. No PAINs (Pan-assay interference compounds) were observed. Minimal to no interaction with CYP enzymes were predicted. Most of the compounds were compatible with the Lipinski’s rules of five. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
- Authors: Rukweza, Kudakwashe Gerald
- Date: 2023-10-13
- Subjects: Quinolone antibacterial agents , Mycobacterium tuberculosis
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/390901 , vital:68596
- Description: Tuberculosis is one of the leading causes of death worldwide caused by an infectious species, Mycobacterium tuberculosis (Mtb). Some of the factors that contribute to the prevalence of this disease include the complexity of diagnosis, prolonged period of therapy, side effects associated with current TB drugs, the prevalence of resistance against the current treatment options and a high incidence of co-infection with HIV/AIDS. Thus, there is a need for new alternative drugs to provide safer and shorter treatment therapy options that are not susceptible to the development of drug resistance. In this project, we focus our attention on the quinolone pharmacophore. Quinolones are currently used as alternative options in the treatment of resistant strains of Mtb. Previous work pertaining to quinolone-isoniazid hybrid compounds showed promising in vitro activity against the H37Rv strain of Mtb and served as the inspiration to pursue this project. The journey commenced with the synthesis of quinolone-pyrazinamide hybrid compounds (Figure 3.1). These compounds were synthesised, through the attachment of the quinolone and the pyrazinamide entity through a hydrazine linker. The synthesised compounds were purified, and their structural identity confirmed using common spectroscopic techniques including 1H and 13C NMR, infra-red (IR) and mass spectrometry. In vitro biological assays were performed by testing for the activity against the H37RvMA strain of Mtb. The bioassays were performed in triplicates to ensure the accuracy of the results. Moxifloxacin and isoniazid were tested as control compounds. Finally, the resultant compounds were profiled in silico for physicochemical and ADMET properties using open access software SwissADME. All the synthesised compounds 3.8a-f showed no activity against H37RvMA. In most cases, the resulting compounds showed minimal to no activity (MICs ≥ 57.3 μM) in all three media. During the in vitro studies, the compounds showed significant precipitation in the media over time suggesting poor aqueous solubility. The SwissADME analysis of these compounds indicated poor solubility in aqueous media, which is likely linked to their molecular size and complexity. Despite poor aqueous solubility, compounds 3.8a-f showed acceptable physicochemical properties and ADME parameters. No PAINs (Pan-assay interference compounds) were observed. Minimal to no interaction with CYP enzymes were predicted. Most of the compounds were compatible with the Lipinski’s rules of five. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-10-13
Rapid Synthesis of Thiol-Co-Capped CdTe/CdSe/ZnSe Multi-Core-Shell QDs and Their Encapsulation in Liposomes and Chitosan Nanoparticles; Comparative Bio-compatibility Studies Using Hela and Vero Cells
- Authors: Daramola, Olamide Abiodun
- Date: 2023-03-31
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422617 , vital:71962 , DOI 10.21504/10962/422617
- Description: The common method that has been used to reduce the toxicity posed to living cells by CdTe Quantum Dots (QDs) is through the synthesis of CdTe multi-core-shells nanoparticles. In this process, the surface of CdTe QDs is usually coated by less toxic ZnS or ZnSe shells. This heterostructure compound does not only reduce the toxicity of CdTe QDs but can also be used in applications such as deep tissue imaging. The heterostructures can be in numerous forms such as CdTe/CdSe/ZnSe or CdTe/CdSe/ZnS or CdTe/CdS/ZnS multi-core-shell QDs. However, the drawbacks attributed to the fabrication of these compounds is long synthesis times (6- 24 h) in achieving the highest wavelength emission maxima. Others are the use of toxic reagents and poor reproducibility of synthesized materials. An additional problem is that the ZnSe or ZnS coating is insufficient to completely protect the highly toxic Cd metal from escaping into immediate solution. This limits their use in biochemistry and with living systems. Liposomes and biopolymers such as chitosan are known to be environmentally friendly compounds that have been used in various studies as delivery systems for QDs and model drugs for drug delivery applications. They are generally non-toxic and highly bio-compatible. In this study, the rapid synthesis of thiol-co-capped CdTe/CdSe/ZnSe multi-core-shell QDs with a maximum reaction time of 35 mins, gave reliable QDs with emission maxima at 625 nm. The multi-core-shell QDs were encapsulated in two different bio-compatible environments, namely liposome and chitosan nanoparticles (CNP) at 14 different formulations (F) for liposome and 12 different formulations for CNP. Cytotoxicity and florescence imaging studies using HeLa and Vero cells, were used to investigate the improved bio-compatibility. Various characterization techniques were used to elucidate the optical properties, morphology and physico-chemical properties of the QDs and nanocomposites. Two of the best formulations, QD-liposome vesicles (LVs)-F12 and QD-CNP-F9 (with chitosan), demonstrated high loading efficiencies of 42 ± 6 % and 59 ± 5 %, respectively. While the plain CdTe QDs showed high toxicity, some of the encapsulated materials, QD-LVs-F1 and F12, depicted no-toxicity against the cells (IC50 > 0.5 mg/ml). The QDs also retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus, indicating the successful internalization of the QDs in the cytosol. These results shows that encapsulation of CdTe multi-core-shell QDs in liposomes produce better bio-compatibility compared to multi-core-shell QDs and better than CNP coating. These particles therefore show good promise in cell-labelling, drug delivery studies. Their core-shell nanoparticles have also shown good behavior in enhancing the memory of a device which is based on some recent collaborated works. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
- Authors: Daramola, Olamide Abiodun
- Date: 2023-03-31
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422617 , vital:71962 , DOI 10.21504/10962/422617
- Description: The common method that has been used to reduce the toxicity posed to living cells by CdTe Quantum Dots (QDs) is through the synthesis of CdTe multi-core-shells nanoparticles. In this process, the surface of CdTe QDs is usually coated by less toxic ZnS or ZnSe shells. This heterostructure compound does not only reduce the toxicity of CdTe QDs but can also be used in applications such as deep tissue imaging. The heterostructures can be in numerous forms such as CdTe/CdSe/ZnSe or CdTe/CdSe/ZnS or CdTe/CdS/ZnS multi-core-shell QDs. However, the drawbacks attributed to the fabrication of these compounds is long synthesis times (6- 24 h) in achieving the highest wavelength emission maxima. Others are the use of toxic reagents and poor reproducibility of synthesized materials. An additional problem is that the ZnSe or ZnS coating is insufficient to completely protect the highly toxic Cd metal from escaping into immediate solution. This limits their use in biochemistry and with living systems. Liposomes and biopolymers such as chitosan are known to be environmentally friendly compounds that have been used in various studies as delivery systems for QDs and model drugs for drug delivery applications. They are generally non-toxic and highly bio-compatible. In this study, the rapid synthesis of thiol-co-capped CdTe/CdSe/ZnSe multi-core-shell QDs with a maximum reaction time of 35 mins, gave reliable QDs with emission maxima at 625 nm. The multi-core-shell QDs were encapsulated in two different bio-compatible environments, namely liposome and chitosan nanoparticles (CNP) at 14 different formulations (F) for liposome and 12 different formulations for CNP. Cytotoxicity and florescence imaging studies using HeLa and Vero cells, were used to investigate the improved bio-compatibility. Various characterization techniques were used to elucidate the optical properties, morphology and physico-chemical properties of the QDs and nanocomposites. Two of the best formulations, QD-liposome vesicles (LVs)-F12 and QD-CNP-F9 (with chitosan), demonstrated high loading efficiencies of 42 ± 6 % and 59 ± 5 %, respectively. While the plain CdTe QDs showed high toxicity, some of the encapsulated materials, QD-LVs-F1 and F12, depicted no-toxicity against the cells (IC50 > 0.5 mg/ml). The QDs also retained most of their fluorescence and properties and could easily be tracked in cells and visualized around the nucleus, indicating the successful internalization of the QDs in the cytosol. These results shows that encapsulation of CdTe multi-core-shell QDs in liposomes produce better bio-compatibility compared to multi-core-shell QDs and better than CNP coating. These particles therefore show good promise in cell-labelling, drug delivery studies. Their core-shell nanoparticles have also shown good behavior in enhancing the memory of a device which is based on some recent collaborated works. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
The development of ionic zinc(II) phthalocyanines for sono-photodynamic combination therapy of cervical and breast cancer
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
- Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
- Authors: Nene, Lindokuhle Cindy
- Date: 2023-03-31
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/422565 , vital:71958 , DOI 10.21504/10962/422565
- Description: This study focuses on the development of the sono-photodynamic combination therapy (SPDT) activity of phthalocyanines (Pcs) on the cervical and breast cancer cell lines in vitro. The SPDT technique utilizes ultrasound in combination with light to elicit cytotoxic effects for cancer eradication. In this work, a selection of tetra-peripherally substituted Zn(II) cationic and zwitterionic Pcs were prepared. The photophysical parameters of the Pcs were determined including their fluorescence behaviours and efficiency of the triplet excited state population. The effects of the ultrasonic parameters (frequencies (MHz) and power (W.cm-2)) on the stability of the Pcs were evaluated. Four parameters were evaluated: Par I (1 MHz: 1 W.cm-2), Par II (1 MHz: 2 W.cm-2), Par III (3 MHz: 1 W.cm-2) and Par IV (3 MHz: 2 W.cm-2). The stability of the Pcs reduced with the increase in the ultrasonic power (for Par II and Par IV). The Par I showed the least degradation compared to the other parameters and was therefore used for the SPDT treatments. The sonodynamic (SDT), photodynamic (PDT) therapy activities of the Pcs were studied and compared to their SPDT efficacies. The Pcs showed reactive oxygen species generation during the SDT, PDT and SPDT treatments. For the SDT and SPDT, singlet oxygen (1O2) and hydroxyl radicals (•OH) were detected. For PDT, only the 1O2 were detected. The cell cytotoxicity studies for the Pcs showed relatively higher therapeutic efficacies for the SDT treatments compared to the PDT treatments, where the SPDT showed higher therapeutic efficacies compared to both the SDT and PDT monotreatments on both the cell lines in vitro. Overall, the combination treatments were better compared to the monotreatments. The activities of the Pcs were compared by their differences in structures, including the type of R-group, type of quaternizing agent and type of nanoparticle conjugates. , Thesis (PhD) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-31
Pharmaco-chemical investigation of Erythrina caffra: extracts, isolated compounds and their biological activities
- Authors: Nogqala, Simnikiwe
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422459 , vital:71944
- Description: In this study, secondary metabolites isolated from Erythrina caffra, a medicinal plant indigenous to South Africa, were investigated. E. caffra is well-known for its healing properties and it is traditionally used for treating bacterial infections like tuberculosis (TB), abscesses, tooth aches and ear infections. Its extracts have also been used to treat cancer. Though many studies have been done on this plant, most of them tended to focus solely on the isolated compounds. In the present study however, extracts, fractions and isolated compounds from E. caffra were evaluated for their anticancer, anti-oxidant, anti-enzymatic, antibacterial and cytotoxicity. The methanol crude extract (B1) from the stem bark of E. caffra was used to extract alkaloidic fractions (B2 and B3) using ethyl acetate and n-butanol respectively, a third fraction (B4) was also extracted using ethyl acetate this fraction was called a neutral fraction. The neutral fraction (B4) was fractionated and through a sequence of column chromatography three active secondary metabolites were isolated. The isolated compounds included Lupeol (1), stigmasterol (2) and 5,7-Dihydroxy-4'-methoxy-3',5'-diprenylflavanone (3). These isolated compounds were characterized and identified using spectroscopic techniques including IR, NMR and high-resolution Mass Spectrometry. Using the cell line HCC-70, isolated from a primary ductal carcinoma, in vitro anticancer assays were carried out on the crude extract from the bark, fractions, isolated compounds and an unseparated mixture of two compounds. These samples were also evaluated for their anti-oxidant, anti-enzymatic, antibacterial and cytotoxicity activities. The crude extract inhibited the cell viability by over 30% and had no effect on the HeLa cells at concentrations of 20μM. Abyssinone V’ 4-methyl-ether (3) and the mixture of stigmasterol (2) and an unidentified compound exhibited potent anticancer activity against the HCC-70 cell line with IC50 of 18.05μM and 9.04μM respectively. Antibacterial assays were also carried out on the crude extracts, fractions and concoctions made from the fractions with the best activity combined with the ones that performed poorly. The concoctions were prepared as two separate series (S and N series). The crude extract inhibited more than 80% of the Staphylococcus aureus cells at a concentration of 20μM with only minimal damage to the HeLa cells. In the concoctions however, the N series managed to inhibit over 96% of the S. aureus while exhibiting no cytotoxicity towards HeLa cells. The extract and its fractions also showed good anti-oxidant activities. Molecular docking of these compounds was done on the Human estrogen receptor (PDB ID:3ERT) and Abyssinone V’ 4-methyl-ether (3) showed the best docking score of -6.6 Kcal/mol, for the simulation against Epidermal growth factor receptor (PDB ID: 1M17) Stigmasterol (2) showed the best docking score of -3.8 Kcal/mol. In silico docking on 3ERT and 1M17 were done to test the binding affinity of the isolated compounds to the proteins which are well known to be overexpressed in some types of cancer. Flavonoids isolated from Erythrina species have been reported to possess good antiplasmodial activity. However, due to the minute amounts isolated in the present study in-vitro assays could not be carried out. Nevertheless, in-silico assays were conducted on the most prominent protozoal parasite which causes malaria in the majority of African countries. In-silico simulations were done against Plasmodium falciparum protein (PDB ID: 7KJH), of the tested compounds Abyssinone V’ 4-methyl-ether (3) was found possess the best docking score of -4.4 Kcal/mol. The molecular docking of 7KJH was done to assess the inhibitory potential of the isolated compounds on protozoal parasites. Pharmacokinetic properties of the isolated compounds were also assessed in silico to assist in evaluating the drug likeness of these compounds. The compounds showed a percent human oral absorption of 100% except for Abyssinone V’ 4-methyl-ether (3), which showed 93.83%, this indicates a remarkable oral bioavailability. Stigamsterol (2) exhibited a Caco-2 cell permeability (QPPCaco) greater than 500 which indicates outstanding results for good intestinal absorption. The compounds also displayed a blood-brain partition co-efficient (QPlogBB) ranging from -1.433 to 0.128 suggesting they will have less potential to cross the blood-brain barrier, thus reducing any CNS related toxicity. Molecular networking of the crude extracts and the fractions was done through GNPS which allowed the identification of known compounds including one isolated in the present study, Abyssinone V’ 4-methyl-ether (3). Possible derivatives that have not been isolated from this plant before were also putatively identified. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-29
- Authors: Nogqala, Simnikiwe
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422459 , vital:71944
- Description: In this study, secondary metabolites isolated from Erythrina caffra, a medicinal plant indigenous to South Africa, were investigated. E. caffra is well-known for its healing properties and it is traditionally used for treating bacterial infections like tuberculosis (TB), abscesses, tooth aches and ear infections. Its extracts have also been used to treat cancer. Though many studies have been done on this plant, most of them tended to focus solely on the isolated compounds. In the present study however, extracts, fractions and isolated compounds from E. caffra were evaluated for their anticancer, anti-oxidant, anti-enzymatic, antibacterial and cytotoxicity. The methanol crude extract (B1) from the stem bark of E. caffra was used to extract alkaloidic fractions (B2 and B3) using ethyl acetate and n-butanol respectively, a third fraction (B4) was also extracted using ethyl acetate this fraction was called a neutral fraction. The neutral fraction (B4) was fractionated and through a sequence of column chromatography three active secondary metabolites were isolated. The isolated compounds included Lupeol (1), stigmasterol (2) and 5,7-Dihydroxy-4'-methoxy-3',5'-diprenylflavanone (3). These isolated compounds were characterized and identified using spectroscopic techniques including IR, NMR and high-resolution Mass Spectrometry. Using the cell line HCC-70, isolated from a primary ductal carcinoma, in vitro anticancer assays were carried out on the crude extract from the bark, fractions, isolated compounds and an unseparated mixture of two compounds. These samples were also evaluated for their anti-oxidant, anti-enzymatic, antibacterial and cytotoxicity activities. The crude extract inhibited the cell viability by over 30% and had no effect on the HeLa cells at concentrations of 20μM. Abyssinone V’ 4-methyl-ether (3) and the mixture of stigmasterol (2) and an unidentified compound exhibited potent anticancer activity against the HCC-70 cell line with IC50 of 18.05μM and 9.04μM respectively. Antibacterial assays were also carried out on the crude extracts, fractions and concoctions made from the fractions with the best activity combined with the ones that performed poorly. The concoctions were prepared as two separate series (S and N series). The crude extract inhibited more than 80% of the Staphylococcus aureus cells at a concentration of 20μM with only minimal damage to the HeLa cells. In the concoctions however, the N series managed to inhibit over 96% of the S. aureus while exhibiting no cytotoxicity towards HeLa cells. The extract and its fractions also showed good anti-oxidant activities. Molecular docking of these compounds was done on the Human estrogen receptor (PDB ID:3ERT) and Abyssinone V’ 4-methyl-ether (3) showed the best docking score of -6.6 Kcal/mol, for the simulation against Epidermal growth factor receptor (PDB ID: 1M17) Stigmasterol (2) showed the best docking score of -3.8 Kcal/mol. In silico docking on 3ERT and 1M17 were done to test the binding affinity of the isolated compounds to the proteins which are well known to be overexpressed in some types of cancer. Flavonoids isolated from Erythrina species have been reported to possess good antiplasmodial activity. However, due to the minute amounts isolated in the present study in-vitro assays could not be carried out. Nevertheless, in-silico assays were conducted on the most prominent protozoal parasite which causes malaria in the majority of African countries. In-silico simulations were done against Plasmodium falciparum protein (PDB ID: 7KJH), of the tested compounds Abyssinone V’ 4-methyl-ether (3) was found possess the best docking score of -4.4 Kcal/mol. The molecular docking of 7KJH was done to assess the inhibitory potential of the isolated compounds on protozoal parasites. Pharmacokinetic properties of the isolated compounds were also assessed in silico to assist in evaluating the drug likeness of these compounds. The compounds showed a percent human oral absorption of 100% except for Abyssinone V’ 4-methyl-ether (3), which showed 93.83%, this indicates a remarkable oral bioavailability. Stigamsterol (2) exhibited a Caco-2 cell permeability (QPPCaco) greater than 500 which indicates outstanding results for good intestinal absorption. The compounds also displayed a blood-brain partition co-efficient (QPlogBB) ranging from -1.433 to 0.128 suggesting they will have less potential to cross the blood-brain barrier, thus reducing any CNS related toxicity. Molecular networking of the crude extracts and the fractions was done through GNPS which allowed the identification of known compounds including one isolated in the present study, Abyssinone V’ 4-methyl-ether (3). Possible derivatives that have not been isolated from this plant before were also putatively identified. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-29
Photodynamic therapy using morpholine substituted porphyrins in the presence of cancer specific molecules linked to graphene quantum dots
- Magaela, Ngwanabjala Bridged
- Authors: Magaela, Ngwanabjala Bridged
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422486 , vital:71947
- Description: This thesis reports on the synthesis, characterization, photophysiochemical properties of morpholine substituted symmetrical and asymmetrical porphyrins. The synthesized porphyrins are conjugated to cancer selective biomolecules (folic acid and biotin) which are linked to nitrogen doped graphene quantum dots, as potential photosensitizers for photodynamic therapy (PDT). The symmetrical morpholine porphyrin complexes 2 (Sn(IV) 5,10,15,20 tetra-4-morpholinyl porphyrin) and 3 (Zn 5,10,15,20 tetra-4-morpholinyl porphyrin) had the same substituent but different central metals, and they were both conjugated to biotin decorated nitrogen doped graphene quantum dots (B-NGQDs), however complex 2 (Sn(IV) 5,10,15,20 tetra-4-morpholinyl porphyrin) was conjugated to B-NGQDs through an ester bond and complex 3 (Zinc 5,10,15,20 tetra-4-morpholinyl porphyrin) through 𝜋-𝜋 stacking. The effect of asymmetry was studied by comparing complex 3 (Zn 5,10,15,20 tetra-4-morpholinyl porphyrin) and complex 5 (Zn 5- bromophenyl-10-15-20-(tris-4- morpholinyl) porphyrin). Complex 5 (Zn 5- bromophenyl-10-15-20-(tris-4- morpholinyl) porphyrin) was an asymmetric porphyrin with morpholine and bromine as substituents. It was observed that asymmetry enhances singlet oxygen quantum yield and PDT activity. It was also observed that folic acid is a better targeting biomolecule when compared to biotin, and this was studied by comparing complex 3 conjugated to B-NGQDs and complex 3 conjugated to folic acid decorated nitrogen doped graphene quantum dots (FA-NGQDs). 3-FA-NGQDs had a better cellular uptake and PDT activity. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-29
- Authors: Magaela, Ngwanabjala Bridged
- Date: 2023-03-29
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/422486 , vital:71947
- Description: This thesis reports on the synthesis, characterization, photophysiochemical properties of morpholine substituted symmetrical and asymmetrical porphyrins. The synthesized porphyrins are conjugated to cancer selective biomolecules (folic acid and biotin) which are linked to nitrogen doped graphene quantum dots, as potential photosensitizers for photodynamic therapy (PDT). The symmetrical morpholine porphyrin complexes 2 (Sn(IV) 5,10,15,20 tetra-4-morpholinyl porphyrin) and 3 (Zn 5,10,15,20 tetra-4-morpholinyl porphyrin) had the same substituent but different central metals, and they were both conjugated to biotin decorated nitrogen doped graphene quantum dots (B-NGQDs), however complex 2 (Sn(IV) 5,10,15,20 tetra-4-morpholinyl porphyrin) was conjugated to B-NGQDs through an ester bond and complex 3 (Zinc 5,10,15,20 tetra-4-morpholinyl porphyrin) through 𝜋-𝜋 stacking. The effect of asymmetry was studied by comparing complex 3 (Zn 5,10,15,20 tetra-4-morpholinyl porphyrin) and complex 5 (Zn 5- bromophenyl-10-15-20-(tris-4- morpholinyl) porphyrin). Complex 5 (Zn 5- bromophenyl-10-15-20-(tris-4- morpholinyl) porphyrin) was an asymmetric porphyrin with morpholine and bromine as substituents. It was observed that asymmetry enhances singlet oxygen quantum yield and PDT activity. It was also observed that folic acid is a better targeting biomolecule when compared to biotin, and this was studied by comparing complex 3 conjugated to B-NGQDs and complex 3 conjugated to folic acid decorated nitrogen doped graphene quantum dots (FA-NGQDs). 3-FA-NGQDs had a better cellular uptake and PDT activity. , Thesis (MSc) -- Faculty of Science, Chemistry, 2023
- Full Text:
- Date Issued: 2023-03-29
Design, synthesis, manufacture, characterization and evaluation of lipid nanocapsules in chitosan-iota-carrageenan based hydrogel scaffold as a potential anti-Covid-19 drug delivery system
- Authors: Mukubwa, Grady Kathondo
- Date: 2022-10-14
- Subjects: Nanocapsules Design , Hydrogel , COVID-19 (Disease) , Characterization , Drug delivery systems
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/364955 , vital:65665
- Description: Covid-19 is a deadly viral disease that has been rampant around the world since 2019. Although the successful introduction of the vaccine has reduced the spread of covid-19, new cases and deaths are still being recorded. To date, no specific curative antiviral treatment has been approved for covid-19. However, many existing antiviral drugs have been and are still being studied against covid-19 and some of them, such as Remdesivir, have shown promise and could be repurposed to treat this infection. Unfortunately, antiviral drugs are prone to resistance as most of them have poor biopharmaceutical properties, including low solubility, permeability and bioavailability, which could hinder any clinical success. Recent advances in nanotechnology-based delivery systems have made it possible to improve the biopharmaceutical properties of many drugs, especially those of poorly water-soluble drugs, by formulating them as lipid nanoparticles (LNP). Thus, in order to contribute to the fight against covid-19, this work aimed to develop Lipid Nanocapsules (LNC), based on some natural raw materials, which could improve the biopharmaceutical properties of antiviral drugs. In addition, since covid-19 infection is mainly respiratory, this work also aimed to fabricate a targeted delivery system based on a hydrogel capable of entrapping LNC and ensuring their efficient deposition and release in the lungs. The LNC consisted of a mixture of medium-chain triglycerides oil (MCT oil), crude soy lecithin, tween 80, NaCl and water, while the hydrogel consisted of a chitosan-grafted-iota carrageenan-grafted-poly (acrylamide-co-acrylic acid) system (CS-iCar-p (AAm-Co-AA)). Efavirenz (EFV), a drug with very low water solubility that has recently been demonstrated to have the potential to influence sars-cov-2 life cycle through different targets (3CLP, RdRp, Hellicase, 3’to5’exonuclease, 2’-O-ribose methyltransferase and EndoRNAse), was chosen as the model drug to evaluate the developed delivery system. The combination of LNP and hydrogel results in a delivery system known as the LNP-hydrogel composite, an emerging area of research in the field of drug delivery. To date, no research has reported the design and fabrication of an LNC-CS-iCar-p (AAm-Co-AA) hydrogel composite that could effectively deliver an antiviral drug to the lungs in addition to its advantages in terms of biological activities. Prior to the design of experiment, EFV solubility was assessed in water, labrafac lipophile 1349 and MCT oil. After that, the Design Expert Software version 13 was used to design the different experiments performed in this work. The I-optimal mixture design of experiments was performed for both LNC preparation and CS-iCar-p (AAm-Co-AA) hydrogel synthesis to study the impact of raw materials on the characteristics of these delivery systems. LNC were prepared using the phase inversion method while the free radical precipitation graft copolymerization method was used to synthesize hydrogel. In order to build polynomial models that could predict the amount of drug both LNC and CS-iCar-p (AAm-Co-AA) hydrogel can entrap, a D-optimal (custom) randomized design was performed. Moreover, various characterization techniques were used to investigate the physicochemical properties of the developed delivery systems. Thereafter, drug release studies were performed using a 1% sodium lauryl sulfate solution adjusted to either pH 4 or 7. Solubility studies revealed that EFV was more soluble in labrafac lipophile 1349 and in MCT oil than in water; therefore, given its affordability, MCT oil was used for the LNC formulation. The design of experiment carried out allowed the construction of polynomial models that could predict, on the one hand, the droplet size, the polydispersity index and the Zeta potential of LNC, which were respectively around 50nm, below 0.2 and below -33. On the other hand, the model could predict the swelling capacity of the synthesized hydrogel, which was optimised to about 30,000% (300 g of water to 1 g of hydrogel). This turned out to be influenced by the proportion of polymers, the ratio of monomers as well as the concentration of the cross-linking agent. In addition, the characterization techniques further supported the improvement of EFV solubility by highlighting its conversion into its amorphous state after encapsulation in LNC. They also confirmed successful synthesis of CS-iCar-p (AAm-co-AA) hydrogel. LNC were able to encapsulate about 87% of EFV while the synthesized CS-iCar-p (AAm-co-AA) hydrogel entrapped around 53% of EFV encapsulated in LNC. While LNC were able to release 42% and 27% of EFV after 74 hours in a 1% sodium lauryl sulfate solution (SLS) at pH 7 and pH 4 respectively, the LNC-CS-iCar-p (AAm-co-AA) hydrogel composite released about 50% and 40% of the drug after 9 days in the same release medium. Interestingly, the chemical integrity of the drug was preserved throughout the manufacturing process up to after its release, suggesting that the developed LNC-CS-iCar-p (AAm-co-AA) hydrogel composite could be used as a novel potential anticovid-19 drugs delivery system. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Mukubwa, Grady Kathondo
- Date: 2022-10-14
- Subjects: Nanocapsules Design , Hydrogel , COVID-19 (Disease) , Characterization , Drug delivery systems
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/364955 , vital:65665
- Description: Covid-19 is a deadly viral disease that has been rampant around the world since 2019. Although the successful introduction of the vaccine has reduced the spread of covid-19, new cases and deaths are still being recorded. To date, no specific curative antiviral treatment has been approved for covid-19. However, many existing antiviral drugs have been and are still being studied against covid-19 and some of them, such as Remdesivir, have shown promise and could be repurposed to treat this infection. Unfortunately, antiviral drugs are prone to resistance as most of them have poor biopharmaceutical properties, including low solubility, permeability and bioavailability, which could hinder any clinical success. Recent advances in nanotechnology-based delivery systems have made it possible to improve the biopharmaceutical properties of many drugs, especially those of poorly water-soluble drugs, by formulating them as lipid nanoparticles (LNP). Thus, in order to contribute to the fight against covid-19, this work aimed to develop Lipid Nanocapsules (LNC), based on some natural raw materials, which could improve the biopharmaceutical properties of antiviral drugs. In addition, since covid-19 infection is mainly respiratory, this work also aimed to fabricate a targeted delivery system based on a hydrogel capable of entrapping LNC and ensuring their efficient deposition and release in the lungs. The LNC consisted of a mixture of medium-chain triglycerides oil (MCT oil), crude soy lecithin, tween 80, NaCl and water, while the hydrogel consisted of a chitosan-grafted-iota carrageenan-grafted-poly (acrylamide-co-acrylic acid) system (CS-iCar-p (AAm-Co-AA)). Efavirenz (EFV), a drug with very low water solubility that has recently been demonstrated to have the potential to influence sars-cov-2 life cycle through different targets (3CLP, RdRp, Hellicase, 3’to5’exonuclease, 2’-O-ribose methyltransferase and EndoRNAse), was chosen as the model drug to evaluate the developed delivery system. The combination of LNP and hydrogel results in a delivery system known as the LNP-hydrogel composite, an emerging area of research in the field of drug delivery. To date, no research has reported the design and fabrication of an LNC-CS-iCar-p (AAm-Co-AA) hydrogel composite that could effectively deliver an antiviral drug to the lungs in addition to its advantages in terms of biological activities. Prior to the design of experiment, EFV solubility was assessed in water, labrafac lipophile 1349 and MCT oil. After that, the Design Expert Software version 13 was used to design the different experiments performed in this work. The I-optimal mixture design of experiments was performed for both LNC preparation and CS-iCar-p (AAm-Co-AA) hydrogel synthesis to study the impact of raw materials on the characteristics of these delivery systems. LNC were prepared using the phase inversion method while the free radical precipitation graft copolymerization method was used to synthesize hydrogel. In order to build polynomial models that could predict the amount of drug both LNC and CS-iCar-p (AAm-Co-AA) hydrogel can entrap, a D-optimal (custom) randomized design was performed. Moreover, various characterization techniques were used to investigate the physicochemical properties of the developed delivery systems. Thereafter, drug release studies were performed using a 1% sodium lauryl sulfate solution adjusted to either pH 4 or 7. Solubility studies revealed that EFV was more soluble in labrafac lipophile 1349 and in MCT oil than in water; therefore, given its affordability, MCT oil was used for the LNC formulation. The design of experiment carried out allowed the construction of polynomial models that could predict, on the one hand, the droplet size, the polydispersity index and the Zeta potential of LNC, which were respectively around 50nm, below 0.2 and below -33. On the other hand, the model could predict the swelling capacity of the synthesized hydrogel, which was optimised to about 30,000% (300 g of water to 1 g of hydrogel). This turned out to be influenced by the proportion of polymers, the ratio of monomers as well as the concentration of the cross-linking agent. In addition, the characterization techniques further supported the improvement of EFV solubility by highlighting its conversion into its amorphous state after encapsulation in LNC. They also confirmed successful synthesis of CS-iCar-p (AAm-co-AA) hydrogel. LNC were able to encapsulate about 87% of EFV while the synthesized CS-iCar-p (AAm-co-AA) hydrogel entrapped around 53% of EFV encapsulated in LNC. While LNC were able to release 42% and 27% of EFV after 74 hours in a 1% sodium lauryl sulfate solution (SLS) at pH 7 and pH 4 respectively, the LNC-CS-iCar-p (AAm-co-AA) hydrogel composite released about 50% and 40% of the drug after 9 days in the same release medium. Interestingly, the chemical integrity of the drug was preserved throughout the manufacturing process up to after its release, suggesting that the developed LNC-CS-iCar-p (AAm-co-AA) hydrogel composite could be used as a novel potential anticovid-19 drugs delivery system. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Development of biosensor systems for the detection of anti-cancer drugs and prostate cancer
- Authors: Mwanza, Daniel
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365929 , vital:65803
- Description: Thesis embargoed. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Mwanza, Daniel
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365929 , vital:65803
- Description: Thesis embargoed. Expected release date early 2025. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Dual and targeted photodynamic therapy ablation of bacterial and cancer cells using phthalocyanines and porphyrins in the presence of carbon-based nanomaterials
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Openda, Yolande Ikala
- Date: 2022-10-14
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365945 , vital:65804 , DOI https://doi.org/10.21504/10962//365946
- Description: Phthalocyanines (Pcs) and porphyrins bearing substituents that possess antibacterial/anticancer properties are used as photosensitizers (PS) for the first time in the work. For targeting specificity and improved photoactivity, the PSs were afterward functionalized with carbon nanomaterials such as graphene quantum dots (GQDs) and detonation nanodiamonds (DNDs) via covalent conjugation (amide or ester bonds) or by non-covalent conjugation (π-π stacking and electrostatic interactions). Furthermore, the PSs-DNDs nanoconjugates were conjugated to either chitosan-capped silver nanoparticles (CSAg) via amide bonds or to the bare silver nanoparticles (Ag NPs) using the silver- nitrogen affinity. The as-synthesized nanoconjugates were also fully characterized by spectroscopic and microscopic methods together with thermal analysis. The potential photocytotoxicity of the complexes alone and their nanoconjugates against S. aureus and/or E. coli planktonic and biofilm cultures has been evaluated in vitro. Compared to the non- quaternized PSs, the cationic analogs exhibited a higher photodynamic inactivation against the planktonic cells with log10 reduction values above 9 in the viable count using a concentration of ca. 1.25 μM following 30 min exposure to light (Light dose: 943 J/cm2 for Pcs and 250 mW/cm2 for porphyrins). Whereas, at a concentration of ca. 100 μM the cationic PSs showed complete eradication of biofilms upon 30 min exposure to light. As a result of conjugation to carbon-based nanomaterials and silver nanoparticles, the compounds proved to be more effective as they exhibited stronger antibacterial and anti-biofilm activities on the multi-drug resistant bacteria strains due to synergetic effect, compared to PSs alone. This suggests that the newly prepared nanohybrids (PS concentration ca. 100 μM) could be used as potential antimicrobial agents in the treatment of biofilm-related infections. The target nanoconjugates showed all the advantages of two different groups existing on a single entity. In light of the potential advantages of combined chemotherapy and photodynamic antimicrobial chemotherapy (PACT), this work reports for the first time the use of PACT-ciprofloxacin (CIP) dual therapy using selected indium quaternized PSs which showed higher photoactivity with complete eradication of both Gram-positive and Gram-negative bacteria biofilms at concentrations of 8 μM of PS versus 2 μg/mL of the antibiotic following 15 min irradiation time (light dose: 471 J/cm2 for Pcs and fluence: 250 mW/cm2 for porphyrins) on S. aureus. Whereas the total killing of E. coli was obtained when combining 8 or 16 μM of PS combined with 4 μg/mL of CIP. The combined treatment resulted in the complete eradication of the matured biofilms with the highest log10 reduction values of 7.05 and 7.20 on S. aureus and E. coli, respectively. Used as a model, positively charged dimethylamino-chalcone Pcs also exhibited interesting photodynamic therapy (PDT) activity against MCF-7 cancer cells giving IC50 values of 17.9 and 7.4 μM, respectively following 15 min irradiation. Additionally, the TD-B3LYP/LanL2DZ calculations were run on the dimethylaminophenyl- porphyrins to compare the singlet excitation energies of quaternized and non-quaternized porphyrins in vacuo. the study shows excellent agreement between time-dependent density- functional theory (TD-DFT) exciting energies and the experimental S1>S0 excitation energies. The small deviation observed between the calculated and experimental spectra arises from the solvent effect. The excitation energies observed in these UV-Vis spectra mostly originated from electron promotion between the highest occupied molecular orbital (HOMO) for the less intense band and the HOMO-1 for the most intense band of the ground states to the lower unoccupied molecular orbital (LUMO) of the excited states. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Electrocatalytic activity of symmetric and asymmetric Co(II) and Mn(III) porphyrins in the presence of graphene quantum dots towards the oxidation of hydrazine
- Authors: Jokazi, Mbulelo
- Date: 2022-10-14
- Subjects: Electrocatalysis , Hydrazine , Quantum dots , Graphene , Porphyrins
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362894 , vital:65372
- Description: The influence of metal porphyrins in electro-oxidation of hydrazine is explored. A series of symmetric and asymmetric porphyrins alone and in the presence of graphene quantum dots (GQDs) are employed in this work. Tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin--GQDs, and manganese tetra 4-aminophenyl porphyrin@GQDs are the symmetric porphyrins. The asymmetric porphyrin and composites are 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs, and cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs. These complexes were synthesized and characterized accordingly and applied for electrocatalysis. The electrocatalytic experiments were carried out using glassy carbon electrode and the modification was through drop-dry method. The porphyrin and GQDs synthesized were characterized using UV-Vis spectroscopy, Mass spectrometry, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and energy dispersive x-ray spectroscopy. The modified electrodes were characterized using cyclic voltammetry and electrochemical Impedance spectroscopy. The introduction of metal ion in the center of the porphyrin improved electrocatalysis. The presence of push-pull substituents in the porphyrin lowered the oxidation potential and improved the catalysis. The presence of GQDs improved catalysis in both symmetric and asymmetric porphyrin compared to individual components. Cobalt porphyrins showed better activity than manganese porphyrin. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Jokazi, Mbulelo
- Date: 2022-10-14
- Subjects: Electrocatalysis , Hydrazine , Quantum dots , Graphene , Porphyrins
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362894 , vital:65372
- Description: The influence of metal porphyrins in electro-oxidation of hydrazine is explored. A series of symmetric and asymmetric porphyrins alone and in the presence of graphene quantum dots (GQDs) are employed in this work. Tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin, manganese tetra 4-aminophenyl porphyrin--GQDs, and manganese tetra 4-aminophenyl porphyrin@GQDs are the symmetric porphyrins. The asymmetric porphyrin and composites are 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins, manganese 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs, and cobalt 5, 10, 15-tris(aminophenyl)-20-(4-carboxyphenyl) porphyrins--GQDs. These complexes were synthesized and characterized accordingly and applied for electrocatalysis. The electrocatalytic experiments were carried out using glassy carbon electrode and the modification was through drop-dry method. The porphyrin and GQDs synthesized were characterized using UV-Vis spectroscopy, Mass spectrometry, X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy and energy dispersive x-ray spectroscopy. The modified electrodes were characterized using cyclic voltammetry and electrochemical Impedance spectroscopy. The introduction of metal ion in the center of the porphyrin improved electrocatalysis. The presence of push-pull substituents in the porphyrin lowered the oxidation potential and improved the catalysis. The presence of GQDs improved catalysis in both symmetric and asymmetric porphyrin compared to individual components. Cobalt porphyrins showed better activity than manganese porphyrin. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Photodynamic anticancer and antimicrobial activities of π-extended BODIPY dyes and cationic mitochondria-targeted porphyrins
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Chiyumba, Choonzo Nachoobe
- Date: 2022-10-14
- Subjects: Dyes and dyeing Chemistry , Mitochondria , Cancer Chemotherapy , Porphyrins , Molecules Models , Photochemotherapy
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/362785 , vital:65362
- Description: Cancer is among the most devastating diseases and is mainly caused by gene mutation. This could be hereditary, or the mutation could be stimulated due to a lifestyle one lives, such as smoking, which induces lung cancer. The high morbidity rates of cancer are attributed to it being metastatic. The relatively poor physicochemical properties of existing drugs have caused treatment to be ineffective. Photofrin®, Foscan®, and Photogem® are some of the porphyrin-based derivatives approved by the Food and Drug Administration (FDA) for use in photodynamic therapy (PDT). Despite having such drugs, the quest to find better cancer drugs is still ongoing and 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) dyes are among the molecules that are being studied as potential photosensitisers (PS) in PDT. However, these molecules suffer from poor solubility and ineffective generation of singlet oxygen, the main ingredient in PDT treatment. Furthermore, photosensitisers used in PDT face a problem with hypoxic conditions associated with cancer cells, which causes the generation of singlet oxygen to be relatively low. The PS also suffer from the untargeted treatment, increasing their toxicity. Therefore, the main aim of this study was to improve the bioavailability of BODIPY dyes. Thus, a series of BODPIY dyes were synthesised with hydrogen bond accepting atoms and heavy atoms that enhance singlet oxygen generation. Additionally, to override hypoxia conditions, porphyrins with mitochondria targeting properties were synthesised since it has been well established that the mitochondria will always have a decent amount of oxygen in cancerous cells. When employed as PS in PDT studies, these molecules have better cytotoxic abilities than BODIPY dyes, and this potency was credited to their mitochondria targeting ability and efficient singlet oxygen generation. Finally, this study reports the synthesis of di- and mono-substituted BODIPY dyes with improved solubility and porphyrins substituted with triphenyl phosphine, a mitochondria targeting moiety. On the other hand, the work further illustrates the synthesis of β-substituted cationic porphyrin with mitochondria targeting properties. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Synthesis, characterization and host-guest complexes of supramolecular assemblies based on calixarenes and cucurbiturils
- Authors: Baa, Ebenezer
- Date: 2022-10-14
- Subjects: Supramolecular chemistry , Calixarenes , Cucurbiturils , Metal-organic frameworks , Macrocyclic compounds , Drug delivery systems
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365621 , vital:65765 , DOI https://doi.org/10.21504/10962/365621
- Description: The field of supramolecular chemistry has grown large and wide in both deepness of understanding, range of topics covered and scope and applications. Supramolecular self-assemblies are facilitated by a wide range of non-covalent intra and inter molecular interactions that range from hydrogen bonding to π-interaction and van der Waals. Macrocyclic compounds such as cucurbiturils and calixarenes have emerged as important classes of compounds with excellent potential of forming supramolecular assemblies. The porous nature of these compounds enables them to form host-guest supramolecular complexes stabilized by diverse range of non-covalent interactions. Furthermore, these compounds contain donor atoms capable of forming bonds with metal ions to yield metal complexes with interesting porous characteristics that deviate from their traditional hydrophobic cavity. The versatile nature of the resulting pores imply that they can accommodate diverse types of guests. This work explores the synthesis and characterization of a host of calixarenes and cucurbiturils. Self-assembly of these macrocycles with various metal ions results to the formation of porous metal organic framework (MOF) complexes. Four new calixarene typed compounds obtained from aromatic aldehydes and twenty-six cucurbituril metal complexes are reported. These macrocylces and their metal complexes also form supramolecular complexes with DMSO, methanol, isoniazid hydrochloride and ciprofloxacin hydrochlorides through either self-assembly, mechanochemistry and exposure to solvent vapors. The bulk materials have been characterized using nuclear magnetic resonance spectroscopy (NMR), Fourier transformed infrared spectroscopy (FTIR), powder and single crystal diffraction techniques and thermal studies thermogravimetric analysis (TGA) and differential thermal calorimetry (DSC). Data obtained from this study reveals that calixarenes can form supramolecular complexes with a frequently used laboratory solvents with BN22 showing appreciable selectivity for DMSO sorption from a solvent mixture. These compounds also form supramolecular complexes with drug molecules such as isoniazid and ciprofloxacin. Furthermore, the data reveals that choice of synthetic route of supramolecular ensembles dictates if the guest drug molecule will occupy the intrinsic or extrinsic pores of cucurbituril complexes. Biological studies on the obtained complexes reveal that the cucurbituril complexes are non-cytotoxic while the calixarenes show antibacterial activity against Escherichia coli and Staphylococcus aureus. Additionally, the study showed that ciprofloxacin can be successfully released from a calixarene host in a simulated body fluid although the host was also found to cross the dialysis membrane. The results of this study are important in that; - they can be exploited and developed in the selective sorption of certain guests and - that they can be used in the development of drug delivery systems that play a dual role of delivery and therapeutic activity. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Baa, Ebenezer
- Date: 2022-10-14
- Subjects: Supramolecular chemistry , Calixarenes , Cucurbiturils , Metal-organic frameworks , Macrocyclic compounds , Drug delivery systems
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365621 , vital:65765 , DOI https://doi.org/10.21504/10962/365621
- Description: The field of supramolecular chemistry has grown large and wide in both deepness of understanding, range of topics covered and scope and applications. Supramolecular self-assemblies are facilitated by a wide range of non-covalent intra and inter molecular interactions that range from hydrogen bonding to π-interaction and van der Waals. Macrocyclic compounds such as cucurbiturils and calixarenes have emerged as important classes of compounds with excellent potential of forming supramolecular assemblies. The porous nature of these compounds enables them to form host-guest supramolecular complexes stabilized by diverse range of non-covalent interactions. Furthermore, these compounds contain donor atoms capable of forming bonds with metal ions to yield metal complexes with interesting porous characteristics that deviate from their traditional hydrophobic cavity. The versatile nature of the resulting pores imply that they can accommodate diverse types of guests. This work explores the synthesis and characterization of a host of calixarenes and cucurbiturils. Self-assembly of these macrocycles with various metal ions results to the formation of porous metal organic framework (MOF) complexes. Four new calixarene typed compounds obtained from aromatic aldehydes and twenty-six cucurbituril metal complexes are reported. These macrocylces and their metal complexes also form supramolecular complexes with DMSO, methanol, isoniazid hydrochloride and ciprofloxacin hydrochlorides through either self-assembly, mechanochemistry and exposure to solvent vapors. The bulk materials have been characterized using nuclear magnetic resonance spectroscopy (NMR), Fourier transformed infrared spectroscopy (FTIR), powder and single crystal diffraction techniques and thermal studies thermogravimetric analysis (TGA) and differential thermal calorimetry (DSC). Data obtained from this study reveals that calixarenes can form supramolecular complexes with a frequently used laboratory solvents with BN22 showing appreciable selectivity for DMSO sorption from a solvent mixture. These compounds also form supramolecular complexes with drug molecules such as isoniazid and ciprofloxacin. Furthermore, the data reveals that choice of synthetic route of supramolecular ensembles dictates if the guest drug molecule will occupy the intrinsic or extrinsic pores of cucurbituril complexes. Biological studies on the obtained complexes reveal that the cucurbituril complexes are non-cytotoxic while the calixarenes show antibacterial activity against Escherichia coli and Staphylococcus aureus. Additionally, the study showed that ciprofloxacin can be successfully released from a calixarene host in a simulated body fluid although the host was also found to cross the dialysis membrane. The results of this study are important in that; - they can be exploited and developed in the selective sorption of certain guests and - that they can be used in the development of drug delivery systems that play a dual role of delivery and therapeutic activity. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Synthesis, In-Silico molecular modelling and biological studies of 1,4-Dihydroxyanthraquinone and its derivatives
- Authors: Kisula, Lydia Mboje
- Date: 2022-10-14
- Subjects: Computer simulation , Molecules Models , Dihydroxyanthraquinone , Trypanosomiasis , Leishmaniasis , Docking
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365828 , vital:65793 , DOI https://doi.org/10.21504/10962/365828
- Description: This current study of investigation reports on the synthesis of 1,4-dihydroxyanthraquinone and its derivatives on explorations of their medicinal potential. The study initially aimed to synthesize an analogue of a natural anthraquinone, 1,3,6-trihydroxy-7-((S)-1- hydroxyethyl)anthracene-9,10-dione 5 using Friedel-Crafts acylation of phthalic anhydride and a benzene derivative. Synthetic transformation of anacardic acid 63, obtained as a by- product of the cashew industry successfully afforded 4-ethoxyisobenzofuran-1,3-dione 89. However, when attempted to couple 4-ethoxyisobenzofuran-1,3-dione 89 with 2- hydroxyacetophenone 91 in a Friedel-Crafts acylation manner to form 2-acetyl-1,8- dihydroxyanthracene-9,10-dione 87 the reaction did not work efficiently. A simple derivative of benzene which is; benzene-1,4-diol 102 was reacted instead with 3-ethoxyphthalic acid 71 and isobenzofuran-1,3-dione 96 to form 1,4,5-trihydroxy anthraquinone 72 and 1,4- dihydroxyanthraquinone 42, respectively. A modified Marschalk reaction was then used to introduce the hydroxyl alkyl group to 1,4-dihydroxy anthraquinone 42, which allowed further elaboration of the hydroxyl-substituent in moderate to good yields (22-80%). A molecular docking study was performed using Schrödinger software to predict the binding affinity of the test compounds to the target protein trypanothione reductase (PDB ID: 6BU7). An in-vitro screening of 1,4-dihydroxyanthraquinone derivatives and some selected precursors for antitrypanosomal, antiplasmodial, antibacterial, and cytotoxicity activities produced encouraging results. Derivatives of anacardic acid and cardanol from CNSL were found to have moderate activity against trypanosomes with no activity against Plasmodium falciparum. Almost 63% of synthesized 1,4-dihydroxyanthraquinone derivatives displayed activity against trypanosomes. The in-vitro evaluation and the in silico molecular docking studies revealed that 1,4-dihydroxyanthraquinone derivatives can be potential drug-like candidates active against T.brucei parasites (IC50 = 0.70-1.20 μM). Only four 1,4- iv dihydroxyanthraquinone derivatives with thiosemicarbazone, chloride, pyrrole, and diethanolamine functionality displayed activity against Plasmodium falciparum (IC50 = 3.17- 14.36 μM). In-vitro evaluated of test compounds against antibacterial screen and cytotoxicity effects significantly showed that 2-hydroxy-6-pentadecylbenzoic acid 63a and 2-((2- chlorophenyl)(piperazin-1-yl) methyl)-1,4-dihydroxyanthracene-9,10-dione 78 have potency against Staphylococcus aureus and reduced the viability of the cells below 20% at an initial concentration of 50 μg/mL. Only 1,4-dihydroxyanthraquinone derivatives with thiosemicarbazone 76, piperazine 78, and diethanolamine 80 motifs were active against HeLa cells and reduced the viability of cells below 20% at a concentration of 50 μg/mL. In conclusion, this current reported study has generated useful knowlege on the applicability of the agro-waste CNSL as an agent active against trypanosomiasis but also as a low-cost starting material to synthesize hydroxy anthraquinones. The study has further given an overview to the understanding of the medicinal value 1,4-dihydroxyanthraquinone derivatives as promising candidates towards developing drugs suitable for treating neglected tropical diseases particularly trypanosomiasis. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
- Authors: Kisula, Lydia Mboje
- Date: 2022-10-14
- Subjects: Computer simulation , Molecules Models , Dihydroxyanthraquinone , Trypanosomiasis , Leishmaniasis , Docking
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/365828 , vital:65793 , DOI https://doi.org/10.21504/10962/365828
- Description: This current study of investigation reports on the synthesis of 1,4-dihydroxyanthraquinone and its derivatives on explorations of their medicinal potential. The study initially aimed to synthesize an analogue of a natural anthraquinone, 1,3,6-trihydroxy-7-((S)-1- hydroxyethyl)anthracene-9,10-dione 5 using Friedel-Crafts acylation of phthalic anhydride and a benzene derivative. Synthetic transformation of anacardic acid 63, obtained as a by- product of the cashew industry successfully afforded 4-ethoxyisobenzofuran-1,3-dione 89. However, when attempted to couple 4-ethoxyisobenzofuran-1,3-dione 89 with 2- hydroxyacetophenone 91 in a Friedel-Crafts acylation manner to form 2-acetyl-1,8- dihydroxyanthracene-9,10-dione 87 the reaction did not work efficiently. A simple derivative of benzene which is; benzene-1,4-diol 102 was reacted instead with 3-ethoxyphthalic acid 71 and isobenzofuran-1,3-dione 96 to form 1,4,5-trihydroxy anthraquinone 72 and 1,4- dihydroxyanthraquinone 42, respectively. A modified Marschalk reaction was then used to introduce the hydroxyl alkyl group to 1,4-dihydroxy anthraquinone 42, which allowed further elaboration of the hydroxyl-substituent in moderate to good yields (22-80%). A molecular docking study was performed using Schrödinger software to predict the binding affinity of the test compounds to the target protein trypanothione reductase (PDB ID: 6BU7). An in-vitro screening of 1,4-dihydroxyanthraquinone derivatives and some selected precursors for antitrypanosomal, antiplasmodial, antibacterial, and cytotoxicity activities produced encouraging results. Derivatives of anacardic acid and cardanol from CNSL were found to have moderate activity against trypanosomes with no activity against Plasmodium falciparum. Almost 63% of synthesized 1,4-dihydroxyanthraquinone derivatives displayed activity against trypanosomes. The in-vitro evaluation and the in silico molecular docking studies revealed that 1,4-dihydroxyanthraquinone derivatives can be potential drug-like candidates active against T.brucei parasites (IC50 = 0.70-1.20 μM). Only four 1,4- iv dihydroxyanthraquinone derivatives with thiosemicarbazone, chloride, pyrrole, and diethanolamine functionality displayed activity against Plasmodium falciparum (IC50 = 3.17- 14.36 μM). In-vitro evaluated of test compounds against antibacterial screen and cytotoxicity effects significantly showed that 2-hydroxy-6-pentadecylbenzoic acid 63a and 2-((2- chlorophenyl)(piperazin-1-yl) methyl)-1,4-dihydroxyanthracene-9,10-dione 78 have potency against Staphylococcus aureus and reduced the viability of the cells below 20% at an initial concentration of 50 μg/mL. Only 1,4-dihydroxyanthraquinone derivatives with thiosemicarbazone 76, piperazine 78, and diethanolamine 80 motifs were active against HeLa cells and reduced the viability of cells below 20% at a concentration of 50 μg/mL. In conclusion, this current reported study has generated useful knowlege on the applicability of the agro-waste CNSL as an agent active against trypanosomiasis but also as a low-cost starting material to synthesize hydroxy anthraquinones. The study has further given an overview to the understanding of the medicinal value 1,4-dihydroxyanthraquinone derivatives as promising candidates towards developing drugs suitable for treating neglected tropical diseases particularly trypanosomiasis. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-10-14
Inhibition of aluminium corrosion using phthalocyanines: Experimental and computational studies
- Authors: Nnaji, Nnaemeka Joshua
- Date: 2022-04-08
- Subjects: Aluminum Corrosion , Electrochemistry , Phthalocyanines , Corrosion and anti-corrosives , Protective coatings , Density functionals
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294643 , vital:57240 , DOI 10.21504/10962/294643
- Description: Metal deterioration over time is a process known as corrosion, an electrochemical process, which can occur by surface chemical actions on metals by its environment. Metal corrosion have great economic, security, and environmental consequences, and its control is a major research area in corrosion science. Amongst the different corrosion protecting approaches, the use of corrosion inhibitors and protective coatings have attracted enormous research interest in this area of scholasticism. This has necessitated the computational and electrochemical investigations of aluminium corrosion inhibitive potentials of some compounds in 1M HCl. Metal free (5_H2), ClGa(III) (5_Ga) and Co(II) (5_Co) tetrakis(4-acetamidophenoxy)phthalocyanines as well as Co(II) 2,9,16-tris(4-(tert-butyl)phenoxy)-23-(pyridin-4-yloxy)phthalocyanine (6) and Co(II) 2,9,16,24-tetrakis(4-(tert-butyl)phenoxy)phthalocyanine (7) were synthesized for the first time and studied for corrosion inhibition. The reported ClGa(III) tetrakis(benzo[d]thiazol-2-yl-thio)phthalocyaninine (1), ClGa(III) tetrakis(benzo[d]thiazol-2ylphenoxy)phthalocyanine (2), ClGa(III) tetrakis-4-(hexadecane-1,2-dioxyl)-bis(phthalocyanine) (3) and ClGa(III) tetrakis-4,4′-((4-(benzo[d]thiazol-2-yl)-1,2-bis(phenoxy)-bis(phthalocyanine) (4) were also employed for corrosion inhibition of Al in HCl. Corrosion inhibition measurements using electrochemical techniques showed that increased π conjugation caused (1) to (2) to outperform (1a) and (2a) respectively as aluminium corrosion inhibitors in 1.0 M hydrochloric acid. For similar reason, (4) outperformed 2. (1) and (2) were successfully electrodeposited onto aluminium for corrosion retardation in 1.0 M hydrochloric acid solution. Measurements obtained from electrochemical impedance spectroscopy gave corrosion inhibition efficiency values of 82% for 1 and 86% for 2 in 1.0 M hydrochloric acid solution and showed that electrodeposited phthalocyanines have enhanced aluminium corrosion retardation than when in solution. The use of reduced graphene oxide nanosheets (rGONS) alone as aluminium corrosion inhibitor is discouraged because of poor aluminium corrosion inhibition in 1M HCl. However, synergistic effects were observed when rGONS was mixed each with (4) and (3). (5_H2), (5_Ga) and (5_Co) decreased aluminium corrosion in 1M HCl and observation was that the heavier the atom the more decreased the protection and the free base performed best of the three. Studied tertbutylphenoxy-derived CoPcs (6 and 7) exhibited good aluminium corrosion inhibition properties in studied acidic solution and the unsymmetric CoPc (6) which has more heteroatoms, gave better performance. Quantum chemical calculations involved the use of density functional theoretical (DFT) approaches and gave results which corroborated with experimental findings. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Nnaji, Nnaemeka Joshua
- Date: 2022-04-08
- Subjects: Aluminum Corrosion , Electrochemistry , Phthalocyanines , Corrosion and anti-corrosives , Protective coatings , Density functionals
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294643 , vital:57240 , DOI 10.21504/10962/294643
- Description: Metal deterioration over time is a process known as corrosion, an electrochemical process, which can occur by surface chemical actions on metals by its environment. Metal corrosion have great economic, security, and environmental consequences, and its control is a major research area in corrosion science. Amongst the different corrosion protecting approaches, the use of corrosion inhibitors and protective coatings have attracted enormous research interest in this area of scholasticism. This has necessitated the computational and electrochemical investigations of aluminium corrosion inhibitive potentials of some compounds in 1M HCl. Metal free (5_H2), ClGa(III) (5_Ga) and Co(II) (5_Co) tetrakis(4-acetamidophenoxy)phthalocyanines as well as Co(II) 2,9,16-tris(4-(tert-butyl)phenoxy)-23-(pyridin-4-yloxy)phthalocyanine (6) and Co(II) 2,9,16,24-tetrakis(4-(tert-butyl)phenoxy)phthalocyanine (7) were synthesized for the first time and studied for corrosion inhibition. The reported ClGa(III) tetrakis(benzo[d]thiazol-2-yl-thio)phthalocyaninine (1), ClGa(III) tetrakis(benzo[d]thiazol-2ylphenoxy)phthalocyanine (2), ClGa(III) tetrakis-4-(hexadecane-1,2-dioxyl)-bis(phthalocyanine) (3) and ClGa(III) tetrakis-4,4′-((4-(benzo[d]thiazol-2-yl)-1,2-bis(phenoxy)-bis(phthalocyanine) (4) were also employed for corrosion inhibition of Al in HCl. Corrosion inhibition measurements using electrochemical techniques showed that increased π conjugation caused (1) to (2) to outperform (1a) and (2a) respectively as aluminium corrosion inhibitors in 1.0 M hydrochloric acid. For similar reason, (4) outperformed 2. (1) and (2) were successfully electrodeposited onto aluminium for corrosion retardation in 1.0 M hydrochloric acid solution. Measurements obtained from electrochemical impedance spectroscopy gave corrosion inhibition efficiency values of 82% for 1 and 86% for 2 in 1.0 M hydrochloric acid solution and showed that electrodeposited phthalocyanines have enhanced aluminium corrosion retardation than when in solution. The use of reduced graphene oxide nanosheets (rGONS) alone as aluminium corrosion inhibitor is discouraged because of poor aluminium corrosion inhibition in 1M HCl. However, synergistic effects were observed when rGONS was mixed each with (4) and (3). (5_H2), (5_Ga) and (5_Co) decreased aluminium corrosion in 1M HCl and observation was that the heavier the atom the more decreased the protection and the free base performed best of the three. Studied tertbutylphenoxy-derived CoPcs (6 and 7) exhibited good aluminium corrosion inhibition properties in studied acidic solution and the unsymmetric CoPc (6) which has more heteroatoms, gave better performance. Quantum chemical calculations involved the use of density functional theoretical (DFT) approaches and gave results which corroborated with experimental findings. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
Singlet oxygen and optical limiting applications of BODIPYs and other molecular dyes
- Authors: May, Aviwe Khanya
- Date: 2022-04-08
- Subjects: Dyes and dyeing Chemistry , Phthalocyanines , Photochemotherapy , Active oxygen , Nonlinear optics , Time-dependent density functional theory , Photochemistry
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294618 , vital:57238 , DOI 10.21504/10962/294620
- Description: A series of structurally diverse novel and previously synthesized BODIPY core dyes are synthesized and characterized in this thesis. These BODIPYs were synthesized using 2-methylpyrrole, 2-ethylpyrrole, 2,4-dimethylpyrrole and 3-ethyl-2,4-dimethylpyrrole as the starting pyrroles. The combination of different pyrroles with the same aldehyde results in BODIPY core dyes that are structural analogues. These core dyes were used as precursors to synthesise halogenated BODIPYs and novel styrylBODIPY dyes, which were successfully characterized using FT-IR and 1H NMR spectroscopy. The halogenated BODIPY core dyes and the styrylBODIPY dyes were also characterized using MALDI-TOF mass spectrometry. The introduction of heavy atoms on the BODIPY core leads to a red shift of the main spectral. In the presence of styryl groups, the main spectral band red shifts to the far red end of the visible region. As expected, the halogenated BODIPY core dyes also had moderate singlet oxygen quantum yields. These halogenated core dyes were found to be suitable as photosensitizers as all the dyes reduced bacterial viability to below 50% during photodynamic antimicrobial chemotherapy (PACT) studies against Staphylococcus aureus. The structure-property relationships studied demonstrate that the presence of protons rather than methyls at the 1,7-positions or iodines at the 2,6-positions results in more favorable PACT activity. This is likely to be related to the greater ability of the meso-aryl to rotate into the plane of the dipyrromethene ligand and suggests that there should be a stronger focus on dyes of this type in future studies in this field. During nonlinear optical (NLO) studies, all the styrylBODIPYs exhibited favorable reverse saturable absorption (RSA) responses. In the absence of methyl groups at the 1,7-positions, the meso-aryl ring lies closer to the π-system of the BODIPY core, enhancing donor (D)–π–acceptor (A) properties and resulting in slightly enhanced optical limiting (OL) parameters. Additionally, there is no evidence that the introduction of heavy atoms at the 2,6-positions significantly enhances OL properties. In a similar manner, alkyl substituents at these positions also do not significantly enhance OL properties; this was studied for the first time using 15 with ethyl groups at the 2,6-positions. The combination of z-scan data and transient spectroscopy for 16 demonstrated that the main mechanism responsible for the NLO properties of nonhalogenated BODIPY dyes is one-photon absorption from the ground state followed by ESA in the singlet manifold. From the NLO studies of 25, OL parameters of 1,3,5-tristyrylBODIPY dyes were found to be similar in magnitude to properties of distyrylBODIPY dyes, but to have less favorable optical properties for OL applications. The OL properties of scandium phthalocyanines were assessed for the first time, since the Sc(III) ion, unusually for a first row transition metal ion, is known to readily form sandwich complexes. The presence of a Sc(III) ion does not significantly enhance the OL properties of phthalocyanines relative to those of rare earth metal ions that also form complexes of this type. Because BODIPYs and phthalocyanines typically absorb significantly in the visible region, transparent PBC polymer thin films of disilane-bridged compounds with minimal absorption in this region were studied and exhibited an excellent RSA response. These compounds may be useful in the design of OL materials that can protect the human eye. The optimized geometries and spectroscopic properties of selected BODIPYs were studied. As expected, the presence of bromine, iodine, ethyl and styryl groups at different positions of the BODIPY core leads to a narrowing of the HOMO–LUMO band gap, which results in a red-shift of the main spectral band. Partial atomic charges have also been calculated for some of the styrylBODIPY dyes studied for application in OL, and electrostatic potential energy maps were also visualized to better assess how the dipole moment of BODIPY dyes can be modulated since this can affect the OL properties. For all the BODIPYs studied, the electronegativity of the atoms present influences charge distribution on the BODIPY structure. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: May, Aviwe Khanya
- Date: 2022-04-08
- Subjects: Dyes and dyeing Chemistry , Phthalocyanines , Photochemotherapy , Active oxygen , Nonlinear optics , Time-dependent density functional theory , Photochemistry
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/294618 , vital:57238 , DOI 10.21504/10962/294620
- Description: A series of structurally diverse novel and previously synthesized BODIPY core dyes are synthesized and characterized in this thesis. These BODIPYs were synthesized using 2-methylpyrrole, 2-ethylpyrrole, 2,4-dimethylpyrrole and 3-ethyl-2,4-dimethylpyrrole as the starting pyrroles. The combination of different pyrroles with the same aldehyde results in BODIPY core dyes that are structural analogues. These core dyes were used as precursors to synthesise halogenated BODIPYs and novel styrylBODIPY dyes, which were successfully characterized using FT-IR and 1H NMR spectroscopy. The halogenated BODIPY core dyes and the styrylBODIPY dyes were also characterized using MALDI-TOF mass spectrometry. The introduction of heavy atoms on the BODIPY core leads to a red shift of the main spectral. In the presence of styryl groups, the main spectral band red shifts to the far red end of the visible region. As expected, the halogenated BODIPY core dyes also had moderate singlet oxygen quantum yields. These halogenated core dyes were found to be suitable as photosensitizers as all the dyes reduced bacterial viability to below 50% during photodynamic antimicrobial chemotherapy (PACT) studies against Staphylococcus aureus. The structure-property relationships studied demonstrate that the presence of protons rather than methyls at the 1,7-positions or iodines at the 2,6-positions results in more favorable PACT activity. This is likely to be related to the greater ability of the meso-aryl to rotate into the plane of the dipyrromethene ligand and suggests that there should be a stronger focus on dyes of this type in future studies in this field. During nonlinear optical (NLO) studies, all the styrylBODIPYs exhibited favorable reverse saturable absorption (RSA) responses. In the absence of methyl groups at the 1,7-positions, the meso-aryl ring lies closer to the π-system of the BODIPY core, enhancing donor (D)–π–acceptor (A) properties and resulting in slightly enhanced optical limiting (OL) parameters. Additionally, there is no evidence that the introduction of heavy atoms at the 2,6-positions significantly enhances OL properties. In a similar manner, alkyl substituents at these positions also do not significantly enhance OL properties; this was studied for the first time using 15 with ethyl groups at the 2,6-positions. The combination of z-scan data and transient spectroscopy for 16 demonstrated that the main mechanism responsible for the NLO properties of nonhalogenated BODIPY dyes is one-photon absorption from the ground state followed by ESA in the singlet manifold. From the NLO studies of 25, OL parameters of 1,3,5-tristyrylBODIPY dyes were found to be similar in magnitude to properties of distyrylBODIPY dyes, but to have less favorable optical properties for OL applications. The OL properties of scandium phthalocyanines were assessed for the first time, since the Sc(III) ion, unusually for a first row transition metal ion, is known to readily form sandwich complexes. The presence of a Sc(III) ion does not significantly enhance the OL properties of phthalocyanines relative to those of rare earth metal ions that also form complexes of this type. Because BODIPYs and phthalocyanines typically absorb significantly in the visible region, transparent PBC polymer thin films of disilane-bridged compounds with minimal absorption in this region were studied and exhibited an excellent RSA response. These compounds may be useful in the design of OL materials that can protect the human eye. The optimized geometries and spectroscopic properties of selected BODIPYs were studied. As expected, the presence of bromine, iodine, ethyl and styryl groups at different positions of the BODIPY core leads to a narrowing of the HOMO–LUMO band gap, which results in a red-shift of the main spectral band. Partial atomic charges have also been calculated for some of the styrylBODIPY dyes studied for application in OL, and electrostatic potential energy maps were also visualized to better assess how the dipole moment of BODIPY dyes can be modulated since this can affect the OL properties. For all the BODIPYs studied, the electronegativity of the atoms present influences charge distribution on the BODIPY structure. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
Synthesis and evaluation of the medicinal potential of novel 4-hydroxycoumarin derivatives
- Authors: Manyeruke, Meloddy Hlatini
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164458 , vital:41120 , doi:10.21504/10962/164458
- Description: This research has focused on the synthesis and biological evaluation of a broad range of compounds characterised by the presence of the pharmacologically significant 4-hydroxycoumalin scaffold. The compounds were designed to contain additional pharmachophoric centres to enhance bioactivity and generate lead compounds with dualaction potential. The use of 4-hydroxycoumarin as the primary synthon enabled access to various series of 4-hydroxycoumarin conjugates, the reactive 3-position on the 4-hydroxycoumarin moiety being exploited for regioselective construction of the targeted compounds in several steps. Some of the reactants required in the construction of these compounds were specially synthesised and included propargyloxy benzaldehydes, benzyloxy benzaldehydes and 2,3-dihydroxysuccino-dihydride. Overall, eight different families of novel compounds were accessed, comprising conjugates of 4-hydroxycoumarin with bisethylidenesuccinohyrazide, trifluoroacetamide, amino, benzyloxyphenyl-iminoethyl, benzylidenehyrazinyl-thiazoyl, benzylidenehydrazonoethyl, propargyloxybenzylidenehydrazonoethyl and phenylacryloyl moieties using protocols that required minimal work-up and purification. The eighty novel compounds synthesised in the study were fully characterised using HMRS and advanced NMR techniques. Cytotoxicity, HIV-1 IN and PR inhibitory, and antitrypanosomal, antimalarial and anti-Mtb assays were conducted on the synthesised coumarin derivatives. Several compounds exhibited activity against HIV-1 IN, the most potent being a bis-ethylidenesuccinohyrazide with an IC50 value of 3.5 μM. Various compounds exhibited anti-malarial activity (% pLDH viability in the range 62-77%), anti-trypanosomal activity (the most potent with an IC50 = 0.9 μM against T.b. brucei) and a measure of anti-Mtb activity. Apart from two chalconyl derivatives, none of the synthesised compounds exhibited significant cytotoxicity. Conflicting results were obtained from the in silico docking studies; in some cases supporting the observed in vitro assay data while, in others, exhibiting no correlation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2022-04-08
- Authors: Manyeruke, Meloddy Hlatini
- Date: 2022-04-08
- Subjects: Uncatalogued
- Language: English
- Type: Academic theses , Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/164458 , vital:41120 , doi:10.21504/10962/164458
- Description: This research has focused on the synthesis and biological evaluation of a broad range of compounds characterised by the presence of the pharmacologically significant 4-hydroxycoumalin scaffold. The compounds were designed to contain additional pharmachophoric centres to enhance bioactivity and generate lead compounds with dualaction potential. The use of 4-hydroxycoumarin as the primary synthon enabled access to various series of 4-hydroxycoumarin conjugates, the reactive 3-position on the 4-hydroxycoumarin moiety being exploited for regioselective construction of the targeted compounds in several steps. Some of the reactants required in the construction of these compounds were specially synthesised and included propargyloxy benzaldehydes, benzyloxy benzaldehydes and 2,3-dihydroxysuccino-dihydride. Overall, eight different families of novel compounds were accessed, comprising conjugates of 4-hydroxycoumarin with bisethylidenesuccinohyrazide, trifluoroacetamide, amino, benzyloxyphenyl-iminoethyl, benzylidenehyrazinyl-thiazoyl, benzylidenehydrazonoethyl, propargyloxybenzylidenehydrazonoethyl and phenylacryloyl moieties using protocols that required minimal work-up and purification. The eighty novel compounds synthesised in the study were fully characterised using HMRS and advanced NMR techniques. Cytotoxicity, HIV-1 IN and PR inhibitory, and antitrypanosomal, antimalarial and anti-Mtb assays were conducted on the synthesised coumarin derivatives. Several compounds exhibited activity against HIV-1 IN, the most potent being a bis-ethylidenesuccinohyrazide with an IC50 value of 3.5 μM. Various compounds exhibited anti-malarial activity (% pLDH viability in the range 62-77%), anti-trypanosomal activity (the most potent with an IC50 = 0.9 μM against T.b. brucei) and a measure of anti-Mtb activity. Apart from two chalconyl derivatives, none of the synthesised compounds exhibited significant cytotoxicity. Conflicting results were obtained from the in silico docking studies; in some cases supporting the observed in vitro assay data while, in others, exhibiting no correlation. , Thesis (PhD) -- Faculty of Science, Chemistry, 2020
- Full Text:
- Date Issued: 2022-04-08
The systematic assembly of prostate specific antigen electrochemical sensors based on asymmetric Co(II) phthalocyanines, graphitic quantum dots and an aptamer
- Authors: Nxele, Siphesihle Robin
- Date: 2022-04-08
- Subjects: Prostate-specific antigen , Electrochemical sensors , Phthalocyanines , Quantum dots , Co(II) phthalocyanines , Aptamer
- Language: English
- Type: Doctoral thesis , text
- Identifier: http://hdl.handle.net/10962/232893 , vital:50035 , DOI 10.21504/10962/232893
- Description: The need for low-cost, efficient and simple diagnostic tools has led to more research going into this subject, with the aim of making such medical devices more accessible where they are needed. This has led to more researchers developing point-of-care devices for this purpose worldwide, by sensor fabrication. This thesis focuses on electrochemical sensor development for the early diagnosis of prostate cancer. It is common knowledge that prostate cancer is one of the most prevalent carcinomas that have claimed lives due to late diagnosis where even the most invasive treatments have failed. For this reason, development of early detection devices that can even be used in the comfort of home is necessary and quite crucial. Electrochemical sensors have gained much attention due to their ease of fabrication, cost effectiveness, simplicity, ease of use and high efficiency. Using nanocomposites as modifiers has also become popular as they provide greater stability and improve detection limits when used together with biomolecules. With that said, the work reported herein has combined nanocomposites of graphenebased quantum dots, gold nanoparticles, phthalocyanines and an aptamer in order to fabricate aptasensors for the electrochemical detection of prostate cancer biomarker. The aptamer is specifically designed to bind to the biomarker, and the nanocomposites are expected to enhance current output thus lowering detection limits and increasing stability and efficiency. Reproducible results are also expected. Prior to the detection of the prostate cancer biomarker, the quantum dots-phthalocyanine nanohybrids were used to detect L-cysteine, which is an amino acid, in order to verify the synergistic effects as electrode modifiers that lead to the enhancement of current output. This increase in current output is then v exploited for the improvement of aptasensor functionality upon incorporation of the aptamer, for the detection of prostate specific antigen. The research in this thesis has been carried out with the intention of contributing to the world of medical research, more so because of the ever-increasing need for medical care to become accessible to all and not only to those who can afford expensive technologies and treatments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
- Authors: Nxele, Siphesihle Robin
- Date: 2022-04-08
- Subjects: Prostate-specific antigen , Electrochemical sensors , Phthalocyanines , Quantum dots , Co(II) phthalocyanines , Aptamer
- Language: English
- Type: Doctoral thesis , text
- Identifier: http://hdl.handle.net/10962/232893 , vital:50035 , DOI 10.21504/10962/232893
- Description: The need for low-cost, efficient and simple diagnostic tools has led to more research going into this subject, with the aim of making such medical devices more accessible where they are needed. This has led to more researchers developing point-of-care devices for this purpose worldwide, by sensor fabrication. This thesis focuses on electrochemical sensor development for the early diagnosis of prostate cancer. It is common knowledge that prostate cancer is one of the most prevalent carcinomas that have claimed lives due to late diagnosis where even the most invasive treatments have failed. For this reason, development of early detection devices that can even be used in the comfort of home is necessary and quite crucial. Electrochemical sensors have gained much attention due to their ease of fabrication, cost effectiveness, simplicity, ease of use and high efficiency. Using nanocomposites as modifiers has also become popular as they provide greater stability and improve detection limits when used together with biomolecules. With that said, the work reported herein has combined nanocomposites of graphenebased quantum dots, gold nanoparticles, phthalocyanines and an aptamer in order to fabricate aptasensors for the electrochemical detection of prostate cancer biomarker. The aptamer is specifically designed to bind to the biomarker, and the nanocomposites are expected to enhance current output thus lowering detection limits and increasing stability and efficiency. Reproducible results are also expected. Prior to the detection of the prostate cancer biomarker, the quantum dots-phthalocyanine nanohybrids were used to detect L-cysteine, which is an amino acid, in order to verify the synergistic effects as electrode modifiers that lead to the enhancement of current output. This increase in current output is then v exploited for the improvement of aptasensor functionality upon incorporation of the aptamer, for the detection of prostate specific antigen. The research in this thesis has been carried out with the intention of contributing to the world of medical research, more so because of the ever-increasing need for medical care to become accessible to all and not only to those who can afford expensive technologies and treatments. , Thesis (PhD) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-08
Antimalarial activity of quinoline thiosemicarbazones: synthesis and antiplasmodial evaluation
- Nqeno, Lukhanyiso Khanyisile
- Authors: Nqeno, Lukhanyiso Khanyisile
- Date: 2022-04-06
- Subjects: Antimalarials , Quinoline , Thiosemicarbazones , Malaria Chemotherapy , Plasmodium falciparum , Malaria Africa, Sub-Saharan , Iron chelates Therapeutic use
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/291292 , vital:56841
- Description: Africa is one of the regions that is most affected by malaria, as 90% of all malaria deaths occur in sub-saharan Africa. Malaria is a life threatening disease responsible for an estimated 800000 deaths each year, the majority of these deaths occurred in children under the age of five. The disease is a mosquito-borne, and it is transmitted to humans by the female Anopheles mosquito. The parasite responsible for this disease belong to the Plasmodium genus with Plasmodium falciparum causing the most severe cases of the disease in humans. The most widely available anti-malarials were designed to specifically target the pathogenic blood stage in humans, however, in order to completely eradicate malaria there is a need for the development of medicines that not only target the pathogenic blood stage of the parasite but also block parasite transmission and eliminate asymptomatic and cryptic hepatic forms of the parasite. Iron chelators have recently gained importance as potent antimalarials, to cause infection nearly all protozoa obtain growth essential iron from their hosts. Iron is required for the development of the parasite. Deprivation of utilizable iron by chelation is a proficient approach to arrest parasite growth and associated infection. Thiosemicarbazones are known iron chelating agents by bonding through the sulfur and azomethine nitrogen atoms. This study is aimed at the identification of thiosemicarbazone based derivatives as possible antimalarial agents. Due to their iron chelation abilities there has been increasing interest in the investigation of thiosemicarbazones as possible antimalarials. During the course of this project, several thiosemicarbazone derivatives were synthesized and their structure confirmed using routine analytical techniques (NMR, FTIR, and HRMS). The synthesized compounds were evaluated in vitro against the chloroquine sensitive strain (3D7) of P. falciparum for antimarial activity. The compounds were also evaluated agsinst Hela cells for overt cytotoxicity. The compounds generally showed poor antimalarial activity. One compound (LKN11) was identified to possess intrinsic and moderate antimalarial activity of 6.6 μM. The compounds were generally not cytotoxic against Hela cell at concentrations of up to 20 μM, with only compound LKN10 showing modest cytotoxic activity of 9.5 μM. This research went on to identify two thiosemicarbazone based derivatives which had a significant effect on HeLa and pLDH cells. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Nqeno, Lukhanyiso Khanyisile
- Date: 2022-04-06
- Subjects: Antimalarials , Quinoline , Thiosemicarbazones , Malaria Chemotherapy , Plasmodium falciparum , Malaria Africa, Sub-Saharan , Iron chelates Therapeutic use
- Language: English
- Type: Academic theses , Master's theses , text
- Identifier: http://hdl.handle.net/10962/291292 , vital:56841
- Description: Africa is one of the regions that is most affected by malaria, as 90% of all malaria deaths occur in sub-saharan Africa. Malaria is a life threatening disease responsible for an estimated 800000 deaths each year, the majority of these deaths occurred in children under the age of five. The disease is a mosquito-borne, and it is transmitted to humans by the female Anopheles mosquito. The parasite responsible for this disease belong to the Plasmodium genus with Plasmodium falciparum causing the most severe cases of the disease in humans. The most widely available anti-malarials were designed to specifically target the pathogenic blood stage in humans, however, in order to completely eradicate malaria there is a need for the development of medicines that not only target the pathogenic blood stage of the parasite but also block parasite transmission and eliminate asymptomatic and cryptic hepatic forms of the parasite. Iron chelators have recently gained importance as potent antimalarials, to cause infection nearly all protozoa obtain growth essential iron from their hosts. Iron is required for the development of the parasite. Deprivation of utilizable iron by chelation is a proficient approach to arrest parasite growth and associated infection. Thiosemicarbazones are known iron chelating agents by bonding through the sulfur and azomethine nitrogen atoms. This study is aimed at the identification of thiosemicarbazone based derivatives as possible antimalarial agents. Due to their iron chelation abilities there has been increasing interest in the investigation of thiosemicarbazones as possible antimalarials. During the course of this project, several thiosemicarbazone derivatives were synthesized and their structure confirmed using routine analytical techniques (NMR, FTIR, and HRMS). The synthesized compounds were evaluated in vitro against the chloroquine sensitive strain (3D7) of P. falciparum for antimarial activity. The compounds were also evaluated agsinst Hela cells for overt cytotoxicity. The compounds generally showed poor antimalarial activity. One compound (LKN11) was identified to possess intrinsic and moderate antimalarial activity of 6.6 μM. The compounds were generally not cytotoxic against Hela cell at concentrations of up to 20 μM, with only compound LKN10 showing modest cytotoxic activity of 9.5 μM. This research went on to identify two thiosemicarbazone based derivatives which had a significant effect on HeLa and pLDH cells. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
Large and multi scale mechanistic modeling of Diels-Alder reactions
- Authors: Isamura, Bienfait Kabuyaya
- Date: 2022-04-06
- Subjects: Computational chemistry , Diels-Alder reaction , Python (Computer program language) , Reaction force theory , Fullerenes , Diolefins , AMADAR (Automated workflow for Mechanistic Analysis of Diels-Alder Reactions , ONIOM
- Language: English
- Type: Master's thesis , text
- Identifier: http://hdl.handle.net/10962/232317 , vital:49981
- Description: The [4+2] cycloaddition reaction between conjugated dienes and substituted alkenes is known as the Diels-Alder (DA) reaction, in honor of two German chemists, Otto Diels and Kurt Alder, who first reported this marvelous chemical transformation. The DA reaction is one of the most popular reactions in organic chemistry, allowing for the regio- and stereospecific establishment of six-membered rings with up to four stereogenic centers. This pericyclic reaction has found many applications in areas as diverse as natural products chemistry, polymer chemistry, and agrochemistry. Over the past decades, the mechanism of the Diels-Alder (DA) reaction has been the subject of numerous studies, dealing with questions as diverse as the mechanistic pathway, the synchronicity, the use of catalysts, the effect of solvents and salts, etc. On the other hand, as an example, fullerenes (and particularly [60] fullerene) have been found to act as good dienophiles in DA reactions to the extent that many functionalized fullerenes with interesting applications are still synthesized by reacting C60 with dienes. However, despite the very abundant literature about the mechanism of the DA reaction, some pertinent questions have been still pending, including, without being restricted to, the prediction of transition state (TS) geometries and the modeling of DA reactions involving large systems, such as those of C60 fullerene. It must be emphasized that TSs are not easy to predict and the main reason is that many existing algorithms require that the search is initiated from a good starting point (guess TS), which must be very similar to the actual TS. This problem is even more difficult when many TSs are to be located as may be the case in large-scale studies. Moreover, due to the large size of the C60 molecule, the usage of accurate high-level computational methods in the investigation of its reactivity towards dienes is computationally costly, implying the need to find the best threshold between accuracy and computational cost. Therefore, the present study was carried out to contribute to solving the problems of large-scale prediction of DA transition state geometries and the multi-scale modeling of C60 fullerene DA reactions. To address the first problem (large-scale prediction of TSs), we have developed a python program named “AMADAR”, which predicts an unlimited number of DA transition states, using only the SMILES strings of the cycloadducts. AMADAR is customizable and allows for the description of intramolecular DA reactions as well as systems resulting in competing paths. In addition, The AMADAR tool contains two separate modules that perform reaction force analyses and atomic decomposition of energy derivatives from the predicted Intrinsic Reaction Coordinates (IRC) paths. The performance of AMADAR was assessed using 2000 DA cycloadducts and showed a success rate of ~ 95%. Most of the errors were due to basis set inconsistencies or convergence issues that we are still working on. Furthermore, a set of 150 IRC paths generated by the AMADAR program were analyzed to get insight into the (a)synchronicity of DA reactions. This investigation confirmed that the reaction force constant 𝜅 (second derivatives of the system energy with respect to the reaction coordinate) was a good indicator of synchronicity in DA reactions. A close inspection of the profile of 𝜅 has enabled us to propose an alternative classification of DA reactions based on their synchronicity degree, in terms of (quasi)-synchronous, moderate asynchronous, asynchronous, and likely two-steps DA reactions. Natural population analyses seemed to indicate that the global maximum of the reaction force constant could be identified with the formation of all the bonds in the reaction site. Finally, the atomic resolution of energy derivatives suggested that the mechanism of the DA reaction involves two inner elementary processes associated with the formation of each C-C bond. A striking mechanistic difference between synchronous and asynchronous DA reactions emerging from this study is that, in asynchronous reactions, the driving and retarding forces are mainly caused by the fast and slow-forming bonds (elementary process) respectively, while in the case of synchronous ones both elementary processes retard and drive the process concomitantly and equivalently. Regarding the DA reaction of C60 fullerene that was considered to illustrate the problem of multiscale modeling, we have constructed 12 ONIOM2 and 10 ONIOM3 models combining five semi-empirical methods (AM1, PM3, PM3MM, PDDG, PM6) and the LDA(SVWN) functional in conjunction with the B3LYP/6-31G(d) level. Then, their accuracy and efficiency were assessed in comparison with the pure B3LYP/6-31G(d) level considering first the DA reaction between C60 and cyclopentadiene whose experimental data are available. Further, different DFT functionals were employed in place of the B3LYP functional to describe the higher-layer of the best ONIOM partition, and the results obtained were compared to experimental data. At this step, the ONIOM2(M06-2X/6-31 G(d): SVWN/STO-3G) model, where the higher layer encompasses the diene and pyracyclene portion of C60, was found to provide the best tradeoff between accuracy and cost, with respect to experimental data. This model showed errors lower than 2.6 and 2.0 kcal/mol for the estimation of the activation and reaction enthalpies respectively. We have also demonstrated, by comparing several ONIOM2(DFT/6-31G(d): SVWN/STO-3G) models, the importance of dispersion corrections in the accurate estimation of reaction and activation energies. Finally, we have considered a set of 21 dienes, including anthracene, 1,3-butadiene, 1,3-cyclopentadiene, furan, thiophene, selenothiophene, pyrrole and their mono-cyano and hydroxyl derivatives to get insight into the DA reaction of C60 using the best ONIOM2(M06-2X/6-31 G(d): SVWN/STO-3G) model. For a given diene and its derivatives, the analysis of frontier molecular orbitals provides a consistent explanation for the substituent effect on the activation barrier. It revealed that electron-donating (withdrawing) groups such as -OH (–CN) cut down on the activation barrier of the reaction by lowering (extending) of the HOMOdiene – LUMOC60 gap and consequently enhancing (weakening) the interaction between the two reactants. Further, the decomposition of the activation energy into the strain and interaction components suggested that, for a given diene, electron-donating groups (here –OH) diminish the height of the activation barrier not only by favoring the attractive interaction between the diene and C60, but also by reducing the strain energy of the system; the opposite effect is observed for electron-withdrawing groups (here –CN). In contrast with some previous findings on typical DA reactions, we could not infer any general rule applicable to the entire dataset for the prediction of activation energies because the latter does not correlate well with either of the TS polarity, electrophilicity of the diene, or the reaction energy. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Isamura, Bienfait Kabuyaya
- Date: 2022-04-06
- Subjects: Computational chemistry , Diels-Alder reaction , Python (Computer program language) , Reaction force theory , Fullerenes , Diolefins , AMADAR (Automated workflow for Mechanistic Analysis of Diels-Alder Reactions , ONIOM
- Language: English
- Type: Master's thesis , text
- Identifier: http://hdl.handle.net/10962/232317 , vital:49981
- Description: The [4+2] cycloaddition reaction between conjugated dienes and substituted alkenes is known as the Diels-Alder (DA) reaction, in honor of two German chemists, Otto Diels and Kurt Alder, who first reported this marvelous chemical transformation. The DA reaction is one of the most popular reactions in organic chemistry, allowing for the regio- and stereospecific establishment of six-membered rings with up to four stereogenic centers. This pericyclic reaction has found many applications in areas as diverse as natural products chemistry, polymer chemistry, and agrochemistry. Over the past decades, the mechanism of the Diels-Alder (DA) reaction has been the subject of numerous studies, dealing with questions as diverse as the mechanistic pathway, the synchronicity, the use of catalysts, the effect of solvents and salts, etc. On the other hand, as an example, fullerenes (and particularly [60] fullerene) have been found to act as good dienophiles in DA reactions to the extent that many functionalized fullerenes with interesting applications are still synthesized by reacting C60 with dienes. However, despite the very abundant literature about the mechanism of the DA reaction, some pertinent questions have been still pending, including, without being restricted to, the prediction of transition state (TS) geometries and the modeling of DA reactions involving large systems, such as those of C60 fullerene. It must be emphasized that TSs are not easy to predict and the main reason is that many existing algorithms require that the search is initiated from a good starting point (guess TS), which must be very similar to the actual TS. This problem is even more difficult when many TSs are to be located as may be the case in large-scale studies. Moreover, due to the large size of the C60 molecule, the usage of accurate high-level computational methods in the investigation of its reactivity towards dienes is computationally costly, implying the need to find the best threshold between accuracy and computational cost. Therefore, the present study was carried out to contribute to solving the problems of large-scale prediction of DA transition state geometries and the multi-scale modeling of C60 fullerene DA reactions. To address the first problem (large-scale prediction of TSs), we have developed a python program named “AMADAR”, which predicts an unlimited number of DA transition states, using only the SMILES strings of the cycloadducts. AMADAR is customizable and allows for the description of intramolecular DA reactions as well as systems resulting in competing paths. In addition, The AMADAR tool contains two separate modules that perform reaction force analyses and atomic decomposition of energy derivatives from the predicted Intrinsic Reaction Coordinates (IRC) paths. The performance of AMADAR was assessed using 2000 DA cycloadducts and showed a success rate of ~ 95%. Most of the errors were due to basis set inconsistencies or convergence issues that we are still working on. Furthermore, a set of 150 IRC paths generated by the AMADAR program were analyzed to get insight into the (a)synchronicity of DA reactions. This investigation confirmed that the reaction force constant 𝜅 (second derivatives of the system energy with respect to the reaction coordinate) was a good indicator of synchronicity in DA reactions. A close inspection of the profile of 𝜅 has enabled us to propose an alternative classification of DA reactions based on their synchronicity degree, in terms of (quasi)-synchronous, moderate asynchronous, asynchronous, and likely two-steps DA reactions. Natural population analyses seemed to indicate that the global maximum of the reaction force constant could be identified with the formation of all the bonds in the reaction site. Finally, the atomic resolution of energy derivatives suggested that the mechanism of the DA reaction involves two inner elementary processes associated with the formation of each C-C bond. A striking mechanistic difference between synchronous and asynchronous DA reactions emerging from this study is that, in asynchronous reactions, the driving and retarding forces are mainly caused by the fast and slow-forming bonds (elementary process) respectively, while in the case of synchronous ones both elementary processes retard and drive the process concomitantly and equivalently. Regarding the DA reaction of C60 fullerene that was considered to illustrate the problem of multiscale modeling, we have constructed 12 ONIOM2 and 10 ONIOM3 models combining five semi-empirical methods (AM1, PM3, PM3MM, PDDG, PM6) and the LDA(SVWN) functional in conjunction with the B3LYP/6-31G(d) level. Then, their accuracy and efficiency were assessed in comparison with the pure B3LYP/6-31G(d) level considering first the DA reaction between C60 and cyclopentadiene whose experimental data are available. Further, different DFT functionals were employed in place of the B3LYP functional to describe the higher-layer of the best ONIOM partition, and the results obtained were compared to experimental data. At this step, the ONIOM2(M06-2X/6-31 G(d): SVWN/STO-3G) model, where the higher layer encompasses the diene and pyracyclene portion of C60, was found to provide the best tradeoff between accuracy and cost, with respect to experimental data. This model showed errors lower than 2.6 and 2.0 kcal/mol for the estimation of the activation and reaction enthalpies respectively. We have also demonstrated, by comparing several ONIOM2(DFT/6-31G(d): SVWN/STO-3G) models, the importance of dispersion corrections in the accurate estimation of reaction and activation energies. Finally, we have considered a set of 21 dienes, including anthracene, 1,3-butadiene, 1,3-cyclopentadiene, furan, thiophene, selenothiophene, pyrrole and their mono-cyano and hydroxyl derivatives to get insight into the DA reaction of C60 using the best ONIOM2(M06-2X/6-31 G(d): SVWN/STO-3G) model. For a given diene and its derivatives, the analysis of frontier molecular orbitals provides a consistent explanation for the substituent effect on the activation barrier. It revealed that electron-donating (withdrawing) groups such as -OH (–CN) cut down on the activation barrier of the reaction by lowering (extending) of the HOMOdiene – LUMOC60 gap and consequently enhancing (weakening) the interaction between the two reactants. Further, the decomposition of the activation energy into the strain and interaction components suggested that, for a given diene, electron-donating groups (here –OH) diminish the height of the activation barrier not only by favoring the attractive interaction between the diene and C60, but also by reducing the strain energy of the system; the opposite effect is observed for electron-withdrawing groups (here –CN). In contrast with some previous findings on typical DA reactions, we could not infer any general rule applicable to the entire dataset for the prediction of activation energies because the latter does not correlate well with either of the TS polarity, electrophilicity of the diene, or the reaction energy. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
The elucidation of nickel and zinc based Metal Organic Frameworks (MOFs) using a polycarboxylate-benzene ligand: a synthetic, spectroscopic, and thermoanalytical study
- Authors: Hodgson, Ivan Mark
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290877 , vital:56795
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
- Authors: Hodgson, Ivan Mark
- Date: 2022-04-06
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/290877 , vital:56795
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04-06
Design, synthesis, characterization and evaluation of Chitosan-based hydrogel for controlled drug delivery system
- Authors: Safari, Justin Bazibuhe
- Date: 2022-04
- Subjects: Chitosan , Drug delivery systems , Drugs Controlled release , Tenofovir , Colloids , Hepatitis B Chemotherapy , Hydrogel
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232182 , vital:49969
- Description: Hepatitis B infection is a deadly infectious disease caused by the hepatitis B virus and is responsible for many deaths every year worldwide. Despite medication and vaccines against hepatitis B infection, it still presents high morbidity and mortality among populations. This is partly due to factors such as a long medication period of the existing treatments, resulting in poor patient compliance and leading to treatment failure. In addition, this situation can be responsible for the observed emerging drug resistance. Hence, novel drugs and drug delivery systems are needed to tackle this matter. Many strategies have been used to develop long-acting drug delivery systems treatment for several infectious diseases. Hydrogel drug delivery systems have shown interesting results as controlled drug delivery systems for several drugs. Therefore, the present study aimed to develop chitosan grafted poly (acrylamide-co-acrylic acid) hydrogel and apply it as a pH-sensitive controlled delivery system of tenofovir disoproxil fumarate (TDF). TDF is a nucleoside reverse transcriptase inhibitor used as first-line treatment of hepatitis B chronic infection and in the treatment of other viral infections. The free-radical polymerization method was utilized to modify chitosan by grafting acrylamide and acrylic acid and using N, N’-methylene bisacrylamide as the crosslinking agent to prepare the hydrogel, followed by an optimization of parameters that could affect the swelling capacity. The prepared chitosan-g-poly(acrylamide-co-acrylic acid) hydrogel was characterized using Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS), Scanning Electron Microscopy (SEM), and was evaluated for cytotoxicity using a HeLa cell assay. TDF was used as a drug model, it was loaded by the swelling equilibrium method, following by the investigation of the release profile of TDF-loaded hydrogel at pH 1.2 and 7.4. A successful synthesis of chitosan grafted poly(acrylamide-co-acrylic acid) hydrogel was confirmed by Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction Spectroscopy (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS) and Scanning Electron Microscopy (SEM). Optimization results showed that the ratio of monomers impacted the swelling ratio of the hydrogel and both the concentration of the crosslinking agent, and the reaction initiator also affected the swelling ratio. The synthesized hydrogels were sensitive to pH and ionic strength. Hydrogel swelling was lower in acidic solutions and higher in neutral and basic solutions and decreased with the increasing ionic strength. Furthermore, SEM results revealed that hydrogel have a rough and fibrous surface structure with numerous pores. Cytotoxicity studies demonstrated that the hydrogel was non-cytotoxic at 50 μg/ml against HeLa cells which suggested a good biocompatibility of the material. TDF was loaded and released from the hydrogels and showed an encapsulation efficiency and drug loading percentage ranging from 81-96% and 8-10%, respectively. TDF release profile was found to be low in buffer solution of pH 1.2 (in the range of 5-10%) and much higher (38-53%) at pH 7.4 within 96 hours. TDF maintained its chemical integrity after release and the hydrogels can therefore be proposed as a new controlled-release drug delivery system for hepatitis B treatment. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04
- Authors: Safari, Justin Bazibuhe
- Date: 2022-04
- Subjects: Chitosan , Drug delivery systems , Drugs Controlled release , Tenofovir , Colloids , Hepatitis B Chemotherapy , Hydrogel
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/232182 , vital:49969
- Description: Hepatitis B infection is a deadly infectious disease caused by the hepatitis B virus and is responsible for many deaths every year worldwide. Despite medication and vaccines against hepatitis B infection, it still presents high morbidity and mortality among populations. This is partly due to factors such as a long medication period of the existing treatments, resulting in poor patient compliance and leading to treatment failure. In addition, this situation can be responsible for the observed emerging drug resistance. Hence, novel drugs and drug delivery systems are needed to tackle this matter. Many strategies have been used to develop long-acting drug delivery systems treatment for several infectious diseases. Hydrogel drug delivery systems have shown interesting results as controlled drug delivery systems for several drugs. Therefore, the present study aimed to develop chitosan grafted poly (acrylamide-co-acrylic acid) hydrogel and apply it as a pH-sensitive controlled delivery system of tenofovir disoproxil fumarate (TDF). TDF is a nucleoside reverse transcriptase inhibitor used as first-line treatment of hepatitis B chronic infection and in the treatment of other viral infections. The free-radical polymerization method was utilized to modify chitosan by grafting acrylamide and acrylic acid and using N, N’-methylene bisacrylamide as the crosslinking agent to prepare the hydrogel, followed by an optimization of parameters that could affect the swelling capacity. The prepared chitosan-g-poly(acrylamide-co-acrylic acid) hydrogel was characterized using Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS), Scanning Electron Microscopy (SEM), and was evaluated for cytotoxicity using a HeLa cell assay. TDF was used as a drug model, it was loaded by the swelling equilibrium method, following by the investigation of the release profile of TDF-loaded hydrogel at pH 1.2 and 7.4. A successful synthesis of chitosan grafted poly(acrylamide-co-acrylic acid) hydrogel was confirmed by Fourier Transmission Infra-red spectroscopy (FTIR), X-Ray Diffraction Spectroscopy (XRD), Thermal Gravimetric Analysis (TGA), Differential Scanning Calorimetry (DSC), Energy-dispersive X-ray spectroscopy (EDS) and Scanning Electron Microscopy (SEM). Optimization results showed that the ratio of monomers impacted the swelling ratio of the hydrogel and both the concentration of the crosslinking agent, and the reaction initiator also affected the swelling ratio. The synthesized hydrogels were sensitive to pH and ionic strength. Hydrogel swelling was lower in acidic solutions and higher in neutral and basic solutions and decreased with the increasing ionic strength. Furthermore, SEM results revealed that hydrogel have a rough and fibrous surface structure with numerous pores. Cytotoxicity studies demonstrated that the hydrogel was non-cytotoxic at 50 μg/ml against HeLa cells which suggested a good biocompatibility of the material. TDF was loaded and released from the hydrogels and showed an encapsulation efficiency and drug loading percentage ranging from 81-96% and 8-10%, respectively. TDF release profile was found to be low in buffer solution of pH 1.2 (in the range of 5-10%) and much higher (38-53%) at pH 7.4 within 96 hours. TDF maintained its chemical integrity after release and the hydrogels can therefore be proposed as a new controlled-release drug delivery system for hepatitis B treatment. , Thesis (MSc) -- Faculty of Science, Chemistry, 2022
- Full Text:
- Date Issued: 2022-04