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
A green approach for the synthesis of symmetrical and unsymmetrical 1,2,4,5-tetraoxanes as anti-protozoal agents
- Authors: Cossa, Teresa Manuel
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192786 , vital:45264
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Cossa, Teresa Manuel
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192786 , vital:45264
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Phthalocyanine-nanoparticle conjugates supported on inorganic nanofibers as photocatalysts for the treatment of biological and organic pollutants as well as for hydrogen generation
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Mapukata, Sivuyisiwe
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanofibers , Nanoparticles , Zinc , Hydrogen , Organic water pollutants , Water Purification , Electrospinning , Photocatalysis , Photodegradation , Anti-infective agents
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192831 , vital:45268 , 10.21504/10962/192831
- Description: This thesis reports on the synthesis, photophysicochemical and photocatalytic properties of various zinc phthalocyanines (Pcs). For enhanced properties and catalyst support, the reported Pcs were conjugated to different nanoparticles (NPs) through chemisorption as well as amide bond formation to yield Pc-NP conjugates. For increased catalyst surface area and catalyst reusability, the Pcs and some of their conjugates were also supported on electrospun inorganic nanofibers i.e. SiO2, hematite (abbreviated Hem and has formula α-Fe2O3), ZnO and TiO2 nanofibers. The effect that the number of charges on a Pc has on its antimicrobial activities was evaluated by comparing the photoactivities of neutral, octacationic and hexadecacationic Pcs against S. aureus, E. coli and C. albicans. The extent of enhancement of their antimicrobial activities upon conjugation (through chemisorption) to Ag NPs was also studied in solution and when supported on SiO2 nanofibers. The results showed that the hexadecacationic complex 3 possessed the best antimicrobial activity against all three microorganisms, in solution and when supported on the SiO2 nanofibers. Covalent conjugation of Pcs with carboxylic acid moieties (complexes 4-6) to amine functionalised NPs (Cys-Ag, NH2-Fe3O4 and Cys-Fe3O4@Ag) resulted in enhanced singlet oxygen generation and thus antibacterial efficiencies. Comparison of the photodegradation efficiencies of semiconductor nanofibers (hematite, ZnO and TiO2) when bare and when modified with a Pc (complex 6) were evaluated. Modification of the nanofibers with the Pc resulted in enhanced photoactivities for the nanofibers with the hematite nanofibers being the best. Modification of the hematite nanofibers with two different Pcs i.e. monosubstituted (complex 5) and an asymmetrical tetrasubstituted Pc (complex 6) showed that complex 6 better enhanced the activity of the nanofibers. Evaluation of the hydrogen generation efficiencies of the bare and modified TiO2 nanofibers calcined at different temperatures demonstrated that the anatase nanofibers calcined at 500 oC possessed the best catalytic efficiency. The efficiency of the TiO2 nanofibers was enhanced in the presence of the Co and Pd NPs as well as a Pc (complex 7), with the extent of enhancement being the greatest for the nanofibers modified with the Pd NPs. The reported findings therefore demonstrate the versatility of applications of Pcs for different water purification techniques when supported on different nanomaterials. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Stable Covalent pH-Sensitive Metallophthalocyanines Thin Monolayer Films for Selective Detection of Neurotransmitters
- Idowu, Abosede Omowumi Atinuke
- Authors: Idowu, Abosede Omowumi Atinuke
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192922 , vital:45279
- Description: Thesis (PhD) -- Faculty of Humanities, Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Idowu, Abosede Omowumi Atinuke
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192922 , vital:45279
- Description: Thesis (PhD) -- Faculty of Humanities, Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Synthesis and antiparasitic activity of hybrid compounds based on quinoline and thiosemicarbazone pharmacophoric units
- Authors: Makalima, Gwiba Hlonela
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192508 , vital:45232
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Makalima, Gwiba Hlonela
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/192508 , vital:45232
- Description: Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Synthesis, characterization and antiparasitic evaluation of chalcone hybrids
- Authors: Zulu, Ayanda Ignatia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192853 , vital:45271
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Zulu, Ayanda Ignatia
- Date: 2021-10-29
- Subjects: Uncatalogued
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/192853 , vital:45271
- Description: Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
The construction of phthalocyanine- carbon nanoparticle conjugates for applications in photodynamic therapy and non-linear optics
- Matshitse, Refilwe Manyama Stephina
- Authors: Matshitse, Refilwe Manyama Stephina
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanodiamonds , Photochemotherapy , Nonlinear optics , Quantum dots
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/188397 , vital:44750 , 10.21504/10962/188397
- Description: The syntheses and characterization of symmetric and asymmetric Pcs functionalized at the peripheral position and sometimes positively charged are reported. The Pcs had either H2, zinc or silicon as central metals and have pyridyloxy, benzothiozole phenoxy, and respective cationic analogues as ring substituents. The Pcs were linked to carbon based nanoparticles such as graphene quantum dots, carbon dots, and detonation nanodiamonds (DNDs) via an ester, amide bond and/or π - π stacking. The physicochemical characteristics of the Pcs were assessed when alone and when in a conjugated system. Both symmetrically and asymmetrically substituted benzothiozole Pcs when quaternised displayed higher triplet and singlet oxygen quantum yields than their unquaternised counterparts. Linkage to carbon nanoparticles (especially to detonation nanodiamonds) had an increasing effect on triplet and singlet oxygen quantum yield. However, a general decrease in singlet oxygen quantum yield on linkage to doped detonation nanodiamonds was associated with the screening effect of DNDs. Heteroatom doped DNDs-Pc nanohybrids have less singlet oxygen than Pcs alone due to molecular structural stability associated with strain that is relatively reduced upon linking Pcs. The In vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates against MCF-7 cells was tested. All studied Pc complexes and conjugates showed minimum dark toxicity making them applicable for PDT. When Pc complexes are alone, there is less phototoxicity with >22% cell viability at concentrations ≤ 50 μg/mL relative to conjugates with <22% cell viability at concentrations ≤ 50 μg/mL. There was no direct relationship between PDT and singlet oxygen quantum yields. Nonlinear optical characteristics of complexes was improved upon conjugation of DNDs. Absorbance, input energy, percentage loading, central metal, substituent of Pc and nature of interaction (covalent, noncovalent) are amongst some of the factors that influence nonlinear absorption properties of materials used in this study. All materials followed reverse saturable absorption through two photon absorption mechanism at the excitation wavelength of 532 nm. Aggregates reduce excited state lifetime and Beff under high concentrations/absorbance. A direct relationship between absorbance and Beff of DNDs nanoconjugated systems at low concentrations result in increased optical limiting characteristics of materials. The findings from this work show the importance of linking (nonlinear optics and photodynamic therapy) and doping (photodynamic therapy) photosensitisers such as phthalocyanines and sometimes boron dipyrromethenes onto carbon based nanoparticles for the enhanced characteristics in variable applications. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
- Authors: Matshitse, Refilwe Manyama Stephina
- Date: 2021-10-29
- Subjects: Phthalocyanines , Nanodiamonds , Photochemotherapy , Nonlinear optics , Quantum dots
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10962/188397 , vital:44750 , 10.21504/10962/188397
- Description: The syntheses and characterization of symmetric and asymmetric Pcs functionalized at the peripheral position and sometimes positively charged are reported. The Pcs had either H2, zinc or silicon as central metals and have pyridyloxy, benzothiozole phenoxy, and respective cationic analogues as ring substituents. The Pcs were linked to carbon based nanoparticles such as graphene quantum dots, carbon dots, and detonation nanodiamonds (DNDs) via an ester, amide bond and/or π - π stacking. The physicochemical characteristics of the Pcs were assessed when alone and when in a conjugated system. Both symmetrically and asymmetrically substituted benzothiozole Pcs when quaternised displayed higher triplet and singlet oxygen quantum yields than their unquaternised counterparts. Linkage to carbon nanoparticles (especially to detonation nanodiamonds) had an increasing effect on triplet and singlet oxygen quantum yield. However, a general decrease in singlet oxygen quantum yield on linkage to doped detonation nanodiamonds was associated with the screening effect of DNDs. Heteroatom doped DNDs-Pc nanohybrids have less singlet oxygen than Pcs alone due to molecular structural stability associated with strain that is relatively reduced upon linking Pcs. The In vitro dark cytotoxicity and photodynamic therapy of selected Pc complexes and conjugates against MCF-7 cells was tested. All studied Pc complexes and conjugates showed minimum dark toxicity making them applicable for PDT. When Pc complexes are alone, there is less phototoxicity with >22% cell viability at concentrations ≤ 50 μg/mL relative to conjugates with <22% cell viability at concentrations ≤ 50 μg/mL. There was no direct relationship between PDT and singlet oxygen quantum yields. Nonlinear optical characteristics of complexes was improved upon conjugation of DNDs. Absorbance, input energy, percentage loading, central metal, substituent of Pc and nature of interaction (covalent, noncovalent) are amongst some of the factors that influence nonlinear absorption properties of materials used in this study. All materials followed reverse saturable absorption through two photon absorption mechanism at the excitation wavelength of 532 nm. Aggregates reduce excited state lifetime and Beff under high concentrations/absorbance. A direct relationship between absorbance and Beff of DNDs nanoconjugated systems at low concentrations result in increased optical limiting characteristics of materials. The findings from this work show the importance of linking (nonlinear optics and photodynamic therapy) and doping (photodynamic therapy) photosensitisers such as phthalocyanines and sometimes boron dipyrromethenes onto carbon based nanoparticles for the enhanced characteristics in variable applications. , Thesis (PhD) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10-29
Echogenic liposomes for ultrasound-triggered drug delivery
- Authors: Izuchukwu, Ezekiel Charles
- Date: 2021-10
- Subjects: Liposomes , Drug delivery systems , Colon (Anatomy) Cancer Treatment , Transmission electron microscopy , Fourier transform infrared spectroscopy , Liquid chromatography , Echogenic liposomes , Ultrasound-triggered drug delivery
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188997 , vital:44805
- Description: Colorectal cancer is one of common cancers worldwide. It is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) alone or in a chemotherapy regime has been the effective treatment of colorectal cancer patients. The efficacy of 5-FU in colorectal cancer treatment is significantly limited by drug resistance, gastrointestinal, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying a need to improve its therapeutic index. Liposomes are colloidal membranes comprising of one or more lipid bilayers enclosing an aqueous core. They have been used to improve the therapeutic index of many anti-cancer drugs by changing drug absorption, elongating biological half-life, reducing metabolism, and reducing toxicity to healthy tissues. Echogenic liposomes are specifically designed to respond to external triggering like ultrasound stimulation by entrapping a gas or an emulsion that can vaporize. A liposome's unique property is that it can entrap both hydrophobic and hydrophilic substances simultaneously in the lipid bilayer and the aqueous core, respectively. These stimuli-responsive liposomes can be triggered externally with ultrasound, to release the chemotherapeutic cargo only at the required site. This research aims to formulate echogenic liposomes encapsulating 5-FU for potential ultrasound triggered release (echogenic). Liposome formulations wereprepared with lipid composition of crude soybean lecithin and cholesterol by thin-filmhydration method and the drug was passively loaded in the formulation. The 5-FU loadedliposomes were evaluated by dynamic light scattering (DLS) for particle size, polydispersityindex, and zeta potential and transmission electron microscopy (TEM) for morphology.Encapsulated liposomal formulations were also evaluated using physicochemical techniquesincluding thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Theencapsulation efficiency and release kinetics were studied using a validated high-performanceliquid chromatography (HPLC) method. Echogenic properties were explored by entrapping abiocompatible gas (argon) at the same time as the drug (5-FU) using a pressure/freezemethodology. The liposomal formulations were typically spherical with a size of about 150 nmand encapsulation efficiency of 62%. Low-frequency ultrasound (20 kHz) was used to triggerthe drug release from the complete formulation at 10%, 15%, and 20% amplitude and exposuretime of 5 min and 10 min. The rate of drug release from the nano-carrier was a function of theultrasound amplitude and exposure time and reached a maximum of 65% release under theconditions investigated. The cumulative release was investigated, with and without theapplication of ultrasound. It was demonstrated that the application of ultrasound resulted in complete release (99%) after 12 h while this dropped to 70% without ultrasound. These results are encouraging for optimizing ultrasound parameters for triggered and controlled release of the 5-FU, for conditions such as the management of cancer where low-power ultrasound can be applied. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Izuchukwu, Ezekiel Charles
- Date: 2021-10
- Subjects: Liposomes , Drug delivery systems , Colon (Anatomy) Cancer Treatment , Transmission electron microscopy , Fourier transform infrared spectroscopy , Liquid chromatography , Echogenic liposomes , Ultrasound-triggered drug delivery
- Language: English
- Type: Masters theses , text
- Identifier: http://hdl.handle.net/10962/188997 , vital:44805
- Description: Colorectal cancer is one of common cancers worldwide. It is the third most diagnosed cancer and the second leading cause of death. The use of 5-fluorouracil (5-FU) alone or in a chemotherapy regime has been the effective treatment of colorectal cancer patients. The efficacy of 5-FU in colorectal cancer treatment is significantly limited by drug resistance, gastrointestinal, and bone marrow toxicity through high-level expression of thymidylate synthase, justifying a need to improve its therapeutic index. Liposomes are colloidal membranes comprising of one or more lipid bilayers enclosing an aqueous core. They have been used to improve the therapeutic index of many anti-cancer drugs by changing drug absorption, elongating biological half-life, reducing metabolism, and reducing toxicity to healthy tissues. Echogenic liposomes are specifically designed to respond to external triggering like ultrasound stimulation by entrapping a gas or an emulsion that can vaporize. A liposome's unique property is that it can entrap both hydrophobic and hydrophilic substances simultaneously in the lipid bilayer and the aqueous core, respectively. These stimuli-responsive liposomes can be triggered externally with ultrasound, to release the chemotherapeutic cargo only at the required site. This research aims to formulate echogenic liposomes encapsulating 5-FU for potential ultrasound triggered release (echogenic). Liposome formulations wereprepared with lipid composition of crude soybean lecithin and cholesterol by thin-filmhydration method and the drug was passively loaded in the formulation. The 5-FU loadedliposomes were evaluated by dynamic light scattering (DLS) for particle size, polydispersityindex, and zeta potential and transmission electron microscopy (TEM) for morphology.Encapsulated liposomal formulations were also evaluated using physicochemical techniquesincluding thermogravimetric analysis (TGA), differential scanning calorimetry (DSC),Fourier-transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). Theencapsulation efficiency and release kinetics were studied using a validated high-performanceliquid chromatography (HPLC) method. Echogenic properties were explored by entrapping abiocompatible gas (argon) at the same time as the drug (5-FU) using a pressure/freezemethodology. The liposomal formulations were typically spherical with a size of about 150 nmand encapsulation efficiency of 62%. Low-frequency ultrasound (20 kHz) was used to triggerthe drug release from the complete formulation at 10%, 15%, and 20% amplitude and exposuretime of 5 min and 10 min. The rate of drug release from the nano-carrier was a function of theultrasound amplitude and exposure time and reached a maximum of 65% release under theconditions investigated. The cumulative release was investigated, with and without theapplication of ultrasound. It was demonstrated that the application of ultrasound resulted in complete release (99%) after 12 h while this dropped to 70% without ultrasound. These results are encouraging for optimizing ultrasound parameters for triggered and controlled release of the 5-FU, for conditions such as the management of cancer where low-power ultrasound can be applied. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
Green Synthesis of HIV-1 Protease Inhibitors
- Authors: Hartley, Shaun Neil
- Date: 2021-10
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190145 , vital:44967
- Description: Thesis embargoed until October 2022 , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Hartley, Shaun Neil
- Date: 2021-10
- Subjects: Uncatalogued
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190145 , vital:44967
- Description: Thesis embargoed until October 2022 , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
Nonlinear optical properties of metal free thio alkyl and tert-butyl phenoxy phthalocyanine
- Authors: Joseph, Otto
- Date: 2021-10
- Subjects: Nonlinear optics , Phthalocyanines , Time-dependent density functional theory , Magnetic circular dichroism , Reverse saturable absorption (RSA) , Real Time Dependent Density Functional Theory (RT-TDDFT)
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190712 , vital:45021
- Description: This work reports on the nonlinear optical properties of tetra - and octa substituted phthalocyanines (Pcs) utilising pentane thiol and 4-tertbutyl phenol as substituents. Their nonlinear absorption coefficient (𝛽) and absorption cross sections were determined using the Z-scan technique with a 10 ns pulse laser at 532 nm. The molecular second order hyperpolarizability Im[γ] was observed and the following Im[γ] trend was obtained for 𝛼-H2Pc(SC5H11)4 isomers, 5.93 ×10−31 (Cs) 2.24×10−32(D2h) > 1.21×10−32(C4h) > 1.05×10−32 (C2v) esu, respectively, in chloroform. Symmetry was seen to have an effect on the observed reverse saturable absorption (RSA) response. Based on the five level model rate equation nonlinear fit of the RSA response curves and Real Time Time Dependant Density Functional Theory (RT-TDDFT) results, the singlet excited state population dynamics was found to play a significant role in producing the observed Im[γ] trend. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10
- Authors: Joseph, Otto
- Date: 2021-10
- Subjects: Nonlinear optics , Phthalocyanines , Time-dependent density functional theory , Magnetic circular dichroism , Reverse saturable absorption (RSA) , Real Time Dependent Density Functional Theory (RT-TDDFT)
- Language: English
- Type: Master's theses , text
- Identifier: http://hdl.handle.net/10962/190712 , vital:45021
- Description: This work reports on the nonlinear optical properties of tetra - and octa substituted phthalocyanines (Pcs) utilising pentane thiol and 4-tertbutyl phenol as substituents. Their nonlinear absorption coefficient (𝛽) and absorption cross sections were determined using the Z-scan technique with a 10 ns pulse laser at 532 nm. The molecular second order hyperpolarizability Im[γ] was observed and the following Im[γ] trend was obtained for 𝛼-H2Pc(SC5H11)4 isomers, 5.93 ×10−31 (Cs) 2.24×10−32(D2h) > 1.21×10−32(C4h) > 1.05×10−32 (C2v) esu, respectively, in chloroform. Symmetry was seen to have an effect on the observed reverse saturable absorption (RSA) response. Based on the five level model rate equation nonlinear fit of the RSA response curves and Real Time Time Dependant Density Functional Theory (RT-TDDFT) results, the singlet excited state population dynamics was found to play a significant role in producing the observed Im[γ] trend. , Thesis (MSc) -- Faculty of Science, Chemistry, 2021
- Full Text:
- Date Issued: 2021-10