Ranking of topical corticosteroids: principles and results
- Smith, Eric W, Haigh, John M
- Authors: Smith, Eric W , Haigh, John M
- Date: 1993
- Language: English
- Type: text , Article
- Identifier: vital:6434 , http://hdl.handle.net/10962/d1006607
- Description: The increasing synthesis and use of topical corticosteroid products over the past 30 years has necessitated the development of suitable methods for evaluating the efficacy and potency of new drug entities. Several in vivo models have been developed in this regard using laboratory animals and human subjects. Generally, these tests measure the difference in the non-immunological inflammatory response to an exogenous inflammatory mediator in the presence and absence of the corticosteroid under test. There are also immunologically based assays and several tests which assess the anti proliferative effects of the drug. Several comparative disease model evaluations have also been developed using human subjects. Most of these assays are non-ideal from one point of view or another: most are invasive methods which require some form of trauma to be induced in the skin and therefore problematic to perform and monitor.
- Full Text:
- Date Issued: 1993
- Authors: Smith, Eric W , Haigh, John M
- Date: 1993
- Language: English
- Type: text , Article
- Identifier: vital:6434 , http://hdl.handle.net/10962/d1006607
- Description: The increasing synthesis and use of topical corticosteroid products over the past 30 years has necessitated the development of suitable methods for evaluating the efficacy and potency of new drug entities. Several in vivo models have been developed in this regard using laboratory animals and human subjects. Generally, these tests measure the difference in the non-immunological inflammatory response to an exogenous inflammatory mediator in the presence and absence of the corticosteroid under test. There are also immunologically based assays and several tests which assess the anti proliferative effects of the drug. Several comparative disease model evaluations have also been developed using human subjects. Most of these assays are non-ideal from one point of view or another: most are invasive methods which require some form of trauma to be induced in the skin and therefore problematic to perform and monitor.
- Full Text:
- Date Issued: 1993
The development of biological tools to aid in the genetic investigation of the black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros mitochondrial genomes
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
- Date Issued: 2015
- Authors: Parsons, Michelle
- Date: 2015
- Language: English
- Type: text , Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10962/56059 , vital:26769
- Description: The black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are found in South Africa. A decline in the populations of these species has resulted due to human activities such as habitat fragmentation and poaching. This has contributed to the loss of genetic diversity amongst the black and white rhinoceros. Conservation and anti-poaching efforts are needed to help maintain genetic diversity. These efforts could be improved through the development of non-invasive techniques to examine DNA from threatened animals. The aim of this research was to develop a molecular technique which would allow for the identification of the black and white rhinoceros and to develop a molecular technique which would allow for intraspecies genetic variation to be examined. DNA extractions were performed on matched faecal and tissue samples that were collected from two regions in South Africa. Polymerase chain reaction (PCR) primer sets were designed to investigate several regions of the rhinoceros mitochondrial genome. PCR optimisation was completed for the target regions. Sequencing was conducted on all final PCR products. The cytochrome c oxidase subunit 1 (COIi) gene allowed for the rhinoceros family to be identified. This region was digested with the HindIII restriction enzyme, which allowed for the specific identification of either the black or white rhinoceros. A subsequent region of the cytochrome c oxidase subunit 1 (COIii) as well as the D-loop, hypervariable regions (HV1 and HV2), cytochrome b (cytb) and 16s rRNA regions were investigated. These regions displayed potential for establishing geographic origin for black rhinoceros samples, whereas the D-loop and HV2 show potential for the white rhinoceros. The white rhinoceros displayed sequence variation in the HV2 and cytb region, while variation was observed in the COIi and HV1 for the black rhinoceros. All investigated target regions allowed for the rhinoceros family to be identified. The COI (COIi and COIii), HV2 and cytb regions allowed for the subspecies of rhinoceros to be identified, however the D-loop was not able to identify the white rhinoceros species. The 16s rRNA and HV1 regions allowed for the correct subspecies of rhinoceros to be identified, however as the primers were only compatible for the black rhinoceros therefore a subsequent investigation is required for the white rhinoceros. The establishment of this novel PCR based technique to identify white and black rhinoceros will allow for efficient species identification in wildlife forensic cases. A biological method was established to study intraspecies variation for the white and black rhinoceros; however the investigated target regions did not yield sufficient genetic variation. The core techniques developed in this study will be valuable for future studies that wish to investigate genetic variation in mammal species.
- Full Text:
- Date Issued: 2015
Leonotis leonurus beside railway-line east of Berlin
- Authors: Skead, C J (Cuthbert John)
- Date: 1960-04-30
- Subjects: Leonotis leonurus -- South Africa -- Photographs
- Language: English
- Type: mixed material , photographs , landscape photographs
- Identifier: http://hdl.handle.net/10962/75756 , vital:30460
- Description: Caption: "Leonotis leonurus beside railway-line east of Berlin, C.P. 22 May 1960."
- Full Text: false
- Date Issued: 1960-04-30
- Authors: Skead, C J (Cuthbert John)
- Date: 1960-04-30
- Subjects: Leonotis leonurus -- South Africa -- Photographs
- Language: English
- Type: mixed material , photographs , landscape photographs
- Identifier: http://hdl.handle.net/10962/75756 , vital:30460
- Description: Caption: "Leonotis leonurus beside railway-line east of Berlin, C.P. 22 May 1960."
- Full Text: false
- Date Issued: 1960-04-30
Synthesis and characterisation of lanthanide complexes with nitrogen- and oxygen-donor ligands
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
- Authors: Madanhire, Tatenda
- Date: 2016
- Subjects: Rare earth metals
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: http://hdl.handle.net/10948/13127 , vital:27154
- Description: The reactions of Ln(NO3)3∙6H2O (Ln = Pr, Nd or Er) with the potentially tridentate O,N,O chelating ligand 2,6-pyridinedimethanol (H2pydm) were investigated, and complexes with the formula, [Ln(H2pydm)2(NO3)2](NO3) (Ln = Pr or Nd) and [Er(H2pydm)3](NO3)3 were isolated. The ten-coordinate Pr(III) and Nd(III) compounds crystallise in the triclinic space group P-1 while the nine-coordinate Er(III) complex crystallises in the monoclinic system (P21/n). The reaction of PrCl3∙6H2O with H2pydm yielded the compound, [Pr(H2pydm)3](Cl)3, that crystallises in the monoclinic system, space group P21/c with α = 90, β = 98.680(1) and γ = 90°. The nine-coordinate Pr(III) ion is bound to three H2pydm ligands, with bond distances Pr-O 2.455(2)-2.478(2) Å and Pr-N 2.6355(19)-2.64(2) Å. X-ray crystal structures of all the H2pydm complexes reveal that the ligand coordinates tridentately, via the pyridyl nitrogen atom and the two hydroxyl oxygen atoms. The electronic absorption spectra of complexes show 4f-4f transitions. Rare-earth complexes, [Ln(H2L1)2(NO3)3] [Ln = Gd, Ho or Nd], were also prepared from a Schiff base. The X-ray single-crystal diffraction studies and SHAPE analyses of the Gd(III) and Ho(III) complexes shows that the complexes are ten-coordinate and exhibit distorted tetradecahedron geometries. With proton migration occurring from the phenol group to the imine function, complexation of the lanthanides to the ligand gives the ligand a zwitterionic phenoxo-iminium form. A phenolate oxygen-bridged dinuclear complex, [Ce2(H2L1)(ovan)3(NO3)3], has been obtained by reacting Ce(NO3)3∙6H2O with an o-vanillin derived Schiff base ligand, 2-((E)-(1-hydroxy-2-methylpropan-2-ylimino)methyl)-6-methoxyphenol (H2L1). Hydrolysis of the Schiff base occurred to yield o-vanillin, which bridged two cerium atoms with the Ce∙∙∙Ce distance equal to 3.823 Å. The Ce(III) ions are both tencoordinate, but have different coordination environments, showing tetradecahedron and staggered dodecahedron geometries, respectively. The reaction of salicylaldehyde-N(4)-diethylthiosemicarbazone (H2L2) in the presence of hydrated Ln(III) nitrates led to the isolation of two novel compounds: (E)-2[(ortho-hydroxy)benzylidene]-2-(thiomethyl)-thionohydrazide (1) and bis[2,3-diaza4-(2-hydroxyphenyl)-1-thiomethyl-buta-1,3-diene]disulfide. The latter is a dimer of the former. For this asymmetric Schiff base, 1 and the symmetric disulfide, classical hydrogen bonds of the O–H∙∙∙N as well as N–H∙∙∙S (for 1) type are apparent next to C–H∙∙∙O contacts. 4-(4-Bromophenyl)-1-(propan-2-ylidene)thiosemicarbazide was also prepared upon reacting 4-(4-bromophenyl)-3-thiosemicarbazide with acetone in the presence of ethanol and La(NO3)3∙6H2O. The C=S bond length was found to be 1.6686(16) Å which is in good agreement with other thioketones whose metrical parameters have been deposited with the Cambridge Structural Database. Classical hydrogen bonds of the N–H∙∙∙N and the N–H∙∙∙Br type are observed next to C–H∙∙∙S contacts. All synthesised compounds were characterised by microanalyses, single-crystal X-ray diffraction (except for [Nd(H2L1)2(NO3)3]), 1H NMR and IR spectroscopy.
- Full Text:
- Date Issued: 2016
Assessment of topical corticosteroid preparations: the human skin-blanching assay
- Haigh, John M, Kanfer, Isadore
- Authors: Haigh, John M , Kanfer, Isadore
- Date: 1984
- Language: English
- Type: text , Article
- Identifier: vital:6374 , http://hdl.handle.net/10962/d1006284
- Description: (From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations.
- Full Text:
- Date Issued: 1984
- Authors: Haigh, John M , Kanfer, Isadore
- Date: 1984
- Language: English
- Type: text , Article
- Identifier: vital:6374 , http://hdl.handle.net/10962/d1006284
- Description: (From the introduction) Since the introduction of topical corticosteroid formulations, their use has become widespread, being prescribed for a large variety of dermatological conditions. This widespread use has created a need for a reliable method of assessing the various dosage forms of these compounds. Clinical trials are laborious, costly and difficult to mount as well as being impractical for the screening of large numbers of drugs. Patients suffering from dermatological complaints are not ideal subjects for the testing of topical corticosteroid preparations as it is difficult to obtain standardized lesions which are necessary for the comparison of results between patients (Baker and Sattar, 1968). For these reasons a number of methods have been developed for the screening of novel corticosteroids and testing of topical corticosteroid formulations.
- Full Text:
- Date Issued: 1984
Fungal remediation of winery and distillery wastewaters using Trametes pubescens MB 89 and the enhanced production of a high-value enzyme therein
- Authors: Strong, Peter James
- Date: 2008
- Subjects: Fungal remediation Distilleries -- Waste disposal Wine and wine making -- Waste disposal Bioremediation Laccase Enzymes -- Biotechnology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3932 , http://hdl.handle.net/10962/d1003991
- Description: In this study white-rot fungi were investigated for their efficiency at distillery wastewater remediation and the production of laccase as a valuable by-product. Distillery wastewaters are high in organic load and low in pH. The presence of phenolic compounds can lead to extremely colour-rich wastewaters and can be toxic to microorganisms. The presence of the inorganic ions may also affect biological treatment. White-rot fungi are unique among eukaryotic or prokaryotic microbes in possessing powerful oxidative enzyme systems that can degrade lignin to carbon dioxide. These ligninolytic enzymes, such as lignin peroxidase, manganese peroxidase and laccase, are capable of degrading a vast range of toxic, recalcitrant environmental pollutants and this makes the white-rot fungi strong candidates for the bioremediation of polluted soils and waters. The laccase enzyme alone has shown remediation potential in wastewaters such as beer production effluent, olive mill wastewater, alcohol distillery wastes, dye-containing wastewaters from the textile industry as well as wastewaters from the paper and pulp industry. It has been shown to be capable of remediating soils and waters polluted with chlorinated phenolic compounds, polyaromatic hydrocarbons, nitrosubstituted compounds and fungicides, herbicides and insecticides.
- Full Text:
- Date Issued: 2008
- Authors: Strong, Peter James
- Date: 2008
- Subjects: Fungal remediation Distilleries -- Waste disposal Wine and wine making -- Waste disposal Bioremediation Laccase Enzymes -- Biotechnology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:3932 , http://hdl.handle.net/10962/d1003991
- Description: In this study white-rot fungi were investigated for their efficiency at distillery wastewater remediation and the production of laccase as a valuable by-product. Distillery wastewaters are high in organic load and low in pH. The presence of phenolic compounds can lead to extremely colour-rich wastewaters and can be toxic to microorganisms. The presence of the inorganic ions may also affect biological treatment. White-rot fungi are unique among eukaryotic or prokaryotic microbes in possessing powerful oxidative enzyme systems that can degrade lignin to carbon dioxide. These ligninolytic enzymes, such as lignin peroxidase, manganese peroxidase and laccase, are capable of degrading a vast range of toxic, recalcitrant environmental pollutants and this makes the white-rot fungi strong candidates for the bioremediation of polluted soils and waters. The laccase enzyme alone has shown remediation potential in wastewaters such as beer production effluent, olive mill wastewater, alcohol distillery wastes, dye-containing wastewaters from the textile industry as well as wastewaters from the paper and pulp industry. It has been shown to be capable of remediating soils and waters polluted with chlorinated phenolic compounds, polyaromatic hydrocarbons, nitrosubstituted compounds and fungicides, herbicides and insecticides.
- Full Text:
- Date Issued: 2008
Benzoyl isothiocyanates derived ligands as potential HIV-1 protease inhibitors and their reactions with gold ions
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
- Authors: Odame, Felix
- Date: 2016
- Subjects: HIV (Viruses) -- Enzymes Enzyme inhibitors -- Research , Pharmaceutical chemistry Biochemistry
- Language: English
- Type: Thesis , Doctoral , DPhil
- Identifier: http://hdl.handle.net/10948/33228 , vital:32585
- Description: The synthesis and evaluation of benzoyl isothiocyanate derivatives as potential HIV-1 protease inhibitors is presented. The ligands were first designed to fit the protease active site using Autodock 4.2. The design was based on the deNOVO method of drug design in which the active site coordinates from the crystal structure of protease bound to ritonavir was used. An attempt to access the scaffolds designed initially led to the formation of 2,2,4-trimethyl 2,3-dihydro-1H-1,5-benzodiazepin-5-ium isophthalate and 2-2-(3-methylphenyl-1Hbenzimidazole which could not be converted to the desired intermediate. A further attempt led to formation of amino acid and amino acid ester derivatives of benzoyl isothiocyanates which have been fully characterized and the reasons why the desired intermediates were not readily accessible explained. Scaffolds based on the benzoyl isothiocyanate derivatives of structurally diverse diamines were then screened. Sixty compounds have been synthesized and fully characterized using elemental analysis, spectroscopy, GC-MS and twenty-six crystal structures have been discussed. The DFT transition state studies of 11-phenyl- 1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), N-(1Hbenzimidazol-2-yl)benzamide (21), 3-(1,3-benzothiazol-2-yl)-1-(benzoyl)thiourea (23), and N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (39), have been carried out and their detailed density functional theory reaction mechanism have be computed. The Bernly algorithm was used in the determination of saddle points (transtions states), and the intrinsic reaction coordinates leading to the determination of intermediates were traced and optimized to a global minimum or in some cases a local minimum was obtained. The cell viability tests of diamine derivatives which was done by exposing white blood cells to the compounds (inhibitors) at 37 °C and a pH of 7.4 showed that 1-(4-bromobenzoyl)-3-[2- ({[(4-bromophenyl)formamido]methanethioyl}amino)phenyl]thiourea (46), 1-(3-chloro benzoyl)-3-[2-({[(3-chlorophenyl)formamido]methanethioyl}amino)phenyl]thiourea (48), 1- (3-bromobenzoyl)-3-[2-({[(3-bromophenyl)formamido]methanethioyl}amino)phenyl] thiourea (49) and 3-benzoyl-1-(4-{[(phenylformamido)methanethioyl]amino}butyl)thiourea (54), in that group of compounds were cytotoxic with EC50 values of 17.04 ± 9.75 μM, 69.20± 38.16 μM, 35.90 ± 20.55 μM and 68.37 ± 26.45 μM, respectively. 4-Bromo-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (32), 4-methoxy-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene]benzamide (33) and 3-chloro-N-[(9E)-8,10,17-triazatetracyclo[8.7.0.02,7.011,16]heptadeca-1(17),2,4,6,11(16),12,14-heptaen-9-ylidene] benzamide (37) were also cytotoxic giving EC50 values of 45.47 ± 21.92, 45.09 ±13.79 and 74.94 ± 13.17 μM, respectively. 3-(1,3-Benzothiazol-2-yl)-1-(3-bromobenzoyl)thiourea (31) and 3-(1,3-benzothiazoyl-2-yl)-1-(4-nitrobenzoyl)thiourea (30) derivatives were also found to be cytotoxic with EC50 values of 1.207 ± 0.58 and 24.08 ±13.14 nM, respectively. 11-(4-Chlorophenyl-1,8,10, 12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (12), 11-(4-methoxyphenyl)-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,9,1-pentaene-13-thione (14), and 11-phenyl-1,8,10,12-tetraazatricyclo[7.4.0.02,7]trideca-2(7),3,5,9,11-pentaene-13-thione (20), were found to be cytotoxic giving EC50 values of 0.152 ± 0.051, 37.96 ± 21.87 and 5.28 ± 2.95 μM, respectively. In the enzyme inhibition studies compound 49 gave a percentage inhibition of 97.03 ± 10.61% at 100 μM, but the fact that it is cytoxic might make it less useful, whilst compounds 19 and 16 had a percentage inhibition of 59.57 ± 13.59% (4-nitro derivative) and 79.97 ± 11.97% (3-nitro derivative) respectively at 100 μM of inhibitor and 20 μM of enzyme (HIV-1 protease). The results suggests that the presence of the nitro group at position 3 (16) and 4 (19) leads to an increase in activity against HIV-1 protease.
- Full Text:
- Date Issued: 2016
Reactivity of Rhenium (iii) and Rhenium (V) with multidentate NN-and no-donor ligands
- Yumata, Nonzaliseko Christine
- Authors: Yumata, Nonzaliseko Christine
- Date: 2010
- Subjects: Rhenium , Ligands
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10373 , http://hdl.handle.net/10948/1085 , Rhenium , Ligands
- Description: The reaction of the potentially tridentate Schiff-base chelate Hhaep [Haep = N’-(1- (2-hydroxyphenyl)ethylidene)benzohydrazide] with [ReCl3(benzil)(PPh3)] and trans-[ReOCl3(PPh3)2] produced the neutral oxorhenium(V) complexes cis- [ReOCl2(mep)] [Hmep = 2-(1-iminoethyl)phenol] and cis-[ReOCI2(meb)(PPh3)] [Hmeb = N’-(propan-2-ylidene)benzohydrazide] in ethanol and acetone respectively. In both reactions the Hhaep molecule cleaves to give different coordinated bidentate NO-donor chelates coordinated to the rhenium(V) centers. The X-ray studies reveal that mep is present as a bidentate, monoanionic Schiffbase coordinating through the neutral imino nitrogen and the deprotonated phenolate oxygen in cis-[ReOCl2(mep)]. The bond distances and angles in cis- [ReOCI2(meb)(PPh3)] confirm that meb coordinates to the metal in the enolate form. The distorted octahedral complex fac-[ReCl3(dpa)(PPh3)] was prepared by the reaction of trans-[ReCl3(MeCN)(PPh3)2] with a twofold molar excess of dpa in acetonitrile under a nitrogen atmosphere. The compound dpa.HCl.2H2O was obtained as a by-product in the reaction of dpa with trans-[ReCI3(MeCN)(PPh3)2] in acetonitrile. The reaction of trans-[ReCl3(MeCN)(PPh3)2] with a twofold molar excess of 6- amino-3-methyl-1-phenyl-4-azahept-2-ene-1-one (Hamp) in acetonitrile led to the isolation of cis-[ReCl2(bat)(PPh3)2]. On complexation to the metal center Hamp decomposed to give the coordinated benzoylacetone (bat). Bat is present as a monoanionic bidentate chelate. The complexes [ReVOCI(had)] and [ReIVCl(had)(PPh3)](ReO4) were prepared from the reaction of trans-[ReCl3(MeCN)(PPh3)2] with N,N-bis((2-hydroxybenzyl)-2- aminoethyl)dimethylamine (H2had) in ethanol under various reaction conditions. The treatment of [ReCl3(benzil)(PPh3)] with 2-[((2- pyridinylmethyl)amino)methyl]phenol (Hham) in a 2:1 molar ratio in acetonitrile led to the isolation of the hydrogen-bonded dimer [ReOCl2(ham)]2. The distorted octahedral complex [ReOCl(hap)] [H2hap = N,N-bis(2- hydroxybenzyl)aminomethylpyridine] was prepared from the reaction of trans- [ReCl3(MeCN)(PPh3)2] with a twofold molar excess of H2hap in acetonitrile. The X-ray crystal structure analysis shows that the chloride is coordinated trans to the tripodal tertiary amino nitrogen, with a phenolate oxygen trans to the oxo oxygen.
- Full Text:
- Date Issued: 2010
- Authors: Yumata, Nonzaliseko Christine
- Date: 2010
- Subjects: Rhenium , Ligands
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:10373 , http://hdl.handle.net/10948/1085 , Rhenium , Ligands
- Description: The reaction of the potentially tridentate Schiff-base chelate Hhaep [Haep = N’-(1- (2-hydroxyphenyl)ethylidene)benzohydrazide] with [ReCl3(benzil)(PPh3)] and trans-[ReOCl3(PPh3)2] produced the neutral oxorhenium(V) complexes cis- [ReOCl2(mep)] [Hmep = 2-(1-iminoethyl)phenol] and cis-[ReOCI2(meb)(PPh3)] [Hmeb = N’-(propan-2-ylidene)benzohydrazide] in ethanol and acetone respectively. In both reactions the Hhaep molecule cleaves to give different coordinated bidentate NO-donor chelates coordinated to the rhenium(V) centers. The X-ray studies reveal that mep is present as a bidentate, monoanionic Schiffbase coordinating through the neutral imino nitrogen and the deprotonated phenolate oxygen in cis-[ReOCl2(mep)]. The bond distances and angles in cis- [ReOCI2(meb)(PPh3)] confirm that meb coordinates to the metal in the enolate form. The distorted octahedral complex fac-[ReCl3(dpa)(PPh3)] was prepared by the reaction of trans-[ReCl3(MeCN)(PPh3)2] with a twofold molar excess of dpa in acetonitrile under a nitrogen atmosphere. The compound dpa.HCl.2H2O was obtained as a by-product in the reaction of dpa with trans-[ReCI3(MeCN)(PPh3)2] in acetonitrile. The reaction of trans-[ReCl3(MeCN)(PPh3)2] with a twofold molar excess of 6- amino-3-methyl-1-phenyl-4-azahept-2-ene-1-one (Hamp) in acetonitrile led to the isolation of cis-[ReCl2(bat)(PPh3)2]. On complexation to the metal center Hamp decomposed to give the coordinated benzoylacetone (bat). Bat is present as a monoanionic bidentate chelate. The complexes [ReVOCI(had)] and [ReIVCl(had)(PPh3)](ReO4) were prepared from the reaction of trans-[ReCl3(MeCN)(PPh3)2] with N,N-bis((2-hydroxybenzyl)-2- aminoethyl)dimethylamine (H2had) in ethanol under various reaction conditions. The treatment of [ReCl3(benzil)(PPh3)] with 2-[((2- pyridinylmethyl)amino)methyl]phenol (Hham) in a 2:1 molar ratio in acetonitrile led to the isolation of the hydrogen-bonded dimer [ReOCl2(ham)]2. The distorted octahedral complex [ReOCl(hap)] [H2hap = N,N-bis(2- hydroxybenzyl)aminomethylpyridine] was prepared from the reaction of trans- [ReCl3(MeCN)(PPh3)2] with a twofold molar excess of H2hap in acetonitrile. The X-ray crystal structure analysis shows that the chloride is coordinated trans to the tripodal tertiary amino nitrogen, with a phenolate oxygen trans to the oxo oxygen.
- Full Text:
- Date Issued: 2010
Novel applications of Morita-Baylis-Hillman methodology in organic synthesis
- Authors: Mciteka, Lulama Patrick
- Date: 2013 , 2013-04-22
- Subjects: Organic compounds -- Synthesis -- Research Asymmetric synthesis Asymmetry (Chemistry) Chemical reactions -- Research Camphor -- Research AZT (Drug) -- Research Chemical inhibitors -- Research Chemistry -- Methodology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4439 , http://hdl.handle.net/10962/d1007598
- Description: The overall approach in the present investigation has been to explore applications of the Morita-Baylis-Hillman (MBH) reaction in asymmetric synthesis and in the continuation of systems with medicinal potential. To this end, a series of varied camphor-derived acrylate esters was prepared to serve as chiral substrates in asymmetric Morita-Baylis- Hillman reactions. Reduction of N-substituted camphor-10-sulfonamides afforded the 3- exo-hydroxy derivatives as the major products. Acylation of the corresponding sodium alkoxides gave the desired 3-exo-acrylate esters, isolation of which was complicated by concomitant formation of hydrochlorinated and diastereomeric competition products. Bulky camphorsulfonamides containing alkyl, dialkyl, aromatic and adamantyl groups were selected as N-substituents with the view of achieving stereoselective outcome in subsequent MBH reactions. The synthesis of novel camphor-derived Morita-Baylis-Hillman adducts using various pyridine-carboxaldehydes proceeded with exceptionally high yields with diastereoselectivities ranging from 7-33 % d.e. Both 1D and 2D NMR and HRMS techniques were employed to confirm the structures and an extensive study of the electropositive fragmentation patterns of a number of camphor-derived chiral acrylate esters was conducted. Attention has also been given to the application of MBH methodology in the construction of heterocyclic ‘cinnamate-like’ AZT conjugates which were designed to serve as dualaction HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. A number of pyridine carboxaldehyde-derived MBH adducts were synthesized using methyl, ethyl and t-butyl acrylates in the presence of 3-hydroxyquinuclidine (3-HQ) as catalyst. The yields for these reactions were excellent. The resulting MBH adducts were acetylated and subjected to aza-Michael addition using propargylamine. The resulting alkylamino compounds were then used in ‘Click reactions’ to form the targeted AZT-conjugates in moderate to excellent yield. In silico docking of computer modelled AZT-conjugates into the HIV-1 integrase and reverse transcriptase enzyme-active sites and potential hydrogen-bonding interaction with active-site amino acid residues were identified. The electrospray MS fragmentations of the AZT and the novel AZT-conjugates were also investigated and common fragmentation pathways were identified.
- Full Text:
- Date Issued: 2013
- Authors: Mciteka, Lulama Patrick
- Date: 2013 , 2013-04-22
- Subjects: Organic compounds -- Synthesis -- Research Asymmetric synthesis Asymmetry (Chemistry) Chemical reactions -- Research Camphor -- Research AZT (Drug) -- Research Chemical inhibitors -- Research Chemistry -- Methodology
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4439 , http://hdl.handle.net/10962/d1007598
- Description: The overall approach in the present investigation has been to explore applications of the Morita-Baylis-Hillman (MBH) reaction in asymmetric synthesis and in the continuation of systems with medicinal potential. To this end, a series of varied camphor-derived acrylate esters was prepared to serve as chiral substrates in asymmetric Morita-Baylis- Hillman reactions. Reduction of N-substituted camphor-10-sulfonamides afforded the 3- exo-hydroxy derivatives as the major products. Acylation of the corresponding sodium alkoxides gave the desired 3-exo-acrylate esters, isolation of which was complicated by concomitant formation of hydrochlorinated and diastereomeric competition products. Bulky camphorsulfonamides containing alkyl, dialkyl, aromatic and adamantyl groups were selected as N-substituents with the view of achieving stereoselective outcome in subsequent MBH reactions. The synthesis of novel camphor-derived Morita-Baylis-Hillman adducts using various pyridine-carboxaldehydes proceeded with exceptionally high yields with diastereoselectivities ranging from 7-33 % d.e. Both 1D and 2D NMR and HRMS techniques were employed to confirm the structures and an extensive study of the electropositive fragmentation patterns of a number of camphor-derived chiral acrylate esters was conducted. Attention has also been given to the application of MBH methodology in the construction of heterocyclic ‘cinnamate-like’ AZT conjugates which were designed to serve as dualaction HIV-1 integrase-reverse transcriptase (IN-RT) inhibitors. A number of pyridine carboxaldehyde-derived MBH adducts were synthesized using methyl, ethyl and t-butyl acrylates in the presence of 3-hydroxyquinuclidine (3-HQ) as catalyst. The yields for these reactions were excellent. The resulting MBH adducts were acetylated and subjected to aza-Michael addition using propargylamine. The resulting alkylamino compounds were then used in ‘Click reactions’ to form the targeted AZT-conjugates in moderate to excellent yield. In silico docking of computer modelled AZT-conjugates into the HIV-1 integrase and reverse transcriptase enzyme-active sites and potential hydrogen-bonding interaction with active-site amino acid residues were identified. The electrospray MS fragmentations of the AZT and the novel AZT-conjugates were also investigated and common fragmentation pathways were identified.
- Full Text:
- Date Issued: 2013
ATP mimics as glutamine synthetase inhibitors : an exploratory synthetic study
- Authors: Salisu, Sheriff Tomilola
- Date: 2008
- Subjects: Glutamine synthetase Tuberculosis -- Treatment Tuberculosis -- Chemotherapy Adenosine triphosphate Adenosine triphosphate -- Synthesis Drug development
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4408 , http://hdl.handle.net/10962/d1006715
- Description: Using a mechanism-based approach to drug discovery, efforts have been directed towards developing novel ATP mimics that can act as GS inhibitors. The purine-based systems, adenosine, adenine and allopurinol, were identified as possible scaffolds for potential ATP mimics, while various meta-disubstituted benzenoid compounds, 3-aminobenzonitrile, 3-aminophenol, resorcinol, 3-aminobenzyl alcohol, 3-hydroxybenzoic acid and 3-aminobenzoic acid have been explored as adenine analogues. These compounds were treated with different alkylating and acylating agents. Allylation of all the substrates was achieved using allyl bromide and N-9 alkylation of protected allopurinol was effected using a number of specially prepared Baylis-Hillman adducts. Acylation of the benzenoid precursors with chloroacetyl chloride, acetoxyacetyl chloride, acryloyl chloride and specially prepared 2,3,4,5,6-pentaacetylgluconoyl chloride afforded the corresponding mono- and /or diacylated products in varying yields (4-96%). Elaboration of the alkylated and acylated products has involved the reaction of hydroxy systems with diethyl chloro phosphate and chloro derivatives with triethyl phosphite in Arbuzov-type reactions to afford phosphorylated products. In all cases, products were fully characterized using 1- and 2-D NMR analysis and, where appropriate, high-resolution mass spectrometry. The application of Modgraph and ChemWindow NMR prediction programmes has been explored and the resulting data have been compared with experimental chemical shift assignments to confirm chemical structures and, in some cases, to establish the position of allylation or acylation. Experimental assignments were found to be generally comparable with the Modgraph data, but not always with the ChemWindow values. The docking of selected products in the 'active-site' of GS and their structural homology with ATP, both in their free and bound conformations have been studied using the ACCELERYS Cerius² platform. All the selected ATP mimics exhibit some form of interaction with the 'active-site' residues, and a number of them appear to be promising GS ligands.
- Full Text:
- Date Issued: 2008
- Authors: Salisu, Sheriff Tomilola
- Date: 2008
- Subjects: Glutamine synthetase Tuberculosis -- Treatment Tuberculosis -- Chemotherapy Adenosine triphosphate Adenosine triphosphate -- Synthesis Drug development
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4408 , http://hdl.handle.net/10962/d1006715
- Description: Using a mechanism-based approach to drug discovery, efforts have been directed towards developing novel ATP mimics that can act as GS inhibitors. The purine-based systems, adenosine, adenine and allopurinol, were identified as possible scaffolds for potential ATP mimics, while various meta-disubstituted benzenoid compounds, 3-aminobenzonitrile, 3-aminophenol, resorcinol, 3-aminobenzyl alcohol, 3-hydroxybenzoic acid and 3-aminobenzoic acid have been explored as adenine analogues. These compounds were treated with different alkylating and acylating agents. Allylation of all the substrates was achieved using allyl bromide and N-9 alkylation of protected allopurinol was effected using a number of specially prepared Baylis-Hillman adducts. Acylation of the benzenoid precursors with chloroacetyl chloride, acetoxyacetyl chloride, acryloyl chloride and specially prepared 2,3,4,5,6-pentaacetylgluconoyl chloride afforded the corresponding mono- and /or diacylated products in varying yields (4-96%). Elaboration of the alkylated and acylated products has involved the reaction of hydroxy systems with diethyl chloro phosphate and chloro derivatives with triethyl phosphite in Arbuzov-type reactions to afford phosphorylated products. In all cases, products were fully characterized using 1- and 2-D NMR analysis and, where appropriate, high-resolution mass spectrometry. The application of Modgraph and ChemWindow NMR prediction programmes has been explored and the resulting data have been compared with experimental chemical shift assignments to confirm chemical structures and, in some cases, to establish the position of allylation or acylation. Experimental assignments were found to be generally comparable with the Modgraph data, but not always with the ChemWindow values. The docking of selected products in the 'active-site' of GS and their structural homology with ATP, both in their free and bound conformations have been studied using the ACCELERYS Cerius² platform. All the selected ATP mimics exhibit some form of interaction with the 'active-site' residues, and a number of them appear to be promising GS ligands.
- Full Text:
- Date Issued: 2008
Agreement and coordination in XiTsonga, SeSotho and IsiXhosa: an optimality theoretic perspective
- Authors: Mitchley, Hazel
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3423 , vital:20491
- Description: This thesis provides a unified Optimality Theoretic analysis of subject-verb agreement with coordinated preverbal subjects in three Southern Bantu languages: Xitsonga (S53), Sesotho (S33), and isiXhosa (S41). This analysis is then used to formulate a typology of agreement resolution strategies and the contexts which trigger them. Although some accounts in the Bantu literature suggest that agreement with coordinate structures is avoided by speakers (e.g. Schadeberg 1992, Voeltz 1971) especially when conjuncts are from different noun classes, I show that there is ample evidence to the contrary, and that the subject marker used is dependent on several factors, including (i) the [-HUMAN] specification on the conjuncts, (ii) whether the conjuncts are singular or plural, (iii) whether or not the conjuncts both carry the same noun class feature, and (iv) the order of the conjuncts. This thesis shows that there are various agreement resolution strategies which can beused: 1) agreement with the [+HUMAN] feature on the conjuncts, 2) agreement with the[-HUMAN] feature on the conjuncts, 3) agreement with the noun class feature on both conjuncts, 4) agreement with the noun class feature on the conjunct closest to the verb, and 5) agreement with the noun class feature on the conjunct furthest from the verb. Not all of these strategies are used by all languages, nor are these strategies interchangeable in the languages which do use them – instead, multiple factors conspire to trigger the use of a specific agreement strategy within a specific agreement featural context. I show that these effects can be captured using Optimality Theory (Prince and Smolensky 2004). The analysis makes use of seven constraints: RES#, MAX[+H], MAX[-H], DEP[-H], MAXNC, DEPNC, and AGREECLOSEST. The hierarchical ranking of these constraints not only accounts for the confinement of particular strategies to specific agreement featural contexts within a language, but also accounts for the cross-linguistic differences in the use of these strategies. I end off by examining the typological implications which follow from the OT analysis provided in this thesis.
- Full Text:
- Date Issued: 2016
- Authors: Mitchley, Hazel
- Date: 2016
- Language: English
- Type: Thesis , Masters , MA
- Identifier: http://hdl.handle.net/10962/3423 , vital:20491
- Description: This thesis provides a unified Optimality Theoretic analysis of subject-verb agreement with coordinated preverbal subjects in three Southern Bantu languages: Xitsonga (S53), Sesotho (S33), and isiXhosa (S41). This analysis is then used to formulate a typology of agreement resolution strategies and the contexts which trigger them. Although some accounts in the Bantu literature suggest that agreement with coordinate structures is avoided by speakers (e.g. Schadeberg 1992, Voeltz 1971) especially when conjuncts are from different noun classes, I show that there is ample evidence to the contrary, and that the subject marker used is dependent on several factors, including (i) the [-HUMAN] specification on the conjuncts, (ii) whether the conjuncts are singular or plural, (iii) whether or not the conjuncts both carry the same noun class feature, and (iv) the order of the conjuncts. This thesis shows that there are various agreement resolution strategies which can beused: 1) agreement with the [+HUMAN] feature on the conjuncts, 2) agreement with the[-HUMAN] feature on the conjuncts, 3) agreement with the noun class feature on both conjuncts, 4) agreement with the noun class feature on the conjunct closest to the verb, and 5) agreement with the noun class feature on the conjunct furthest from the verb. Not all of these strategies are used by all languages, nor are these strategies interchangeable in the languages which do use them – instead, multiple factors conspire to trigger the use of a specific agreement strategy within a specific agreement featural context. I show that these effects can be captured using Optimality Theory (Prince and Smolensky 2004). The analysis makes use of seven constraints: RES#, MAX[+H], MAX[-H], DEP[-H], MAXNC, DEPNC, and AGREECLOSEST. The hierarchical ranking of these constraints not only accounts for the confinement of particular strategies to specific agreement featural contexts within a language, but also accounts for the cross-linguistic differences in the use of these strategies. I end off by examining the typological implications which follow from the OT analysis provided in this thesis.
- Full Text:
- Date Issued: 2016
A study of a class of invariant optimal control problems on the Euclidean group SE(2)
- Authors: Adams, Ross Montague
- Date: 2011
- Subjects: Matrix groups Lie groups Extremal problems (Mathematics) Maximum principles (Mathematics) Hamilton-Jacobi equations Lyapunov stability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5420 , http://hdl.handle.net/10962/d1006060
- Description: The aim of this thesis is to study a class of left-invariant optimal control problems on the matrix Lie group SE(2). We classify, under detached feedback equivalence, all controllable (left-invariant) control affine systems on SE(2). This result produces six types of control affine systems on SE(2). Hence, we study six associated left-invariant optimal control problems on SE(2). A left-invariant optimal control problem consists of minimizing a cost functional over the trajectory-control pairs of a left-invariant control system subject to appropriate boundary conditions. Each control problem is lifted from SE(2) to T*SE(2) ≅ SE(2) x se (2)*and then reduced to a problem on se (2)*. The maximum principle is used to obtain the optimal control and Hamiltonian corresponding to the normal extremals. Then we derive the (reduced) extremal equations on se (2)*. These equations are explicitly integrated by trigonometric and Jacobi elliptic functions. Finally, we fully classify, under Lyapunov stability, the equilibrium states of the normal extremal equations for each of the six types under consideration.
- Full Text:
- Date Issued: 2011
- Authors: Adams, Ross Montague
- Date: 2011
- Subjects: Matrix groups Lie groups Extremal problems (Mathematics) Maximum principles (Mathematics) Hamilton-Jacobi equations Lyapunov stability
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:5420 , http://hdl.handle.net/10962/d1006060
- Description: The aim of this thesis is to study a class of left-invariant optimal control problems on the matrix Lie group SE(2). We classify, under detached feedback equivalence, all controllable (left-invariant) control affine systems on SE(2). This result produces six types of control affine systems on SE(2). Hence, we study six associated left-invariant optimal control problems on SE(2). A left-invariant optimal control problem consists of minimizing a cost functional over the trajectory-control pairs of a left-invariant control system subject to appropriate boundary conditions. Each control problem is lifted from SE(2) to T*SE(2) ≅ SE(2) x se (2)*and then reduced to a problem on se (2)*. The maximum principle is used to obtain the optimal control and Hamiltonian corresponding to the normal extremals. Then we derive the (reduced) extremal equations on se (2)*. These equations are explicitly integrated by trigonometric and Jacobi elliptic functions. Finally, we fully classify, under Lyapunov stability, the equilibrium states of the normal extremal equations for each of the six types under consideration.
- Full Text:
- Date Issued: 2011
Synthesis, characterization and biological activity of some Dithiourea Derivatives:
- Odame, Felix, Hosten, Eric, Krause, Jason, Isaacs, Michelle, Hoppe, Heinrich C, Khanye, Setshaba D, Sayed, Yasien, Frost, Carminita, Lobb, Kevin A, Tshentu, Zenixole
- Authors: Odame, Felix , Hosten, Eric , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita , Lobb, Kevin A , Tshentu, Zenixole
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
- Authors: Odame, Felix , Hosten, Eric , Krause, Jason , Isaacs, Michelle , Hoppe, Heinrich C , Khanye, Setshaba D , Sayed, Yasien , Frost, Carminita , Lobb, Kevin A , Tshentu, Zenixole
- Date: 2020
- Language: English
- Type: text , article
- Identifier: http://hdl.handle.net/10962/163046 , vital:41007 , DOI: 10.17344/acsi.2019.5689
- Description: Novel dithiourea derivatives have been designed as HIV-1 protease inhibitors using Autodock 4.2, synthesized and characterized by spectroscopic methods and microanalysis.
- Full Text:
- Date Issued: 2020
Studies in Carangid fishes no 6: key to western Indian Ocean species of the genus Carangoides Bleeker, 1851, with a desciption of Carangoides Nitidus Smith
- Authors: Smith, Margaret Mary
- Date: 1972
- Language: English
- Type: Text
- Identifier: vital:15053 , http://hdl.handle.net/10962/d1020235
- Full Text:
- Date Issued: 1972
- Authors: Smith, Margaret Mary
- Date: 1972
- Language: English
- Type: Text
- Identifier: vital:15053 , http://hdl.handle.net/10962/d1020235
- Full Text:
- Date Issued: 1972
Rhenium complexes with multidentate benzazoles and related N,X-donor (X = N, O, S) ligands
- Authors: Potgieter, Kim Carey
- Date: 2012
- Subjects: Rhenium , Benzimidazoles , Ligands (Biochemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10438 , http://hdl.handle.net/10948/d1020773
- Description: The coordination behaviour of 4-aminoantipyrine (H2pap) and its Schiff base derivatives with the oxorhenium(V) and tricarbonyl rhenium(I) cores are reported. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with H2pap were studied, and the complexes cis-[ReX2(pap)(H2pap)(PPh3)](ReO4) were isolated. The ligand pap is coordinated monodentately through the doubly deprotonated amino nitrogen as an imide, and H2pap acts as a neutral bidentate chelate, with coordination through the neutral amino nitrogen and the ketonic oxygen. The reactions of trans-[ReOBr3(PPh3)2] and cis-[ReO2I(PPh3)2] with -(2-aminobenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (H2nap) and 4-(2-hydroxybenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (Hoap) are also reported. The complexes cis-[Re(nap)Br2(PPh3)]Br, [ReO(OEt)(Hnap)(PPh3)]I and [ReO(OMe)(oap)(PPh3)]I were isolated and structurally characterized. The reactions of the Schiff base derivatives 1,2-(diimino-4’-antipyrinyl)ethane (dae) and 2,6-bis(4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one)pyridine (bap) with [Re(CO)5X] (X = Br or Cl) produced fac-[Re(CO)3(dae)Cl] and fac-[Re(CO)3(bap)Br] respectively. A series of rhenium(I) tricarbonyl complexes containing bidentate derivatives of aniline was synthesized and structurally characterized. With 1,2-diaminobenzene (Hpda) the ‘2+1’ complex salt fac-[Re(CO)3(κ1-Hpda)(κ2-Hpda)]Br was isolated, but with 2-mercaptophenol (Hspo) the bridged dimer [Re2(CO)7(spo)2] was found. The neutral complex [Re(CO)3(ons)(Hno)] was isolated from the reaction of [Re(CO)5Br] with 2-[(2-methylthio)benzylideneimino]phenol (Hons; Hno = 2-aminophenol), with ons coordinated as a bidentate chelate with a free SCH3 group. In the complex [Re(CO)3(Htpn)Br] (Htpn = N-(2-(methylthio)benzylidene)benzene-1,2-diamine) the potentially tridentate ligand Htpn is coordinated via the methylthiol sulfur and imino nitrogen atoms only, with a free amino group. These rhenium(I) complexes, with the exception of [Re2(CO)7(spo)2], revealed broad emissions centred around 535 nm. The reactions of the rhenium(V) complex cis-[ReO2I(PPh3)2] with 2-aminothiophenol (H2atp), benzene-1,2-dithiol (H2tdt) and 2-hydroxybenzenethiol (H2otp) led to the formation of the rhenium(III) compounds [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 (ibsq = 2-iminothiobenzosemiquinonate, sbsq = 1,2-dithiobenzosemiquinonate, obsq = 2-hydroxothiobenzosemiquinonate) respectively. The complexes adopt a trigonal prismatic geometry around the rhenium centre with average twists angles between 3.20-26.10˚. The E1/2 values for the Re(III)/Re(IV) redox couple were found to be 0.022, 0.142 and 0.126 V for [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 respectively. The reactions of the benzoxazole ligands, 3-(benzoxazol-2-yl)pyridin-2-ol (Hbop) and 5-amino-2-(benzoxazol-2-yl)phenol (Habo) with a [ReO]3+ precursor led to the rhenium(III) complex, [ReCl2(bop)(PPh3)2], and the complex salt, [ReO(abo)I(PPh3)2]ReO4, respectively. A variety of benzothiazole and benzimidazole derivatives were reacted with [Re(CO)5Br]. In the case of bis(benzothiazol-2-ylethyl)sulfide (bts), the neutral complex fac-[Re(CO)3(bts)Br] was obtained. The dimeric complexes (μ-dbt)2[Re(CO)3]2 and (μ-mbt)2[Re(CO)3]2 were formed when 1,3-bis(benzothiazol-2-yl)thiourea (Hdbt) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) were used as ligands. The reaction of 2,2’-(oxybis(methylene))bis(benzimidazole) (bmb) with [Re(CO)5Cl] resulted in the rhenium(I) complex salt fac-[Re(CO)3(bmb)]+, with the tri-μ-chlorohexacarbonyl dirhenate [Re2(CO)6Cl3]- as the counter anion. The neutral complex fac-[Re(CO)3(btp)Cl] was isolated from the reaction of the 2,9-bis(benzothiazol-2-yl)-1,10-phenanthroline (btp) ligand and [Re(CO)5Cl]. The reactions of trans-[ReOCl3(PPh3)2] with bis(benzimidazol-2-ylethyl)sulfide (btn) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) led to the formation of the cationic compounds (μ-O)2[Re2O2(btn)2]I2 and [ReCl2(bte)(PPh3)2]Cl (bte = (benzothiazole-2-yl)-N-ethylidenemethanamine) respectively.
- Full Text:
- Date Issued: 2012
- Authors: Potgieter, Kim Carey
- Date: 2012
- Subjects: Rhenium , Benzimidazoles , Ligands (Biochemistry)
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:10438 , http://hdl.handle.net/10948/d1020773
- Description: The coordination behaviour of 4-aminoantipyrine (H2pap) and its Schiff base derivatives with the oxorhenium(V) and tricarbonyl rhenium(I) cores are reported. The reactions of trans-[ReOX3(PPh3)2] (X = Cl, Br) with H2pap were studied, and the complexes cis-[ReX2(pap)(H2pap)(PPh3)](ReO4) were isolated. The ligand pap is coordinated monodentately through the doubly deprotonated amino nitrogen as an imide, and H2pap acts as a neutral bidentate chelate, with coordination through the neutral amino nitrogen and the ketonic oxygen. The reactions of trans-[ReOBr3(PPh3)2] and cis-[ReO2I(PPh3)2] with -(2-aminobenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (H2nap) and 4-(2-hydroxybenzylideneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (Hoap) are also reported. The complexes cis-[Re(nap)Br2(PPh3)]Br, [ReO(OEt)(Hnap)(PPh3)]I and [ReO(OMe)(oap)(PPh3)]I were isolated and structurally characterized. The reactions of the Schiff base derivatives 1,2-(diimino-4’-antipyrinyl)ethane (dae) and 2,6-bis(4-amino-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one)pyridine (bap) with [Re(CO)5X] (X = Br or Cl) produced fac-[Re(CO)3(dae)Cl] and fac-[Re(CO)3(bap)Br] respectively. A series of rhenium(I) tricarbonyl complexes containing bidentate derivatives of aniline was synthesized and structurally characterized. With 1,2-diaminobenzene (Hpda) the ‘2+1’ complex salt fac-[Re(CO)3(κ1-Hpda)(κ2-Hpda)]Br was isolated, but with 2-mercaptophenol (Hspo) the bridged dimer [Re2(CO)7(spo)2] was found. The neutral complex [Re(CO)3(ons)(Hno)] was isolated from the reaction of [Re(CO)5Br] with 2-[(2-methylthio)benzylideneimino]phenol (Hons; Hno = 2-aminophenol), with ons coordinated as a bidentate chelate with a free SCH3 group. In the complex [Re(CO)3(Htpn)Br] (Htpn = N-(2-(methylthio)benzylidene)benzene-1,2-diamine) the potentially tridentate ligand Htpn is coordinated via the methylthiol sulfur and imino nitrogen atoms only, with a free amino group. These rhenium(I) complexes, with the exception of [Re2(CO)7(spo)2], revealed broad emissions centred around 535 nm. The reactions of the rhenium(V) complex cis-[ReO2I(PPh3)2] with 2-aminothiophenol (H2atp), benzene-1,2-dithiol (H2tdt) and 2-hydroxybenzenethiol (H2otp) led to the formation of the rhenium(III) compounds [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 (ibsq = 2-iminothiobenzosemiquinonate, sbsq = 1,2-dithiobenzosemiquinonate, obsq = 2-hydroxothiobenzosemiquinonate) respectively. The complexes adopt a trigonal prismatic geometry around the rhenium centre with average twists angles between 3.20-26.10˚. The E1/2 values for the Re(III)/Re(IV) redox couple were found to be 0.022, 0.142 and 0.126 V for [Re(Hatp)(ibsq)2].OPPh3, [Re(sbsq)3].OPPh3 and [Re(obsq)3].OPPh3 respectively. The reactions of the benzoxazole ligands, 3-(benzoxazol-2-yl)pyridin-2-ol (Hbop) and 5-amino-2-(benzoxazol-2-yl)phenol (Habo) with a [ReO]3+ precursor led to the rhenium(III) complex, [ReCl2(bop)(PPh3)2], and the complex salt, [ReO(abo)I(PPh3)2]ReO4, respectively. A variety of benzothiazole and benzimidazole derivatives were reacted with [Re(CO)5Br]. In the case of bis(benzothiazol-2-ylethyl)sulfide (bts), the neutral complex fac-[Re(CO)3(bts)Br] was obtained. The dimeric complexes (μ-dbt)2[Re(CO)3]2 and (μ-mbt)2[Re(CO)3]2 were formed when 1,3-bis(benzothiazol-2-yl)thiourea (Hdbt) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) were used as ligands. The reaction of 2,2’-(oxybis(methylene))bis(benzimidazole) (bmb) with [Re(CO)5Cl] resulted in the rhenium(I) complex salt fac-[Re(CO)3(bmb)]+, with the tri-μ-chlorohexacarbonyl dirhenate [Re2(CO)6Cl3]- as the counter anion. The neutral complex fac-[Re(CO)3(btp)Cl] was isolated from the reaction of the 2,9-bis(benzothiazol-2-yl)-1,10-phenanthroline (btp) ligand and [Re(CO)5Cl]. The reactions of trans-[ReOCl3(PPh3)2] with bis(benzimidazol-2-ylethyl)sulfide (btn) and 1-(benzothiazol-2-ylidene)-3-methylthiourea (Hmbt) led to the formation of the cationic compounds (μ-O)2[Re2O2(btn)2]I2 and [ReCl2(bte)(PPh3)2]Cl (bte = (benzothiazole-2-yl)-N-ethylidenemethanamine) respectively.
- Full Text:
- Date Issued: 2012
The use of Landsat ETM imagery as a suitable data capture source for alien acacia species for the WFW programme
- Authors: Cobbing, Benedict Louis
- Date: 2007
- Subjects: Geographic information systems , Global Positioning System , Landsat satellites , Agriculture -- Remote sensing , Geography -- Remote sensing
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4856 , http://hdl.handle.net/10962/d1005532 , Geographic information systems , Global Positioning System , Landsat satellites , Agriculture -- Remote sensing , Geography -- Remote sensing
- Description: Geographic Information System technology today allows for the rapid analysis of vast amounts of spatial and non-spatial data. The power of a GIS can only be effected with the rapid collection of accurate input data. This is particularly true in the case of the South African National Working for Water (WFW) Programme where large volumes of spatial data on alien vegetation infestations are captured throughout the country. Alien vegetation clearing contracts cannot be generated, for WFW, without this data, so that the accurate capture of such data is crucial to the success of the programme. Mapping Invasive Alien Plant (IAP) data within WFW is a perennial problem (Coetzee, pers com, 2002), because not enough mapping is being done to meet the annual requirements of the programme in the various provinces. This is re-iterated by Richardson, 2004, who states that there is a shortage of accurate data on IAP abundance in South Africa. Therefore there is a need to investigate alternate methods of data capture; such as remote sensing, whilst working within the existing WFW data capture standards. The aim of this research was to investigate the use of Landsat ETM imagery as a data capture source for mapping alien vegetation for the WFW Programme in terms of their approved mapping methods, for both automated and manual classification techniques. The automated and manual classification results were compared to control data captured by differential Global Positioning Systems (DGPS). The research tested the various methods of data capture using Landsat ETM images over a range of study sites of varying complexity: a simple grassland area, a medium complexity grassy fynbos site and a complicated indigenous forest site. An important component of the research was to develop a mapping (classification) Ranking System based upon variables identified by WFW as fundamental in data capture decision making: spatial and positional accuracy, time constraints and cost constraints for three typical alien invaded areas. The mapping Ranking System compared the results of the various mapping methods for each factor for the study sites against each other. This provided an indication of which mapping method is the most efficient or suitable for a particular area.
- Full Text:
- Date Issued: 2007
- Authors: Cobbing, Benedict Louis
- Date: 2007
- Subjects: Geographic information systems , Global Positioning System , Landsat satellites , Agriculture -- Remote sensing , Geography -- Remote sensing
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4856 , http://hdl.handle.net/10962/d1005532 , Geographic information systems , Global Positioning System , Landsat satellites , Agriculture -- Remote sensing , Geography -- Remote sensing
- Description: Geographic Information System technology today allows for the rapid analysis of vast amounts of spatial and non-spatial data. The power of a GIS can only be effected with the rapid collection of accurate input data. This is particularly true in the case of the South African National Working for Water (WFW) Programme where large volumes of spatial data on alien vegetation infestations are captured throughout the country. Alien vegetation clearing contracts cannot be generated, for WFW, without this data, so that the accurate capture of such data is crucial to the success of the programme. Mapping Invasive Alien Plant (IAP) data within WFW is a perennial problem (Coetzee, pers com, 2002), because not enough mapping is being done to meet the annual requirements of the programme in the various provinces. This is re-iterated by Richardson, 2004, who states that there is a shortage of accurate data on IAP abundance in South Africa. Therefore there is a need to investigate alternate methods of data capture; such as remote sensing, whilst working within the existing WFW data capture standards. The aim of this research was to investigate the use of Landsat ETM imagery as a data capture source for mapping alien vegetation for the WFW Programme in terms of their approved mapping methods, for both automated and manual classification techniques. The automated and manual classification results were compared to control data captured by differential Global Positioning Systems (DGPS). The research tested the various methods of data capture using Landsat ETM images over a range of study sites of varying complexity: a simple grassland area, a medium complexity grassy fynbos site and a complicated indigenous forest site. An important component of the research was to develop a mapping (classification) Ranking System based upon variables identified by WFW as fundamental in data capture decision making: spatial and positional accuracy, time constraints and cost constraints for three typical alien invaded areas. The mapping Ranking System compared the results of the various mapping methods for each factor for the study sites against each other. This provided an indication of which mapping method is the most efficient or suitable for a particular area.
- Full Text:
- Date Issued: 2007
Asymmetric induction in reactions of chiral carboxylic esters and silyl enol ethers
- Authors: Evans, Melanie Daryl
- Date: 1998
- Subjects: Ethers -- Synthesis Esters -- Synthesis Chirality Asymmetric synthesis Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4409 , http://hdl.handle.net/10962/d1006762
- Description: Several camphor and pinane derivatives have been synthesised and evaluated for use as chiral auxiliaries in asymmetric synthesis. Various blocking groups have been attached to the camphor skeleton in attempts to improve stereofacial selectivity; these include α-methoxybenzyl and xylyl groups, and novel stereoisomeric ketal moieties derived from meso- and (R,R)-(-)-2,3-butanediol. Benzylation reactions carried out on the lithium enolates of ester derivatives of the camphor-derived chiral auxiliaries afforded α-benzylated products in 5-60% diastereomeric excess. Stereochemical aspects have been explored using high resolution NMR, X-ray crystallographic and computer modelling techniques, and hydrolysis of selected α-benzylated products has permitted the diasteroselective bias to be confirmed. Opposite configurations at the new stereogenic centre are clearly favoured by the xylyl and ketal blocking groups - an observation rationalised in terms of the presence or absence of chelating potential in the blocking group. Baylis-Hillman reactions carried out on a series of specially prepared camphor-derived acrylic esters containing the ketal blocking group exhibited both low diastereoselectivities (0-30% d.e.) and very long reaction times. Chiral silyl enol ethers, synthesised using both pinane and camphor derivatives as chiral auxiliaries, showed up to 20% diastereomeric excess in MCPBA oxidation, alkylation and Mukaiyama reactions. Attempts to bring the prochiral centre in the silyl enol ether substrates closer to the chiral auxiliary, and thus improve the stereofacial selectivity, proved unsuccessful. The silyl enol ether derivatives, however, display interesting fragmentation patterns in their electron impact mass spectra, which were investigated using a combination of high resolution MS, comparative low resolution MS and metastable peak analysis.
- Full Text:
- Date Issued: 1998
- Authors: Evans, Melanie Daryl
- Date: 1998
- Subjects: Ethers -- Synthesis Esters -- Synthesis Chirality Asymmetric synthesis Organic compounds -- Synthesis
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4409 , http://hdl.handle.net/10962/d1006762
- Description: Several camphor and pinane derivatives have been synthesised and evaluated for use as chiral auxiliaries in asymmetric synthesis. Various blocking groups have been attached to the camphor skeleton in attempts to improve stereofacial selectivity; these include α-methoxybenzyl and xylyl groups, and novel stereoisomeric ketal moieties derived from meso- and (R,R)-(-)-2,3-butanediol. Benzylation reactions carried out on the lithium enolates of ester derivatives of the camphor-derived chiral auxiliaries afforded α-benzylated products in 5-60% diastereomeric excess. Stereochemical aspects have been explored using high resolution NMR, X-ray crystallographic and computer modelling techniques, and hydrolysis of selected α-benzylated products has permitted the diasteroselective bias to be confirmed. Opposite configurations at the new stereogenic centre are clearly favoured by the xylyl and ketal blocking groups - an observation rationalised in terms of the presence or absence of chelating potential in the blocking group. Baylis-Hillman reactions carried out on a series of specially prepared camphor-derived acrylic esters containing the ketal blocking group exhibited both low diastereoselectivities (0-30% d.e.) and very long reaction times. Chiral silyl enol ethers, synthesised using both pinane and camphor derivatives as chiral auxiliaries, showed up to 20% diastereomeric excess in MCPBA oxidation, alkylation and Mukaiyama reactions. Attempts to bring the prochiral centre in the silyl enol ether substrates closer to the chiral auxiliary, and thus improve the stereofacial selectivity, proved unsuccessful. The silyl enol ether derivatives, however, display interesting fragmentation patterns in their electron impact mass spectra, which were investigated using a combination of high resolution MS, comparative low resolution MS and metastable peak analysis.
- Full Text:
- Date Issued: 1998
Synthesis, characterization, and biological studies of pyrazolone Schiff bases and their transition metal complexes
- Authors: Idemudia, Omoruyi Gold
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD (Chemistry)
- Identifier: vital:11340 , http://hdl.handle.net/10353/d1016068
- Description: Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.
- Full Text:
- Date Issued: 2014
- Authors: Idemudia, Omoruyi Gold
- Date: 2014
- Language: English
- Type: Thesis , Doctoral , PhD (Chemistry)
- Identifier: vital:11340 , http://hdl.handle.net/10353/d1016068
- Description: Some new acylpyrazolone Schiff bases have been synthesized from the condensation reaction of two acylpyrazolone diketone precursors with phenylhydrazine, 2,4-dinitrophenylhydrazine and sulfanilamide. They have been fully characterized by elemental analysis and spectroscopic techniques (IR,1H and 13C NMR, and mass-spectra). The single crystal structure of the benzoyl derivative acylpyrazolone Schiff bases have been obtained and analyzed by X-ray crystallography technique. Solid state X-ray diffraction revealed a keto tautomer Schiff base in solid state. Mn(II), Co(II), Ni(II) and Cu(II) complexes with the Schiff bases have been synthesized and characterized by elemental analysis, IR and UV-VIS spectroscopy, magnetic susceptibility measurements, and thermal studies (TGA and DTG). An octahedral geometry around the transition metal ion, consisting of two bidentate Schiff base ligands bonding through the azometine nitrogen and ketonic oxygen have been proposed based on careful interpretation of available analytical and spectroscopic characterization results. Two water molecules as ligands complete the octahedral geometry in all cases. Using the invitro disc diffusion method for screening synthesized compounds against selected gram positive and gram negative bacterial at 40 mg/mL, and the DPPH free radical scavenging methods at 0.50, 0.25 and 0.13 mg/mL, the synthesized Schiff base and metal complexes showed varying biological activities. 4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one sul29 fanilamide showed more activity generally, exhibiting a broad spectrum activity against all selected bacterial in some cases. Mn(II), Co(II) and Ni(II) complexes of sulfanilamide Schiff base with the acetylpyrazolone derivative 4-acetyl-3-methyl-1-phenyl-2-pyrazolin-5-one sulfanilamide, exhibited a stronger and very good DPPH radical scavenging activity as good as ascorbic acid on comparing, but not with Cu(II). As such they could be important antitumour candidates.
- Full Text:
- Date Issued: 2014
The synthesis, empirical and theoretical studies of various (N→B) diarylborinate esters
- Authors: Manana, Pholani Sakhile
- Date: 2021-12
- Subjects: Port Elizabeth (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/53869 , vital:46027
- Description: A series of core-functionalized borinic acids was synthesized from Grignard reagents and tributylborate and reacted with ethanolamine, amino acids, 2-pyridylmethanol as well as 2-(ethyl amino ethanol). Among the borinic acids synthesized were the ones bearing: para-(2, 15, 16, 22, 27)-methyl, (3, 20, 25)-chloro, (4, 23, 26)-fluoro, (5)-methoxy; meta-(7, 17)-methyl, (9)-fluoro; ortho-(6)-methyl, (8)-chloro, (10, 18, 19)-methoxy substituents on their respective aromatic systems. All compounds obtained by condensation of the borinic acids with the aforementioned nitrogen-containing substrates were characterized structurally by means of diffraction studies based on single crystals and found to constitute chelate esters/amides featuring covalent B-O and dative N→B bonds. The chelate compounds researched in this study could be classified into four families and represent the compounds: ethanol amine: (1) 2,2-diphenyl-1,3,2-oxazaborolidines, (2) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (3) 2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (4) 2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (5) 2,2-bis(p-methoxyphenyl)-1,3,2-oxazaborolidines, (6) 2,2-bis(o-tolyl)-1,3,2-oxazaborolidines, (7) 2,2-bis(m-tolyl)-1,3,2-oxazaborolidines, (8) 2,2-bis(o-chlorophenyl)-1,3,2-oxazaborolidines, (9) 2,2-bis(m-fluorophenyl)-1,3,2-oxazaborolidines, (10) 2,2-bis(o-methoxyphenyl)-1,3,2-oxazaborolidines. α-amino acids : (14) 4-methyl-2,2-diphenyl-1,3,2-oxazaborolidin-5-ones, (15) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (16) 4-methyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (17) 4-isopropyl-2,2-bis(m-tolyl)-1,3,2-oxazaborolidin-5-ones, (18) 4-methyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (19) 4-acetamidyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (20) 4-phenylethane-2,2-bis(p-chlorophenyl)-1,3,2 oxazaborolidin-5-ones. 2-pyridylmethanol: (21) 1,3-hydroxypyridyl-2,2-diphenyl 1,3,2-oxazaborolidines, (22) 1,3-hydroxypyridyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (23) 1,3-hydroxypyridyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines 2-(ethyl amino ethanol): (24) 3-ethyl-2,2-diphenyl-1,3,2-oxazaborolidines, (25) 3-ethyl-2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (26) 3-ethyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (27) 3-ethyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines. Apart from structural studies in the solid state, the compounds were also characterized by means of multinuclear NMR spectroscopy (1H, 11B, 13C) as well as UV/vis and FTIR. The typical 11B resonances were found in the range of (4-10 ppm). A series of characteristic metrical parameters for the compounds in the solid state as well as typical NMR shifts for the chelate target molecules was established that allowed for the determination of the coordination induced shift. The carbon atom bonded to the oxygen atom shifted upfield, while the carbon atom bonded to the nitrogen atom shifted downfield. Factors mentioned in the literature that has an influence on the hydrolytic stability on the heterocyclic borinate motif have been taken into consideration and verified for the systems researched in this study. The substitution at the nitrogen atom with one ethyl group caused the greatest increases in the N→B bond length (27) 1.714 Å, due to the increase in the nitrogen Lewis basicity, making it the least hydrolytically stable, these include compounds (24-26). Furthermore, DFT calculations were performed by employing Becke’s three parameter hybrid exchange functional with Lee–Yang–Parr functional (B3LYP) method using the Gaussian 16 program package (Rev. B01) employing the basis set 6-311++G(d,p), to corroborate and correlate the experimental findings, which gave a general R-squared value of 0.9978 for calculated vs experimental 13C chemical shifts. Thermal properties are recorded for select compounds, indicating the ΔH and the melting points. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Full Text:
- Date Issued: 2021-12
- Authors: Manana, Pholani Sakhile
- Date: 2021-12
- Subjects: Port Elizabeth (South Africa) , Eastern Cape (South Africa) , South Africa
- Language: English
- Type: Doctoral theses , text
- Identifier: http://hdl.handle.net/10948/53869 , vital:46027
- Description: A series of core-functionalized borinic acids was synthesized from Grignard reagents and tributylborate and reacted with ethanolamine, amino acids, 2-pyridylmethanol as well as 2-(ethyl amino ethanol). Among the borinic acids synthesized were the ones bearing: para-(2, 15, 16, 22, 27)-methyl, (3, 20, 25)-chloro, (4, 23, 26)-fluoro, (5)-methoxy; meta-(7, 17)-methyl, (9)-fluoro; ortho-(6)-methyl, (8)-chloro, (10, 18, 19)-methoxy substituents on their respective aromatic systems. All compounds obtained by condensation of the borinic acids with the aforementioned nitrogen-containing substrates were characterized structurally by means of diffraction studies based on single crystals and found to constitute chelate esters/amides featuring covalent B-O and dative N→B bonds. The chelate compounds researched in this study could be classified into four families and represent the compounds: ethanol amine: (1) 2,2-diphenyl-1,3,2-oxazaborolidines, (2) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (3) 2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (4) 2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (5) 2,2-bis(p-methoxyphenyl)-1,3,2-oxazaborolidines, (6) 2,2-bis(o-tolyl)-1,3,2-oxazaborolidines, (7) 2,2-bis(m-tolyl)-1,3,2-oxazaborolidines, (8) 2,2-bis(o-chlorophenyl)-1,3,2-oxazaborolidines, (9) 2,2-bis(m-fluorophenyl)-1,3,2-oxazaborolidines, (10) 2,2-bis(o-methoxyphenyl)-1,3,2-oxazaborolidines. α-amino acids : (14) 4-methyl-2,2-diphenyl-1,3,2-oxazaborolidin-5-ones, (15) 2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (16) 4-methyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidin-5-ones, (17) 4-isopropyl-2,2-bis(m-tolyl)-1,3,2-oxazaborolidin-5-ones, (18) 4-methyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (19) 4-acetamidyl-2,2-bis(o-methoxyphenyl)-1,3,2- oxazaborolidin-5-ones, (20) 4-phenylethane-2,2-bis(p-chlorophenyl)-1,3,2 oxazaborolidin-5-ones. 2-pyridylmethanol: (21) 1,3-hydroxypyridyl-2,2-diphenyl 1,3,2-oxazaborolidines, (22) 1,3-hydroxypyridyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines, (23) 1,3-hydroxypyridyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines 2-(ethyl amino ethanol): (24) 3-ethyl-2,2-diphenyl-1,3,2-oxazaborolidines, (25) 3-ethyl-2,2-bis(p-chlorophenyl)-1,3,2-oxazaborolidines, (26) 3-ethyl-2,2-bis(p-fluorophenyl)-1,3,2-oxazaborolidines, (27) 3-ethyl-2,2-bis(p-tolyl)-1,3,2-oxazaborolidines. Apart from structural studies in the solid state, the compounds were also characterized by means of multinuclear NMR spectroscopy (1H, 11B, 13C) as well as UV/vis and FTIR. The typical 11B resonances were found in the range of (4-10 ppm). A series of characteristic metrical parameters for the compounds in the solid state as well as typical NMR shifts for the chelate target molecules was established that allowed for the determination of the coordination induced shift. The carbon atom bonded to the oxygen atom shifted upfield, while the carbon atom bonded to the nitrogen atom shifted downfield. Factors mentioned in the literature that has an influence on the hydrolytic stability on the heterocyclic borinate motif have been taken into consideration and verified for the systems researched in this study. The substitution at the nitrogen atom with one ethyl group caused the greatest increases in the N→B bond length (27) 1.714 Å, due to the increase in the nitrogen Lewis basicity, making it the least hydrolytically stable, these include compounds (24-26). Furthermore, DFT calculations were performed by employing Becke’s three parameter hybrid exchange functional with Lee–Yang–Parr functional (B3LYP) method using the Gaussian 16 program package (Rev. B01) employing the basis set 6-311++G(d,p), to corroborate and correlate the experimental findings, which gave a general R-squared value of 0.9978 for calculated vs experimental 13C chemical shifts. Thermal properties are recorded for select compounds, indicating the ΔH and the melting points. , Thesis (PhD) -- Faculty of Science, School of Biomolecular and Chemical Sciences, 2021
- Full Text:
- Date Issued: 2021-12
Karyology of three evolutionarily hexaploid southern African species of yellowfish, Labeobarbus Rüppel, 1836 (Cyprinidae)
- Naran, D, Skelton, Paul H, Villet, Martin H
- Authors: Naran, D , Skelton, Paul H , Villet, Martin H
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6855 , http://hdl.handle.net/10962/d1011138 , http://dx.doi.org/10.3377/1562-7020(2007)42[254:KOTEHS]2.0.CO;2
- Description: The karyotypes of three species of yellowfish, namely Labeobarbus marequensis (A. Smith, 1841), L. capensis (A. Smith, 1841) and L. polylepis (Boulenger, 1907), were examined by Giemsa staining using an approach improved for the description of high chromosome numbers. In each case, 2n = 150; no heteromorphic chromosomes were detected; chromosomes in all morphological categories ranged smoothly from large to small, with no distinctly large submetacentric pairs; and metacentric chromosomes showed little variation in size. Labeobarbus marequensis had 26 metacentric (m), 44 submetacentric (sm), 42 subtelocentric (st) and 38 acrocentric (a) chromosomes and a fundamental number (FN) of 262; L. capensis had 16 m, 58 sm, 42 st and 34 a chromosomes and FN = 266; and L. polylepis had 18 m, 60 sm, 42 st and 30 a chromosomes and FN = 270. These results, combined with published literature, imply that Labeobarbus Rüppel, 1836 is an evolutionarily hexaploid African lineage and support its removal from synonymy with the evolutionarily tetraploid Asian genus Tor Gray, 1834. A review of fundamental numbers for conspecific Labeobarbus species examined in different studies implicated karyological technique as a confounding factor in assessing details of karyotypes, leading to recommendations for future karyological studies of barbine fishes. Potential synapomorphies are pointed out in karyological characters of species within Labeobarbus.
- Full Text:
- Date Issued: 2007
- Authors: Naran, D , Skelton, Paul H , Villet, Martin H
- Date: 2007
- Language: English
- Type: Article
- Identifier: vital:6855 , http://hdl.handle.net/10962/d1011138 , http://dx.doi.org/10.3377/1562-7020(2007)42[254:KOTEHS]2.0.CO;2
- Description: The karyotypes of three species of yellowfish, namely Labeobarbus marequensis (A. Smith, 1841), L. capensis (A. Smith, 1841) and L. polylepis (Boulenger, 1907), were examined by Giemsa staining using an approach improved for the description of high chromosome numbers. In each case, 2n = 150; no heteromorphic chromosomes were detected; chromosomes in all morphological categories ranged smoothly from large to small, with no distinctly large submetacentric pairs; and metacentric chromosomes showed little variation in size. Labeobarbus marequensis had 26 metacentric (m), 44 submetacentric (sm), 42 subtelocentric (st) and 38 acrocentric (a) chromosomes and a fundamental number (FN) of 262; L. capensis had 16 m, 58 sm, 42 st and 34 a chromosomes and FN = 266; and L. polylepis had 18 m, 60 sm, 42 st and 30 a chromosomes and FN = 270. These results, combined with published literature, imply that Labeobarbus Rüppel, 1836 is an evolutionarily hexaploid African lineage and support its removal from synonymy with the evolutionarily tetraploid Asian genus Tor Gray, 1834. A review of fundamental numbers for conspecific Labeobarbus species examined in different studies implicated karyological technique as a confounding factor in assessing details of karyotypes, leading to recommendations for future karyological studies of barbine fishes. Potential synapomorphies are pointed out in karyological characters of species within Labeobarbus.
- Full Text:
- Date Issued: 2007