Synthetic and bioactivity studies of antiplasmodial and antibacterial marine natural products
- Authors: Young, Ryan Mark
- Date: 2012
- Subjects: Antibacterial agents Marine natural products Marine pharmacology Plasmodium falciparum Staphylococcus aureus Isocyanides Imidazoles
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4378 , http://hdl.handle.net/10962/d1005043
- Description: This thesis is divided into two parts, assessing marine and synthetic compounds active firstly against Plasmodium falciparum (Chapter 3 and 4) and secondly active against methicillin resistant Staphylococcus aureus (MRSA, Chapter 5). In Chapter 3 the synthesis of nine new tricyclic podocarpanes (3.203-3.207 and 3.209-3.212) from the diterpene (+)-manool is described. Initial SAR study of synthetic podocarpanes concluded that the most active compound was a C-13 phenyl substituted podocarpane (3.204, IC₅₀ 6.6 μM). By preparing analogues with varying halogenated substituents on the phenyl ring (3.209-3.212) the antiplasmodial activity was improved (IC₅₀ 1.4 μM), while simultaneously decreasing the haemolysis previously reported for this class of compounds. Inspired by the antiplasmodial activity of Wright and Wattanapiromsakul’s tricycle marine isonitriles (2.16-2.21 and 2.24-2.27) an unsuccessfully attempt was made to convert tertiary alcohol moieties to isonitrile functionalities in compounds 3.188, 3.204-3.207 and 3.209-3.212. Over a decade ago Wright et al. proposed a putative antiplasmodial mechanism of action for marine isonitriles (2.4, 2.9, 2.15, 2.19 and 2.35) and isothiocyanate (2.34) which involved interference in haem detoxification by P. falciparum thus inhibiting the growth of the parasite. In Chapter 4 we describe how we successfully managed to scale down Egan’s β-haematin inhibition assay for the analyses of small quantities of marine natural products as potential β-haematin inhibitors. Our modified assay revealed that the most active antiplasmodial marine isonitrile 2.9 (IC₅₀ 13 nM) showed total β-haematin inhibition while 2.15 (IC₅₀ 81 nM) and 2.19 (IC₅₀ 31 nM) showed partial inhibition at three equivalents relative to haem. Using contempary molecular modelling techniques the charge on the isonitrile functionality was more accurately describe and the modified charge data sets was used to explore docking of marine isonitriles to haem using AutoDock. In Chapter 5 we describe how a lead South African marine bisindole MRSA pyruvate kinase inhibitor (5.8) was discovered in collaboration with colleagues at the University of British Columbia (UBC) and how this discovery inspired us to design a synthetic route to the dibrominated bisindole, isobromotopsentin (5.20) in an attempt to increase the bioactivity displayed by 5.8. We devised a fast and high yielding synthetic route using microwave assited organic synthesis. We first tested this synthesis using simple aryl glyoxals (5.27-5.32) as precursors to synthesize biphenylimidazoles (5.21-5.26), which later allowed us to synthesize the ascidian natural product 5.111. This method was sucessfully extended to the synthesis of deoxytopsentin (5.33) from an N-Boc protected indole methyl ketone (5.89). We subsequently were able to effectively remove the carbamate protection via thermal decomposition by heating the protected bisindole imidazole (5.90) in a microwave reactor for 5 min under argon. The synthesis of 5.20 resulted in an inseparable mixture of monoprotected and totally deprotected topsentin products, and due to time constraints we were not able to optimise this synthesis. Nonetheless our synthesis of the marine natural product 5.33 which was faster and higher yielding than previously reported routes could be extended to the synthesis of other topsentin bisindoles (5.138-5.140). Work towards this goal continues in our laboratory.
- Full Text:
- Date Issued: 2012
- Authors: Young, Ryan Mark
- Date: 2012
- Subjects: Antibacterial agents Marine natural products Marine pharmacology Plasmodium falciparum Staphylococcus aureus Isocyanides Imidazoles
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4378 , http://hdl.handle.net/10962/d1005043
- Description: This thesis is divided into two parts, assessing marine and synthetic compounds active firstly against Plasmodium falciparum (Chapter 3 and 4) and secondly active against methicillin resistant Staphylococcus aureus (MRSA, Chapter 5). In Chapter 3 the synthesis of nine new tricyclic podocarpanes (3.203-3.207 and 3.209-3.212) from the diterpene (+)-manool is described. Initial SAR study of synthetic podocarpanes concluded that the most active compound was a C-13 phenyl substituted podocarpane (3.204, IC₅₀ 6.6 μM). By preparing analogues with varying halogenated substituents on the phenyl ring (3.209-3.212) the antiplasmodial activity was improved (IC₅₀ 1.4 μM), while simultaneously decreasing the haemolysis previously reported for this class of compounds. Inspired by the antiplasmodial activity of Wright and Wattanapiromsakul’s tricycle marine isonitriles (2.16-2.21 and 2.24-2.27) an unsuccessfully attempt was made to convert tertiary alcohol moieties to isonitrile functionalities in compounds 3.188, 3.204-3.207 and 3.209-3.212. Over a decade ago Wright et al. proposed a putative antiplasmodial mechanism of action for marine isonitriles (2.4, 2.9, 2.15, 2.19 and 2.35) and isothiocyanate (2.34) which involved interference in haem detoxification by P. falciparum thus inhibiting the growth of the parasite. In Chapter 4 we describe how we successfully managed to scale down Egan’s β-haematin inhibition assay for the analyses of small quantities of marine natural products as potential β-haematin inhibitors. Our modified assay revealed that the most active antiplasmodial marine isonitrile 2.9 (IC₅₀ 13 nM) showed total β-haematin inhibition while 2.15 (IC₅₀ 81 nM) and 2.19 (IC₅₀ 31 nM) showed partial inhibition at three equivalents relative to haem. Using contempary molecular modelling techniques the charge on the isonitrile functionality was more accurately describe and the modified charge data sets was used to explore docking of marine isonitriles to haem using AutoDock. In Chapter 5 we describe how a lead South African marine bisindole MRSA pyruvate kinase inhibitor (5.8) was discovered in collaboration with colleagues at the University of British Columbia (UBC) and how this discovery inspired us to design a synthetic route to the dibrominated bisindole, isobromotopsentin (5.20) in an attempt to increase the bioactivity displayed by 5.8. We devised a fast and high yielding synthetic route using microwave assited organic synthesis. We first tested this synthesis using simple aryl glyoxals (5.27-5.32) as precursors to synthesize biphenylimidazoles (5.21-5.26), which later allowed us to synthesize the ascidian natural product 5.111. This method was sucessfully extended to the synthesis of deoxytopsentin (5.33) from an N-Boc protected indole methyl ketone (5.89). We subsequently were able to effectively remove the carbamate protection via thermal decomposition by heating the protected bisindole imidazole (5.90) in a microwave reactor for 5 min under argon. The synthesis of 5.20 resulted in an inseparable mixture of monoprotected and totally deprotected topsentin products, and due to time constraints we were not able to optimise this synthesis. Nonetheless our synthesis of the marine natural product 5.33 which was faster and higher yielding than previously reported routes could be extended to the synthesis of other topsentin bisindoles (5.138-5.140). Work towards this goal continues in our laboratory.
- Full Text:
- Date Issued: 2012
The synthesis of α-alkoxy and α-aminostannanes as precursors to Novel Chromium Fischer Carbenes
- Authors: Meyer, Annalene
- Date: 2012
- Subjects: Alkoxides , Organometallic compounds , Carbenes (Methylene compounds) , Chromium , Molybdenum , Tungsten , Organolithium compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4371 , http://hdl.handle.net/10962/d1005036 , Alkoxides , Organometallic compounds , Carbenes (Methylene compounds) , Chromium , Molybdenum , Tungsten , Organolithium compounds
- Description: The present study involves the use of main group organometallics: organostannanes and organolithiums as precursors to chromium Fischer carbene complexes. Fischer carbenes are well stabilized by the π‐donor substituents such as alkoxy and amino groups and low oxidation state metals such as Group 6 (Chromium, Molybdenum or Tungsten). Carbenes are an important intermediate in the synthesis of a range of compounds through cyclopropanations, insertions, coupling and photochemical reactions. Synthesis and successful characterisation of three α‐alkoxystannanes was achieved via nucleophilic addition of tributylstannyllithium to the respective aldehydes, followed by an immediate MOM protection of the resulting alcohol. Six α‐aminostanannes were synthesised, consisting of N‐BOC, N‐acetyl and N‐ethyl derivatives of pyrrolidine and piperidine, via α‐lithiation and subsequent tinlithium transmetallation in the presence of TMEDA. The ¹³C NMR analysis highlighted an interesting phenomenon of tin‐carbon coupling that revealed unique structural information of both types of stannanes. DFT analysis was completed on the series of stannanes; a predicted frequency analysis was obtained which complemented the experimental Infra‐red data in elucidation of the compounds. The α‐alkoxy and α‐aminostannanes provided stable precursors to the organolithiums required for the synthesis of the novel Fischer chromium carbenes. The organolithiums were obtained via tinlithium exchange at low temperatures, followed by the addition of chromium hexacarbonyl to form the acylpentacarbonyl‐chromate salt. Alkylation of this intermediate using a Meerwein salt, Me₃OBF₄, gave rise to the novel Fischer chromium carbene complexes. Fischer chromium carbenes derived from the two isomeric butyl and isobutyl stannanes and the two N‐ethyl α‐aminostannanes were successfully synthesised. The difficulty encountered in the purification of the Fischer carbene complexes hindered the full characterisation, due to the presence of a by‐product, tetrabutyltin.
- Full Text:
- Date Issued: 2012
- Authors: Meyer, Annalene
- Date: 2012
- Subjects: Alkoxides , Organometallic compounds , Carbenes (Methylene compounds) , Chromium , Molybdenum , Tungsten , Organolithium compounds
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4371 , http://hdl.handle.net/10962/d1005036 , Alkoxides , Organometallic compounds , Carbenes (Methylene compounds) , Chromium , Molybdenum , Tungsten , Organolithium compounds
- Description: The present study involves the use of main group organometallics: organostannanes and organolithiums as precursors to chromium Fischer carbene complexes. Fischer carbenes are well stabilized by the π‐donor substituents such as alkoxy and amino groups and low oxidation state metals such as Group 6 (Chromium, Molybdenum or Tungsten). Carbenes are an important intermediate in the synthesis of a range of compounds through cyclopropanations, insertions, coupling and photochemical reactions. Synthesis and successful characterisation of three α‐alkoxystannanes was achieved via nucleophilic addition of tributylstannyllithium to the respective aldehydes, followed by an immediate MOM protection of the resulting alcohol. Six α‐aminostanannes were synthesised, consisting of N‐BOC, N‐acetyl and N‐ethyl derivatives of pyrrolidine and piperidine, via α‐lithiation and subsequent tinlithium transmetallation in the presence of TMEDA. The ¹³C NMR analysis highlighted an interesting phenomenon of tin‐carbon coupling that revealed unique structural information of both types of stannanes. DFT analysis was completed on the series of stannanes; a predicted frequency analysis was obtained which complemented the experimental Infra‐red data in elucidation of the compounds. The α‐alkoxy and α‐aminostannanes provided stable precursors to the organolithiums required for the synthesis of the novel Fischer chromium carbenes. The organolithiums were obtained via tinlithium exchange at low temperatures, followed by the addition of chromium hexacarbonyl to form the acylpentacarbonyl‐chromate salt. Alkylation of this intermediate using a Meerwein salt, Me₃OBF₄, gave rise to the novel Fischer chromium carbene complexes. Fischer chromium carbenes derived from the two isomeric butyl and isobutyl stannanes and the two N‐ethyl α‐aminostannanes were successfully synthesised. The difficulty encountered in the purification of the Fischer carbene complexes hindered the full characterisation, due to the presence of a by‐product, tetrabutyltin.
- Full Text:
- Date Issued: 2012
a pH-metric speciation and anti-diabetic study of oxovanadium (IV) amino acid derivatives
- Authors: Gundhla, Isaac Zvikomborero
- Date: 2011 , 2011-03-15
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4399 , http://hdl.handle.net/10962/d1006691
- Description: Novel oxovanadium(IV) complexes of glycine, ʟ-alanine, 1-methylimidazole-2-carboxylic acid, imidazole-2-caboxylic acid and imidazole-4-carboxylic acid were synthesized and isolated in the solid state. The ligands and complexes were characterized by elemental analysis, melting point, NMR, IR and UV-vis spectroscopy. The IR studies showed that glycine and ʟ-alanine coordinate monodentately through the amine nitrogen whilst the imidazole-carboxylic acid derivatives assume a bidentate chelation. The electronic spectroscopic studies indicate distorted octahedral geometry for the oxovanadium complexes of amino acids and a square pyramidal geometry for oxovanadium(IV) complexes of imidazole carboxylic acid derivatives. The reaction of vanadyl (VO2+) with glycine, ʟ-alanine, imidazole-2-cabrboxylic acid, imidazole-4-carboxylic acid and 1-methylimidazole-2-carboxylic acid was studied in aqueous solution by pH-potentiometry under oxygen and carbon dioxide-free conditions. The data obtained from these titrations were used to calculate the protonation and stability constants. The results showed that all ligands are suitable for bidentate coordination in the formation of monomeric species although the solid state studies of the oxovanadium(IV) complexes of amino acids showed a monodentate coordination. The overall stability constants for the (VIVO)-ʟ-alanine system (log β120 = 18.27(6)), (VIVO)-glycine system (β120 = 17.22(6)), (VIVO)-imidazole-4-carboxyic acid (β120 = 11.38(8)), (VIVO)-imidazole-2-carboxylic acid (β120 = 11.62(6)) and (VIVO)-1-methylimidazole-2-carboxylic acid (β120 = 15.49(9)) were obtained. The calculations for the species distribution in the experimental pH range showed that the neutral bis-coordinated complexes are dominant over the biological pH range. The glucose uptake effect of oxovanadium(IV) complex of ʟ-alanine, imidazole-4-carboxylic acid, imidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid was investigated using 3T3-L1 adipocytes, Chang liver and C2C12 muscle cells at various concentrations. The compounds had significant glucose uptake on Chang liver cells only at a concentration of 0.1-10 μM whilst in the C2C12 muscle and 3T3-L1 cells the compounds showed little to no activity probably due to the lower concentrations employed as a result of the cytotoxicity of these compounds on these two cell lines.
- Full Text:
- Date Issued: 2011
- Authors: Gundhla, Isaac Zvikomborero
- Date: 2011 , 2011-03-15
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4399 , http://hdl.handle.net/10962/d1006691
- Description: Novel oxovanadium(IV) complexes of glycine, ʟ-alanine, 1-methylimidazole-2-carboxylic acid, imidazole-2-caboxylic acid and imidazole-4-carboxylic acid were synthesized and isolated in the solid state. The ligands and complexes were characterized by elemental analysis, melting point, NMR, IR and UV-vis spectroscopy. The IR studies showed that glycine and ʟ-alanine coordinate monodentately through the amine nitrogen whilst the imidazole-carboxylic acid derivatives assume a bidentate chelation. The electronic spectroscopic studies indicate distorted octahedral geometry for the oxovanadium complexes of amino acids and a square pyramidal geometry for oxovanadium(IV) complexes of imidazole carboxylic acid derivatives. The reaction of vanadyl (VO2+) with glycine, ʟ-alanine, imidazole-2-cabrboxylic acid, imidazole-4-carboxylic acid and 1-methylimidazole-2-carboxylic acid was studied in aqueous solution by pH-potentiometry under oxygen and carbon dioxide-free conditions. The data obtained from these titrations were used to calculate the protonation and stability constants. The results showed that all ligands are suitable for bidentate coordination in the formation of monomeric species although the solid state studies of the oxovanadium(IV) complexes of amino acids showed a monodentate coordination. The overall stability constants for the (VIVO)-ʟ-alanine system (log β120 = 18.27(6)), (VIVO)-glycine system (β120 = 17.22(6)), (VIVO)-imidazole-4-carboxyic acid (β120 = 11.38(8)), (VIVO)-imidazole-2-carboxylic acid (β120 = 11.62(6)) and (VIVO)-1-methylimidazole-2-carboxylic acid (β120 = 15.49(9)) were obtained. The calculations for the species distribution in the experimental pH range showed that the neutral bis-coordinated complexes are dominant over the biological pH range. The glucose uptake effect of oxovanadium(IV) complex of ʟ-alanine, imidazole-4-carboxylic acid, imidazole-2-carboxylic acid and 1-methylimidazole-2-carboxylic acid was investigated using 3T3-L1 adipocytes, Chang liver and C2C12 muscle cells at various concentrations. The compounds had significant glucose uptake on Chang liver cells only at a concentration of 0.1-10 μM whilst in the C2C12 muscle and 3T3-L1 cells the compounds showed little to no activity probably due to the lower concentrations employed as a result of the cytotoxicity of these compounds on these two cell lines.
- Full Text:
- Date Issued: 2011
An ion imprinted polymer for the determination of Ni (II) ions from mine tailing samples
- Authors: Rammika, Modise
- Date: 2011
- Subjects: Imprinted polymers , Metal ions , Polymerization , Mineral industries -- Waste disposal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4323 , http://hdl.handle.net/10962/d1004981 , Imprinted polymers , Metal ions , Polymerization , Mineral industries -- Waste disposal
- Description: A Ni(II)-dimethylglyoxime ion imprinted polymer {Ni(II)-DMG IIP} was synthesized by the trapping method using the bulk polymerisation format. The structures of the imprinted and non-imprinted polymer were evaluated by infrared spectroscopy and the morphology was observed by scanning electron microscopy. The Ni(II)-DMG IIP was optimised for pH, mass, time and by the uniform design experimental method for the molar ratios of monomer to crosslinker to porogen and template to ligands as well as keeping these parameters constant and varying the quantities of initiator, 2,2'-azobisisobutyronitrile (AIBN). The optimum pH was 8.5, optimum mass was 50 mg, optimum time was 1 min and the optimum molar ratios of crosslinker to monomer, monomer to template and nickel(II) sulfate hexahydrate (NiSO₄.6H₂O) to 4-vinylpyridine to dimethylglyoxime were found to be 3.3:1.0, 0.6:1.0 and 1.0:0.6:3.6 respectively with 30 mg and 8 mL as the optimum amounts of initiator and porogen respectively. Through this optimisation, recovery of Ni(II) was increased from 98 to 100%. Selectivity of the ion imprinted polymer was evaluated by analysing, using an inductively coupled plasma-optical emission spectrometer, for Ni(II) ions that were spiked with varying concentrations of Co(II), Cu(II), Zn(II), Pd(II), Fe(II), Ca(II), Mg(II), Na(I) and K(I) in aqueous samples. Selectivity studies also confirmed that the ion imprinted polymer had very good selectivity characterised by % RSD of less than 5 %. Co(II) was the only ion found to slightly interfere with the determination of Ni(II). The limits of detection and quantification were found to be 3x10⁻⁴ μg/mL and 9x10⁻⁴ μg/mL respectively. The method was evaluated by a custom solution of ground water certified reference material (SEP-3) and sandy soil reference material (BCR-142R) and the concentrations of Ni(II) obtained were not significantly different to the certified ones. The Ni(II)-DMG IIP was then evaluated in aqueous and soil samples where recoveries of 93 to 100% and 98 to 99% respectively were obtained with enrichment factors ranging from 2 to 18 in aqueous and 27 to 40 in soil samples. Finally, the Ni(II)-DMG IIP was used to analyse mine tailings samples and Ni(II) recovery of 99% was obtained with an enrichment factor of 2.
- Full Text:
- Date Issued: 2011
- Authors: Rammika, Modise
- Date: 2011
- Subjects: Imprinted polymers , Metal ions , Polymerization , Mineral industries -- Waste disposal
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4323 , http://hdl.handle.net/10962/d1004981 , Imprinted polymers , Metal ions , Polymerization , Mineral industries -- Waste disposal
- Description: A Ni(II)-dimethylglyoxime ion imprinted polymer {Ni(II)-DMG IIP} was synthesized by the trapping method using the bulk polymerisation format. The structures of the imprinted and non-imprinted polymer were evaluated by infrared spectroscopy and the morphology was observed by scanning electron microscopy. The Ni(II)-DMG IIP was optimised for pH, mass, time and by the uniform design experimental method for the molar ratios of monomer to crosslinker to porogen and template to ligands as well as keeping these parameters constant and varying the quantities of initiator, 2,2'-azobisisobutyronitrile (AIBN). The optimum pH was 8.5, optimum mass was 50 mg, optimum time was 1 min and the optimum molar ratios of crosslinker to monomer, monomer to template and nickel(II) sulfate hexahydrate (NiSO₄.6H₂O) to 4-vinylpyridine to dimethylglyoxime were found to be 3.3:1.0, 0.6:1.0 and 1.0:0.6:3.6 respectively with 30 mg and 8 mL as the optimum amounts of initiator and porogen respectively. Through this optimisation, recovery of Ni(II) was increased from 98 to 100%. Selectivity of the ion imprinted polymer was evaluated by analysing, using an inductively coupled plasma-optical emission spectrometer, for Ni(II) ions that were spiked with varying concentrations of Co(II), Cu(II), Zn(II), Pd(II), Fe(II), Ca(II), Mg(II), Na(I) and K(I) in aqueous samples. Selectivity studies also confirmed that the ion imprinted polymer had very good selectivity characterised by % RSD of less than 5 %. Co(II) was the only ion found to slightly interfere with the determination of Ni(II). The limits of detection and quantification were found to be 3x10⁻⁴ μg/mL and 9x10⁻⁴ μg/mL respectively. The method was evaluated by a custom solution of ground water certified reference material (SEP-3) and sandy soil reference material (BCR-142R) and the concentrations of Ni(II) obtained were not significantly different to the certified ones. The Ni(II)-DMG IIP was then evaluated in aqueous and soil samples where recoveries of 93 to 100% and 98 to 99% respectively were obtained with enrichment factors ranging from 2 to 18 in aqueous and 27 to 40 in soil samples. Finally, the Ni(II)-DMG IIP was used to analyse mine tailings samples and Ni(II) recovery of 99% was obtained with an enrichment factor of 2.
- Full Text:
- Date Issued: 2011
Assessment of organochlorine pesticide residues in fish samples from the Okavango Delta, Botswana
- Authors: Mpofu, Christopher
- Date: 2011 , 2011-02-28
- Subjects: Pesticides , Organochlorine compounds , Freshwater fishes -- Effect of pesticides on -- Botswana -- Okavango River Delta , Water -- Pesticide content -- Botswana -- Okavango River Delta , Catfishes -- Botswana -- Okavango River Delta , Tigerfish -- Botswana -- Okavango River Delta , Redbreast tilapia -- Botswana -- Okavango River Delta
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4404 , http://hdl.handle.net/10962/d1006707 , Pesticides , Organochlorine compounds , Freshwater fishes -- Effect of pesticides on -- Botswana -- Okavango River Delta , Water -- Pesticide content -- Botswana -- Okavango River Delta , Catfishes -- Botswana -- Okavango River Delta , Tigerfish -- Botswana -- Okavango River Delta , Redbreast tilapia -- Botswana -- Okavango River Delta
- Description: This thesis presents an evaluation of the dispersive solid-phase extraction (d-SPE) method referred to as the quick, easy, cheap, effective, rugged and safe (QuEChERS) method for the determination of four organochlorine pesticide residues in fish samples. The pesticides investigated in this study were o, p′-DDT, p, p′-DDE, aldrin and dieldrin. The combined use of Gas Chromatography with an Electron Capture Detector (GC-ECD) and sensitive Time of Flight (TOF) mass detector facilitated the identification of the target analytes. In the absence of certified reference material, the overall analytical procedure was validated by systematic recovery experiments on spiked samples at three levels of 2, 5 and 10 ng/g. The targeted compounds were successfully extracted and their recovery ranged from 76 to 96% with relative standard deviations of less than 13%. The optimum QuEChERS conditions were 2g of fish powder, 10 ml acetonitrile and 1 min shaking time. The optimal conditions were applied to assess the levels of chlorinated pesticides in blunt-tooth catfish (Clarias ngamensis), tigerfish (Hydrocynus vittatus), Oreochromis andersonii and red-breasted tilapia (Tilapia rendalli) from the Okavango Delta, Botswana. Dieldrin, p, p′-DDE and aldrin were detected in all the analysed samples with a concentration range of 0.04 – 0.29, 0.07 – 0.33, 0.04 – 0.28 and 0.03 – 0.24 ng/g per dry weight in O. andersonii, C. ngamensis, T. rendalli and H. vittatus respectively. These concentrations were below the US-EPA 0.1 μg/g allowable limit in edible fish and the Australian Maximum Residue Limit (MRL) of 50 - 1000 ng/g in fresh fish. DDT was not detected in all the fish species investigated. The mean lipid content recorded in the fish samples were 1.24, 2.16, 2.18 and 4.21% for H. vittatus, T. rendalli, O. andersonni and C. ngamensis respectively. No systematic trend was observed between fish age and pesticide levels in fish. Acetylcholinesterase (AChE) activity assays were performed to assess the effects of organochlorine pesticides in Clarias ngamensis. The enzyme activity recorded in Clarias ngamensis from the Okavango Delta and the reference site was 12.31 μmol of acetylcholine iodide hydrolysed/min/g brain tissue. The enzyme activity remained the same indicating no enzyme inhibition. The conclusions drawn from this study are that the QuEChERS method is applicable for the determination of organochlorine pesticide residues in fish matrices. The fish from the Okavango Delta are safe for human consumption.
- Full Text:
- Date Issued: 2011
- Authors: Mpofu, Christopher
- Date: 2011 , 2011-02-28
- Subjects: Pesticides , Organochlorine compounds , Freshwater fishes -- Effect of pesticides on -- Botswana -- Okavango River Delta , Water -- Pesticide content -- Botswana -- Okavango River Delta , Catfishes -- Botswana -- Okavango River Delta , Tigerfish -- Botswana -- Okavango River Delta , Redbreast tilapia -- Botswana -- Okavango River Delta
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4404 , http://hdl.handle.net/10962/d1006707 , Pesticides , Organochlorine compounds , Freshwater fishes -- Effect of pesticides on -- Botswana -- Okavango River Delta , Water -- Pesticide content -- Botswana -- Okavango River Delta , Catfishes -- Botswana -- Okavango River Delta , Tigerfish -- Botswana -- Okavango River Delta , Redbreast tilapia -- Botswana -- Okavango River Delta
- Description: This thesis presents an evaluation of the dispersive solid-phase extraction (d-SPE) method referred to as the quick, easy, cheap, effective, rugged and safe (QuEChERS) method for the determination of four organochlorine pesticide residues in fish samples. The pesticides investigated in this study were o, p′-DDT, p, p′-DDE, aldrin and dieldrin. The combined use of Gas Chromatography with an Electron Capture Detector (GC-ECD) and sensitive Time of Flight (TOF) mass detector facilitated the identification of the target analytes. In the absence of certified reference material, the overall analytical procedure was validated by systematic recovery experiments on spiked samples at three levels of 2, 5 and 10 ng/g. The targeted compounds were successfully extracted and their recovery ranged from 76 to 96% with relative standard deviations of less than 13%. The optimum QuEChERS conditions were 2g of fish powder, 10 ml acetonitrile and 1 min shaking time. The optimal conditions were applied to assess the levels of chlorinated pesticides in blunt-tooth catfish (Clarias ngamensis), tigerfish (Hydrocynus vittatus), Oreochromis andersonii and red-breasted tilapia (Tilapia rendalli) from the Okavango Delta, Botswana. Dieldrin, p, p′-DDE and aldrin were detected in all the analysed samples with a concentration range of 0.04 – 0.29, 0.07 – 0.33, 0.04 – 0.28 and 0.03 – 0.24 ng/g per dry weight in O. andersonii, C. ngamensis, T. rendalli and H. vittatus respectively. These concentrations were below the US-EPA 0.1 μg/g allowable limit in edible fish and the Australian Maximum Residue Limit (MRL) of 50 - 1000 ng/g in fresh fish. DDT was not detected in all the fish species investigated. The mean lipid content recorded in the fish samples were 1.24, 2.16, 2.18 and 4.21% for H. vittatus, T. rendalli, O. andersonni and C. ngamensis respectively. No systematic trend was observed between fish age and pesticide levels in fish. Acetylcholinesterase (AChE) activity assays were performed to assess the effects of organochlorine pesticides in Clarias ngamensis. The enzyme activity recorded in Clarias ngamensis from the Okavango Delta and the reference site was 12.31 μmol of acetylcholine iodide hydrolysed/min/g brain tissue. The enzyme activity remained the same indicating no enzyme inhibition. The conclusions drawn from this study are that the QuEChERS method is applicable for the determination of organochlorine pesticide residues in fish matrices. The fish from the Okavango Delta are safe for human consumption.
- Full Text:
- Date Issued: 2011
Characterization and electrocatalytic applications of metallophthalocyanine-single walled carbon nanotube conjugates
- Authors: Mugadza, Tawanda
- Date: 2011 , 2011-03-30
- Subjects: Phthalocyanines Pesticides Nanotubes Electrocatalysis Electrochemistry Transmission electron microscopy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4419 , http://hdl.handle.net/10962/d1006855
- Description: Metallophthalocyanine-single walled carbon nanotube conjugates were successfully synthesized and applied in the electrochemical characterizations of pesticides (amitrole and diuron) and 2-mercaptoethanol (2-ME). The formation of conjugates was confirmed through the use of the following analytical techniques: UV-vis, FTIR, Raman and XRD spectroscopies, atomic force and transmission electron microscopies and voltammetry. Chemically linking SWCNT to MPcs created platforms that offered efficient transfer of electrons and this was confirmed through electrochemical impedance studies (EIS) and voltammetry as shown by lower ΔEp values observed in conjugates. Carboxy carrying MPcs have very poor electron transfer kinetics (both tetrasubstituted and low symmetry), but the presence of SWCNTs activates their catalysis. All electrochemical studies were done at pH 4. Cyclic voltammetry, rotating disk linear sweep voltammetry, chronoamperometry and EIS were used in the electrochemical characterization of 2-ME and the pesticides on poly-Ni(OH)TAPc and MPc-SWCNT modified glassy carbon electrodes (GCEs). High Tafel slopes were observed for the pesticides relative to 2-ME, an indication of the passivating nature of their oxidation products. However, conjugates showed very high resistances to passivation and were easily regenerated by shaking in methanol. Improved catalysis of the conjugates is also indicated by the high catalytic rate constants for the analytes, observed on these electrodes. Conjugates of low symmetry MPcs with SWCNTs gave the highest catalytic rate constants, confirming better catalysis on these electrode surfaces. The nature of SWCNT functionalization also affected catalysis, with amine functionalized SWCNTs inducing better catalytic properties into the MPcs than carboxylic acid terminated CNTs. The presence of amine functionalized SWCNTs activates the catalysis of non-catalytic carboxy-carrying MPcs and this is more pronounced in conjugates of tetrasubstituted MPcs relative to those of low symmetry Pcs. Ethylene amine (EA) functionalized SWCNTs reduced redox overpotentials of the MPcs more than the phenyl-amine (PA) functionalized counterparts. Poly-NiTAPc was successfully converted to poly-Ni(OH)TAPc through cyclisation in pH 4 buffer and showed very good catalytic properties towards diuron, relative to the former.
- Full Text:
- Date Issued: 2011
- Authors: Mugadza, Tawanda
- Date: 2011 , 2011-03-30
- Subjects: Phthalocyanines Pesticides Nanotubes Electrocatalysis Electrochemistry Transmission electron microscopy
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4419 , http://hdl.handle.net/10962/d1006855
- Description: Metallophthalocyanine-single walled carbon nanotube conjugates were successfully synthesized and applied in the electrochemical characterizations of pesticides (amitrole and diuron) and 2-mercaptoethanol (2-ME). The formation of conjugates was confirmed through the use of the following analytical techniques: UV-vis, FTIR, Raman and XRD spectroscopies, atomic force and transmission electron microscopies and voltammetry. Chemically linking SWCNT to MPcs created platforms that offered efficient transfer of electrons and this was confirmed through electrochemical impedance studies (EIS) and voltammetry as shown by lower ΔEp values observed in conjugates. Carboxy carrying MPcs have very poor electron transfer kinetics (both tetrasubstituted and low symmetry), but the presence of SWCNTs activates their catalysis. All electrochemical studies were done at pH 4. Cyclic voltammetry, rotating disk linear sweep voltammetry, chronoamperometry and EIS were used in the electrochemical characterization of 2-ME and the pesticides on poly-Ni(OH)TAPc and MPc-SWCNT modified glassy carbon electrodes (GCEs). High Tafel slopes were observed for the pesticides relative to 2-ME, an indication of the passivating nature of their oxidation products. However, conjugates showed very high resistances to passivation and were easily regenerated by shaking in methanol. Improved catalysis of the conjugates is also indicated by the high catalytic rate constants for the analytes, observed on these electrodes. Conjugates of low symmetry MPcs with SWCNTs gave the highest catalytic rate constants, confirming better catalysis on these electrode surfaces. The nature of SWCNT functionalization also affected catalysis, with amine functionalized SWCNTs inducing better catalytic properties into the MPcs than carboxylic acid terminated CNTs. The presence of amine functionalized SWCNTs activates the catalysis of non-catalytic carboxy-carrying MPcs and this is more pronounced in conjugates of tetrasubstituted MPcs relative to those of low symmetry Pcs. Ethylene amine (EA) functionalized SWCNTs reduced redox overpotentials of the MPcs more than the phenyl-amine (PA) functionalized counterparts. Poly-NiTAPc was successfully converted to poly-Ni(OH)TAPc through cyclisation in pH 4 buffer and showed very good catalytic properties towards diuron, relative to the former.
- Full Text:
- Date Issued: 2011
Effect of nanoparticles on the photophysicochemical behaviour of metallophthalocyanines
- Moeno, Sharon Keitumetse Gail Mpheletso
- Authors: Moeno, Sharon Keitumetse Gail Mpheletso
- Date: 2011 , 2011-03-30
- Subjects: Phthalocyanines Nanoparticles Photochemistry Quantum dots
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4310 , http://hdl.handle.net/10962/d1004968
- Description: The synthesis, spectroscopic characterization, and studies of the photophysicochemical behaviour of selective anionic, cationic and neutral metallophthallocyanine (MPc) complexes were carried out and the results are presented herein. Studies on the effect of the central metal ion, the solvent used and the presence of nanoparticles on the photophysicochemical properties were conducted. The findings showed that the photophysicochemical parameters were mostly enhanced in the presence of central metal ions of high atomic numbers and also in the presence of nanoparticles. It was also observed that solvents that encouraged the monomericity of the MPc complexes also lead to improved photophysical and photochemical behaviour. CdTe quantum dots (QDs) stabilized with mercaptocarbonic acids were also observed to cause stimulated emission of the MPcs through Förster resonance energy transfer (FRET) thus acting as energy donors while the respective MPc acted as energy acceptors in all the FRET studies. FRET was observed following the photoexcitation of QDs for all monomeric anionic MPcs but it was also shown to occur for some cationic MPcs in organic media. Both the substituent and solvent used were found to exert a strong influence on the occurrence of FRET. Other cationic MPcs however showed different behaviour in the presence of the meraptocarbonic stabilized CdTe QDs; with the cationic porphyrazine giving clear indications of Pc ring reduction. The rest of the cationic MPcs did not give clear evidence of Pc ring reduction, instead they showed signs of aggregate formation possibly from the assembly of electrostatic ion pair complexes which could result in reduction of the quaternized pyridinium ring of the substituent. Both the QDs and the MPc complex emission spectra were significantly quenched for each in the presence of the other. Stern-Volmer quenching studies indicated that both static and dynamic quenching of the QDs in the presence of MPcs took place. The fluorescence lifetimes of the mercaptopropionic acid (MPA) capped CdTe QDs in the presence of various MPc complexes showed quenching of mostly the longer lifetimes of the QDs in the presence of MPcs suggesting that the surface defects and states are involved in the interaction of the QDs and MPcs. An MPc complex terminating in thio tethers was employed in the conjugation to AuNPs. Spectroscopic and microscopic studies confirmed the formation of the MPc-AuNP conjugate which was also shown to exhibit improved photophysicochemical properties compared to the free MPc.
- Full Text:
- Date Issued: 2011
- Authors: Moeno, Sharon Keitumetse Gail Mpheletso
- Date: 2011 , 2011-03-30
- Subjects: Phthalocyanines Nanoparticles Photochemistry Quantum dots
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4310 , http://hdl.handle.net/10962/d1004968
- Description: The synthesis, spectroscopic characterization, and studies of the photophysicochemical behaviour of selective anionic, cationic and neutral metallophthallocyanine (MPc) complexes were carried out and the results are presented herein. Studies on the effect of the central metal ion, the solvent used and the presence of nanoparticles on the photophysicochemical properties were conducted. The findings showed that the photophysicochemical parameters were mostly enhanced in the presence of central metal ions of high atomic numbers and also in the presence of nanoparticles. It was also observed that solvents that encouraged the monomericity of the MPc complexes also lead to improved photophysical and photochemical behaviour. CdTe quantum dots (QDs) stabilized with mercaptocarbonic acids were also observed to cause stimulated emission of the MPcs through Förster resonance energy transfer (FRET) thus acting as energy donors while the respective MPc acted as energy acceptors in all the FRET studies. FRET was observed following the photoexcitation of QDs for all monomeric anionic MPcs but it was also shown to occur for some cationic MPcs in organic media. Both the substituent and solvent used were found to exert a strong influence on the occurrence of FRET. Other cationic MPcs however showed different behaviour in the presence of the meraptocarbonic stabilized CdTe QDs; with the cationic porphyrazine giving clear indications of Pc ring reduction. The rest of the cationic MPcs did not give clear evidence of Pc ring reduction, instead they showed signs of aggregate formation possibly from the assembly of electrostatic ion pair complexes which could result in reduction of the quaternized pyridinium ring of the substituent. Both the QDs and the MPc complex emission spectra were significantly quenched for each in the presence of the other. Stern-Volmer quenching studies indicated that both static and dynamic quenching of the QDs in the presence of MPcs took place. The fluorescence lifetimes of the mercaptopropionic acid (MPA) capped CdTe QDs in the presence of various MPc complexes showed quenching of mostly the longer lifetimes of the QDs in the presence of MPcs suggesting that the surface defects and states are involved in the interaction of the QDs and MPcs. An MPc complex terminating in thio tethers was employed in the conjugation to AuNPs. Spectroscopic and microscopic studies confirmed the formation of the MPc-AuNP conjugate which was also shown to exhibit improved photophysicochemical properties compared to the free MPc.
- Full Text:
- Date Issued: 2011
Investigation of photosensitising behaviour of Ni, Pd and Pt phthalocyanines towards phenolic pollutants
- Authors: Ogunbayo, Taofeek Babatunde
- Date: 2011
- Subjects: Phthalocyanines Pollutants Photochemistry Photosensitizing compounds
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4321 , http://hdl.handle.net/10962/d1004979
- Description: Syntheses of various octasubstituted open-shell (Ni(II), Pd(II) and Pt(II)) metallophthalocyanines and their metal-free analogues have been carried out. Spectroscopic characterizations, photophysical and photochemical studies were carried out to determine the effects of these metals on the molecules using the metal-free phthalocyanine analogues as benchmark. Metal-binding studies of few thio-derivatised phthalocyanines were done to increase the number of palladium metal on the phthalocyanine ligands and determine the effect of increasing number of this metal on phthalocyanine properties. Palladium (PdPc) and platinum phthalocyanines (PtPc) gave good triplet and singlet oxygen quantum yields making them suitable for further investigation in application as photosensitisers. Using 4-nitrophenol as model pollutant, photosensitization reactions were carried out under homogenous and heterogeneous conditions. The reactions were monitored using UV-vis spectroscopy. The MPcs were adsorbed on functionalized single wall carbon nanotube (SWCNT-COOH) to form heterogeneous photosensitizers with PtPc failing to adsorb on the SWCNT-COOH. Under the heterogeneous condition, all the PdPcs photosensitization kinetics was consistent with Langmuir-Hinshelwood reaction model. The best photosenstiser, β-palladium dodecylthio phthalocyanine was also deployed in sensitization of oxidation of 4-chlorophenol and pentachlorophenol under homogenous and heterogeneous conditions to establish the ability of the molecules to sensitize oxidation of wide range of phenolic pollutants. Identifications of the products of the reactions were conducted using gas chromatography and high pressure liquid chromatography (HPLC) hyphenated with mass analyzer (LC-MS). Mechanisms of all the reactions were investigated and all the complexes, in spite of reduced lifetime resulting from open-shell nature of the metals, sensitized the reactions through singlet oxygen mediated pathway. All the heterogeneous sensitisers were recyclable in the 4- nitrophenol oxidation but β-palladium dodecylthio phthalocyanine proved unrecyclable in the oxidation of pentachlorophenol.
- Full Text:
- Date Issued: 2011
- Authors: Ogunbayo, Taofeek Babatunde
- Date: 2011
- Subjects: Phthalocyanines Pollutants Photochemistry Photosensitizing compounds
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4321 , http://hdl.handle.net/10962/d1004979
- Description: Syntheses of various octasubstituted open-shell (Ni(II), Pd(II) and Pt(II)) metallophthalocyanines and their metal-free analogues have been carried out. Spectroscopic characterizations, photophysical and photochemical studies were carried out to determine the effects of these metals on the molecules using the metal-free phthalocyanine analogues as benchmark. Metal-binding studies of few thio-derivatised phthalocyanines were done to increase the number of palladium metal on the phthalocyanine ligands and determine the effect of increasing number of this metal on phthalocyanine properties. Palladium (PdPc) and platinum phthalocyanines (PtPc) gave good triplet and singlet oxygen quantum yields making them suitable for further investigation in application as photosensitisers. Using 4-nitrophenol as model pollutant, photosensitization reactions were carried out under homogenous and heterogeneous conditions. The reactions were monitored using UV-vis spectroscopy. The MPcs were adsorbed on functionalized single wall carbon nanotube (SWCNT-COOH) to form heterogeneous photosensitizers with PtPc failing to adsorb on the SWCNT-COOH. Under the heterogeneous condition, all the PdPcs photosensitization kinetics was consistent with Langmuir-Hinshelwood reaction model. The best photosenstiser, β-palladium dodecylthio phthalocyanine was also deployed in sensitization of oxidation of 4-chlorophenol and pentachlorophenol under homogenous and heterogeneous conditions to establish the ability of the molecules to sensitize oxidation of wide range of phenolic pollutants. Identifications of the products of the reactions were conducted using gas chromatography and high pressure liquid chromatography (HPLC) hyphenated with mass analyzer (LC-MS). Mechanisms of all the reactions were investigated and all the complexes, in spite of reduced lifetime resulting from open-shell nature of the metals, sensitized the reactions through singlet oxygen mediated pathway. All the heterogeneous sensitisers were recyclable in the 4- nitrophenol oxidation but β-palladium dodecylthio phthalocyanine proved unrecyclable in the oxidation of pentachlorophenol.
- Full Text:
- Date Issued: 2011
Marine anti-malarial isonitriles : a synthetic and computational study
- Authors: Adendorff, Matthew Ralph
- Date: 2011 , 2010-05-17
- Subjects: Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4398 , http://hdl.handle.net/10962/d1006674 , Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Description: The development of Plasmodium falciparum malarial resistance to the current armoury of anti-malarial drugs requires the development of new treatments to help combat this disease. The marine environment is a well established source of potential pharmaceuticals. Of interest to us are isonitrile, isocyanate and isothiocyanate compounds isolated from marine sponges and molluscs which have exhibited nano-molar anti-plasmodial activities. Through quantitative structure-activity relation studies (QSAR), a literature precedent exists for a pseudoreceptor model from which a pharmacophore for the design of novel anti-malarial agents was proposed. The current theory suggests that these marine compounds exert their inhibitory action through interfering with the heme detoxification pathway in P. falciparum. We propose that the computational methods used to draw detailed conclusions about the mode of action of these marine compounds were inadequate. This thesis addresses this problem using contemporary computational methodologies and seeks to propose a more robust method for the rational design of new anti-malarial drug compounds that inhibit heme polymerization to hemozoin. In order to investigate the interactions of the marine compounds with their heme targets, a series of modern computational procedures were formulated, validated and then applied to theoretical systems. The validations of these algorithms, before their application to the marine compound-heme systems, were achieved through two case studies. The first was used to investigate the applicability of the statistical docking algorithm AutoDock to be used for the exploration of conformational space around the heme target. A theoretical P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) enzyme model, constructed by the Biochemistry Department at Rhodes University, provided the ideal model to validate the AutoDock program. The protein model was accordingly subjected to rigorous docking simulations with over 30 different ligand molecules using the AutoDock algorithm which allowed for the docking algorithm’s limitations to be ascertained and improved upon. This investigation facilitated the successful validation of the protein model, which can now be used for the rational design of new PfDXR-inhibiting anti-plasmodial compounds, as well as enabling us to propose an improvement of the docking algorithm for application to the heme systems. The second case study was used to investigate the applicability of an ab initio molecular dynamics algorithm for simulation of bond breaking/forming events between the marine compounds and their heme target. This validation involved the exploration of intermolecular interactions in a naturally occurring nonoligomeric zipper using the Car-Parrinello Molecular Dynamics (CPMD) method. This study allowed us to propose a model for the intermolecular forces responsible for zipper self-assembly and showcased the CPMD method’s abilities to simulate and predict bond forming/breaking events. Data from the computational analyses suggested that the interactions between marine isonitriles, isocyanates and isothiocyanates occur through bond-less electrostatic attractions rather than through formal intermolecular bonds as had been previously suggested. Accordingly, a simple bicyclic tertiary isonitrile (5.14) was synthesized using Kitano et al’s relatively underutilized isonitrile synthetic method for the conversion of tertiary alcohols to their corresponding isonitriles. This compound’s potential for heme detoxification inhibition was then explored in vitro via the pyridine-hemochrome assay. The assay data suggested that the synthesized isonitrile was capable of inhibiting heme polymerization in a similar fashion to the known inhibitor chloroquine. Attempts to synthesize tricyclic analogues of 5.14 were unsuccessful and highlighted the limitation of Kitano et al’s isonitrile synthetic methodology.
- Full Text:
- Date Issued: 2011
- Authors: Adendorff, Matthew Ralph
- Date: 2011 , 2010-05-17
- Subjects: Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4398 , http://hdl.handle.net/10962/d1006674 , Isocyanides , Isocyanates , Marine pharmacology , Antimalarials , Antimalarials -- Development , Drug development
- Description: The development of Plasmodium falciparum malarial resistance to the current armoury of anti-malarial drugs requires the development of new treatments to help combat this disease. The marine environment is a well established source of potential pharmaceuticals. Of interest to us are isonitrile, isocyanate and isothiocyanate compounds isolated from marine sponges and molluscs which have exhibited nano-molar anti-plasmodial activities. Through quantitative structure-activity relation studies (QSAR), a literature precedent exists for a pseudoreceptor model from which a pharmacophore for the design of novel anti-malarial agents was proposed. The current theory suggests that these marine compounds exert their inhibitory action through interfering with the heme detoxification pathway in P. falciparum. We propose that the computational methods used to draw detailed conclusions about the mode of action of these marine compounds were inadequate. This thesis addresses this problem using contemporary computational methodologies and seeks to propose a more robust method for the rational design of new anti-malarial drug compounds that inhibit heme polymerization to hemozoin. In order to investigate the interactions of the marine compounds with their heme targets, a series of modern computational procedures were formulated, validated and then applied to theoretical systems. The validations of these algorithms, before their application to the marine compound-heme systems, were achieved through two case studies. The first was used to investigate the applicability of the statistical docking algorithm AutoDock to be used for the exploration of conformational space around the heme target. A theoretical P. falciparum 1-deoxy-D-xylulose-5-phosphate reductoisomerase (PfDXR) enzyme model, constructed by the Biochemistry Department at Rhodes University, provided the ideal model to validate the AutoDock program. The protein model was accordingly subjected to rigorous docking simulations with over 30 different ligand molecules using the AutoDock algorithm which allowed for the docking algorithm’s limitations to be ascertained and improved upon. This investigation facilitated the successful validation of the protein model, which can now be used for the rational design of new PfDXR-inhibiting anti-plasmodial compounds, as well as enabling us to propose an improvement of the docking algorithm for application to the heme systems. The second case study was used to investigate the applicability of an ab initio molecular dynamics algorithm for simulation of bond breaking/forming events between the marine compounds and their heme target. This validation involved the exploration of intermolecular interactions in a naturally occurring nonoligomeric zipper using the Car-Parrinello Molecular Dynamics (CPMD) method. This study allowed us to propose a model for the intermolecular forces responsible for zipper self-assembly and showcased the CPMD method’s abilities to simulate and predict bond forming/breaking events. Data from the computational analyses suggested that the interactions between marine isonitriles, isocyanates and isothiocyanates occur through bond-less electrostatic attractions rather than through formal intermolecular bonds as had been previously suggested. Accordingly, a simple bicyclic tertiary isonitrile (5.14) was synthesized using Kitano et al’s relatively underutilized isonitrile synthetic method for the conversion of tertiary alcohols to their corresponding isonitriles. This compound’s potential for heme detoxification inhibition was then explored in vitro via the pyridine-hemochrome assay. The assay data suggested that the synthesized isonitrile was capable of inhibiting heme polymerization in a similar fashion to the known inhibitor chloroquine. Attempts to synthesize tricyclic analogues of 5.14 were unsuccessful and highlighted the limitation of Kitano et al’s isonitrile synthetic methodology.
- Full Text:
- Date Issued: 2011
Pressurized hot water extraction of nutraceuticals and organic pollutants from medicinal plants
- Authors: Mokgadi, Janes
- Date: 2011
- Subjects: Functional foods Medicinal plants -- Biotechnology Extraction (Chemistry) Goldenseal Botanical pesticides Sorbents Organic solvents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4338 , http://hdl.handle.net/10962/d1004999
- Description: This thesis explores the robustness and the versatility of pressurized hot water extraction (PHWE) for a variety of analytes and matrices. Applications discussed include: selective extraction of alkaloids in goldenseal followed by their degradation studies; in-cell clean-up of pesticides in medicinal plants employing custom made molecularly imprinted polymers (MIPs) sorbents; in-cell pre-concentration followed by desorption of aflatoxins in plants with MIPs; desorption of pesticides from electrospun nanofiber sorbents; and removal of templates from MIPs sorbents. It was demonstrated that selective extractions could be achieved by just changing the temperature of water while adjusting the pressure. For instance, the alkaloids in goldenseal (hydrastine and berberine), were extracted at 140 °C, 50 bars, 1 mL min⁻¹ in 15 min; organochlorine pesticides from medicinal plants were extracted at 260 °C, 80 bars, 1 mL min-1 in 10 min; while aflatoxins AFG2, AFG1, AFB2 and AFB1 were extracted at 180 °C, 60 bars and a flow rate of 0.5 mL min⁻¹ in 10 min. The selectivity of PHWE was further enhanced by combining it with selective MIPs sorbents at higher temperatutes. In-cell clean-up of interfering chlorophyll was successfully removed from the medicinal plants during pesticides analysis while clean-up of aflatoxins AFG2, AFG1, AFB2 and AFB1 was achieved in two extraction cells connected in series. Ultrasound was also combined with PHWE for extraction of hydrastine and berberine at 80 °C and 40 bars in 30 min. PHWE was further evaluated for removal of templates from quercetin, phthalocynine and chlorophyll MIPs. The templates were thoroughly washed off their MIPs within 70 min with PHWE compared to over 8 h for Soxhlet and ultrasound assisted extraction. Pesticides were also desorbed from electrospun nanofibers at 260 °C, 80 bars in 10 min employing only water at 0.5 mL min⁻¹. In the light of green chemistry, the decrease in the usage of organic solvents was 100%, resulting in no organic solvent waste.
- Full Text:
- Date Issued: 2011
- Authors: Mokgadi, Janes
- Date: 2011
- Subjects: Functional foods Medicinal plants -- Biotechnology Extraction (Chemistry) Goldenseal Botanical pesticides Sorbents Organic solvents
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4338 , http://hdl.handle.net/10962/d1004999
- Description: This thesis explores the robustness and the versatility of pressurized hot water extraction (PHWE) for a variety of analytes and matrices. Applications discussed include: selective extraction of alkaloids in goldenseal followed by their degradation studies; in-cell clean-up of pesticides in medicinal plants employing custom made molecularly imprinted polymers (MIPs) sorbents; in-cell pre-concentration followed by desorption of aflatoxins in plants with MIPs; desorption of pesticides from electrospun nanofiber sorbents; and removal of templates from MIPs sorbents. It was demonstrated that selective extractions could be achieved by just changing the temperature of water while adjusting the pressure. For instance, the alkaloids in goldenseal (hydrastine and berberine), were extracted at 140 °C, 50 bars, 1 mL min⁻¹ in 15 min; organochlorine pesticides from medicinal plants were extracted at 260 °C, 80 bars, 1 mL min-1 in 10 min; while aflatoxins AFG2, AFG1, AFB2 and AFB1 were extracted at 180 °C, 60 bars and a flow rate of 0.5 mL min⁻¹ in 10 min. The selectivity of PHWE was further enhanced by combining it with selective MIPs sorbents at higher temperatutes. In-cell clean-up of interfering chlorophyll was successfully removed from the medicinal plants during pesticides analysis while clean-up of aflatoxins AFG2, AFG1, AFB2 and AFB1 was achieved in two extraction cells connected in series. Ultrasound was also combined with PHWE for extraction of hydrastine and berberine at 80 °C and 40 bars in 30 min. PHWE was further evaluated for removal of templates from quercetin, phthalocynine and chlorophyll MIPs. The templates were thoroughly washed off their MIPs within 70 min with PHWE compared to over 8 h for Soxhlet and ultrasound assisted extraction. Pesticides were also desorbed from electrospun nanofibers at 260 °C, 80 bars in 10 min employing only water at 0.5 mL min⁻¹. In the light of green chemistry, the decrease in the usage of organic solvents was 100%, resulting in no organic solvent waste.
- Full Text:
- Date Issued: 2011
Solid-phase extraction based sample preparation for the determination of drug and organic pollutant residue
- Authors: Pule, Bellah Oreeditse
- Date: 2011 , 2011-02-08
- Subjects: Food contamination , Drugs -- Analysis , Pharmaceutical chemistry , Extraction (Chemistry) , Sorbents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4406 , http://hdl.handle.net/10962/d1006711 , Food contamination , Drugs -- Analysis , Pharmaceutical chemistry , Extraction (Chemistry) , Sorbents
- Description: This thesis presents solid phase extraction (SPE) methodologies based on mixed-mode polymeric sorbents; a mixed mode strong anion exchanger (Agilent SampliQ SAX) and a mixed mode strong cation exchanger (Agilent SampliQ SCX). Furthermore, dispersive-SPE based on a quick, easy, cheap, effective, rugged and safe (QuEChERS) method was assessed for applicability in the determination of drug residues. The mixed-mode polymeric sorbents were evaluated for the simultaneous fractionation of drugs that exhibit diverse polarities with acidic, basic and neutral functionalities in biological matrices (plasma and urine). The polymeric skeleton of these sorbents entails an exchanger group and therefore provides two retention mechanisms, strong cation or anion exchange retention mechanisms with hydrophobic interactions. It was demonstrated that with a sequential elution protocol for sample clean-up analytes were fractionated into acidic, basic and neutral classes. The SAX was employed for analysis of ketoprofen, naproxen (acidic drugs), nortriptyline (basic) and secobarbital (neutral) from urine sample. The SCX was used for fractionating phenobarbital, p-toluamide (acidic), amphetamine, m-toluidine (basic) and acetaminophen (neutral drug) from plasma sample. QuEChERS method was employed for quantitative determination of 16 polycyclic aromatic hydrocarbons (PAHs) from fish fillets and soil; 9 sulfonamides (SAs) from chicken muscles and acrylamide (AA) in cooking oil. The analyte recoveries ranged from 79.6 - 109% with RSDs ranging from 0.06 - 1.9% at three different fortification levels. Good linearity (r2 > 0.9990) was attained for most analytes. The limits of detection and quantification ranged from 0.03 - 0.84 μg/ml and 0.81 - 1.89 μg/ml respectively for analytes in biological samples. LODs and LOQs for analytes in food and environmental samples ranged from 0.02 to 0.39 and 0.25 to 1.30 ng/g respectively.
- Full Text:
- Date Issued: 2011
- Authors: Pule, Bellah Oreeditse
- Date: 2011 , 2011-02-08
- Subjects: Food contamination , Drugs -- Analysis , Pharmaceutical chemistry , Extraction (Chemistry) , Sorbents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4406 , http://hdl.handle.net/10962/d1006711 , Food contamination , Drugs -- Analysis , Pharmaceutical chemistry , Extraction (Chemistry) , Sorbents
- Description: This thesis presents solid phase extraction (SPE) methodologies based on mixed-mode polymeric sorbents; a mixed mode strong anion exchanger (Agilent SampliQ SAX) and a mixed mode strong cation exchanger (Agilent SampliQ SCX). Furthermore, dispersive-SPE based on a quick, easy, cheap, effective, rugged and safe (QuEChERS) method was assessed for applicability in the determination of drug residues. The mixed-mode polymeric sorbents were evaluated for the simultaneous fractionation of drugs that exhibit diverse polarities with acidic, basic and neutral functionalities in biological matrices (plasma and urine). The polymeric skeleton of these sorbents entails an exchanger group and therefore provides two retention mechanisms, strong cation or anion exchange retention mechanisms with hydrophobic interactions. It was demonstrated that with a sequential elution protocol for sample clean-up analytes were fractionated into acidic, basic and neutral classes. The SAX was employed for analysis of ketoprofen, naproxen (acidic drugs), nortriptyline (basic) and secobarbital (neutral) from urine sample. The SCX was used for fractionating phenobarbital, p-toluamide (acidic), amphetamine, m-toluidine (basic) and acetaminophen (neutral drug) from plasma sample. QuEChERS method was employed for quantitative determination of 16 polycyclic aromatic hydrocarbons (PAHs) from fish fillets and soil; 9 sulfonamides (SAs) from chicken muscles and acrylamide (AA) in cooking oil. The analyte recoveries ranged from 79.6 - 109% with RSDs ranging from 0.06 - 1.9% at three different fortification levels. Good linearity (r2 > 0.9990) was attained for most analytes. The limits of detection and quantification ranged from 0.03 - 0.84 μg/ml and 0.81 - 1.89 μg/ml respectively for analytes in biological samples. LODs and LOQs for analytes in food and environmental samples ranged from 0.02 to 0.39 and 0.25 to 1.30 ng/g respectively.
- Full Text:
- Date Issued: 2011
Studies in marine quinone chemistry
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
- Authors: Sunassee, Suthananda Naidu
- Date: 2011
- Subjects: Quinone Marine natural products Marine invertebrates Marine pharmacology Cancer -- Treatment
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4355 , http://hdl.handle.net/10962/d1005020
- Description: This thesis is divided into two parts and the rationale of the research conducted is based on the cytotoxicity of the prenylated quinones 1.24-1.29, isolated from the South African nudibranch Leminda millecra, against oesophageal cancer cells. The first part (Chapters 2 and 3) of the thesis initially documents the distribution of cytotoxic and antioxidant prenylated quinones and hydroquinones in the marine environment. We have been able to show, for the first time, that these compounds can be divided into eight structural classes closely related to their phyletic distribution. Secondly, we attempted to synthesize the two marine natural products 1.24 and 1.26 in an effort to contribute to an ongoing collaborative search with the Division of Medical Biochemistry at the University of Cape Town for new compounds with anti-oesophageal cancer activity. Accordingly, we followed the published synthetic procedure for 1.26 and, although we were unable to reproduce the reported results, we have generated five new prenylated quinone analogues 3.53-3.55, 3.63 and 3.71, which are a potentially viable addition to our ongoing structure-activity relationship (SAR) studies. Moreover, we embarked on a 7Li NMR mechanistic study for the synthesis of 3.2 from 3.1 which rewarded us with an improved and reproducible methodology for this crucial reaction that is detailed in Chapter 3. The second part of this thesis (Chapters 4 and 5) is concerned with a synthetic, structural, electrochemical and biological exploration of the 1,4-naphthoquinone nucleus as a primary pharmacophore in our search for new chemical entities which can induce apoptosis in oesophageal cancer cells, thus contributing to our overall ongoing SAR study in this class of compounds. Seven new naphthoquinone derivatves (4.19, 4.30, 4.31, 4.33 and 4.46-4.48) of the natural products 2-deoxylapachol (2.44), lapachol (4.1) and β-lapachone (5.2) were synthesized and 2-(1`-hydroxy-`-phenylmethyl)-1,4-naphthoquinone (4.29) was found to be the most cytotoxic (IC50 1.5 μM) against the oesophageal cancer cell line WHCO1, while 5.2, which is currently in phase II clinical trials as an anticancer drug, was found to be similarly active (IC50 1.6 μM). Electrochemical investigations of the redox properties of the benzylic alcohol derivatives 4.29-4.31 indicated a higher reduction potential compared to their oxidized counterparts 4.45-4.48, and this finding has been correlated to the increased activity of 4.29-4.31 against the WHCO1 cell line. Additionally, 4.29 is synthetically more accessible than either 1.26 or 5.2 and potentially a lead compound in our search for new and more effective chemotherapeutic agents against oesophageal cancer
- Full Text:
- Date Issued: 2011
Studies in South African marine molluscan chemistry
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
- Authors: Bromley, Candice Leigh
- Date: 2011
- Subjects: Mollusks -- South Africa , Marine invertebrates -- South Africa , Marine metabolites -- South Africa , Chemical oceanography -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4356 , http://hdl.handle.net/10962/d1005021
- Description: This thesis investigates the variability occurring in the secondary metabolites produced by three South African marine molluscs. Chapter Two discusses the isolation and spectroscopic structure elucidation of the metabolites isolated from two Siphonaria species. The re-investigation of Siphonaria capensis yielded siphonarienfuranone (2.2) as the only common polypropionate isolated from both the 1998 and 2009 collections of S. capensis from the same areas suggesting possible seasonal or genetic variation in polypropionate production. The sterol cholest-7-en-3,5,7- triol (2.33) was also isolated form the 2009 collection of S. capensis and this is the first time this compound has been isolated from a Siphonaria species. The second species, Siphonaria oculus is closely related to S. capensis and the investigation into the former’s secondary metaboliteproduction revealed 2.2 as a major metabolite suggesting an inter-species overlap in polypropionate production. Three new polypropionate metabolites, 2.35, 2.36 and 2.37 were also isolated from S. oculus. An unsuccessful attempt was made to establish the absolute configuration of 2.37 using the modified Mosher’s method and the limited amount of 2.37 available prevented any further attempts at resolving the absolute configuration of this compound. The 1H NMR analysis of the defensive mucus collected directly from S. oculus revealed the presence of the acyclic polypropionate 2.37 as a minor metabolite. The absence of characteristic signals for the furanone containing compounds 2.2, 2.35 and 2.36, might suggest that these compounds cyclise from a hypothetical acyclic precursor (2.38) during standard work up of bulk acetone extracts of Siphonaria species. Chapter Three discusses the re-isolation and spectroscopic structure elucidation of the metabolites isolated from the nudibranch, Leminda millecra. Three known natural products, millecrone A (3.1), 8-hydroxycalamenene (3.6) and cubebenone (3.8) were re-isolated from our 2010 collection of L. millecra, as well as the new minor metabolite 8-acetoxycalamenene (3.16). The cytotoxic prenylated toluquinones and toluhydroquinones (3.9-3.15) initially isolated from the 1998 collection of L. millecra were not found in the 2010 collection supporting the hypothesis that these compounds may be of fungal origin. L. millecra clearly shows variability in the compounds sequestered by this species with millecrone A (3.1) being the only common metabolite in the three investigations of L. millecra to date. An unsuccessful attempt was made to establish the absolute configuration of 3.1, 3.6 and 3.8 through initial LAH reduction of the ketone moiety contained in 3.1 and 3.8 and esterification of the resultant diastereomeric alcohol mixtures and the phenol functionality in 3.6 with (1S)-camphanic chloride. Crystallisation of the (S)- camphanate esters of 3.6 and 3.8 for X-ray analysis were unsuccessful, while the unexpected conjugate addition of a hydride in 3.1 resulted in complex diastereomeric mixtures which could not be separated by HPLC.
- Full Text:
- Date Issued: 2011
Surface properties and electrocatalytic applications of metallophthalocyanines confined on electrode surfaces
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
- Authors: Akinbulu, Isaac Adebayo
- Date: 2011
- Subjects: Phthalocyanines Electrochemistry Electrocatalysis Pesticides
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4365 , http://hdl.handle.net/10962/d1005030
- Description: New cobalt (13, 16 19 and 22), manganese (14, 17, 20 and 23) and iron (15, 18, 21 and 24)phthalocyanine complexes were synthesized and characterized. The UV-Vis spectral properties of the complexes were typical of the nature of central metal and position of substituent on the Pc ligand. Their electrochemical behaviors were signatures of the central metals, with varying influences of the nature and position of substituents. Nanocomposite of complex 18 and single walled carbon nanotubes (SWCNTs) (SWCNT-18)was fabricated. Formation of this nano-composite was confirmed by infrared (IR)spectroscopy, X-ray diffraction (XRD) spectroscopy and transmission electron microscopy (TEM). Self-assembled monolayers (SAMs) of SWCNT-18, complexes 13-15, and 20 were electropolymerized on glassy carbon electrodes (GCE). Complex 14 was also electrodeposited on GCE. Surface properties of the SAMs were consistent with the molecular feature of the substituent and the nature of central metal in the adsorbed species, while those of the MnPc modified GCEs were dependent on point of substitution and number of substituent. The SAM-modified gold electrodes were used for the electrocatalytic oxidation of the carbamate insecticide, carbofuran. Amplification of the current signal of the insecticide, at more energetically feasible oxidation potentials, on the SAM-modified gold electrodes, relative to bare gold electrode,justified electrocatalysis. There was enhanced sensitivity (attributed to the presence of SWCNT) of the SWCNT-18-SAM-modified gold electrode towards carbofuran, relative to the signals observed on the other SAMs. Current response of the insecticide,bendiocarb, was also intensified, at more favorable oxidation potentials, on the MnPc (14 and 17) modified GCEs, relative to the response on bare GCE, substantiating electrocatalysis. Also, catalysis of the oxidation of the herbicide, bentazon, was observed on polymeric film of complex 20. The current response of the herbicide on this film was better than that observed on bare GCE. Electrocatalysis of the analytes, on the respective modified electrodes, occurred via closely related mechanisms.
- Full Text:
- Date Issued: 2011
Synthesis and evaluation of novel HIV-1 enzyme inhibitors
- Olomola, Temitope Oloruntoba
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
- Authors: Olomola, Temitope Oloruntoba
- Date: 2011
- Subjects: HIV infections -- Treatment HIV infections -- Chemotherapy HIV (Viruses) Enzyme inhibitors AZT (Drug) Reverse transcriptase Proteolytic enzymes Ligands Psoralens Resorcinol
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4369 , http://hdl.handle.net/10962/d1005034
- Description: This study has involved the design, synthesis and evaluation of novel HIV-1 enzyme inhibitors accessed by synthetic elaboration of Baylis-Hillman adducts. Several series of complex coumarin-AZT and cinnamate ester-AZT conjugates have been prepared, in high yields, by exploiting the click reaction between appropriate Baylis-Hillman derived precursors and azidothymidine (AZT), all of which have been fully characterised using spectroscopic techniques. These conjugates, designed as potential dual-action HIV-1 inhibitors, were tested against the appropriate HIV-1 enzymes, i.e. HIV-1 reverse transcriptase and protease or HIV-1 reverse transcriptase and integrase. A number of the ligands have exhibited % inhibition levels and IC50 values comparable to drugs in clinical use, permitting their identification as lead compounds for the development of novel dual-action inhibitors. In silico docking of selected ligands into the active sites of the respective enzymes has provided useful insight into binding conformations and potential hydrogen-bonding interactions with active-site amino acid residues. A series of furocoumarin carboxamide derivatives have been synthesised in four steps starting from resorcinol and these compounds have also been tested for HIV-1 integrase inhibition activity. The structures of unexpected products isolated from Aza-Baylis-Hillman reactions of N-tosylaldimines have been elucidated by spectroscopic analysis, and confirmed by single crystal X-ray analysis. A mechanism for what appears to be an unprecedented transformation has been proposed. Microwave-assisted SeO₂ oxidation of Baylis-Hillman-derived 3-methylcoumarins has provided convenient and efficient access to coumarin-3-carbaldehydes, and a pilot study has revealed the potential of these coumarin-3-carbaldehydes as scaffolds for the construction of tricyclic compounds. The HCl-catalysed reaction of tert-butyl acrylate derived Baylis-Hillman adducts has been shown to afford 3-(chloromethyl)coumarins and α-(chloromethyl)cinnamic acids, the Zstereochemistry of the latter being established by X-ray crystallography. ¹H NMR-based experimental kinetic and DFT-level theoretical studies have been undertaken to establish the reaction sequence and other mechanistic details. Base-catalysed cyclisation on the other hand, has been shown to afford 2H-chromene rather than coumarin derivatives.
- Full Text:
- Date Issued: 2011
Synthesis of novel inhibitors of 1-Deoxy-D-xylulose-5-phosphate reductoisomerase as potential anti-malarial lead compounds
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011
- Authors: Mutorwa, Marius Kudumo
- Date: 2011
- Subjects: Antimalarials -- Development Plasmodium falciparum Malaria -- Chemotherapy Drug development Lead compounds Phosphonates Phosphonic acids Ligands
- Language: English
- Type: Thesis , Doctoral , PhD
- Identifier: vital:4372 , http://hdl.handle.net/10962/d1005037
- Description: This research has focused on the development of novel substrate mimics as potential DXR inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR), an essential enzyme in the mevalonate-independent pathway for the biosynthesis of isoprenoids in Plasmodium falciparum. DXR mediates the isomerisation and reduction of 1-deoxy-D-xylulose-5-phosphate (DOXP) into 2C-methyl-D-erithrytol 4-phosphate (MEP) and has been validated as an attractive target for the development of novel anti-malarial chemotherapeutic agents. Reaction of various amines with specially prepared 4-phosphonated crotonic acid in the presence of the peptide coupling reagent, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), has afforded a series of amido-phosphonate esters in moderate to good yields (48% - 73%) which, using a RuCl₃/CeCl₃/NaIO₄ catalyst system, have been dihydroxylated to furnish the dihydroxy-amido phosphonate ester pro-drugs; subsequent hydrolysis under microwave irradiation has afforded the corresponding phosphonic acids. A second series of potential inhibitors viz., 3-substituted aniline-derived phosphonate esters, their corresponding phosphonic acids and mono-sodium salts, have also been successfully synthesised. In these compounds, the essential functional groups are separated by one, two, three or four methylene groups, Deprotonation of the 3-substituted aniline substrates, followed by reaction with the appropriate ω-chloroalkanoyl chloride produced the ω-chloroamide intermediates, which were subjected to the Michaelis-Arbuzov reaction to afford the diethyl phosphonate esters in moderate to good yields (48% - 74%). Microwave-assisted TMSBrmediated cleavage of the phosphonate esters furnished the phosphonic acids, neutralisation of which afforded the mono-sodium salts. Furan-derived phosphate esters and phosphonic acids have been prepared as conformationally-restricted DOXP analogues. Functionalization at C-5 of the trityl-protected furan was achieved using the Vilsmeier-Haack formylation and Friedel-Crafts acylation reactions and, following de-tritylation, phosphorylation and oximation, using hydroxylamine hydrochloride, the novel oxime derivatives have been isolated as a third series of potential DXR inhibitors in very good yields (87% - 96%). Finally, in order to exploit an additional binding pocket in the PƒDXR active site, a series of N-benzylated phosphoramidic derivatives were obtained in seven steps from the starting material, diethyl phosphoramidate. The known inhibitors, fosmidomycin and its acetyl derivative FR900098, were also successfully synthesised as standards for STD-NMR binding and inhibition assays. In all, over 200 compounds (136 novel) have been prepared and appropriately characterised using 1-and 2-D NMR and IR spectroscopic analysis and, where necessary, HRMS or combustion analysis. Saturation Transfer Difference (STD) protein-NMR experiments, undertaken using selected compounds, have revealed binding of most of the ligands examined to EcDXR. Computersimulated docking studies have also been used to explore the preferred ligand-binding conformations and interactions between the ligands and essential DXR active-site residues, while DXR-enzyme inhibition assays of selected synthesised ligands have revealed certain patterns of inhibitory activity.
- Full Text:
- Date Issued: 2011
The design and synthesis of multidentate N-heterocyclic carbenes as metathesis catalyst ligands
- Authors: Truscott, Byron John
- Date: 2011
- Subjects: Carbenes (Methylene compounds) , Heterocyclic compounds , Ligands , Ligands -- Design , Metathesis (Chemistry) , Catalysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4304 , http://hdl.handle.net/10962/d1004962 , Carbenes (Methylene compounds) , Heterocyclic compounds , Ligands , Ligands -- Design , Metathesis (Chemistry) , Catalysis
- Description: This study has focused on the design and preparation of bi– and tridentate N–Heterocyclic Carbene (NHC) ligands in order to investigate the effect of a multidentate approach to the formation, stability and catalytic activity of coordination complexes. Chapters 1 – 3 provide background information of relevant catalysis, carbene and coordination chemistry, followed by previous work performed within our research group. In Chapter 4 attention is given to the synthetic aspects of the research conducted, comprising two distinct approaches to the preparation of unsymmetrical saturated and unsaturated NHCs. Firstly, an investigation of the saturated NHC ligands yielded three novel, unsymmetrical pro–ligands, viz., two halopropyl imidazolinium salts and a bidentate hydroxypropyl imidazolinium salt. Secondly, eight imidazolium salts have been generated, including a hydroxypropyl analogue and novel decyl and tridentate malonyl derivatives. These compounds were prepared using microwave–assisted methodology for the alkylation of N– mesitylimidazole – an approach that drastically reduced reaction times (from 8 hours – 7 days to ca. 0.5 – 2 hours) and facilitated isolation of the imidazolium salts. Many of the compounds prepared in this study are novel and were fully characterized using HRMS and 1– and 2–D NMR analysis. Coordination studies using a selection of the prepared pro–ligands afforded an alkoxy–NHC silver derivative and four novel Ru–complexes, viz., Grubbs II–type Ru–complexes containing:– chloropropyl imidazolinylidene; propenyl imidazolylidene; and bidentate alkoxypropyl imidazolylidene ligands. Furthermore, a well–defined benzyl mesitylimidazolylidene Ru–complex has been isolated, which exhibited good stability in air. DFT–level geometry–optimization studies, using the Accelrys DMol3 package have given valuable insights into the likely geometries of the prepared and putative catalysts.
- Full Text:
- Date Issued: 2011
- Authors: Truscott, Byron John
- Date: 2011
- Subjects: Carbenes (Methylene compounds) , Heterocyclic compounds , Ligands , Ligands -- Design , Metathesis (Chemistry) , Catalysis
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4304 , http://hdl.handle.net/10962/d1004962 , Carbenes (Methylene compounds) , Heterocyclic compounds , Ligands , Ligands -- Design , Metathesis (Chemistry) , Catalysis
- Description: This study has focused on the design and preparation of bi– and tridentate N–Heterocyclic Carbene (NHC) ligands in order to investigate the effect of a multidentate approach to the formation, stability and catalytic activity of coordination complexes. Chapters 1 – 3 provide background information of relevant catalysis, carbene and coordination chemistry, followed by previous work performed within our research group. In Chapter 4 attention is given to the synthetic aspects of the research conducted, comprising two distinct approaches to the preparation of unsymmetrical saturated and unsaturated NHCs. Firstly, an investigation of the saturated NHC ligands yielded three novel, unsymmetrical pro–ligands, viz., two halopropyl imidazolinium salts and a bidentate hydroxypropyl imidazolinium salt. Secondly, eight imidazolium salts have been generated, including a hydroxypropyl analogue and novel decyl and tridentate malonyl derivatives. These compounds were prepared using microwave–assisted methodology for the alkylation of N– mesitylimidazole – an approach that drastically reduced reaction times (from 8 hours – 7 days to ca. 0.5 – 2 hours) and facilitated isolation of the imidazolium salts. Many of the compounds prepared in this study are novel and were fully characterized using HRMS and 1– and 2–D NMR analysis. Coordination studies using a selection of the prepared pro–ligands afforded an alkoxy–NHC silver derivative and four novel Ru–complexes, viz., Grubbs II–type Ru–complexes containing:– chloropropyl imidazolinylidene; propenyl imidazolylidene; and bidentate alkoxypropyl imidazolylidene ligands. Furthermore, a well–defined benzyl mesitylimidazolylidene Ru–complex has been isolated, which exhibited good stability in air. DFT–level geometry–optimization studies, using the Accelrys DMol3 package have given valuable insights into the likely geometries of the prepared and putative catalysts.
- Full Text:
- Date Issued: 2011
The implementation and evaluation of a service-learning component in a second year undergraduate organic chemistry course
- Authors: Abel, Sarah Ruth
- Date: 2011 , 2010-10-03
- Subjects: Chemistry, Organic -- Study and teaching (Higher) -- South Africa , Action research in education -- South Africa , Experiential learning -- South Africa , Service learning -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4393 , http://hdl.handle.net/10962/d1006008 , Chemistry, Organic -- Study and teaching (Higher) -- South Africa , Action research in education -- South Africa , Experiential learning -- South Africa , Service learning -- South Africa
- Description: The project describes the action research implementation, and evaluation of learning, of a service-learning component in a second year undergraduate organic chemistry course. The research aims to explore the learning that takes place in a service-learning context while utilizing an action research methodology within the critical theory paradigm. This occurs in response to the world-wide call for Higher Education to produce people with civic competencies and responsiveness to the society in which they live (Boyer 1996). Educating young Chemists to see the importance of their knowledge and their responsibilities in society is an important pedagogical step in the effort to cross boundaries and make connections between people communities (Eyler and Giles 1999). The goal of this project was to explore and categorize the learning that takes place in a service-learning context and discover how these areas of learning impact the awareness of the parties involved with regard to the discipline of chemistry as well as social issues. The project makes use of Kolb‘s (1984) Experiential Learning Theory, and Eyler and Giles‘ (1999) categories of learning in service-learning and results indicate that service-learning can be a powerful pedagogical tool to increase learning in chemistry as well as in the areas of critical thinking, personal and social development, reflection and citizenship. Students‘ perceptions of themselves, their discipline and their responsibility to society were transformed by their experience of service-learning in their undergraduate chemistry course.
- Full Text:
- Date Issued: 2011
- Authors: Abel, Sarah Ruth
- Date: 2011 , 2010-10-03
- Subjects: Chemistry, Organic -- Study and teaching (Higher) -- South Africa , Action research in education -- South Africa , Experiential learning -- South Africa , Service learning -- South Africa
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4393 , http://hdl.handle.net/10962/d1006008 , Chemistry, Organic -- Study and teaching (Higher) -- South Africa , Action research in education -- South Africa , Experiential learning -- South Africa , Service learning -- South Africa
- Description: The project describes the action research implementation, and evaluation of learning, of a service-learning component in a second year undergraduate organic chemistry course. The research aims to explore the learning that takes place in a service-learning context while utilizing an action research methodology within the critical theory paradigm. This occurs in response to the world-wide call for Higher Education to produce people with civic competencies and responsiveness to the society in which they live (Boyer 1996). Educating young Chemists to see the importance of their knowledge and their responsibilities in society is an important pedagogical step in the effort to cross boundaries and make connections between people communities (Eyler and Giles 1999). The goal of this project was to explore and categorize the learning that takes place in a service-learning context and discover how these areas of learning impact the awareness of the parties involved with regard to the discipline of chemistry as well as social issues. The project makes use of Kolb‘s (1984) Experiential Learning Theory, and Eyler and Giles‘ (1999) categories of learning in service-learning and results indicate that service-learning can be a powerful pedagogical tool to increase learning in chemistry as well as in the areas of critical thinking, personal and social development, reflection and citizenship. Students‘ perceptions of themselves, their discipline and their responsibility to society were transformed by their experience of service-learning in their undergraduate chemistry course.
- Full Text:
- Date Issued: 2011
The photophysical properties of low symmetry phthalocyanines in conjunction with quantum dots
- Authors: D'Souza, Sarah
- Date: 2011
- Subjects: Phthalocyanines , Photochemistry , Zinc , Quantum dots , Spectrum analysis , Nanoparticles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4331 , http://hdl.handle.net/10962/d1004992 , Phthalocyanines , Photochemistry , Zinc , Quantum dots , Spectrum analysis , Nanoparticles
- Description: he synthesis, extensive spectroscopic characterization and photophysical studies of low symmetry zinc phthalocyanine have been conducted. Comparisons have been made taking into consideration the influence of the solvent properties as well as substituent type and position. Photosensitizing properties of the zinc phthalocyanine derivatives in the presence of thiol capped CdTe quantum dots (QDs) were compared. The QDs were used as energy transfer donors and to facilitate with energy transfer through Förster resonance energy transfer (FRET) from the QDs to the MPcs. The linkage of unsymmetrically substituted 4-monoaminophenoxy zinc phthalocyanine (ZnAPPc) to CdTe quantum dots capped with mercaptopropionic acid (MPA), L-cysteine (L-cys) or thioglycolic acid (TGA) has been achieved using the coupling agents ethyl-N3 dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy succinimide (NHS), which facilitate formation of an amide bond to form the QD-ZnAPPc-linked complex. The formation of the amide bond was confirmed using UV-Vis, Raman and IR spectroscopies, as well as AFM (atomic force microscopy). Förster resonance energy transfer (FRET) resulted in stimulated emission of ZnAPPc in both the linked (QDZnAPPc-linked) and mixed (QD:ZnAPPc-mixed) conjugates for MPA only. The linked L-cys and TGA complexes (QD-ZnAPPc-linked) gave the largest FRET efficiencies hence showing the advantages of covalent linking. Fluorescence quantum yields of QDs were decreased in QD:ZnAPPc-mixed and QD:ZnAPPc-linked. High triplet state quantum yields were obtained for the linked QD-phthalocyanine derivatives (ZnAPPc)and monoaminozinc phthalocyanine (ZnAPc) compared to when ZnAPPc and ZnAPc were mixed with MPA QDs without a chemical bond.
- Full Text:
- Date Issued: 2011
- Authors: D'Souza, Sarah
- Date: 2011
- Subjects: Phthalocyanines , Photochemistry , Zinc , Quantum dots , Spectrum analysis , Nanoparticles
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4331 , http://hdl.handle.net/10962/d1004992 , Phthalocyanines , Photochemistry , Zinc , Quantum dots , Spectrum analysis , Nanoparticles
- Description: he synthesis, extensive spectroscopic characterization and photophysical studies of low symmetry zinc phthalocyanine have been conducted. Comparisons have been made taking into consideration the influence of the solvent properties as well as substituent type and position. Photosensitizing properties of the zinc phthalocyanine derivatives in the presence of thiol capped CdTe quantum dots (QDs) were compared. The QDs were used as energy transfer donors and to facilitate with energy transfer through Förster resonance energy transfer (FRET) from the QDs to the MPcs. The linkage of unsymmetrically substituted 4-monoaminophenoxy zinc phthalocyanine (ZnAPPc) to CdTe quantum dots capped with mercaptopropionic acid (MPA), L-cysteine (L-cys) or thioglycolic acid (TGA) has been achieved using the coupling agents ethyl-N3 dimethylaminopropyl)carbodiimide (EDC) and N-hydroxy succinimide (NHS), which facilitate formation of an amide bond to form the QD-ZnAPPc-linked complex. The formation of the amide bond was confirmed using UV-Vis, Raman and IR spectroscopies, as well as AFM (atomic force microscopy). Förster resonance energy transfer (FRET) resulted in stimulated emission of ZnAPPc in both the linked (QDZnAPPc-linked) and mixed (QD:ZnAPPc-mixed) conjugates for MPA only. The linked L-cys and TGA complexes (QD-ZnAPPc-linked) gave the largest FRET efficiencies hence showing the advantages of covalent linking. Fluorescence quantum yields of QDs were decreased in QD:ZnAPPc-mixed and QD:ZnAPPc-linked. High triplet state quantum yields were obtained for the linked QD-phthalocyanine derivatives (ZnAPPc)and monoaminozinc phthalocyanine (ZnAPc) compared to when ZnAPPc and ZnAPc were mixed with MPA QDs without a chemical bond.
- Full Text:
- Date Issued: 2011
A bioinorganic investigation of some metal complexes of the Schiff base, N,N'-bis(3-methoxysalicylaldimine)propan-2-ol
- Authors: Mopp, Estelle
- Date: 2010 , 2012-04-13
- Subjects: Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4413 , http://hdl.handle.net/10962/d1006768 , Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Description: This thesis includes the synthesis, characterisation, antioxidant and antimicrobial activities of Cu(II)-, Co(II)- and Co(III) complexes with N,N'-bis(3- methoxysalicylaldimine)propan-2-ol, 2-OH-oVANPN. The Schiff base ligand, 2-OHoVANPN, is derived from o-vanillin and 1,3-diaminopropan-2-ol. The o-vanillin condensed with 1,3-diaminopropan-2-ol in a 2:1 molar ratio yields this potential tetraor pentadentate ligand. The complexes synthesized are tetra (or penta or hexa) coordinated. Formation of the complexes is symbolized as follows:- MX₂ + 2-OH-oVANPN (2:1) -> [M(2-OH-oVANPN)Xn] + HnX MX₂ + 2-OH-oVANPN (2:1) -> [Mn(2-OH-oVANPN)OH] + H₂X₂ MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M(1:1)X₂] MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M₃(1:1)X₄] M = Cu(II), Co(II) or Co(III); X = Cl; n = 1, 2. Their structural features have been deduced from their elemental analytical data, IR spectral data, and electronic spectral data. With the exception of {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆}(A4), the Cu(II) complexes were monomeric with 2-OH-oVANPN acting as a tetradentate ligand. A binuclear Co(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), was synthesised and the rest of the Co(II) and Co(III) complexes were monomeric with chloride ions coordinating to the metal centre in some cases. Electronic data suggest that the cobalt(II) complexes have octahedral geometries and the copper(II) complexes have square planar structures – Co(III) is likely to be octahedral. Thermal analyses, which included the copper-block-method for determining sublimation temperatures, revealed that some copper(II) and cobalt(II) complexes are hygroscopic and sublime at 200 °C and below. DSC analyses of the Cu(II) complexes gave exotherms around 300 °C for complexes K[Cu(C₁₉H₂₀N₂O₅)(OH)]·2H₂O (A1) and [Cu(C₁₁H15N₂O₃)(Cl)₂]·2H₂O (A2) and above 400 °C for [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3) and {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4). Antioxidant studies were carried out against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·). The cobalt(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), which was synthesized in the presence of KOH, had no antioxidant activity, whilst the other cobalt(II) complexes, [Co(C₁₇H₁₇N₂O₅(Cl))]·1½H₂O (B2), [Co(C₁₉H₂₂N₂O₅) (Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B4), which were synthesised in the absence of KOH, demonstrated antioxidant activity. The latter complexes are candidates for cancer cell line testing, while [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3), {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4), [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) may show anticancer activity through possible hydrolysis products. Most of the complexes synthesized displayed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. The results indicated that complexes [Cu(C₁₁H₁₆N₂O₃)(Cl)₂](A3), [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) are active against the Gram-negative Ps. aeruginosa and that the ligand, 2-OH-oVANPN, did not have any activity. The same trend was observed with 2-OH-oVANPN, {Cu₃(C₁₁H₁₄N₂O₃)(Cl)4(H₂O)₆} (A4) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) against the Gram-positive S. aureus. As for activity against E. coli and C. albicans, some complexes showed more activity than the ligand. There is an observed trend here that the metal complexes are more active (toxic) than the corresponding ligand, which is in agreement with Tweedy’s chelation theory.
- Full Text:
- Date Issued: 2010
- Authors: Mopp, Estelle
- Date: 2010 , 2012-04-13
- Subjects: Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Language: English
- Type: Thesis , Masters , MSc
- Identifier: vital:4413 , http://hdl.handle.net/10962/d1006768 , Schiff bases , Bioinorganic chemistry , Metal complexes , Transition metal complexes , Transition metals , Cancer -- Chemotherapy , Ligands -- Toxicity , Antineoplastic agents
- Description: This thesis includes the synthesis, characterisation, antioxidant and antimicrobial activities of Cu(II)-, Co(II)- and Co(III) complexes with N,N'-bis(3- methoxysalicylaldimine)propan-2-ol, 2-OH-oVANPN. The Schiff base ligand, 2-OHoVANPN, is derived from o-vanillin and 1,3-diaminopropan-2-ol. The o-vanillin condensed with 1,3-diaminopropan-2-ol in a 2:1 molar ratio yields this potential tetraor pentadentate ligand. The complexes synthesized are tetra (or penta or hexa) coordinated. Formation of the complexes is symbolized as follows:- MX₂ + 2-OH-oVANPN (2:1) -> [M(2-OH-oVANPN)Xn] + HnX MX₂ + 2-OH-oVANPN (2:1) -> [Mn(2-OH-oVANPN)OH] + H₂X₂ MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M(1:1)X₂] MX₂ + (o-vanillin : diaminopropanol) (1:1) -> [M₃(1:1)X₄] M = Cu(II), Co(II) or Co(III); X = Cl; n = 1, 2. Their structural features have been deduced from their elemental analytical data, IR spectral data, and electronic spectral data. With the exception of {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆}(A4), the Cu(II) complexes were monomeric with 2-OH-oVANPN acting as a tetradentate ligand. A binuclear Co(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), was synthesised and the rest of the Co(II) and Co(III) complexes were monomeric with chloride ions coordinating to the metal centre in some cases. Electronic data suggest that the cobalt(II) complexes have octahedral geometries and the copper(II) complexes have square planar structures – Co(III) is likely to be octahedral. Thermal analyses, which included the copper-block-method for determining sublimation temperatures, revealed that some copper(II) and cobalt(II) complexes are hygroscopic and sublime at 200 °C and below. DSC analyses of the Cu(II) complexes gave exotherms around 300 °C for complexes K[Cu(C₁₉H₂₀N₂O₅)(OH)]·2H₂O (A1) and [Cu(C₁₁H15N₂O₃)(Cl)₂]·2H₂O (A2) and above 400 °C for [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3) and {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4). Antioxidant studies were carried out against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH·). The cobalt(II) complex, [Co₂(C₁₉H₁₉N₂O₅)(OH)] (B1), which was synthesized in the presence of KOH, had no antioxidant activity, whilst the other cobalt(II) complexes, [Co(C₁₇H₁₇N₂O₅(Cl))]·1½H₂O (B2), [Co(C₁₉H₂₂N₂O₅) (Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B4), which were synthesised in the absence of KOH, demonstrated antioxidant activity. The latter complexes are candidates for cancer cell line testing, while [Cu(C₁₁H₁₆N₂O₃)(Cl)₂] (A3), {Cu₃(C₁₁H₁₄N₂O₃)(Cl)₄(H₂O)₆} (A4), [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) may show anticancer activity through possible hydrolysis products. Most of the complexes synthesized displayed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Aspergillus niger and Candida albicans. The results indicated that complexes [Cu(C₁₁H₁₆N₂O₃)(Cl)₂](A3), [Co(C₁₉H₂₂N₂O₅)(Cl)₂]·5½H₂O (B3) and [Co(C₁₉H₂₁N₂O₅)(Cl)₂ ]·5H₂O (C2) are active against the Gram-negative Ps. aeruginosa and that the ligand, 2-OH-oVANPN, did not have any activity. The same trend was observed with 2-OH-oVANPN, {Cu₃(C₁₁H₁₄N₂O₃)(Cl)4(H₂O)₆} (A4) and [Co(C₁₉H₂₀N₂O₅)(Cl)]·3H₂O (C3) against the Gram-positive S. aureus. As for activity against E. coli and C. albicans, some complexes showed more activity than the ligand. There is an observed trend here that the metal complexes are more active (toxic) than the corresponding ligand, which is in agreement with Tweedy’s chelation theory.
- Full Text:
- Date Issued: 2010