Masters Degrees (Chemistry and Polymer Science)

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Browsing Masters Degrees (Chemistry and Polymer Science) by browse.metadata.advisor "Bredenkamp, M. W."

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    Ligand modification of Pluronic F108 for use in immobilized metal affinity separation of bio-macromolecules
    (Stellenbosch : Stellenbosch University, 2002-03) Van Kralingen, Leon; Adendorff, H. J. A.; Bredenkamp, M. W.; Stellenbosch University. Faculty of Science. Dept. of Chemistry & Polymer Science.
    ENGLISH ABSTRACT: Inthis work we aim to put into place a system to separate or immobilise biomacromolecules by means ofimmobilised transition metal ions like nickel(II) or copper(II). Although the concept of immobilised metal affmity chromatography (IMAC) has been around since the early 1960's, the metal ions were always immobilised by covalent modification of the support matrix. Recently the concept of IMAC was applied to membranes, and again the metal ion was immobilised by covalent modification of the membrane surface. Inthis study we covalently modified the support matrix by attaching a linear, EDTA type ligand to the hydroxy end groups of a tri-block copolymer (polyethylene oxide (PEO)m = 129 - polypropylene oxide (PPO)n = 56 - polyethylene oxide (PEO)m= 129), Pluronic® F108. The middle block of this polymer, which is hydrophobic, will non-covalently adsorb onto the membrane surface through hydrophobic interaction. The hydrophilic outer blocks, with the ligand modified end groups, will associate with the aqueous substrate exposing the chelated metal ion for interaction with the bio-macromolecules. This affords a system which is recyclable, without replacing the membranes, simply by stripping the expired ligand modified-polymer and adsorbing fresh polymer. A series of model ligands and their complexes were synthesised and characterised, to study the coordination of the ligand around the metal ions. The model compounds were also essential in characterising the final product - the ligand modified Pluronic. Finally the ligand modified Pluronic was tested for its metal binding capabilities. This was done in aqueous solution by qualitatively comparing the UV-VIS spectra of the modified Pluronic with that of the model ligands and complexes. The spectra indicate that metal coordination does take place.
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    Structure activity relationship studies of ochratoxin A analogues
    (Stellenbosch : Stellenbosch University, 2002-03) Gabrielli, William Fullard; Bredenkamp, M. W.; Steyn, P. S.; Stellenbosch University. Faculty of Science. Dept. of Chemistry & Polymer Science .
    ENGLISH ABSTRACT: Mycotoxins have assumed worldwide importance due to the ubiquitous occurrence of toxigenic fungi, their infestation of plant-based foods and feeds and the subsequent economical and health impact it because of their contamination of commercial products. Ochratoxin A (OA) is a nephrotoxic mycotoxin produced by isolates of Aspergillus ochraceus and Penicillium verrucosum and occurs frequently in nature. The major target for toxicity of OA in mammalian species is the kidneys and it has been the major cause of Danish Porcine Nephropathy. OA has also been extensively implicated in the aetiology of Balkan Endemic Nephropathy and Chronic Interstitial Nephropathy in Northern-Africa. Furthermore, OA has been identified as a carcinogen, an immunosuppressant and a teratogen with respect to the foetal central nervous system. Although a large amount of research has been conducted into the chemical nature of the toxicity of OA, the exact molecular mechanism of action of OA is not yet conclusive. Numerous structure activity relationship studies have suggested that the toxicity of OA may be assigned to three major processes: (i) inhibition of ATP production; (ii) inhibition of protein synthesis; and (iii) the disruption of hepatic microsomal calcium homeostasis through the promotion of membrane lipid peroxidation. It is the aim of this thesis to gain a better understanding, through the synthesis ofOA analogues, of the chemical structure responsible for the toxic function of the ochratoxins. The halogen-group has extensively been implicated in the toxicity of the ochratoxins. This is evident in ochratoxin B (OB), the dechloro analogue of OA, which is approximately ten times less toxic than OA. Preliminary tests have indicated that bromo-ochratoxin B(BrOB), the bromo analogue of OA, is more toxic than ochratoxin A to renal cells. Fluoro-ochratoxin B and other analogues of OA, where other amino acids are incorporated, should provide invaluable information on the structure-activity relationships and the mode of action of the ochratoxins. Our research effort addresses both these aspects (i) fluorination of the dihydroisocoumarin moiety and (ii) the coupling of different amino acids and dipeptides to the non-toxic hydrolysed product of OA, ochratoxin a. Chapter one includes a review of the important biological aspects of OA that has served as a guideline to the synthesis of effective OA analogues. An overview of the relevant chemistry involved in the modification of OA will conclude the chapter. Chapter two entails a discussion of fluorine in bio-organic chemistry. This includes an overview of the impact that fluorine substitution has on the biological reactivity of molecules. A review on the synthesis of organofluorine compounds, which forms the emphasis of this study, concludes the chapter. Chapter three elaborates on the different methodologies used in our attempts to synthesise fluoro-ochratoxin B and other analogues. These included the direct electrophilic fluorination of OB and different analogous aromatic model compounds by xenon difluoride, N-fluorobenzenesulfonimides and Selectfluor™ as fluorinating agents. Also involved is an investigation into an alternative route for the synthesis of fluoro aromatic compounds from bromo and chloro analogues by means of palladium catalysed trimethyl- and tributylstannyl and trimethylsilylation which in tum may be substituted with fluorine by means of xenon difluoride. Efforts towards the direct catalytic fluorosubstitution of aryl halides are also investigated. The synthesis of a key intermediate, fluoroacetoacetaldehyde, in a de nova synthetic route to fluoroochratoxin B is also discussed. Furthermore, the synthesis of novel OA analogues with respect to the replacement of the L-phenylalanine moiety is addressed. This includes the conversion of OA to Oa, by acid hydrolysis, followed by the coupling of ortho-, meta- and para- substituted DL-fluorophenylalanine to the lactone acid. This is followed by the synthesis of histidylhistidine methyl ester and attempted coupling to Oa. The coupling of halosalicylic acids and salicylic acid to L-phenylalanine, for use as model aromatic substrates for fluorination, IS discussed. Peptide coupling by dicyclohexylcarbodiimide carboxyl activation, with reference to the protection of the phenolic hydroxyl group in 5-chlorosalicylic acid for application to Oa, concludes this work.
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    Synthesis and electrochemistry of biodegradable ligands - iminodiglutaric acid and iminoglutaricsuccinic acid - and their complexes with selected metal ions (Zn²⁺, Cd²⁺, Cu²⁺)
    (Stellenbosch : Stellenbosch University, 2004-12) Yohannes Desta, Yonas; Crouch, A. M.; Bredenkamp, M. W.; Stellenbosch University. Faculty of Science. Dept. of Chemistry & Polymer Science.
    ENGLISH ABSTRACT: Two new potentially biodegradable aminopolycarboxylic acid ligands, iminodiglutaric acid tetra sodium salt (IDG-4Na) and iminoglutaricsuccinic acid tetra sodium salt (IGS- 4Na), were synthesized in reasonably good yield and purity. The commercially unavailable precursor for the two ligands, ethyl p-aminoglutarate, was synthesised in high yield and purity, and together with the two ligands were fully characterized by means of melting point measurements and various spectrometric techniques CH-NMR, 13C-NMR, MS and IR). For the first time, an electrochemical study has been conducted on the complexes of these ligands with selected transition metal ions (Zn2+, Cu2+ and Cd2+). An electrochemical technique, cyclic voltammetry (CV), was utilized on the study of the complexing ability of the ligands to the selected metal ions. An electrochemical cell comprising three electrodes was employed: thin film mercury coated carbon microelectrode was used as the working electrode, a Platinum wire as the auxiliary electrode, and a Ag/AgCI as the reference electrode. CV has been used and proven to offer a convenient route towards the determination of metal-ligand complex stability constants in aqueous media". The values of the logarithms of the metal-ligand formation constants obtained by this technique, when compared with other widely used aminopolycarboxylic acids (APCAs), show better complexing ability of the ligands with the transition metal ions. When the two ligands are compared, IGS showed greater affinity towards the selected transition metal ions. This is due to the fact that, in aqueous media, as the side chain ligators decrease, the stabilization energy of the complex increases. The formation stability constants were determined by plotting the change in the reduction potential (ΔE) against solution pH. A process making use of a modification of lingane equation was used.
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    Synthesis of chiral thiourea ligands and their transition metal complexes
    (Stellenbosch : Stellenbosch University, 2003-12) Ghebregziabiher Berhe, Haile; Koch, K. R.; Bredenkamp, M. W.; Stellenbosch University. Faculty of Science . Dept. of Chemistry & Polymer Science.
    ENGLISH ABSTRACT: Modification of chitosan with benzoylisothiocyanate was attempted, however due to solvent problem the study was left incomplete till appropriate solvent is designed. N,N-diethyl-N -camphanoylthiourea (HL8), N-piperidyl-N '-camphanoylthiourea (HL9), N-pyrrolidyl-N -camphanoylthiourea (HL10) and N,N-diethyl-N -adamantylcarbonyl thiourea (HL11)have been synthesised and characterised for the first time. Two of these ligands HL8 and HL11, were used to form a number of transition metal complexes, namely H30+{fae-[Co(L8-S,Obn, cis-[Ni(L8-S,0)2], trans-[Cu(L8-S,0)2], translcis-[Zn(L 8_S,0)2], translcis-[Pt(L 8_S,0)2], Ag2[(HL8-S)(L-J.1-S,O)]2, translcis- [Ni(L11-S,O)2]and translcis-[Cu(L11_S,O)2]. The new products are fully characterised by means of MS, IR spectroscopy, NMR spectroscopy, elemental (C, H, Nand S) analysis and melting point determinations. The H30+{fae-[Co(L8-S,Obn, cis-[Ni(L8- S,O)2], trans-[Cu(L8-S,O)2] and Ag2[(HL8-S)(L-J.1-S,O)]2 are also characterised by Xray diffraction analysis. The structure of the new chiral N,N-dialkyl-N' -camphanoylthiourea ligand (HL8) has a significant effect on its coordination chemistry with transition metal ions. This ligand forms H30+ {fae-[Co(L8-S,Obn, cis-[Ni(L8-S,0)2], trans-[Cu(L-S,O)2] and Ag2[(HL8- S)(L8-J.1-S,O)]2 complexes with the Co(II), Ni(II), Cu(II) and Ag(I) metal ions respectively. The spectroscopic and X-ray diffraction results of these complexes indicate a bidentate mode of coordination of the ligand (with its Sand °donor atoms) to the Co(II), Ni(II) and Cu(II) metal ions. The reaction of this ligand with silver(I) however affords the formation of a binuclear silver(I) complex exhibiting monodentate and bidentate modes of coordination within the same complex. The exclusive formation of trans-[Cu(L8-S,0)2] is a new phenomenon for the HL type thiourea ligands with Sand °donor atoms. Up to this point a maximum of 15 % trans-isomer has been reported in ltterature." All the transition metal complexes made with HL8and HL11are air stable in both the liquid and solid states except the H30+{fae-[Co(L 8-S,Ob]} Interestingly the deep green fae- H30+{fae-[Co(L8-S,Obn complex is air sensitive and the Co(II) oxidizes to Co(III) in the complex by atmospheric O2. The oxidation of Co(II) to Co(III) in the complex is confirmed by 1Hand 13CNMR spectra as well as by UV-Visible spectra of the complex. The NMR spectra of the complexes indicated the presence of one isomer in each complex except for the NMR spectra of the platinum complex of the HL8 ligand. The presence of the minor trans-[Pt(L8-S,Q)21 isomer in combination with the major cis-[Pt(L8-S,Q)21 isomer in the platinum complex was indicated by the 1H, 13Cand 195ptNMR spectra of the complex.