The synthesis of glycolipids containing a variable length polyethylene glycol spacer group between a glucuronic acid (glu) headgroup and a cholesterol (chol) tail glu-0CH₂(CH₂OCH₂ )nCH₂O-chol is described. The homologs (n=2,3,5) were prepared by reaction of an excess of commercially available tri, tetra and hexaethylene glycols with cholesteryl-p-toluene sulfonate. 3-O-(8-hydroxy-3,6-dioxaoctyl) cholest-5-ene (2), 3-O-(ll-hydroxy-3,6,9-trioxaundecyl)cholest-5-ene (3) and 3-O-(17-hydroxy-3,6,9,12,15-pentaoxaheptadecyl)cholest-5-ene (4) were produced, and yields were dependent on the amount of excess used. The headgroup was prepared by esterification and acetylation of glucuronolactone to produce methyl (1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyran)uronate which was then brominated at the anomeric carbon to produce methyl (2, 3, 4-tri-O-acetyl-α-D-glucopyranosyl bromide)uronate (1). The headgroup was coupled to the cholesteroxy oligoethylene glycols by a Koenig Knorr type reaction using freshly prepared silver carbonate as the catalyst. Methyl[3-O-(3,6-dioxaoctyl)cholest-5-en-3β-y1-2,3,4-tri-O-acetyl-β-D-glucopyranosid] uronate (5), Methyl[3-O-(3,6,9-trioxaundecyl) cholest-5-en-3β-yl-2,3,4-tri-0-acetyl-β-D-glucopyranosid] uronate (6), and Methyl[3-O-(3,6,9,12,15-pentaoxaheptadecyl)cholest-5-en-3β-yl-2, 3, 4-tri-O -acetyl-β-D-glucopyranosid] uronate (7) were produced with yields of up to 30%. The removal of the methyl ester and acetate protecting groups on the headgroup was accomplished using NaOH in a mixture of solvents followed by acidification with HCl to produce 3-O-(3,6-dioxaoctyl)cholest-5-en-3β-yl-β-D-glucopyranosiduronic acid (8) and 3-O-(3,6,9-trioxaundecyl)cholest-5-en-3β-yl-β-D-glucopyranosiduronic acid (9). Octaethylene glycol and dodecaethylene glycol were prepared using a solid supported synthesis. The solid polymer used was a trityl chloride functionalized polystyrene 1% divinyl benzene. Mono protected tetraethylene glycol was prepared and attached to the polymer. The protecting group was removed, and the hydroxy terminal was converted to a mesylate leaving group by reaction with methane sulfonyl chloride. To elongate the chain, the anion of tetraethylene glycol was prepared using sodium hydride in DMF. The tetraethylene glycol bound resin was added, and reaction continued at 120 °C for 24 hours. Cleavage of the resultant product from the polymer support yielded octaethylene glycol. Repetition of the mesylation and elongation steps followed by cleavage yielded dodecaethylene glycol. The oligoethylene glycols were purified by passage through a Fractogel 40S gel permeation column. Two different protecting groups for the tetraethylene glycol were tried. Trialkyl silyl groups were first attempted, but were abandoned due to reduced reactivity and monitoring difficulties during the deprotection. An acetate protecting group was finally used and deprotection was monitored with infrared spectroscopy. / Science, Faculty of / Chemistry, Department of / Graduate

A β-glucosidase was isolated from A. faecalis and purified 880 fold by a combination of classical and medium pressure chromatographic techniques to a specific activity of 31.6 units/mg. The protein was homogeneous by the criteria of SDS-PAGE and gel chromatography. The sub-unit molecular weight was determined to be 51,000 by SDS-PAGE. The apparent oligomeric molecular weight was determined to be 75,000 by Superose gel chromatography and 98,000 by Waters 1-250 gel chromatography, suggesting that the enzyme is a dimer. The enzyme was shown to be a retaining β-glucosidase with exo-glucanase activity only. The kinetic parameters of a number of substrates and inhibitors were determined allowing deductions to be made about the nature of the active site and catalytic mechanism. The Km's determined for cellobiose and PNPG were low for a bacterial β-glucosidase, 0.70 mM and 0.083 mM respectively. In the cellodextrin series, cellobiose to cellopentaose, the enzyme was most efficient (as defined by Vm/Km) with cellotriose as substrate. In common with other cellulolytic β-glucosidases, the glycone site showed a high specificity for glucose (although it would tolerate some modifications) and poor specificity at the aglycone site. Catalytic activity was (unusually) observed with p-nitrophenyl-β-D-mannopyranoside as substrate. Activation energies were determined by means of Arrhenius plots. / Science, Faculty of / Chemistry, Department of / Graduate

The syntheses of s-triazolo[3,4-a]phthalazines (15, 3-R-TAP) by reaction of hydralazine (12, 1-hydrazinophthalazine) with N-protected amino acids and dipeptides under homogeneous (solution) and heterogeneous ("solid-phase") conditions are reported. Transition metal complexes containing the TAP ligand were prepared and their spectral properties investigated. The use of metal-ions and a cation-exchange resin (H+ form) were considered for the mild hydrolysis of side-chain amide bonds in TAP derivatives. The objective of these studies was to determine the feasibility of reacting the carboxyl groups in amino acids with hydralazine to afford the TAP derivatives as a method for peptide sequencing from the C-terminal residue. Hydralazine reacts with carboxylic acids to form an amide intermediate which undergoes ring closure with elimination of water to form the s-triazolo[3,4-a]phthalazine derivative. To promote the initial binding of hydralazine to the acid, coupling reagents were used to activate the carboxylate group towards nucleophilic attack. N-Ethyl-5-phenylisoxazolium-3'-sulfonate (17, NEPIS), 1-ethoxy -carbonyl-2-ethoxy-l,2-dihydroquinoline (27, EEDQ), various phosphorus compounds, carbodiimides, and chloroformates were carboxyl activating agents used to synthesize TAP derivatives. In solution studies, the carbodiimides (EDC, 16 and DCC, Si), NEPIS (17), and a combination of triphenylphosphite with imidazole are the most successful procedures for TAP synthesis In solid-phase studies, the best procedures for activating immobilized amino acids, are with isobuty'l chloroformate, NEPIS (l?), and DCC (51). Transition metal complexes were synthesized with the general formula: [M(3-H-TAP) (H20)6_n](C104)m (n = 4, m = 2, M = Co, Ni, Cu; n = 2, m = 2, M = Ni; n = 6, m = 3, M = Co). The infrared and visible spectra of these complexes are reported. [Co(.trien)C3-(N-Ac-gly)-TAP)J(C104)2 was also prepared and under acidic conditions, no hydrolysis of the side-chain amide bond was observed. There was also no significant hydrolysis of the side-chain with free ?+ 2+ 3-(N-Ac-gly)-TAP in the presence of Co and Cu under acidic conditions, or when it was eluted through a cation-exchange (H+ form) column. The decomposition of hydralazine in non-aqueous media was investigated and a major product of the decomposition was identified as diphthalazinylhydrazine {82). The implication of our studies is that the modification of amino acids with hydralazine is not yet a viable method for C-terminal peptide sequencing. Improvements are required for improving the yields of the coupled product, and the lack of a mild and selective method for hydrolyzing the C-terminal peptide bond limits the method at present to determination of the C-terminal residue only. / Science, Faculty of / Chemistry, Department of / Graduate

The use of metal-containing block-copolymer to fabricate magnetic nanoparticles arranged in desired nanostructure has attracted immense attention in the field of materials science. As a result, a series of FePt-containing block copolymers were synthesized. To begin with, a brief survey on the background of magnetic FePt NPs and the use of both organic and metal-containing block copolymer self-assembly was presented in chapter 1. In chapter 2, a series of FePt-containing polymers were synthesized and characterized. The random copolymer FePt-A exhibited poor solubility and ill-characterized morphology in the bulk state self-assembly. The block copolymer FePt-B2 showed incomplete complexation due to the bulky nature of the FePt-complexes B5 used, whereas the block copolymer FePt-C resulted in insoluble polymeric materials after complexation. Fortunately, when using coordination linkage, FePt-Ds were successfully synthesized and characterized with good solubility in common solvents. To retain the cylindrical (FePt-D-Cy1/2) and spherical (FePt-D-Sp1/2) morphologies of the neat block copolymer, the loading of bimetallic complexes D1 was targeted at 20% of stoichiometry ratio to pyridine. The pyrolysis of bulk samples generated fct FePt nanoparticles with size of 6-13 nm. The results showed the systematic tuning of size of nanoparticles by varying the molecular weight of block copolymers, and hence the total metal content by weight percentage in polymers. In chapter 3, the thin film self-assembly of FePt-Ds was further investigated to demonstrate the potential of our system for thin film fabrication. Three approaches were employed, the first method was solid state self-assembly in thin film, and the morphologies in thin film were consistent to those in the bulk state self-assembly. Solvent annealing of FePt-D-Cy2 and FePt-D-Sp1 showed improvement in the order and orientation of microdomains, despite the presence of some defects in order. With well-defined spherical morphology in FePt-D-Sp1, the pyrolysis in thin film was performed and the result showed the retention of spherical morphology with little defects. In the next stage, nanoimprint lithography directed self-assembly was employed to give the long range order. Both flattened and line array patterned molds were employed to imprint the polymers. The results showed alignment direction with the use of flattened mold. However, the results also showed the deformed and damaged patterns due to high adhesion force between the polymer and mold. Without an appropriate releasing agent covered on mold surface and a remedy to tribological problem, it would be hard to reliably obtain the morphology under the molds during the press and release. Going to the last method, the solution state self-assembly of FePt-D-Cy2 in THF/toluene mixture was demonstrated. By varying polymer concentrations and spinning rate, well-defined spherical micelles are possible to achieve with a better order and distribution. Solvent annealing with slightly selective solvent showed reduction in size distribution and domain size in the FePt spherical micelles with slightly improved packing. Although very nice packings in both solid and solution state self-assembly have not been achieved yet, this study still demonstrated the potential approach to use single bimetallic source-containing block copolymer to self-assemble into desired nanostructures for FePt nanoparticles synthesis. Finally, chapters 4 and 5 presented the concluding remarks, future plans and the experimental details described in chapters 2 and 3.

No description available.

Note:

No description available.

Note:

published_or_final_version / abstract / Chemistry / Doctoral / Doctor of Philosophy

The enantioselective approach to bonandiol, also known as magydardiendiol, has utilized two novel synthetic methodologies. The first is the diastereoselective cyclopropanation of a homochiral eneketal prepared from (2R,3R)- or (2S,3S)-2,3-butanediol and possessing C₂ symmetry. Simmons-Smith cyclopropanation gave good diastereoselectivity (69-75%) in addition to excellent amounts of monocyclopropanated material obtained (90-96%). The second method utilized is the nickel acetylacetonate catalyzed coupling of dimethylzinc to a sterically hindered cyclic β-keto enolphosphate in 76-92% yield. This approach to the A ring of hyperforin starting from commercially available citral allows for the introduction of all but one isoprenyl appendage.