School of Chemistry - Theses
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ItemTowards valence tautomerism in polynuclear complexes( 2012)The synthesis, structural and physical characterisation of families of dinuclear cobalt complexes with the bridging bis-o-dioxolene ligands 3,3,3',3'-tetramethyl-1,1'-spirobis(indane-5,5',6,6'-tetrol) (spiroH4) and 3,3'-bis-2-hydroxy-1,4-naphthoquinone (bhnqH2) as well as dinuclear nickel complexes with N1,N2-bis(2-((E)-(3,5-di-tert-butyl-2-hydroxyphenylimino)methyl)phenyl)oxalamide (H4Ltert) and N1,N2-bis(2-((E)-(2-hydroxy-3,5-dimethylphenylimino)methyl)phenyl)oxalamide (H4Lmethyl) were undertaken, with an emphasis on investigating potential valence tautomeric (VT) behaviour. A new family of dinuclear cobalt complexes incorporating deprotonated spiroH4 and ancillary ligands derived from tris(2-pyridylmethyl)amine (TPA) was investigated. Systematically increasing the number of methyl groups at the 6-position of the pyridine arms of the ancillary ligand was shown to fine tune the charge distribution within each complex. Pure samples of [Co2(spiro)(TPA)2]2+ (12+), [Co2(spiro)(MeTPA)2]2+ (22+), [Co2(spiro)(Me2TPA)2]2+ (32+), [Co2(spiro)(Me3TPA)2]2+ (42+), [Co2(spiro)(TPA)2]3+ (53+), [Co2(spiro)(TPA)2]4+ (64+) have been isolated. In the solid state, crystallographic analysis, variable temperature magnetic susceptibility and X-ray absorption spectroscopy (XAS) data revealed 12+, 42+ and 64+ exist in the LS-CoIII-(spirocat-cat)4--LS-CoIII, HS-CoII-(spiroSQ-SQ)2--HS-CoII and LS-CoIII-(spiroSQ-SQ)4--LS-CoIII redox states, respectively, invariant of temperature (2-360 K). In solution, electrochemistry, electronic absorption and EPR spectroscopy analysis are consistent with the above assigned redox states, and also confirmed the presence of another redox state of LS-CoIII-(spiroSQ-cat)3--LS-CoIII in complex 53+. Due to spiroconjugation, electronic communication is observed across the spirocyclic carbon atom in the spiro ligand, which gives rise to weak antiferromagnetic coupling between the two halves of (spiroSQ-SQ)2- in 64+ and electron delocalisation across the ligand for (spiroSQ-cat)3- in 53+. The only complex to exhibit a temperature dependent charge distribution is 32+. Variable temperature magnetic susceptibility and XAS data are consistent with two transitions in the solid state occurring at around 100 and 300 K, whereas UV-visible absorption spectroscopy indicated that two transitions occur at 200 and 250 K in butyronitrile. Therefore, complex 32+ undergoes two thermally-induced VT transitions between LS-CoIII-(spirocat-cat)4--LS-CoIII and HS-CoII-(spiroSQ-cat)3--LS-CoIII and then to HS-CoII-(spiroSQ-SQ)2--HS-CoII. Evidence of a photo-induced VT transition was observed in the solid state at 10 K. Analogous to the spiro complexes, three new dinuclear complexes [Co2(bhnq)(MenTPA)2]2+ (n = 1 for 72+; 2 for 82+; 3 for 92+) with the deprotonated form of bhnqH2 were isolated. In the solid and solution states all three of these complexes existed in the HS-CoII-(bhnqQ-Q)2--HS-CoII redox state independent of temperature (2-300 K). Increasing the number of methyl substituents on the TPA ligand favours the stabilisation of HS-Co(II). An increase in distortion from octahedral coordination around each cobalt centre was correlated with the decrease in room temperature magnetic susceptibility due to quenching of the orbital contribution. A search for potential dinuclear nickel VT systems afforded two square-planar and two octahedral complexes: [Ni2(Ltert)] (10), [Ni2(Lmethyl)] (11), [Ni2(Ltert)(py)4] (12) and [Ni2(Lmethyl)(py)4] (13), where the metal is Ni(II). None of these complexes displayed evidence of a VT transition. Chemical (with (NH4)2Ce(NO3)6) and electrochemical oxidation of 10 led to the decomposition of the complex, giving N1,N2-bis(2(5,7-di-tert-butylbenzo[d]oxazol-2-yl)phenyl)oxalamide (14).
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ItemNovel fluorescent angiotensin AT1 receptor antagonists( 2012)Hypertension is a severe condition that affects many people worldwide. The pathophysiology of hypertension is unknown. Sartans (selective AT1 receptor antagonists) are known to be the most direct and widely used class of antihypertensive drugs that block the vasoconstrictive hormone angiotensin II from binding at its AT1 receptor. Since the discovery of Losartan (2), many drugs are clinically used today. Sartans display a diverse pattern of antagonism however there is some debate as to why this occurs. Some believe it’s due to the antagonist induced changes in the AT1 receptor conformation, others believe it’s due to the levels of cell surface receptor expression and internalisation of the antagonist-receptor complex. Binding of fluorescent sartans to AT1 receptors, will enable the investigation of AT1 receptor localisation. This will provide an insight of the molecular pharmacology of AT1 receptors in cell and tissue systems and in turn will provide a better understanding of the physiological mechanisms involved with the disease. With the aim of preparing fluorescent sartans for use in the study of the molecular pharmacology and cellular localisation of AT1 receptors in cell-based systems, initial work was thus directed towards the synthesis of a series of analogues 103 - 114 of Fonsartan (14), in order to explore the effect of heteroatom substitution and substituent size on the AT1 receptor binding ability of the sartans. The approach involved direct coupling of the common bromo-biphenyl scaffold 32 with several novel aryl-thio substituted imidazoles 90 - 95. Also prepared were coumarin analogues 151 and 152 of Fonsartan, which required synthesis of the novel imidazole 149. In addition, the coumarin analogue 176 of Losartan (2) was also synthesised. Pharmacological testing revealed that compounds 103 – 108, 109 – 114, 151 and 152 were potent AT1 receptor antagonists. The novel AT1 receptor antagonists synthesised in this project that have shown strong inhibition activity and possess fluorescence emission properties suitable for in vitro cellular imaging were sartans 106, 112 - 114, 151 and 152. The novel fluorescent angiotensin AT1 receptor antagonists 113, 114 and 176 showed weak inhibition activity. Results from the in vitro cellular imaging, using Chinese hamster ovary (CHO) cells stably expressing the rat AT1a receptor, revealed that the novel fluorescent sartans 106, 112 - 114, 151 and 152 were too lipophilic to observe the localisation of AT1 receptors in CHO cells. The synthesis of less lipid soluble selective AT1 receptor antagonists with appropriate fluorescence emissions useful for biological investigations may prove as useful tools for the investigation of cellular localisation and trafficking of the AT1 receptors both in vitro and in vivo.
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ItemStructure and functional characterisation of diaminopimelate epimerase from Escherichia coli( 2012)DAP epimerase catalyses the penultimate step in the lysine biosynthesis pathway in bacteria. Given that this pathway produces metabolites crucial in cell wall and protein synthesis, enzymes in this pathway are targets for the development of novel antimicrobials. This thesis investigates the structure and function of the essential bacterial enzyme, DAP epimerase. DAP epimerase from Escherichia coli was cloned from gDNA, expressed and purified to homogeneity. The recombinant enzyme is folded, as determined by CD spectroscopy, and is active in solution. Quaternary structure analysis employing analytical ultracentrifugation indicates that DAP epimerase is dimeric in solution, which contradicts previous work in the field suggesting the enzyme is monomeric. The X-ray crystal structure of E. coli DAP epimerase was determined to a resolution of 2.0 Å showing the enzyme in its open, active conformation. E. coli DAP epimerase crystallised as a dimer in the crystal state. This quaternary structure is consistent with the solution study findings. The kinetic properties of E. coli DAP epimerase was also investigated. It was found that employing an existing DAP epimerase–DAPDH assay4 that uses commercially available DAP isomers is not suitable for full kinetic characterisation of DAP epimerase. This is due to the inhibition of the coupling enzyme, DAPDH. Accordingly, LL DAP was attempted to be synthesised by asymmetric hydrogenation, albeit unsuccessfully. As a result a new method to arrive at the substrate, LL-DAP, was developed employing DAP decarboxylase, the final enzyme in the lysine biosynthesis pathway, leading to the successful kinetic characterisation of E. coli DAP epimerase. To probe the importance of oligomerisation in DAP epimerase, the X-ray crystal structure of E. coli DAP epimerase was used to design single-point mutations at the dimer interface of the enzyme. These variants were engineered using site-directed mutagenesis and the solution and kinetic properties subsequently investigated. It was found that the substituting the Tyr at position 268 to an Ala residue resulted in a variant that was primarily monomeric in solution. This mutant, Y268A, was fully folded as determined by CD spectroscopy and X-ray crystallography, however, had attenuated catalytic activity at low concentrations. This suggests that DAP epimerase requires dimerisation for full functionality. We anticipate that findings from this work will offer insight into the development of new inhibitors of DAP epimerase as novel antibiotic agents.
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ItemThe effects of external fields on the optical properties of nanocrystals( 2012)Nanocrystals (NCs) investigated in this thesis are crystals of semiconductors or metals, each consisting of hundreds to a few thousand atoms. This small size, ranging from 2 to about 100 nm, introduces new electronic and optical properties, such as size-dependent band gaps of semiconductor quantum dots (QDs), or the surface plasmon resonance in Au and Ag NCs. These novel optical properties make NCs promising candidates for optoelectronic devices. However, in order for NCs to realise their full potential in such applications, a comprehensive understanding of their optical properties and the effects of external influences is essential. This thesis aims to build upon current knowledge of the optical properties and behaviour of NCs, through single particle and ensemble measurements under various external conditions. The first three sections of chapter 3 examine the optical properties of QDs at an ensemble level, both in solution and in films, as well as on a single particle level as a function of shell quantity, shell composition and atmosphere. Comparing the response of QDs with varying shell thickness and materials under various conditions, provided insights into contradictory measurements which have been reported in the literature. For example, it is revealed that photo-enhancement depends strongly on prior sample treatment. These sections flow into the last section of chapter 3 which answers the following key question: Does the off-state of a QD correspond to a charged one and can we switch between the on- and off-state in a controlled manner? For this purpose a device structure is presented which allows the reversible quenching of QDs via a photo-ionization process, confirming that quenching of the QD PL is driven by an Auger-process. In chapter 4, the distance dependent energy transfer (ET) involving QDs is studied, motivated by the key question: can the ET between a single QD and another component be measured in a continuous and distance dependent manner? To address this question, a combined AFM/wide-field set-up was designed, capable of measuring the ET of QD-containing two- and three-body systems.
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ItemInvestigating the mechanism of mannosidases: synthesis of novel inhibitors and substrates( 2012)Efforts to treat disease through disruption of asparagine N-linked glycoprotein biosynthesis have mainly focused on inhibiting endoplasmic reticulum-residing glycosidases. Such studies have failed, in part due to the existence of a secondary pathway to mature glycoproteins functioning through the Golgi-resident family 99 glycosidase, endo-alpha-mannosidase. The first part of this thesis investigates this little understood enzyme. Through the synthesis of an activated substrate, alpha-glucosyl-(1,3)-alpha-mannosyl fluoride, the kinetics and stereochemistry of bacterial orthologs of endo-alpha-mannosidase from Bacteroides ssp. were studied. Family 99 glycosidases were shown to catalyse glycosidic cleavage with retention of anomeric stereochemistry. Structural studies of these bacterial orthologs of endo-alpha-mannosidase in complex with transition state mimics did not identify an enzymic nucleophilic residue, as required for hydrolysis mediated by classical retaining glycosidases. A possible non-classical glycosidase mechanism, proceeding through a 1,2-anhydro-beta-mannopyranose intermediate is suggested too for family 99 glycosidases, including endo-alpha-mannosidase. The second part of this thesis examines the conformational itinerary of two beta-mannanases relevant to ‘second generation’ biofuel production. Beta-1,4-Mannans are a significant component of the biomass of lignocellulosic biofuel feedstocks whose saccharification is hampered by their resistance to hydrolysis, demanding the use of chemical, physical and enzymatic degradation strategies to generate microbially-digestible sugars. In order to investigate interactions in the transition state of the family 26 beta-mannanase Cellvibrio japonicus Man26C and the family 113 beta-mannobiohydrolase Alicyclobacillus acidocaldarius Man113A, the transition state mimics mannobio-isofagomine and mannobio-imidazole were synthesised using beta-selective mannosylations in the key steps. Crystallographic studies of these inhibitors in complex with both enzymes showed that mannobio-imidazole bound in a B2,5 conformation to both enzymes. These results support the previously proposed 1S5→B2,5ǂ→OS2 glycosylation conformational itinerary for family 26 beta-mannosidase mediated hydrolysis. This itinerary was initially hypothesised on the basis of the conformations of complexes with molecules that mimic points on the reaction coordinate flanking the transition state. The family 26 complex with mannobio-imidazole obtained in this study is the first that directly examines the conformation of the transition state of a beta-mannanase. The family 113 complex is the first to be solved for any enzyme in the family complexed to any ligand. A 1S5→B2,5ǂ→OS2 glycosylation conformational itinerary is also proposed for family 113 beta-mannosidases. Quantum mechanical modelling of the free energy landscape of mannoimidazole found that this ligand is not inherently biased towards a B2,5 conformation, suggesting its observation on-enzyme is of special significance. These experimental results marginalise theoretical objections to a B2,5-like transition state, and show that these sequence-unrelated families have evolved to converge on a common solution to effecting the hydrolysis of beta-mannans.
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ItemSynthesis of novel amino acid-appended cavitands( 2012)Cavitands have been utilised extensively in host-guest chemistry due to their enforced cavity. These molecules are amenable to a variety of modifications that change the electronic and steric character of the cavity, providing additional binding interactions with guest molecules. The convergence of peptides and cavitands has seen limited research; in particular, the attachment of amino acid residues to the cavitand rim via the α-carbon has not been reported. Such modifications would confer both chirality and novel binding interactions to peptide-cavitand hybrid molecules, with the ultimate goal being their use in molecular recognition, catalysis and molecular transport. Herein, we present a range of methodologies combining amino acid functionality with cavitands, including: the asymmetric synthesis of tetrakis(amino acid)-cavitands, coupling strategies to form cyclic peptide-appended cavitands, synthesis of amino-cavitand carboxylic acids, and the selective amino acid functionalisation of a water-soluble cavitand.
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ItemStructural investigation of organic donor orbitals and their effects on reactivity in cubane, Beckmann fragmentation and seleniranium systems( 2012)A combination of X-ray crystallographic, theoretical and mass spectrometric approaches have been used to assess the extent and affects of several stereoelectronic interactions. The donor ability of strained cubane bonds was assessed with a variable oxygen probe approach and compared to previously studied strained donor C-C bonds and an equivalent unstrained bond. The found slopes for the derivatives of the cubylmethanol and 4-methoxycarbonyl-cubylmethanol to be -2.33 x 10-3 and -2.79 x 10-3 respectively. These slopes indicated a donor ability that was similar to cyclobutyl (3.90 x 10-3 with an additional C-H donor), but lower than cyclopropyl (4.60 x 10-3). NBO analysis was conducted to provide a better understanding of the results. Comparison of experimentally obtained variable oxygen probe slopes with NBO predictions found generally good correlation. In depth NBO analysis was carried out for several single C-C -bond donors and found that the energies of the cyclopropyl and cubyl donor orbitals were approximately similar and the predicted source of the larger effect with cyclopropyl donors was their superior orbital overlap. The early stage of divergence manifestations of Beckmann fragmentation in 2,2-dimethylcyclohexanone oxime derivatives, compared to an earlier study of Beckmann rearrangement was investigated by X-ray crystallography and NMR spectroscopy, and supported by theoretical calculations with NBO analysis. Clear manifestations were indentified in the increasing N-OR bond distance, showing early stages of the heterolysis, and related bond angle changes. However these were not significantly divergent from the Beckmann rearrangement results. Clearer divergence was observed by NMR spectroscopy with the displacement of electron density. Complementary computational work characterised the interactions involving the two methyl substituents which describe the molecular orbital origin of the Beckmann fragmentation pathway. Following previously conducted X-ray and NMR studies, a theoretical investigation of β-chalcogen pyridinium cations was conducted in order to assess the contributions of vertical and nonvertical modes of neighbouring group participation by chalcogen groups. In low to moderately electron demanding pyridinium ions, vertical participation by hyperconjugation was found to be the major mode of stabilisation. However, trends in the cation bond angle and orbital energies indicated that nonvertical participation, with the chalcogen lone pair orbitals, would dominate at higher electron demands. This was confirmed in the more demanding β-chalcogen cycloprop-2-en-1-ylium and seleniranium cations. Prompted by the interesting balance of interactions in the seleniranium ion, its reactivity was investigated by mass spectrometry. This confirmed the validity of direct selenium group transfer and despite impediments managed to indentify a qualitative order of reactivity with a series of π-ligand substrates. Computational modelling was conducted to investigate the important orbital interactions and their effects on the systems. In the ground state complex, the π-bond electrons of the substrates were found to extensively delocalise onto the seleniranium ion, stabilising the initialisation of transfer. The extent of delocalisation from the π-ligand substrates was observed to reflect the reactivity of the alkenes, in addition to providing a stable lead into transition states this dramatically affected the balance of chalcogen neighbouring group participation. Nonvertical participation decreased and more open cation structures were predicted. These results indicated that even highly electron demanding β-chalcogen cations, which would otherwise be expected to adopt a bridged ion structure, could potentially become significantly open with consequences for their reactivity.
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ItemPorous and lightweight networks for hosting guest gas molecules( 2012)A range of metal-ligand compounds for hosting guest gas molecules have been synthesised using a range of metal cations together with simple bridging anionic organic molecules. The structures of these compounds have been characterised using X-ray diffraction methods. In addition to the synthetic and structural work the gas sorption properties of a number of compounds have been investigated. In Chapter 2, compounds consisting of metal cations bridged by carboxylate based ligands that contain positively charged aromatic rings are reported. The crystallisation of Mg2+ 2,5-mpdc- (2,5-mpdc- = 2,5-N-methylpyridinedicarboxylate) and Mg2+ 1,3-imdc- (1,3-imdc- = 1,3-bis(carboxymethyl)imidazolium) from water produces the discrete complexes [Mg(2,5-mpdc)2(H2O)4] and [Mg(1,3-imdc)(H2O)4]. The complexes exist in dense networks that contain hydrogen bonding between the water molecules and non-bonding carboxylate groups. The combination of Cu2+ and 1,3-imdc- in a methanolic solution gives rise to the compound [Cu(1,3-imdc)(MeOH)1.5(H2O)0.5]BF4∙solvate, which consists of layers of 2-D [Cu(1,3-imdc)(MeOH)1.5(H2O)0.5] frameworks. CO2 sorption studies have shown that when the solvent is removed from [Cu(1,3-imdc)(MeOH)1.5(H2O)0.5]BF4∙solvate the remaining solid displays ‘cooperative’ CO2 sorption behaviour. The combination of Mg2+, Ca2+ and Cu2+ with ddc (ddc = N,N-bis(carboxymethyl)-1,4-diazobicylco[2,2,2]octane) forms a series of closely related 2-D networks with 4,4 topology. CO2 sorption studies of [Cu(ddc)2(H2O)]SiF6 ∙8H2O have shown that the desolvated solid also displays cooperative CO2 sorption behaviour. Chapter 2 also describes the crystal structure of [Cu3(4,4-bpmc)3(H2O)2(OH)3]BF4 SiF6 ∙solvate (4,4-bpmc = carboxymethyl-4,4-bipyridinium). The crystals contain unusual inorganic clusters, which consist of a µ3-OH- ion bridging a trio of Cu(II) cations. Each cluster is bridged to five other clusters by the 4,4-bpmc ligands, generating a hexagonal network with channels approximately ~ 2 nm in diameter. The reaction between LiOH•H2O and isonicotinic acid (Hinic) in the appropriate solvent or mixture of solvents affords a family of variously solvated forms of a simple ionic lithium salt, Li(inic)•0.5 solvate (solvate = DMAC, n-propanol, t-butanol, EtOH and MeOH) (Chapter 3). 3-D Li(inic) frameworks containing solvent-filled channels are present in all of these compounds except for the MeOH and EtOH solvates. The non-directional character of the electrostatic interactions between the Li+ and inic- ions bestows an element of “plasticity” upon the framework, manifested in the observation of no less than four different (but closely related) framework structures within the family. An unusual single-crystal-to-single-crystal transformation accompanies removal of solvent from Li(inic).0.5MeOH, in which the ionic Li(inic) framework undergoes a major rearrangement (from a structure containing “8,4,8,4 chains” to one with “6,6,6,6 chains”). Gas sorption experiments have shown that the channels formed upon the desolvation of the compounds: Li(inic)•0.5 solvate (solvate = DMAC, n-propanol, t-butanol, MeOH) can sorb H2. The reaction between lithium hydroxide and nicotinic acid (Hnic) in H2O and MeOH leads to the formation of two densely arranged ionic type networks, [Li(nic)(H2O)] and [Li(nic)]. The crystal structure of [Li(nic)(H2O)] is composed of 1-D Li+-nic- polymers. The water free structure of [Li(nic)] consists of a dense 3-D framework with the α-Po topology, in which Li6 aggregates act as 6-connecting nodes. The non-directional ionic interactions between Li+ and isonicotinate N-oxide (inox-) as well as Li+ and 4-hydroxybenzoate (hbz2-) have resulted in the formation of dense networks when crystallised from H2O, MeOH or t-butanol. When combined in the presence of DMF however, both the resulting Li+-inox- and Li+-hbz2- networks: [Li(inox)]•⅔ DMF and [Li2(hbz)(DMF)] possess large channels that accommodate the DMF molecules. The removal of the solvent from the two open-type compounds through heating results in a non-porous solid. The combination of Ca2+ and inox- in H2O gives rise to the compound [Ca(inox)2(H2O)2]. 2-D Ca2+-inox- sheets that contain water molecules coordinated to the calcium centres are present. Crystallographic studies indicate the removal of the coordinated water molecules from the 2-D sheets of [Ca(inox)2(H2O)2] induces the formation of intersheet Ca2+-inox- bonds, which results in a 3-D [Ca(inox)2] structure. In Chapter 5 the compounds: [Li2(2,2-bpdc)(DMF)2] (2,2-bpdc = 2,2-bipyridine-4,4-dicarboxylate), [Li2(2,6-ndc)(DMF)] (2,6-ndc = 2,6-naphthalenedicarboxylate), [Li4(3,5-pdc)2(DMF)]•DMF (3,5-pdc = 3,5-pyridinedicarboxyalte and [Mg(2,2-bpdc)(DMF)2] were synthesised and their structures determined. All of the compounds contain related crystal structures that consist of metal-carboxylate chains linked to four equivalent chains via the organic bridges to form open 3-D frameworks. The removal of the DMF molecules from the structures results in materials that do not sorb H2. The desolvated [Li4(3,5-pdc)2(DMF)]•DMF however, does show unusual CO2 sorption properties. When Li+-2,2-bpdc2- and Mg2+-2,2-bpdc2- are crystallised from aqueous solutions the discrete complexes [Li(H2O)4]2•[Li(2,2-bpdc)(H2O)2]•[Li(2,2-bpdc)(H2O)3] and 1-D polymer [Mg(2,2-bpdc)(H2O)3]∙5/2H2O are formed. In contrast to the open 3-D Li+-2,2-bpdc2- and Mg2+-2,2-bpdc2- DMF templated networks, the crystal structures of these networks do not contain any voids or cavities. The crystal structure of Li2[Mg3O(2,2-bqdc)3(DMF)3]∙solvate (2,2-bqdc = 2,2-biquinoline-4,4-dicarboxylate) is also presented in Chapter 5. The structure contains basic trigonal carboxylate clusters, which act as 6-connecting nodes to form a 3-D network that possesses spacious hexagonal channels. The channels are occupied by the Li+ ions and solvent molecules. Gas sorption experiments indicate that the removal of the solvent from the large channels results in a material that fails to sorb gas. In Chapter 6, the non-directional electrostatic interactions between the Li+ and 2,5-dihydroxybenzoquinone (H2dhbq) as well as the Li+ and 2,5-dihydroxy-3,6-dinitrobenzoquinone (H2na) ions are shown to be influenced by the solvent molecules H2O, MeOH, t-butanol and DMF. An interesting 2-D hexagonal [Li2(Hdhbq)3]- network is formed when lithium and dhbq are combined in a t-butanol/H2O solution. Each of the hexagonal holes within the 2-D sheets appear to be templated by the [Li(t-butanol)3(H2O)]+ complex. Chapter 6 also describes the synthesis and structure of cis-[Mg(dhbq)(H2O)2]•2MeOH •2H2O, which was prepared using the in-situ generation of dhbq2- from 1,2,4,5-tetrahydroxybenzene (H4thb). The structure consists of cis-[Mg(dhbq)(H2O)2] crankshaft-like chains that pack in a manner that generates large solvent-filled channels. The desolvated solid exhibits the ability to sorb considerable quantities of gas at very low pressures. Remarkably, isosteric heat of H2 sorption calculations indicate a H2 binding energy of approximately -12 kJ/mol over a significant portion of the H2 uptake. This value is much higher than what is normally encountered with coordination polymers. Powder X-ray diffraction experiments of cis-[Mg(dhbq)(H2O)2]•2MeOH •2H2O have indicated the crankshaft-like chains go through at least two structural rearrangements during desolvation.
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ItemSeparation of uranium using polymer inclusion membranes( 2012)Polymer Inclusion Membranes (PIMs) are a relatively new branch of membrane separation technologies which have shown potential for the safe and effective separation of metallic and non-metallic ions and small organic molecules from aqueous solutions. It has been postulated that the use of PIMs as an alternative to liquid-liquid extraction (or solvent extraction, SX) techniques has the potential to reduce occupational and environmental hazards which are commonly associated with solvent extraction processes. The PIM technique involves the encapsulation of a suitable extraction reagent (extractant) in a base polymer matrix, often with the addition of plasticisers or chemical modifiers. The encapsulation process helps minimise loss of extractant into the contacting solution and reduces the inventory of solvents and extractants required for separation processes. This thesis investigates the application of the PIM technique to the separation of uranium from dilute sulfate solutions. Uranium is mined in areas of environmental sensitivity in Australia and a PIM system suitable for use in Australian conditions is investigated. A candidate PIM system is proposed for the separation of uranium and its performance is investigated and evaluated with reference to conditions commonly found in Australian uranium processing. To provide a sound basis for the development of PIM systems, the formulation of PIMs is investigated in detail and a wide range of membrane components are tested for their ability to form chemically homogeneous PIMs of suitable physical characteristics for use in separation processes. The observed behaviour of each membrane component is discussed and rationalised using physicochemical interactions and guidelines for the successful formulation of PIMs are suggested. A novel method for rigorously determining the chemical homogeneity of PIMs on a low micrometre scale using synchrotron-based infrared microspectrometry is demonstrated. A candidate PIM system for the separation of uranium based on di(2-ethylhexyl) phosphoric acid (D2EHPA) and poly(vinyl chloride) (PVC) is investigated. The influence of key variables (including the membrane composition and solution conditions) on the extraction process are studied. A new method for determining the stoichiometry of the extractant-uranium complex is demonstrated and used to show the uranyl cation is extracted from solution by two D2EHPA dimers. The homogeneity of the extracted uranium in the candidate system is confirmed using a new method based on proton-induced x-ray emission microspectrometry (µ-PIXE). The extractive performance of the PIM composed of 40% (m/m) D2EHPA and 60% (m/m) PVC was numerically evaluated and the methods for mathematically modelling the extraction process are discussed; a number of methods for determining the membrane permeability are evaluated. A mathematical model for the extraction of uranium by the PIM is developed and the membrane diffusion and extraction constants are determined. Finally, the transport and separation of uranium by the membrane have been optimised. The membrane composition and solution conditions in the source and receiving phase were systematically optimised and the optimal transport conditions were found to be using a PIM containing 45% D2EHPA and 55% PVC, a source solution containing 0.1 mol L-1 H2SO4 and a receiving phase containing 6.0 mol L-1 H2SO4. The PIM has been shown to be able to separate uranium from a range of common metal ions thermodynamically and from the ferric cation kinetically, by increasing the acidity in the source phase.
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ItemMetal complexes for diagnostic imaging of cerebral perfusion and amyloid-beta plaques in Alzheimer's disease( 2012)Both Ga-68 and Cu-64 radioisotopes have properties suitable for positron emission tomography (PET) diagnostic imaging but their use is hindered by the lack of suitable chelators. Alzheimer’s Disease (AD) is the most common form of irreversible dementia, characterized by the cerebral deposition of (i) insoluble extracellular amyloid-beta plaques, (ii) intracellular neurofbrillary tangles and (iii) overall brain atrophy. Currently, there is no cure for the progressive neurodegenerative disorder but development in AD diagnostic imaging agents can increase the accuracy of clinical diagnosis and assist in identifying patients in the “high risk group” for potential therapeutic interventions. Two approaches were taken to incorporate the Ga-68 and Cu-64 radioisotopes into potential AD diagnostic radiotracers: development of (1) cerebral perfusion radiotracers and (2) amyloid-beta plaques targeting bifunctional chelators and complexes. Inspired by the Tc amine oxime cerebral perfusion radiotracers 99mTc(V)O(PnAO) and 99mTc(V)O(d,l-HMPAO), the triamine trioxime TAMOX ligand was synthesized. The coordination behaviour of TAMOX in presence of Cu(II), Ga(III), Ni(II) and Co(III) was investigated by NMR studies, mass spectrometry, UV-Vis absorption spectroscopy and single crystal X-ray diffraction studies. The robust bis(thiosemicarbazone) ligand systems were known to form stable Cu(II)N2S2 complexes that are well characterized and tested in biodistribution studies. New bifunctional bis(thiosemicarbazone) ligands, with the diacetyl-bis(N4-methylthiosemicarbazone) framework were functionalized with amyloid-beta plaques targeting functional groups. Cu(II)L(2-4,6-8) complexes were successfully synthesized and characterized by ESI-mass spectrometry, reverse-phase HPLC, elemental analyses, cyclic voltammetry, UV-Vis absorption spectroscopy and fluorescence emission spectroscopy. Cu(II)L(2-4,6-8) were found to have binding affinities for amyloid-beta fibrils in vitro. CuL2 and CuL7 were also capable of binding to amyloid-beta plaques on AD human brain tissues. 64Cu(II)L2 and 64Cu(II)L7 were prepared in high radiochemical purities. Preliminary animal microPET carried out using 64Cu(II)L2 revealed significant findings: (i) the 64Cu(II)L2 complex is BBB permeable and (ii) had significantly higher brain uptake (p= 0.005) in APP/PS1 AD transgenic mice when compared with wildtype mice (percentage of injected dose per gram of animal weight, %ID/g= 2.5% ± 0.6 vs 1.7% ± 0.6, respectively).