School of Chemistry - Theses
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ItemStudy of nanostructured metal oxides for electrochromic windows( 2018)Electrochromic materials have attracted the interest of researchers over the last several decades. They are able to change their color upon the application of a voltage. Tungsten oxide (WO3) and titanium oxide (TiO2) are the conventional electrochromic materials and have been studied most, due to their good electrochromic properties and electrochemical stability. Hence the research in this thesis is mainly based on tungsten oxide and titanium oxide electrochromic materials. By adjusting the precursor, nanostructured electrochromic materials were prepared on the substrates with improved electrochromic properties. A thin film of hexagonal WO3 nanowires was grown directly onto a bare fluorine-doped tin oxide glass (FTO) without the assistance of a WO3 seed layer via a facile and low-cost solvothermal method. Compared with the WO3 film synthesized with a seed layer, a faster switching time, higher coloration efficiency and more stable cycling were achieved due to direct nanowire contact with the substrate. In order to improve the contact between the WO3 and FTO, and therefore increase the stability of the electrode, it was annealed under N2 and the cycling life increased by almost a factor of 10. Hierarchical WO3 nanotree-like structures were grown from nanowires by a two-step non-seeded solvothermal technique on FTO. A study of the growth process revealed that the nanotrunks formed before the nanobranches grew, with the trunks orientated along the (002) plane of the hexagonal phase WO3, while the branches were orientated along the (100) and (200) planes. An electrochromic film prepared with WO3 nanotrees are expected to have a large active surface area, which enabled a large optical modulation of 74.7% at 630 nm at the low potential of -0.2 V, fast switching speeds of 2.64 s and 7.28 s for bleaching and coloration, respectively, and a high coloration efficiency of 75.35 cm2 C-1. A nanocomposite TiO2 film was prepared by decorating a rutile TiO2 nanorod (TiO2 NR) array with anatase TiO2 nanopyramids (TiO2 NPyr) via a facile two-step solvothermal method. The addition of NPyr to the TiO2 NR film is expected to increase the total amount of material, hence providing a greater number of sites for lithium ion insertion, and the NPyr are expected to increase the active surface area. As a result, the TiO2 NR–NPyr film displayed higher optical contrast and coloration efficiency compared with NR films, demonstrating that enhanced electrochromic properties could be improved by using the NR–NPyr composite structure. Anatase TiO2 nanowires were grown directly onto FTO by a solvothermal method. Different concentrations of precursor can easily control the length of the nanowires. The TiO2 nanowire films showed antireflective properties, increasing the transmittance of bare FTO by 7.2% at 550 nm. The electrochromic properties of the TiO2 nanowire sample was investigated in KCl electrolyte, giving a large optical modulation of 61.4% at 550 nm, a high coloration efficiency of 23.89 cm2 C-1 and good stability. The TiO2 nanowire film was modified by chemisorption of a monolayer of the redox chromophore 1,4-bis[((N-phosphono-2-ethyl)-4,4’-bipyridinium)-methyl]-benzene tetrachloride (viologen). The best viologen modified TiO2 nanowire film showed an optical modulation of 55.5% in 550 nm, coloration efficiency of 244.5 cm2 C−1 and good stability. Compared with the pure TiO2 nanowire thin film, the coloration efficiency of the viologen modified TiO2 nanowire thin film increased more than 10 times, showing its potential in smart window applications. Prussian blue was electrodeposited on bare FTO and a TiO2 nanowire thin film. The structure of the Prussian blue on FTO was a compact layer, whereas a core-shell (Prussian blue coating the TiO2) nanostructure was achieved on the TiO2 nanowire film. The core-shell nanostructure showed promising electrochromic properties with an optical modulation of 64% at 550 nm, a high coloration efficiency of 86.7 cm2 C-1 and a superior stability of 1000 cycles without significant decrease in optical modulation. The improvement in electrochromic performance was attributed to the support template of TiO2 nanowires increasing the Prussian blue contact with the electrolyte. Furthermore the presence of the TiO2 nanowires also lowered the current density, which improved the coloration efficiency and the stability. The electrochromic properties of the TiO2 nanowire thin films in different electrolytes were studied. The nanowire film in electrolyte containing multivalent ions, such as Al3+, showed a large optical modulation of 60.03% at 550 nm, fast insertion kinetics and good stability over 400 cycles. The electrochromic properties of a cycled TiO2 nanowire thin film in a LiClO4 propylene carbonate electrolyte can be recovered by water washing. This is an interesting concept and possible reasons for this behavior were discussed, however further work is required in this area. A range of nanostructured WO3 and TiO2 thin films have been prepared for this thesis with different morphologies and tested in electrochromic smart window application showing promising potential.
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ItemDesign and synthesis of chemical tools for studies of carbohydrate active enzymes( 2018)Glycoside hydrolases (GH) are enzymes that catalyse the hydrolysis of glycosidic linkages. They are classified into over 150 families based on their primary amino acid sequence. Family GH99 endo-α-1,2-mannosidases/endo-α-1,2-mannases cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannans. They are predicted to perform base-catalysed hydrolysis via an 1,2-anhydro sugar intermediate. The first part of this thesis reports the synthesis of a mechanism-inspired inhibitor, α-mannosyl-1,3-noeuromycin (ManNOE). ManNOE was found to be the most potent GH99 inhibitor to date. The success of ManNOE was attributed to a favourable interaction between the 2-OH on the NOE ring and active site residue E333, predicted to be important in mechanism. Also described is the synthesis of the inhibitor α-mannosyl-1,3-(2-amino)deoxymannojirimycin (Man2NH2DMJ). Modest affinities were observed for Man2NH2DMJ. Structural studies revealed it binds in the same way as other iminosugar inhibitors, suggesting poor inhibition is not due to failure of the 2-NH2 to bind to reside E333, but rather a reduction in basicity of the endocyclic nitrogen in the presence 2-NH2 protonation. The second part of this thesis examines a novel family GH134 β-1,4-mannanases. A GH family 134 endo-β-1,4-mannanase from a Streptomyces sp. was found to possess a fold closely related to that of hen egg white lysozyme (HEWL) and to act with inversion of stereochemistry. X-ray crystallography and ab initio quantum mechanics (QM)/molecular mechanics (MM) metadynamics reveal this enzyme utilizes a unique 1C4→3H4‡→3H1 conformational itinerary along the reaction co-ordinate, different to any known β-1,4-mannanases. The third part of this thesis examines sulfoglycolysis. Sulfoquinovosyl glycerol (SQGro) was synthesised as a mixture of diastereomers. A family GH31 sulfoquinovosidase (YihQ) isolated Escherichia coli (E. coli) was determined to have a 6-fold preference for the naturally occurring isomer (2’R-SQGro) but could cleave both isomers. SQGro supports growth of E. coli to find cell densities comparable to growth on glucose. Preliminary studies revealed that the plant pathogen Agrobacterium tumefaciens performs sulfoglycolysis when grown on SQ as the sole carbon source. Growth of cultures and consumption of SQ were directly correlated to release sulfite into the media, which over time autooxidised to sulfate. Proteomics enabled the discovery of the sulfoglycolysis gene cluster in A. tumefaciens which enabled prediction of a novel sulfoglycolytic pathway.
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ItemIt’s hip to be square: a cyclobutene diester approach to alkyl citrate natural products( 2018)This thesis features an enatiospecfic synthesis of a key alkyl citrate retron that was leveraged in the total syntheses of squalene synthase inhibitors (-)-CJ-13,982, (-)-CJ-13,981 and (-)-L-731,120 (featured in Org. Let. 2018, 20, 4255–4258). This key retron was prepared in 7 linear steps, requiring only 4 purification, with a 40% yield from (S)-(+)-γ-hydroxymethy-γ-butyrolactone. The synthesis highlights the application of a formal [2+2] cycloaddition and a remarkable acid-mediated rearrangement sequence to furnish the correct stereochemistry and oxidation level of the citrate moiety. This thesis demonstrates the shortest enantiospecifc total synthesis of (-)-CJ-13,981 to date, via the use of this key citrate retron, affording this natural product in 7.7% total yield over 10 steps. Efforts towards the squalene synthase inhibitor (-)-L-731,120 and the viridiofungins, a family of serine palmitoyl transferase inhibitors that have activity inhibiting hepatitis C replication, are also featured.
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ItemPhytoextraction of mercury (Hg) and gold (Au) from contaminated mine tailings and biosolids( 2018)The present study is based on a long-term goal of using phytotechnologies to rehabilitate Hg-contaminated substrates like mine tailings and biosolids with the additional value of recovering Au residues. To address this goal, this research aimed to (1) to develop a Hg-Au phytoextraction system employing the best substrate-plant combination by examining the growth and metals uptake of selected plant species on substrates consisting of biosolids, Au mine tailings, or different combinations of both, and (2) to provide in-depth information on the spatial distribution and localization of Hg and Au in the plant root tissues in order to present mechanistic hypotheses for their phytoextraction potential. An extensive survey of literature has been conducted on Hg phytoremediation and Au phytoextraction, as well as the challenges and limitations in this field. The reviewed studies demonstrate that no naturally-occurring Hg or Au hyperaccumulators have been recorded to date. A glasshouse-based screening study was done to examine the growth of candidate plant species, known for their ability to phytoextract Hg and/or Au using chemical amendments, which can grow on substrates consisting of biosolids-amended mine tailings. The germination and establishment of plants over 8-12 weeks were monitored for Brassica juncea (Indian mustard), Daucus carota (carrot), Lupinus albus (white lupin), Beta vulgaris (sugar beet), Solanum tuberosum (potato), and Manihot esculenta (cassava). The most suitable biosolids-mine tailings combination was determined to be 75% biosolids – 25% mine tailings. Of the 3 successfully established plant species—mustard, carrot, and cassava—the latter showed the most promise in terms of ease in propagation and its cyanogenic capability. The potential of M. esculenta to phytoextract Hg and Au was successfully demonstrated for the first time. Metals uptake was found to be greatest in the fibrous roots of plant cuttings grown in Hg- and/or Au-amended hydroponics solutions. A plausible competitive metal effect was observed in plants grown in equal Hg and Au concentrations, where less Hg was taken up by the plants as compared to when the plants were exposed to Hg only. Increasing the Hg concentration while keeping the Au concentration constant substantially increased Hg uptake whilst decreasing Au uptake. The micro-PIXE analysis affirmed these results and gave a clear insight into the distribution of the metals in the roots. Though Hg and Au were found in all parts of the root cross-section they were mainly localized in the vascular bundle when plants were treated with each metal individually. Exposure to equal Hg and Au concentrations revealed both elements to be localized only in the epidermis, thereby suggesting a competition between Hg and Au. High-resolution transmission electron microscopy and X-ray diffraction measurements revealed that Au nanoparticles were formed inside cassava root tissues. Results also indicate that the presence of Hg increases the size of the AuNPs formed. As of date, there have been no studies linking cyanogenesis with the ability of cassava to hyperaccumulate Hg and Au. Preliminary data from Matrix Assisted Laser Desorption Ionisation Mass Spectrometry Imaging suggests that the differential localization of the cyanogenic glucoside linamarin in the root tissue sections from controls and metal treatments might be involved in Hg and Au uptake.
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ItemAmide assembly through Ag(I) promoted reaction of thioamides bearing self cleaving auxiliaries( 2018)Synthesis of amide bonds is an important issue in organic chemistry but is often overlooked as a contemporary challenge. Existing methods are reaching their limits and new chemical approaches are being developed. The Ag(I) promoted coupling reaction of thioamides with protected amino acids, recently reported in our group, leads to imide formation without epimerisation. This approach was shown to be general for various N-protected amino acids and peptides, including preparation of the pentapeptide thymopentin. However, hydrolysis of the imide is not always regioselective and occasionally results in undesired bond cleavage, leading us to investigate alternative solutions. Thioamides bearing a pendant nucleophile have been investigated as a general method for directed self cleavage of the imide. Amino acid derived o hydroxyphenacetyl thioamides have been applied to the Ag(I) promoted coupling reaction with various N-protected amino acids in good to excellent yields. Self immolative cleavage results in extrusion of benzofuranone to generate the desired amide bond. Application of this method to synthesise peptide based proteasome inhibitors was exemplified by the synthesis of epoxomicin natural product analogue and bortezomib analogue.
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ItemUse of thioamides in peptide synthesis: strategies for ring expansion and peptide ligation at asparagine( 2018)Peptide therapeutics are used directly or as carriers of cytotoxic agents and radioisotopes to specifically target diseased cells. The synthesis of peptides is one of the most important issues in organic chemistry. We have developed new synthetic tools for peptide synthesis and manipulation, built upon the recent invention of thioamide-mediated N-to-C direction peptide synthesis in the presence of Ag(I) in our lab. The methods developed exploit acyl transfer reactions of imides and isoimides in the generation of amide bonds, particularly in the ring expansion of small cyclic systems and in peptide ligation. We have successfully applied the Ag(I)-promoted coupling of thioamides and carboxylates to cyclic systems (i.e. thiolactams), which leads to an amino acid insertion process. Thiolactams of ring size 7–13 undergo Ag(I)-promoted coupling with Boc-protected amino acids to generate imides. Subsequent ring expansion occurs in excellent yield for simple thiolactams. We have also successfully developed a fundamentally new approach for peptide fragment coupling. The methodology employs peptides possessing an asparagine thioamide at the Nterminus. Silver-promoted coupling with a peptide acid generates an isoimide-linked intermediate that undergoes a rapid O–N intramolecular acyl migration to afford a native amide bond in high yields without epimerization at the ligation site. This novel asparagine ligation strategy enables the synthesis of larger peptides through coupling at sites not amenable to other coupling/ligation strategies.
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ItemZirconium and copper immunoPET imaging agents for the diagnosis of cancer( 2018)Positron emission tomography (PET) is a medical diagnostic imaging technique that is particularly useful in cancer diagnostics. In addition to tumour burden assessment, the technology can also provide molecular information, such as specific receptor expression profiles of cancer cells. The technique requires administration of an imaging agent to a patient, and the imaging agent must incorporate a positron emitting radionuclude. The positron-emitting radionuclide may be tethered to a targeting motif for accumulation at disease-afflicted tissues in the patient. Tight control over the biodistribution of the radionuclide is essential for both patient safety and image quality, and the extremely high affinity and specificity of monoclonal antibodies (mAbs) for their target antigen makes them an excellent candidate for delivering a radioisotope to a site of interest in vivo. The long pharmacokinetic half-life of antibodies, however, necessitates the use of a long-lived radionuclide such as 89Zr (t1/2 79 h) or 64Cu (t1/2 12.7 h). This thesis presents the development of novel PET imaging agents using 89Zr and 64Cu. Bifunctional chelators that can be used to attach these metal-based radionuclides to antibodies are described. The synthesis, bioconjugation, radiolabelling and preclinical imaging of various 89Zr immunoPET imaging agents using desferrioxamine (DFO) squaramide are presented. Our DFO-squaramide-based imaging agents outmatched the commercially-available isothiocyanate analogue. A DFO squaramide derivative suitable for use in enzyme-assisted, site-specific bioconjugations was developed, and successfully employed in the modification of antibody fragments using the bacterial transpeptidase Sortase A. The various forms of desferrioxamine squaramide conjugates were then assessed for suitability with various targeting agents, including mAbs and antibody fragments. These conjugates were evaluated as imaging agents in mice models of various cancer types that exhibit overexpression of the human epidermal growth factor receptors. The sarcophagine MeCOSar was also evaluated for [64Cu]Cu2+ labelling of antibodies and fragments. The bioconjugation of the ligand was performed using both an activated ester derivative and a Sortase A mediated coupling. The ligand was assessed in mice models of cancer using various antibodies and fragments as each conjugate exhibited unique biodistribution profiles. The most effective immunoPET agent for imaging of HER2-positive tumours was based on a full IgG construct with trastuzumab, although in a clinical setting the practical and logistical benefits of the F(ab’)2 imaging agent may outweigh its comparatively reduced uptake in tumour tissue.
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ItemMechanisms governing plastron retention and the implications for antifouling technologies( 2018)Marine fouling refers to the unwanted settlement of biotic and abiotic dissolved compounds, microorganisms, plants, and animals upon surfaces immersed in seawater. Biofouling presents considerable economic pressure upon the maritime industry, coupled with deleterious environmental impacts. While antifouling technologies of the past centred predominantly on the use of heavy metal biocidal agents, concerns regarding bioaccumulation of such toxicants has led to an increased demand for eco friendly alternatives. The work herein describes the investigation of the plastron as antifoulant: from the broad spectrum but ultimately finite effectiveness of plastrons in their natural, temporal state, to the development of multiple technologies capable of harnessing this phenomenon to achieve sustained antifouling capacity. Chapters Two and Three explore the effects that manipulating the physical parameters of superhydrophobic surfaces have upon the origin and longevity of the plastron, examining how these factors impact the plastron’s antifouling potential. Surface characterisation by atomic force microscopy (AFM), scanning electron microscopy (SEM), and optical profilometry (OP) were used to determine that more evenly distributed, nanorough micro architecture and bulk porosity appear integral to plastron longevity. Settlement data obtained from four biofouling species (barnacle cyprid Amphibalanus reticulatus, bryozoan Bugula neritina, diatom Amphora sp., and marine bacterium Cobetia marina) bore trends correlating reduced microbial adhesion with plastron lifetime, irrespective of factors that conventionally govern settlement behaviour, such as differing biota-to-architecture scale, surface chemistry preference, and motility. Chapters Four and Five explore the development of internally aerated units designed to support persistent plastron presence, and thus reduce fouling. Through numerous iterations, an effective aeration unit design was developed and tested, demonstrating greatly reduced microbial settlement following 14 days in vitro exposure to extreme marine fouling. The most superhydrophobic, nanorough, gas replenished coating (A_P40) performed magnitudes better than its rivals, demonstrating average microbial adhesion rates of 0.10% ±0.04% of the sample surface. Notably, fouling trends between samples in the aerated treatment group were not equivalent, despite receiving comparable gas replenishment. This result suggests that effective antifouling requires more than superhydrophobicity and the act of plastron-replenishment - an even distribution and high degree of nanorough micro architectures are key to retaining fuller plastron coverage and, consequently, antifouling capacity. Chapter Six explores the development of a second novel method of plastron replenishment, a system utilising localised heating to induce nucleation of water bound gas upon superhydrophobic samples. Studies showed these systems exhibit excellent gas harvesting capacity, allowing rapid plastron replenishment via short periods of low-energy heating. 21 day bioassays testing the antifouling capacity of these systems found settlement rates to be greatly diminished when superhydrophobically coated (SHC) surfaces received heat treatment and plastrons were retained. Results add further weight to the hypothesis that a coating exhibiting evenly distributed, highly nanorough micro architecture is integral for formation and retention of a primary plastron – superhydrophobicity and an active plastron replenishment system alone do not suffice. Qualitative observations showed that SHC surfaces have some capacity to regain a planar primary plastron from a secondary plastron, particularly if the plastron is mobile. Additionally, mobile plastrons demonstrated some capacity for foul release, with weakly adhered biofilm shown to peel from substrate. These findings hold implications for the development of antifouling, corrosion resistant, and hydrodynamic technologies and research. Through careful consideration and engineering resolves, future applications may be found in aquaculture, water filtration systems, membrane bioreactors, drag reduction, and marine antifouling and corrosion resistance for vessels and infrastructure.
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ItemFunctionalized mesoporous metal oxide spheres as catalysts for efficient conversion of carbohydrates into 5-hydroxymethylfurfural( 2018)Fossil fuels currently provide more than 90% of global energy needs and feedstocks for the chemical industry. One of the most critical challenges facing mankind is reducing emissions of carbon dioxide. Biomass is a globally accessible resource that could provide an alternative feedstock for synthesizing chemical building blocks. 5-(Hydroxymethyl)furfural (5-HMF) is a commercially useful platform molecule that can be synthesized from biomass. Solid acid catalysts such as metal oxides and modified oxides fill an important role in biomass conversion, due to advantages like carrying both Lewis and Brønsted-acid sites, where the catalytic activity occurs, as well as thermal stability and low cost. The research focus is the preparation, surface modification and characterization of zirconium oxide and binary titanium zirconium oxides spheres as solid-acid catalysts for the conversion of biomass-derived carbohydrates to 5-HMF. In Chapter 2, mesoporous zirconia was functionalized with common di-carboxylic acids and amino acids (i.e. terephthalic acid, 2-amino terephthalic acid, adipic acid, aspartic acid, succinic acid and glutamic acid) to prepare a multifunctional acidic catalyst for conversion of carbohydrates (fructose, glucose, sucrose, cellulose and starch) to 5-HMF. A green and versatile method was utilized to introduce the functional groups on the surface of the zirconia. The final catalyst, which was grafted with terephthalic acid, exhibited acceptable activity towards the dehydration conversion of fructose to 5-HMF with a yield of 42% after 2 h in dimethyl sulfoxide (DMSO) at 150 °C, with negligible loss of activity over five consecutive catalytic recycles. In Chapter 3, mesoporous titanium zirconium oxide spheres were prepared via sol-gel chemistry and templating using a solvothermal and calcination process with varied pore diameters (2.3-10.7 nm), surface areas (76-420 m2 g-1), and surface hydroxyl group densities (4.8-7.0 nm-2). Spheres with high surface area, large pore diameter and high surface hydroxyl density were functionalized with nitrilotri(methylphosphonic acid) via a green and simple method, then used as solid-acid catalysts to produce 5-HMF through the dehydration of carbohydrates. The impact of time, temperature, solvent and amount of catalyst on the yield of 5-HMF was systematically investigated. The recyclability of the catalyst was tested across five consecutive runs. In Chapter 4, sulfated, mesoporous zirconium titanium oxide spheres were synthesized for the catalytic dehydration of carbohydrate to 5-HMF. Five factors affected the sulfate loading: zirconia content, solvothermal temperature, sulfuric acid concentration, duration of the acid treatment, and the post-sulfate grafting calcination temperature. After optimization, the leading catalyst had a maximum sulfate loading of 10.7 wt%, and a total surface acidity of 0.62 mmol g-1. This solid-acid catalyst demonstrated excellent results in the dehydration of fructose to 5-HMF, with a yield of 80% after 1 h in DMSO at 150 °C, and 93% after 6 h. The catalyst was reused in five consecutive cycles with only a 3% loss of activity. Modified zirconia and mesoporous zirconium titanium binary oxide can be considered as promising solid acid catalysts to produce high-value chemicals from biomass feedstocks.
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ItemSynthesis and evaluation of Oncrasin based radiotracers for oncology( 2018)KRAS mutation status in cancer is an important contributing factor to development of cancerous tissue, with the mutation occurring in an estimated 1/3 of all cases of cancer, resulting in an aggressive phenotype. Development of a radiotracer based on the synthetic lethal Oncrasin-1 molecule was envisioned as a possible means of developing an imaging agent to identify and stage KRAS mutant tumours, with the potential to stratify patients into different treatment groups based off this. Small molecule drugs are routinely used as radiotracer leads, however, the mechanism of action of this compound is not well understood as it was identified in a synthetic lethal screen for KRAS. Despite the unknown mechanism of action, the ability of these compounds to differentiate between cancer types shows real promise as an imaging diagnostic to aid in the differentiation between cancer treatment groups and improve treatment outcomes. To evaluate if this class of compound as a potential radiotracer, 7 fluorine containing analogues and derivatives of Oncrasin-1 were synthesized along with the parent compound to evaluate their potencies relative to the parent Oncrasin-1 and investigate their potential to differentiate between tumours harbouring different kRAS mutation status. In this evaluation, potency is used as a surrogate marker for binding affinity, as development of radiotracers is a costly and resource intensive process. Along with the cold standards, precursors of the radiotracers were synthesized, initially through an attempted iodonium salt intermediate, however, it was discovered through the course of this work that the indole scaffold is incompatible with the oxidising conditions required to produce the hypervalent iodonium salt. Synthesis of an alternative pinacol boronic acid ester was therefore undertaken and precursors for 3 radiotracers were successfully produced, with a fourth radiotracer production being achieved through a post labelling reduction reaction. Radiosynthesis was successfully undertaken of 18F labelled KAM001, KAM002, KAM003 and KAM011, with decay corrected radiochemical yields between 10-18% for these radiotracers. 18F labelled KAM011 was successfully synthesized through a post labelling reduction of 18F labelled KAM001 resulting in a decay corrected radiochemical yield of 12%. Biological evaluation of compounds in colon cancer cell lines indicated improved potency and selectivity between the parent and two compounds tested in KRAS mutant cell lines and wild type cell lines, however, the potency testing in BRAF mutant cell lines gave inconclusive toxicity and cell cycle analysis. Preliminary radiotracer uptake studies were carried out in colon cancer cell lines and showed poor differentiation between KRAS mutant and KRAS wild type cell lines with the 18F KAM001 radiotracer. Further development in the understanding of these compounds since the beginning of this project indicate that the family of compounds likely have multiple mechanisms of action, with one of the molecular targets being identified as the enzyme Sulfotransferase 1A1, also known as SULT1A1, which has been shown to be abnormally expressed in many types of cancer, including breast cancer. Identification of SULT1A1 expression in breast tissue can be a marker of cancer, as upregulation of this enzyme is abnormal in this type of tissue. Identification of the presence of this enzyme also has potential value as a prognostic indicator as it has been associated with abnormal metabolism of drugs and has been linked to improved Tamoxifen response in oestrogen sensitive cancers. Potency testing of the compounds showed good differentiation between the commonly used MCF-7 and MDA-MB-231 breast cancer cell lines, with cell cycle analysis showing different trends depending on the substitution pattern in sensitive MCF-7 cell line but no discernible trend in the insensitive MDA-MB-231 cell line. Preliminary radiotracer uptake assays showed differentiation between the cell lines with the 18F labelled KAM001 and even better differentiation with the 18F labelled KAM011 tracer. Subsequent stability and metabolism studies indicated good tracer stability for the 18F labelled KAM011 tracer for the imaging period required. Imaging studies with the 18F labelled KAM011 tracer showed good differentiation of tumours, with high tumour to muscle ratio found in sensitive tumours and visually apparent internalization of radiotracer. In insensitive MDA-MB-231 cell lines a low tumour to muscle ratio was observed, with a build-up of radiotracer around the peripheral tissue still showing the tumour visually. This thesis outlines the methods and procedures of synthesizing cold standards, precursors, and radiotracers which were developed from the Oncrasin molecule. These molecules have been used in biological evaluation and imaging studies which have shown improved potency over the parent compound in cell culture as well as the ability to effectively differentiate between tumour types in both in vivo and in vitro models, with the potential for stratification of patient groups pending further investigation.