School of Chemistry - Theses
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ItemEnhancing Nitrogen Fertilisation Efficiency by Developing Novel Nitrification Inhibitors for a Greener Agriculture( 2023-05)Nitrogen (N) is used as a fertiliser for its essential role in building biomolecules, such as amino acids, porphyrins and nucleic acids, which directly promote plant growth. Better nutrition leads to a better crop yield; this has been a central dogma in agricultural science for more than 150 years. In an agricultural field, where natural resources are depleted due to frequent harvests, soils do not provide naturally sufficient N in a plant-available form (mineral-N, such as nitrate (NO3-) and ammonium (NH4+)). N is, therefore, a limiting nutrient and is added in an enormous amount into the soil as N fertilisers. Whilst the application rate of N fertiliser was 31.8 Tg back in 1970, today, almost 120 Tg of N is introduced into the soil. Unfortunately, there is no direct correlation between N fertilisation rate and crop yield due to a competing N uptake mechanism by soil organisms known as nitrification. Nitrification can lead to N fertiliser losses of up to 80%. By definition, it is a redox cascade from the highest reduced form of N (NH3) to the highest oxidised form of N (NO3-). The eight electrons released in the mechanism provide essential energy for bacteria and archaea equipped with the enzymes to perform this reaction. Agriculture has been facing the challenge of over-fertilising soil to ensure crop yield for over 50 years now. Not only is excessive N fertilisation not economically impactful, but N fertilisation also hosts various environmental problems. Especially in heavily industrialised and densely populated areas, the high N application rate in soils has polluted the atmosphere with ammonia (NH3) and nitrous oxide (N2O), a greenhouse gas (GHG) with a warming potential approximately 300 times higher than carbon dioxide. To control microbial conversion, synthetic nitrification inhibitors (SNIs) are introduced via co-formulation of N fertilisers. SNIs inhibit the microbial enzyme responsible for the N conversion, namely ammonia monooxygenase (AMO) conserved in ammonia oxidising bacteria (AOB) and archaea (AOA) that perform the initial and rate-limiting step of nitrification. Whilst commercial SNIs have been on the market since the 1970s, the nitrogen use efficiency has remained 50% globally, mainly due to their unpredictable and unreliable performances in soil. Interestingly, the inhibition mechanism of commercial NIs has not been fully understood yet. Moreover, the development of new NIs has been a bottleneck in the past. This thesis investigates into the development of a rapid, accessible, and robust nitrification assay to test the efficacy of potential NI within 60 min. This essay employs AOB of the strain Nitrosomonas europaea and Nitrosospira multiformis and test their nitrification activity in the presence of a SNI. The assay summarises the most-suitable parameter for cell growth, cell harvest, inhibitor concentration and substrate concentration, as these protocols do not exist in literature. The second research chapter focuses on determining the mechanism of inhibition of the existing SNIs 3,4-dimethyl-1H-pyrazole (DMP) and dicyandiamide (DCD), which have not been explored previously. This fundamental research is essential to understand current agricultural products and enable the design of novel NIs with more reliable performance. A series of biochemical studies were performed with DMP and DCD using Nitrosomonas europaea (N. europaea) as a model organism to identify the targeted enzyme in the nitrification enzyme cascade, binding affinity, reversibility of binding, Michaelis Menten kinetics, and toxicity. It was found that both NI act as reversible, non-mechanistic inhibitors. Following these findings from the biochemical experiments in the previous chapter, similar experiments were performed for five derivatives of 1,4-disubstituted 1,2,3-triazoles to directly compare them to the commercial SNI. This class of SNI has recently been tested in soil incubation studies by the postdoctoral student Bethany I. Taggert and showed an exceptional NI in comparison to the ‘gold standard’ DMP especially observed at elevated temperatures. Biochemical parameters for this class of compounds have not been determined. Therefore, five candidates 1,4-disubstituted 1,2,3-triazoles with varying functional groups substituents in the 1-position were tested. It was found that the incorporation of functional groups is detrimental to the inhibitory effect, and with increased lipophilicity, an increased inhibitory effect is observed. All inhibitors acted as non-competitive and reversible inhibitor.
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ItemThe Design and Synthesis of Radioactive Metal Complexes for the Diagnosis and Treatment of Disease( 2023-07)Personalised medicine is becoming increasingly important in the treatment of various cancers and diseases. Early diagnosis is important for patient outcomes, and radiation therapy offers a molecular treatment option that allows for highly specific targeting of cancer cells in vivo. The overarching theme of the research described in this thesis relates to the design and synthesis of new radiopharmaceuticals designed to better diagnose or treat various malignancies, including renal cancer, Alzheimer’s disease and cancers that are associated with suppression of the immune system, known as immune checkpoint inhibitors. Selective and targeted delivery of the radionuclide to sites of disease is essential. Radionuclide therapy is possible with radionuclides that emit alpha particles. Actinium-225 emits alpha particles with a radioactive half-life of 9.9 days. Targeted delivery of actinium-225 to tumours has the potential to treat tumours. Chapters Two to Five of this thesis describe new approaches to incorporate actinium-225 into targeting molecules. Chapters, Two, Three and Four discuss the design and synthesis of a new bifunctional ligand, H2MacropaSqOEt designed to form stable complexes with actinium-225. Monoclonal antibodies that target Carbonic Anhydrase IX were chemically modified to incorporate the ligand H2MacropaSqOEt. Carbonic Anhydrase IX is an enzyme that is overexpressed on the surface of cancers such as clear cell renal cell carcinoma. These antibody conjugates were radiolabelled with actinium-225, and [225Ac]Ac(MacropaSq-hG250) was evaluated in a murine model of cancer that overexpresses Carbonic Anhydrase IX. The research presented in these three chapters highlight the future potential of targeted alpha therapy with monoclonal antibodies. The work in Chapter Five focused on the concept of antibody-based pre-targeting. The synthesis of [225Ac]Ac(Macropa-Tetrazine) was a preliminary investigation into the possibilities of pre-targeted alpha therapy, and future work will involve exploring the potential of the iEDDA reaction between [225Ac]Ac(Macropa-Tetrazine) and TCO-modified antibodies. Copper-64 is a positron emitting radionuclide with a half-life of 12.7 hours. Copper-64 is used as a diagnostic radionuclide in positron emission tomography. Chapter Six focused on developing a copper-64-based diagnostic imaging agent for Alzheimer’s disease. The aim of this research project was to develop a proof-of-concept strategy to enable antibody-targeted positron emission tomography imaging via the preparation of small copper-containing molecules designed to cross the blood brain barrier and react with specifically modified Amyloid-beta antibodies. Finally, the research presented in Chapter Seven focused on the development of a new peptide-based imaging agent for the diagnosis of PD-L1-positive tumours. This chapter explored the copper-64 radiochemistry and stability of this new peptide complex.
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ItemNo Preview AvailableFrom Synthesis to Application: III-V Semiconductor Nanocrystals and Magnetic Nanoparticles( 2023-07)Nanoparticles are a class of materials that has fascinated the whole research community due to their vastly different properties to their bulk counterparts, and their size-dependent optical and electronic properties. These colloidal nanoparticles are usually synthesized in a bottom-up solution based method, which is much less expensive and energy intensive compared to the top-down method to make bulk materials, making them ideal for cheap and scalable solution processed devices for various applications from biomedical to energy harvesting. However, limited reaction temperature due to the physical limits of common organic solvents makes it challenging to synthesize materials with high bond energy. The other challenge is controlling the size of the nanoparticles to take advantage of size-dependent properties. III-V semiconductors are a family of semiconductors made of group III and group V elements. The more covalent nature of the bond between the group III and V elements offers them many advantages over the traditional II-VI semiconductors, but also makes them require more energy to be synthesized. In this thesis, a new reaction route using organometallic compounds to make III-V semiconductor nanocrystals in solution is explored in detail. It is shown that InN, GaN and InSb can be synthesized using this approach with size control, and they have also demonstrated to be effective in solution processed photodetectors. Iron oxide magnetic nanoparticles are the most common type of magnetic nanoparticles and are widely used in biomedical applications such as COVID-19 PCR testing. The size and composition (between gamma-Fe2O3 and Fe3O4) of magnetic nanoparticles dictates many aspects of its magnetic properties, such as the form of magnetism and magnetic response to external magnetic fields. Hence it is critical to maintain control of the composition and size for quality control in real world applications. In this thesis, a simple parameter to control the size and composition of iron oxide magnetic nanoparticles is reported. The ordering and alignment of magnetic nanorods in a uniform external magnetic field was also investigated using synchrotron small angle X-ray scattering.
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ItemUltrasound-induced Inactivation of Trypsin Inhibitors for Improving their Functionality( 2023-08)Trypsin inhibitors are anti-nutritional proteins that hinder the digestibility of legume proteins in the gastrointestinal tract, therefore, limiting the application of raw legumes and the consumption of legume products. To improve the commercial and nutritional values of legume products, it is vital to inactivate the two trypsin inhibitors, Kunitz inhibitor and Bowman-Birk inhibitor. However, the traditional thermal inactivation process has unsatisfactory inactivation performance due to the high heat and pH stability of trypsin inhibitors. Therefore, some advanced technologies with high-efficiency and energy-saving should be considered to achieve more effective inactivation of soy trypsin inhibitors. In this thesis, both low- and high-frequency ultrasound treatments were applied to inactivate the Kunitz and Bowman-Birk inhibitors, both in the aqueous phase and in emulsions consisting of the aqueous and non-aqueous phases. The mechanism of ultrasound-induced inactivation and ultrasound-assisted interfacial adsorption and inactivation of soy trypsin inhibitors were proposed and the effect of process-relevant parameters on the ultrasound-assisted inactivation was explored. Additionally, the numerical simulation was used to clarify the mass transfer behaviour of ultrasound-assisted soy amino acid adsorption.
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ItemSelf Assembly Nano Particle Simulation and Modelling of Organic Photovoltaic Materials( 2022-05)This work contributes in predicting effects of OPV materials in solar cell active layers through MD simulations. Through general coarse grained simulations, the rate of change of component solubility, demixing tendency, and the difference in interaction energies, were studied for nano-composite self-assemblies. Routes to form uni- form, core-shell, Janus, and eccentric morphologies were established. Using atom- istic simulations it was established that increasing P3HT chain length the stability of the nanocomposite (P3HT:PCBM/ICBA) decreases, whereas increasing PDI stability increases. Also addressed is why two specific members of the entire BXR series (benzodithiophene- X-thiophene-rhodamine) exhibit liquid-crystalline phase and highest PCE in solar cell usage, compared to the other members. These members exhibit optimum aggregation which is necessary for liquid crystalline phase formation.
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ItemNo Preview AvailableThe Development of SelfImmolative Nanoparticles to Enhance Endosomal Escape( 2023-01)Biopharmaceutical therapeutics, including mRNA, DNA and protein, are emerging as powerful treatment strategies for many diseases. Nanoparticle delivery systems are a crucial component to the delivery of biopharmaceuticals due to their enhanced protection, site-specific delivery and improved safety. However, the intracellular trafficking of the biopharmaceutical delivery, in particular endosomal escape, remains an area for enhancement. While polymer delivery systems have been engineered to enhance endosomal escape, many polymer systems are non-degradable. The incorporation of controlled degradability into the polymer system enhances therapeutic release, reduces material accumulation and lowers toxicity. One type of material with very precise control over the degradability is self-immolative polymers (SIPs), which undergo an end-to-end depolymerisation cascade triggered by a single bond cleavage event, often at the end cap. However, SIPs have not been extensively explored for the use as nanoparticle delivery systems to enhance endosomal escape. In this thesis nanoparticles composed of SIPs were developed and the particle behavior, the extent of depolymerisation and interaction with cells of these SIP particles was investigated. The onset of the polymer depolymerisation was found to impact interactions with cells, including endosomal escape. A framework to controlling the onset of depolymerisation through controlling the access of stimuli to the SIP polymer end cap was developed. Partial control over the onset of depolymerisation, through protection of the SIP end cap, was shown through modulation of the polymer side chain hydrophobicity and pKa of the non-degradable shell polymer used in the particle formulation. However, the migration of the SIP to the particle surface and out of the particle prevented the specific control over the onset of depolymerisation. More precise control over the onset of depolymerisation was demonstrated though the modulation of the SIP side chain hydrophobicity and pKa. These particles were shown to rapidly and extensively depolymerise at low pH, while they remained stabile at pH 7.4 for up to one week. While all SIP particles showed rapid depolymerisation, one particle in the series was shown to enhance endosomal escape with a moderate endosomal escape efficiency. Lastly, the loading and release of nucleic acids with a SIP was explored. The work highlighted the importance of selecting the optimal nanoparticle formation conditions to produce polyplexes with ideal properties. In addition, the importance of incorporating a DNA binding group on the SIP side chain was found to be imperative to maintaining complexation under physiological conditions, while also effectively releasing the nucleic acids with upon exposure to stimuli.
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ItemNo Preview AvailableDesign of P3HT:Fullerene Nanoparticle Dispersions for the Fabrication of Organic Solar Cells( 2023-02)Organic solar cells have many advantages, compared to conventional silicon solar cells. Besides their excellent low-light performance, especially under low light conditions, they can be mechanically flexible and even semi-transparent, depending on their fabrication. Because the light-harvesting layer thickness is typically in the range of a few hundred nanometers, only a small amount of material is required for the production, resulting in a low weight of the solar cell cell and enabling an energy payback time of only a few months. For industrial use, the potential of low-cost production, which can be achieved via printing and coating processes in continuous roll-to-roll machines, is the most important factor. These processes require special inks that match the printing process and the desired film properties. Most organic semiconductors used in solar cells are not soluble in eco-friendly solvents such as water or alcohol, but in halogenated solvents, which are often harmful to the environment and toxic or carcinogenic to humans, thus requiring costly gas purification during the printing process. With this process, current laboratory efficiencies of up to 19 % are achieved. For an industrial process, however, the elimination of solvents of concern is desirable. With the alternative approach of the nanoprecipitation, it is possible to disperse an organic semiconductor inside an eco-friendly liquid agent hence omitting the use of toxic solvents in the printing process. The development of the efficiency from 4 % in the beginning of this work to over 10 % mainly due to the use of high efficient absorber materials and volatile stabilizers underlines the potential of this approach. The common method of synthesizing nanoparticle dispersions is the manual nanoprecipitation inside a beaker, allowing only limited reproducibility. Starting with the blend of P3HT and IC60BA, which enables the synthesis of stable nanoparticle dispersions, the production of nanoparticle dispersions by the continuous flow nanoprecipitation via microfluidics is examined in this work. First, a suitable setup is implemented. Then, the influencing parameters on the nanoprecipitation process are identified and qualified. By controlling the influencing factors, dispersions with tailored nanoparticle sizes can be produced, allowing a highly reproducible nanoprecipitation. These dispersions exhibited an outstanding stability of over one year. To qualify this process, organic solar cells with light-harvesting layers from nanoparticle dispersions are fabricated. In direct comparison, they outperformed the efficiency of solar cells with a light-harvesting layer from the common beaker precipitation. While the blends of P3HT and IC60BA form stable dispersions, when blended with P3HT, many other acceptors flocculate. Therefore, the second part of this thesis focuses on the crucial requirements for the nanoparticle formation of P3HT:acceptor blends. Hence, the well-known group of fullerene derivatives is examined, and the miscibility of P3HT and the acceptor is identified as one of the most important factors. From these results, the use of a third component is investigated to stabilize P3HT:acceptor blend that did not form stable dispersions. For this purpose, acceptors such as the fullerene PC71BM or donors such as regiorandom P3HT are investigated. With miscibility as a relevant factor, fist promising results could be obtained. With the knowledge gained from this work, a scalable concept for the production of non-toxic inks for the fabrication of organic solar cells can be implemented, enabling a reproducible process. Thus, in the future, highly efficient solar cell materials can be specifically designed for layer production using nanoparticle dispersions, which will further promote the eco-friendly production of organic solar cells
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ItemExploring a new generation of nitrification inhibitors( 2023-05)Intensive application of nitrogen-based (N-based) fertilisers has become a common practise to achieve high crop yields to feed the growing global population. However, a substantial fraction of the applied N is lost from the plant-soil system to the surrounding environment, via ammonia volatilisation, nitrate leaching, and denitrification. These N losses negatively impact the environment and lead to unwanted groundwater contamination, eutrophication of waterways, biodiversity loss, greenhouse gas emission and stratospheric ozone depletion. Addition of nitrification inhibitors (NIs) to fertilisers is an effective strategy to minimise N losses and improve overall N-use efficiency in agricultural soils. 3,4-Dimethylpyrazole phosphate (DMPP) is the most successful NI to date but has a highly variable efficacy. New compounds with reliable performance under different agricultural and environmental settings that will assist in better synchronising the fertiliser N supply and crop demand are needed. Therefore, this thesis uses a systematic approach to explore the stability of current and newly developed NIs through degradation studies, to gain a better understanding of how degradation impacts the inhibitory activity, which should assist in the development of more efficient NIs with reliable performance.
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ItemEnergy Transfer Systems for Light Harvesting( 2023-03)Luminescent solar concentrators (LSCs) are solar harvesting devices that employ luminescent materials embedded within a waveguide to collect solar energy. The waveguide is typically made of a low-cost material such as glass or plastic and is designed to capture sunlight and redirect it towards solar cells. The luminescent materials, also known as luminophores, absorb the sunlight and re-emit it at a longer wavelength, allowing it to be trapped within the waveguide and guided towards the edges, where solar cells can convert the light into electricity. However, their performance is associated with several drawbacks, including reabsorption, which refers to the primary emission of the luminophore in the waveguide being reabsorbed by other luminophores in the waveguide. To overcome this, various strategies have been explored such as using different types of luminophores, optimizing the concentration of luminophores, and improving the design of the waveguide. Foster energy transfer (FRET), which reduces luminophore reabsorption, is a crucial aspect for improving energy conversion and device efficiency in LSCs. FRET works on separating the absorption and emission spectra of the luminophores by controlling the intermolecular spacing between donor and emitter molecules. Implementing these strategies can significantly enhance the performance of LSCs and accelerate their practical applications for solar energy harvesting. This thesis aims to advance the understanding of different energy transfer strategies for light harvesting applications. To implement an effective FRET approach, the concentration of luminophores is a crucial factor. The donor luminophore concentration should be higher than that of the emitter to allow energy migration through several donors to reach the emitter. However, increasing the dye concentration often leads to dye aggregation, which can quench the dye's fluorescence properties. To mitigate dye aggregation, molecular insulation in the luminophores can be an effective approach. In this thesis, the molecular insulation strategy is applied to both the donor and emitter luminophores to suppress dye aggregation at high concentrations. Several sterically hindered groups have been employed for both the donor and emitter through the imide position of the luminophore, and their photophysical properties have been observed at various concentrations. The results demonstrate that these sterically hindered groups effectively reduce dye aggregation at high dye concentrations. Furthermore, incorporating luminophores in a polymer backbone enables efficient energy transfer from the donor to the emitter by controlling the distance between the luminophores. The polymer chain acts as a spacer between the luminophores, reducing dye aggregation and suppressing the reabsorption issue. To investigate this approach, a variety of linear polymers with incorporated luminophores were employed in this study, where the luminophores were covalently linked to the polymer chain. Optical properties were analysed in both solid and solution states, and it was determined that this strategy did not adversely affect the luminophore's optical characteristics. Moreover, it was discovered that the more sterically hindered donor efficiently transferred its energy to the emitter, effectively suppressing aggregation-caused quenching (ACQ) in comparison to the less sterically hindered donor molecule. The success of the FRET energy transfer technique in polymer chains has inspired the use of crosslinked luminophore embedded nanoparticles for light harvesting. This approach involves embedding the dye within the polymer particles, resulting in a high dye concentration in a small area and promoting efficient energy transfer. In this study, a series of donor-emitter luminophore embedded crosslinked nanoparticles were synthesized using various luminophore concentrations, and their photophysical properties were studied to examine FRET efficiency. The cross-linked polymer particles effectively reduced luminophore aggregation and reabsorption. These polymer nanoparticles were used to fabricate bulk LSC films, which also demonstrated effective energy transfer. The photophysical observations were subsequently utilized in Monte-Carlo simulations of a large-scale bulk LSC device. The simulation results indicated that the incorporation of cross-linked polymer particles had a significant effect in mitigating the reabsorption process of luminophores in the bulk LSC waveguide.
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ItemZwitterionic Donor-Bridge-Acceptor Solvatochromic Dyes( 2023-03)Push-pull molecules are widely used luminophores for applications in optoelectronics and photonics. They are discrete, functionally desymmetrised molecules, bearing donor and acceptor substituents as end-groups, with their delocalized pi-electron system responsible for nonlinear optical effects. Oligomeric systems with a donor phenol group and an acceptor pyridyl moiety separated by a conjugated para-phenylene chain or fluorene spacer were obtained by iterative Suzuki–Miyaura or Horner–Wadsworth–Emmons couplings. For synthesis of desymmetrised molecules, aryl or heteroaryl halides and aryl triflates are typically used as substrates in the former case. Due to moderate reactivity of aryl triflates and their high cost, aryl nonaflates have been proposed as a good alternative. So far, only few reports related to the application of aryl nonaflates in Suzuki–Miyaura coupling have been published, where aryl nonaflates have shown slightly higher reactivity and better yields compared to corresponding triflates. Zwitterionic forms of these donor-bridge-acceptor molecules were generated by consequent N-methylation and deprotonation reactions leading to large redshifts in absorbance maxima. UV-vis absorbance studies also revealed negative solvatochromic behaviour: a smooth bathochromic shift was observed with the decrease of the solvent polarity. Most of the examples have shown strong solvatochromic characteristics, where the magnitudes of these shifts in the studied polarity range were close or even greater to the one for Reichardt’s dye — one among the most solvatochromic organic dyes known. Additionally, systems with increased disparity between the donor and acceptor ends were synthesised and studied. It was achieved by introducing a stronger acceptor, which lead to molecules with more unusual electronic and structural properties. Among them there were species with a bulky donor phenolate moiety and an acceptor pyridinium group separated by a bridging unit of a different nature. One of the molecules incorporating a vinyl bridge and 2,4-dinitrobenzene acceptor group demonstrated the broadest and the most redshifted absorption profile in the N-arylated series. It also showed extraordinary behaviour in its 1H NMR spectrum as well as in its crystal structure compared to its analogues. Thus, it was found to be near the cyanine limit, which makes it to be a potential candidate for photorefractive materials.
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