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(2022) Nguyen, Minh TrietThesisSinglet fission is a photo-physical process that generates two triplet excitons from one singlet exciton and can potentially enhance efficiency in photovoltaic systems. The combination of photovoltaics and singlet fission is a novel field for solar energy conversion when there is much interest in renewable, non-destructive, and continuously available energy sources. Singlet fission can also overcome thermalization losses in photovoltaics, which happens in traditional cells when the incident photon energy is higher than the silicon bandgap energy, using a carrier multiplication mechanism. This thesis will design, construct, and characterize photovoltaic devices incorporating singlet fission materials to study singlet fission in practical application. The research focuses on materials characterization, spin dynamics, and electron transfers between acene and the semiconductor layer in Au/TiO2 ballistic cells, and the incorporation of singlet fission layers on silicon-based cell structures. In detail, a set of investigations was developed and summarized by implementing singlet fission materials into a state-of-the-art ballistic photovoltaic device and silicon-based solar cell. The studies demonstrate proof of concept and rationally explain the process. The first part of the thesis investigates thin films of pentacene, TIPS-pentacene, and tetracene via crystallinity, morphology, absorption, and thickness characterization. Additionally, Au and TiO2 layers in Schottky device structures were optimized to achieve the best performance for energy transfer from an applied dye layer (merbromin). The drop-casted dye layer influences the device performance by increasing short-circuit current and open-circuit voltage, demonstrating the ability of charge transfer between the device and the applied film. This device structure provides a test bed for studying charge and energy transfer from singlet fission films. The latter part of the thesis describes several investigations to understand singlet fission in a thin film using this architecture. Magneto-photoconductivity measurements were primarily used to observe the spin dynamics via photoconductivity under an external magnetic field. Control experiments with bare Au/TiO2 devices showed no observable magneto-photoconductivity signal. In contrast, devices with pentacene and tetracene singlet fission layers showed a strong magnetoconductivity effect caused by ballistic electron transfer from the singlet fission layer into the TiO2 n-type semiconductor through an ultra-thin gold layer inserted between the layers. A qualitatively different behavior is seen between the pentacene and tetracene, which reveals that the energy alignment plays a crucial part in the charge transfer between the singlet fission layer and the device. The last section investigates the application of pentacene and tetracene evaporated thin-films as sensitizer layers to a silicon-based solar cell. The optimized Si cell structure with the annealing treatment improved the cell's performance by increasing short-circuit current and open-circuit voltage. The deposition of pentacene and tetracene as sensitizer layers into the device showed some results but posed several challenges that need to be addressed. As the current-voltage and external quantum efficiency measurements were taken, it was observed that material interfaces need to be designed to fully achieve the singlet fission of the acene layer into the Si devices.
Design of antibody-polymer conjugates for immunotherapy: the influence of polymer structure on the antibody's activity.(2022) Melodia, DanieleThesisAntibodies are increasingly useful therapeutics, and examples include the checkpoint inhibitors pembrolizumab1 and ipilimumab2 in cancer immunotherapy, and anti tau therapies in Alzheimer’s disease and dementia.3,4 However, specific applications requiring cytosolic delivery of the antibody, or transport across the blood-brain barrier pose challenges to antibody therapeutics. These issues may reduce the effectiveness of immunotherapy and restrict it to extracellular targets. Conjugating polymers to proteins and enzymes has been very effective at improving their stability and pharmacokinetics,5–8 and similar approaches have been studied for antibody conjugation.9–12 Finding an effective polymeric delivery system for antibodies can greatly improve immunotherapy. In this work three strategies were explored for the encapsulation and bioconjugation to antibodies. The first approach is the encapsulation via electrostatic interactions between the antibody and a charged block copolymer to form polyion complex (PIC) micelles. Polyphosphonium block copolymers were studied for the first time to encapsulate antibodies, and were compared to their ammonium counterpart. While this approach has the advantage of being reversible, the polymer-antibody electrostatic interactions were too weak for biological applications, and delivery by this means would require a crosslinking strategy. The second approach involves covalent attachment of polymers on the antibody’s surface via a grafting from polymerisation. An oxygen tolerant technique was employed for the screening of a large number of samples in low volumes (<100 μL). Successful grafting was demonstrated by AF4 and gel electrophoresis. Enzyme-linked immunosorbent assay (ELISA) showed retention of up to 40% binding activity relative to the native antibody with a marked improvement in stability. The third strategy introduces a novel acid sensitive linker for the reversible covalent attachment of polymers to the antibody’s surface. This was achieved by using Diels-Alder chemistry to create an activated PEG that forms an amide with a conformational lock similar to citraconic anhydride upon conjugation to the amines on the antibody. The ability of the linker to cleave at pH 5.5 is demonstrated, resulting in almost complete recovery of the original binding activity of the antibody. Overall, the reversible covalent attachment investigated here seems the most promising, and combining the high throughput method with the cleavable linker approach holds great potential for advancing in immunotherapy. References (1) Reck, M. Pembrolizumab as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer. Futur. Med. 2018, 10, 93–105. (2) Gao, J.; Ward, J. F.; Pettaway, C. A.; Shi, L. Z.; Subudhi, S. K.; Vence, L. M.; Zhao, H.; Chen, J.; Chen, H.; Efstathiou, E.; Troncoso, P.; Allison, J. P.; Logothetis, C. J.; Wistuba, I. I.; Sepulveda, M. A.; Sun, J.; Wargo, J.; Blando, J. VISTA Is an Inhibitory Immune Checkpoint That Is Increased after Ipilimumab Therapy in Patients with Prostate Cancer. Nat. Med. 2017, 23 (5), 551–555.. (3) Pedersen, J. T.; Sigurdsson, E. M. Tau Immunotherapy for Alzheimer’s Disease. Trends Mol. Med. 2015, 21 (6), 394–402. (4) Castillo-Carranza, D. L.; Sengupta, U.; Guerrero-Munoz, M. J.; Lasagna-Reeves, C. A.; Gerson, J. E.; Singh, G.; Estes, D. M.; Barrett, A. D. T.; Dineley, K. T.; Jackson, G. R.; Kayed, R. Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles. J. Neurosci. 2014, 34 (12), 4260–4272. (5) Abolmaali, S. S.; Tamaddon, A. M.; Salmanpour, M.; Mohammadi, S.; Dinarvand, R. Block Ionomer Micellar Nanoparticles from Double Hydrophilic Copolymers, Classifications and Promises for Delivery of Cancer Chemotherapeutics. Eur. J. Pharm. Sci. 2017, 104 (January), 393–405. (6) Kurakhmaeva, K. B.; Djindjikhashvili, I. A.; Petrov, V. E.; Balabanyan, V. U.; Voronina, T. A.; Trofimov, S. S.; Kreuter, J.; Gelperina, S.; Begley, D.; Alyautdin, R. N. Brain Targeting of Nerve Growth Factor Using Poly(Butyl Cyanoacrylate) Nanoparticles. J. Drug Target. 2009, 17 (8), 564–574. (7) Jiang, Y.; Fay, J. M.; Poon, C. D.; Vinod, N.; Zhao, Y.; Bullock, K.; Qin, S.; Manickam, D. S.; Yi, X.; Banks, W. A.; Kabanov, A. V. Nanoformulation of Brain-Derived Neurotrophic Factor with Target Receptor-Triggered-Release in the Central Nervous System. Adv. Funct. Mater. 2017, 1703982, 1–11. (8) Klyachko, N. L.; Manickam, D. S.; Brynskikh, A. M.; Uglanova, S. V.; Li, S.; Higginbotham, S. M.; Bronich, T. K.; Batrakova, E. V.; Kabanov, A. V. Cross-Linked Antioxidant Nanozymes for Improved Delivery to CNS. Nanomedicine Nanotechnology, Biol. Med. 2012, 8 (1), 119–129. (9) Bin Liu, Khushboo Singh , Shuai Gong , Mine Canakci, Barbara A. Osborne, and S. T. Protein Antibody Conjugates PACs A Plug‐and‐Play Strategy for Covalent Conjugation and Targeted Intracellular Delivery of Pristine Proteins. Angew. Chemie 2021, 133, 12923–12928. (10) Chan, L. J.; Bulitta, J. B.; Ascher, D. B.; Haynes, J. M.; Mcleod, V. M.; Porter, C. J. H.; Williams, C. C.; Kaminskas, L. M. PEGylation Does Not Signi Fi Cantly Change the Initial Intravenous or Subcutaneous Pharmacokinetics or Lymphatic Exposure of Trastuzumab in Rats but Increases Plasma Clearance after Subcutaneous Administration. Mol. Pharm. 2015, 12, 794–809. (11) Subasic, C. N.; Ardana, A.; Chan, L. J.; Huang, F.; Scoble, J. A.; Butcher, N. J.; Meagher, L.; Chiefari, J.; Kaminskas, L. M.; Williams, C. Poly ( HPMA- Co -NIPAM ) Copolymer as an Alternative to Polyethylene Glycol-Based Pharmacokinetic Modulation of Therapeutic Proteins. Int. J. Pharm. 2021, 608 (September), 121075. (12) Keita Hironaka,a,b Erika Yoshihara, Ahmed Nabil, James J. Lai, A. K. and M. E. Conjugation of Antibody with Temperature-Responsive Polymer via in Situ Click Reaction to Enable Biomarker Enrichment for Increased Diagnostic Sensitivity. Biomater. Sci. 2021, 9, 4870–4879.
(2022) Wulandari, ErnaThesisChronic wounds are a major issue in public health. One of the contributing factors in the development of chronic wounds is bacterial infection, which is exacerbated by the presence of multidrug-resistant (MDR) bacteria. One approach to tackle wound infection is the use of non-antibiotic antimicrobials with rapid killing effect without inducing resistance. This thesis aims to investigate the application of antimicrobial polymers and iodine in the development of antimicrobial wound dressing platforms. Firstly, contact-active antimicrobial wound dressings were explored. An inert silk sponge was prepared as the substrate and functionalized with antimicrobial polymers on the surface via layer-by-layer assembly. Electrostatic interactions in the multilayer construct confined the antimicrobial polymers and prevented leaching. The sponge was able to suck bacteria into the porous network and kill them upon contact as evidenced by up to 4 log10 reduction against Gram-negative and Gram-positive bacteria. Additionally, the antimicrobial efficacy was found to be strongly affected by the construction of multilayer assembly. As the contact-active mechanism may reach saturation point on the surface, in the second approach, an antimicrobial platform with a release-killing mechanism was developed. Employing the ability of silk to self-assemble into a thin film, antimicrobial polymers were loaded in the silk matrix. The release of antimicrobial polymers correlated to polymer concentration, silk to polymer ratio, and film configuration. The efficacy of the films was demonstrated by 5 to 7 log10 reduction of planktonic and 3 to 7 log10 reduction of biofilm cells against Pseudomonas aeruginosa and Staphylococcus aureus, including MDR strains. Furthermore, the straightforward coating method was as effective on glass or cotton substrates. The third approach investigated the immobilization of iodine onto wound dressings for a sustained release system. The immobilization was facilitated by polyamide iodophors that were synthesized on the dressing via plasma polymerization of the gaseous amide monomers. The antimicrobial activity correlated strongly to the structure of the polyamide with the short and linear polymer recorded 4 log10 reduction against P. aeruginosa and 7 log10 reduction S. aureus, including a MDR strain. Overall, the immobilization of iodophors on wound dressings demonstrated a potential new approach in reducing bacteria proliferation in wounds.
(2023) Siddique, ArslanThesisEpidemic thunderstorm asthma (ETSA) outbreaks are triggered by airborne pollen allergens combined with thunderstorm activity. ETSA can affect anyone, as observed in the world’s largest ETSA event in Australia. Allergens from rye grass pollen affect the respiratory airways and the fundamental physicochemical causes, biochemical interactions, and the role of the thunderstorm in ETSA have been the source of much speculation. In this thesis, the physicochemical interactions of thunderstorm-derived reactive oxygen nitrogen species (RONS) and pollen-derived molecules are examined. It is hypothesised that RONS from the plasma-activated water (PAW) react with the airborne pollen allergens, exerting physicochemical changes to enhance allergenicity and subsequently causing ETSA. Simple biomimetic models are demonstrated, examining the key biointerfacial interactions and the influences of the conditions of plasma formation, pH, and temperature, employing advanced interface-sensitive techniques including QCM-D and neutron reflectometry. Firstly, cellulose-mucin interactions were analysed, mimicking the interactions between the walls of inhaled pollen (intine) and mucosa of the respiratory tract (mucin). Interaction with plasma-treated cellulose surfaces led to adsorption and conformational alterations to mucin, potentially indicating changes to the permeability of the mucosa. Secondly, the effect of PAW on the interactions between a model-allergen plant protein and lipid monolayers mimicking alveolar surfactant was studied. The protein took up RONS and PAW-treated protein showed stronger adsorption to the lipid monolayers, implying PAW-treatment enhances transport of the protein into lung tissue. Lastly, the effect of PAW on allergen penetration into epithelial bilayers was elucidated. Solid-supported model lipid bilayers were allowed to interact with model allergen and rye grass derived proteins to deduce the structural integrity of the membrane. PAW-treatment increased adsorption of the proteins to the lipid bilayers, and enabled the penetration into the membrane, corroborating the enhanced allergenicity of PAW-treated allergens. Overall, PAW was seen to enhance three relevant nonspecific biointerfacial interactions; these physicochemical studies complement extant in vitro cell studies in an effort to enable the development of effective monitoring platforms, diagnostics, and therapeutic interventions for the prevention and treatment of ETSA.
Development of Innovative Ultra-Filtration Fibre Technologies for Waste-Water Treatment in Membrane Bio-Reactors (MBR)(2024) James, LeoThesisThe design of advanced hollow fibre ultrafiltration (UF) membrane technologies for use in wastewater treatment facilities has culminated from a combination of improvements in plant operation and optimising feed water interactions. With global demands in water quality increasing, this has placed increased pressure on MBR factories to develop high strength, anti-fouling fibre modules with improved permeabilities. The fabrication of such membranes, however, is restricted by the trade-off that exists between mechanical strength and filtration properties, as well as scalability concerns that arise when transitioning from laboratory trials to field testing of prototypes. This places increased importance on the need to establish a reliable formulation plan that addresses these trade-off limitations, in addition to furthering our understanding of membrane-foulant interactions. Modifications of polymer concentration will offer deeper insight into the role that polymer phase materials have on membrane formation and high strength performance. Further variations in pore-former content will provide a route towards optimising membrane surface porosity, translating into potential improvements in fibre permeability and anti-fouling propensity. Three different experimental approaches were implemented to assess the impact of fibre composition on membrane performance. These include (1) modifying the total concentration of poly(vinylidene fluoride) (PVDF) material, (2) tailoring the composition of PVDF material with distinct molecular weights, and (3) adjusting the proportion of poly(vinyl pyrrolidone) (PVP) and poly(ethylene glycol) (PEG) pore-forming additives. Microscopy techniques were used to document any structural changes across each formulation series, whilst porometer and tensile testing instruments were utilised to provide insight into membrane permeability and strength, respectively. Membranes formulated with elevated PVDF concentrations were found to exhibit improvements in mechanical integrity at the expense of reduced clean water fluxes. This was overcome by optimizing the incorporated PVDF molecular weight, which allowed for incremental boosts in toughness without adversely affecting permeability. Testing also revealed that fibres formed with higher concentrations of pore-forming agents, most notably PEG material, were found to be more permeable. Feedwater filtration cycling was implemented to provide insight into the relative fouling behaviour of membranes formed via these three approaches. Changes in resistance were found to be primarily dictated by membrane pore size, with intermediary pore size distributions being desirable targets for balancing out the effects of short- and long-term filtration. By tracing these trends in fouling propensity back to underlying fibre compositions, this study reinforces the importance of adjusting polymer formulations for achieving high strength, anti-fouling membranes. This study also acknowledges the limitations that exist in comparing laboratory-scale filtration data of fibre samples to prototype field testing of full-scale modules. Addressing these drawbacks through an analysis of feedwater conditions used in research and industry allows us to reach an informed decision on selecting appropriate formulations in the design of innovative membrane technologies.
Development of Novel Organocatalytic Boration Methods and the Employment of Cycloheptatriene as A Versatile Synthetic Building Block(2024) Ton, NhanThesisThis thesis consists of two main parts. The first part focuses on exploring the application of organocatalysts, small non-metallic organic molecules, to facilitate novel borylation reactions. The second part discusses the development and applications of compounds containing the cycloheptatriene (CHT) moiety, an interesting and valuable building block, in organic synthesis. The two parts of this thesis might seem unrelated at the first glance, however they are connected through the common chemistry of tropylium ion, which is one of the organocatalysts for the first part and the building block for the second part. Chapter 1 provides a brief overview and establishes contexts for the research topics presented in the two subsequent parts of this thesis. This chapter discusses the use of tropylium ions and organic superbases as catalysts in organic reactions, as well as the versality of tropylium ions and cycloheptatriene motifs as synthetic building blocks. It further introduces common approaches for catalytic hydroboration and diboration of unsaturated compounds. Chapter 2 discusses a novel protocol for hydroboration reaction of alkynes, alkenes and epoxides, using tropylium salts as organocatalysts. Organoboron compounds are versatile precursors for cross coupling chemistry. Synthesis of these precursors have traditionally been mediated by transition metal or main group catalysts, which poses several issues with toxicity and product purification, as well as mechanistic understanding. Apart from the synthetic value of this metal-free efficient protocol, tropylium salts proved to be useful probes to explore mechanistic details of hydroboration reactions. This work offers interesting insights into the controversial topic of hidden or true catalysis for hydroboration reactions. Chapters 3 delves into the utilization of the highly efficient phosphazene organocatalyst P1−tBu, renowned for its exceptional strength as an organic Brønsted base, to promote 1,1-diboration reactions of electron-deficient terminal alkynes. A combination of thorough experimental and computational studies suggests interesting mechanistic insights for these phosphazene-catalyzed diboration reactions. Chapter 4 investigates a novel approach that harnesses the tropone oxime tosylate as a privileged synthetic building block. It can react with alcohols, phenols, thiols or terminal alkynes to yield a diverse family of Z,Z,Z-triene products through a rarely reported Nucleophile-intercepted Beckmann fragmentation (NuBFr) reaction. Chapter 5 investigates the ring-contraction rearrangement of cycloheptatrienes to transform them into benzyl groups. Substrate scope studies demonstrate the broad applicability of this method to furans and thiophenes. Simultaneously, the rearrangement of aryl or alkyl cycloheptatrienes into benzyl halides using tellurium(IV) halides as Lewis acid as well as halide source was also explored in this chapter. Chapter 6 offers concluding remarks to the thesis.
(2021) Chua, StephanieThesisImprovements in liquid lithium-ion battery electrolytes using of metal organic frameworks (MOFs) as a functional decoration on polymer membrane separators were investigated using a combination of experimental and theoretical methods. Zirconium-based MOF UiO-66 was introduced to the polymer support using the mixed matrix membrane (MMM) method. The method allowed the one-step manufacture of a robust, mechanically pliable polymer-MOF membrane composite of high MOF loading. MOF-MMMs imparted improved electrochemical behaviours such as a widened potential operating window, near-unity transference number, and increased presence of solid electrolyte interphase (SEI) components crucial to battery performance. Density functional theory (DFT) calculations were also performed to provide insights regarding electrolyte solvation in the presence of MOF. A simple dip-coating technique was utilised to modify the surface of the MOF-MMMs with polydopamine (PDA) for further improvement of the electrochemical properties. Increased transference numbers, as well as stability during rate cycling, were observed with the resulting PDA-MMM owing to the improved electrode/electrolyte interface. However, surface analyses using x-ray photoelectron spectroscopy (XPS) showed that there are reduced amounts vital SEI components compared to the original MOF-MMM support. The last section further explores the versatility of UiO-66 and tackled the preparation of gel polymer electrolytes (GPEs) decorated with UiO-66 via phase inversion technique. Using the phase inversion method, the fabricated GPE contained pores from both polymer substrate and the intrinsic pores of the 3D nanomaterial for improvement of electrochemical properties. It was demonstrated in this work that the MOF GPE is equally inert and suitable in ether or carbonate-based electrolytes. Overall, this study demonstrated the versatility of UiO-66 metal organic frameworks for use as a functional nanofiller for electrolyte membranes. With the use of inexpensive membrane fabrication methods, the composites obtained are viable for lithium-metal battery applications. Similarly, insights drawn can provide a springboard towards future study of MOF-based electrolytes.