Chemistry

Amyloid fibrils are fibrous protein aggregates that arise from misfolding and self-assembly processes, collectively referred to as amyloidosis. These aggregates are strongly associated with incurable neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease, and Amyotrophic Lateral Sclerosis (ALS). Elevated levels of Reactive Oxygen Species (ROS) and dysregulated metal-ion homeostasis often impaired by environmental and lifestyle factors can induce oxidative stress that undermines cellular antioxidant defenses, which cause the amyloid formation and toxicity. This thesis investigates multiple amyloidosis models, emphasizing the contribution of metal ions and ROS to aggregation pathways, and evaluates the potential inhibitory or protective roles of cytokinin (CK) plant hormone.Chapter 2 focuses on Gelsolin amyloidosis, a hereditary condition driven by point mutations that promote aberrant amyloid formation. Using microscopic and spectroscopic approaches, this work characterizes the aggregation behavior of peptides derived from domain 2 of plasma gelsolin and secreted by muscle cells. Three peptides were studied: the wild-type(WT) sequence and two clinically relevant mutants, K184N and N187Y. Each variant exhibited distinct aggregation rates, reflecting mutation-dependent effects on self-assembly. Furthermore, two CKs Kinetin (Kin) and trans-Zeatin (tZ) were shown to modulate gelsolin aggregation, suggesting their potential as anti-aggregation molecules. Chapter 3 revolves on the aggregation properties of TDP-43 peptides associated with ALS pathology. Within the RRM I domain, two cysteine residues serve as key redox-active sites susceptible to oxidation. ESI-MS and spectroscopic methods were used to analyze three peptide variants: WT, a mutant (MT) in which cysteine were substituted with alanine, and WT-S, a disulfide-linked dimer. All variants displayed higher aggregation under mildly acidic conditions. CKs, Kin and isopentenyl-adenine (iP) showed antioxidant capacity and their influence on peptide stability. Chapter 4 investigates the effects of copper(II)-induced oxidative stress in C2C12 muscle cells and evaluates cellular responses to various CK forms. ESI-MS profiling identified 20 CKs in copper-treated samples and revealed 24 untargeted metabolites with significant level changes, indicating their possible involvement in metal-induced oxidative pathways. In conclusion, this thesis highlights the multifaceted roles of CKs in biological systems, particularly their potential to mitigate ROS overproduction, counteract metal-driven amyloidgenesis, promote fibril destabilization, and lessen oxidative stress.

Author Keywords: Amyloid, Anti aggregation, cytokinins, inhibition, Peptide aggregation, Protein aggregation

The oil sands industry is producing large volumes of tailings waste reaching 2 billion cubic meters by 2034 In this study, the industrial standard flocculant, high molecular weight PAM, was grafted from the surface of activated carbon (AC). This material was designed to increase the flocculant's hydrophobicity and density. Different molecular weight PAM was grafted from AC with different AC contents and particle sizes (AC-PAMs). The AC-PAMs were synthesized by surface-initiated atom transfer radical polymerization (SI-ATRP). The AC-PAMs achieved molecular weights 107 – 5,600 kg/mol and AC content of 0.2 – 5.8% on <0.1 and 0.1 – 0.5 mm AC particle diameters. AC-PAM achieved higher solids contents up to 51 wt% using AC-PAM with 5.1 wt% AC due to the grafting from a hydrophobic AC core. To summarize, our work shows the successful grafting of PAM from AC and its potential as a flocculant for mature fine tailings.

Author Keywords: activate carbon, atom transfer radical polymization, flocculation, grafting-from, polyacrylamide, surface-initiated polymerization

In an effort to improve upon existing analytical methods, electrochemical sensors offer portable, cost-effective alternatives to traditional lab-based techniques. Recent advances in supramolecular chemistry offer a unique alternative to achieve high selectivity while also benefitting from facile scaling for mass production. Thus, by incorporating host-guest chemistry with electrochemical sensors, the development of simple and selective sensors is possible. To that extent, novel hosts and electroactive ion pairs were investigated for their ability to transduce an electrochemical signal representative of host-guest complexation. Results demonstrated that the upper rim modifications of resorcinarene hosts attenuated their affinity for electroactive probes whilst maintaining structural integrity upon extended cycling. Further work revealed that guests may be directly quantified via their complexation with electroactive hosts. The sensing method was further validated by quantification of surfactant pollutants in the Otonabee River. Through a fundamental understanding of the electrochemical behaviour of host-guest systems a general sensing platform can be developed, where hosts are interchangeable for specificity towards any desired analyte. Therefore, moving away from expensive lab-based methods and significantly reducing the barriers for biological or environmental monitoring.

Author Keywords: Electrochemistry, Ferrocene, Host-Guest, Resorcinarenes, Supramolecular Chemistry, Surfactants

The detection of ciguatoxins (CTXs) in biological samples is challenging due to their low concentrations, the presence of various congeners, and the absence of standardized methods. This study uses high resolution mass spectrometry (HRMS) with P-CTX-3B as a reference standard. The protonated molecules ([M+H]+) were most prevalent, especially when acetonitrile/water was utilized, providing enhanced sensitivity. Optimized collision energies of 15 eV for protonated molecules and flow rates of 10 µl/min enhance sensitivity and peak intensities, respectively. Acetonitrile/water (ACN/H2O) is recommended as the primary solvent for HRMS method, an aspect underexplored in existing literature. The detection of CTX-3B in fish tissue samples proved to be challenging, caused by variations in ion peak intensities and matrix effects, requiring a deeper exploration of the impact of complex matrices on CTX detection. The study emphasizes the need for a reliable internal standard to mitigate these effects and highlights the ongoing challenge of developing a rapid, simple, and sensitive detection method. The study's specific focus on the P-CTX-3B analogue significantly contributes to methodology development for this congener, serving as a foundational step in understanding and detecting CTX. Despite notable progress, the study acknowledges the absence of an ideal assay, outlining key challenges for future research on ciguatera analysis. It underscores the continuous necessity for method reevaluation, testing, and the broader goal of establishing a more clarified and rugged method for the identification of CTX in fish.

Author Keywords: Analytical Chemistry, Ciguatera Fish Poisoning, Ciguatoxin, High-Resolution Mass Spectrometry, Optimization, P-CTX-3B

This thesis explores the remediation of naphthenic acids (NAs) from oil sands process-affected water (OSPW) using activated carbon (AC) derived from petroleum coke (PC) chemically activated with potassium hydroxide. The research aims to identify the most effective method for the adsorptive removal of NAs by optimizing the use of economically viable KOH quantities and to apply Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FT-ICR-MS) for species-specific detection and characterization of NAs, crucial for targeting specific NAs in future studies.Prior research focused on single-species adsorption, establishing a foundational understanding of non-competitive adsorption before applying these findings to more complex NA mixtures and OSPW. This study builds upon this foundation, addressing a significant gap in the literature concerning the use of petcoke-derived AC with low KOH ratios and short activation times, which are economically advantageous for large scale applications. In this thesis, a comprehensive investigation into the kinetics and isotherms of NA adsorption on various ACs including PAC (petroleum coke AC), PWAC (pore-widened AC), HAC (heat-treated wood-based AC), and CAC (commercial AC) was conducted. The study specifically examines the adsorption behaviors of seven model NAs, reflecting the diverse molecular structures present in real world OSPW. The research also explores the impact of pore widening techniques on the adsorption efficiency of ACs, hypothesizing that increased mesoporosity enhances the adsorption of NA compounds. The findings demonstrate that FT-ICR-MS is an essential tool for precisely characterizing the NA species in OSPW, revealing that pore-widened ACs significantly improve the adsorption of NAFCs. This thesis contributes to the field of environmental remediation by offering new insights into the optimization of AC for NA removal, emphasizing the importance of surface chemistry and mesoporosity in enhancing adsorption efficiency. The study's outcomes have significant implications for the treatment of OSPW, providing a scalable and cost-effective solution to mitigate the environmental impacts of oil sands production.

Author Keywords: activated carbon, FT-ICR-MS, naphthenic acids, oil sands, petroleum coke, process-affected water

N-Heterocyclic Carbenes (NHCs) have significantly impacted organometallic chemistry as ligands in transition metal catalysis, offering strong electron-donating properties and high bond dissociation energies. However, their structural versatility is limited by the scarcity of commercial precursors and challenging modification procedures. Furthermore, we have investigated its coordination to transition metals; copper, silver, and palladium. We further demonstrate the effects of its steric parameters by utilizing the Suzuki-Miyaura cross-coupling of aryl chlorides using [(RO-NHC)Pd(allyl)Cl] as precatalysts. This study demonstrates increased catalyst activity with bulkier ligands in Suzuki-Miyaura cross-coupling reactions. We also present simplified procedures for copper NHC complexes using triethylamine with no requirements for special equipment and techniques. Preliminary investigations towards a more economical approach to measuring the electron donating abilities of NHCs were conducted using CuI and AgI cyanide complexes as probes. The outcomes of this research may contribute to the growing research in the applications of NHCs as ligands in catalysis.

Author Keywords: Catalysis, Ligand synthesis, N-Heterocyclic carbenes, Organic Chemistry, Organometallic Chemistry, Transition metal catalysis

Giardia intestinalis is a parasitic protozoan that possesses a flavohemoglobin (gFlHb), an enzyme that plays a role in the detoxification of reactive nitrogen species (RNS) and reactive oxygen species (ROS) via its nitric oxide dioxygenase (NOD) activity as well as its NADH-oxidase activity. This enzyme is a potential target for imidazole-based antigiardial drugs that act as ligands of the iron within its heme cofactor. In this work, two rapid and relatively inexpensive assays, the colorimetric Griess assay and a fluorescence assay, were adapted, optimized, and implemented to screen for flavohemoglobin inhibitors in parallel studies that compared the response of gFlHb to that of Hmp (Escherichia coli flavohemoglobin) when a group of six different imidazole-based compounds was tested. These assays displayed isotype selectivity, showing how the different drugs elicited different responses from the two enzymes. Comparative results for gFlHb and Hmp revealed that bulkier compounds elicited higher inhibition of Hmp, while smaller compounds resulted in better inhibition of gFlHb, which might be explained by the presence of different amino acid residues in the active sites of the enzymes, with two large amino acid sequence inserts being a unique feature of gFlHb, thus blocking the active site from being reached and blocked by larger compounds.

Author Keywords: 2.3-diaminonaphthalene, Flavohemoglobin, Giardia intestinalis, Griess Assay, imidazole-based drugs, nitric oxide detoxification

Innovative strategies to manage copious waste streams by upcycling feedstocks to valorized products which are then used in environmental remediation applications is an attractive circular economy model. This thesis explores this approach using waste wood generated from the milling of Chlorocardium rodiei (greenheart), a tropical hardwood species abundant in Guyana. We evaluate the thermochemical conversion of this feedstock, using phosphoric acid as the activant, to super activated carbons with surface areas of more than 2200 m2/g. Owing to the presence of surface heteroatoms, these adsorbents are amenable to further surface modifications including base-treatment, O-functionalization and N-functionalization. Using a facile oxidation procedure and shrimp waste-based dopants, we increase oxygen and nitrogen content by 8-fold and 5-fold respectively. These increases are realized without catastrophic loss of surface area and porosity as generally occurs with many reported functionalization approaches. Functionalized materials demonstrated efficient removal of both metal ions and the chlorinated herbicides 2,4-dichlorophenoxy acetic acid and paraquat. Pristine and base-washed ACs removed more than 90% of iron, aluminum and manganese from natural pit-lake waters. O-functionalized adsorbents also showed excellent removal efficiencies for aluminum and lead but only removed moderate amounts of manganese. Nitrogen-enriched composites fabricated with the addition of commercial chitosan removed 67% 2,4-D and 89% paraquat from model solutions at environmentally relevant concentrations of 4 ppm and 40 ppm respectively. Their versatility is further demonstrated in their ability to remove both herbicides from binary mixtures albeit to different extents. Shrimp chitin-based composites were most effective at removing 2,4-D from model solutions with a maximum adsorption capacity of 101 mg/g. Both surface area and surface nitrogen had strong influences on the adsorption capacity of adsorbents. Mechanistically, physisorption interactions predominate the synergistic or antagonistic interaction between N-functionalized composites and herbicide species. These green adsorbent materials, fabricated from sustainable biopolymers, are promising candidates for diverse environmental remediation applications.

Author Keywords: adsorption, Environmental remediation, N-functionalization, O-functionalization, tropical hardwood waste, waste valorization

This thesis describes the preparation, optimization, functionalization, and characterization of activated carbon materials sourced from a petroleum coke feedstock for the tailored removal of heavy metal species in contaminated waters. The goal of this work is to develop an understanding of the mechanisms that drive adsorption of heavy metals onto activated carbon surfaces. By determining the mechanisms that drive adsorption, activated carbon materials can be modified to increase the efficiency of the adsorption process. The novelty of this work comes from the use, modification, and functionalization of activated carbon derived from petroleum coke, a waste by-product of the oil-sands extraction process, a source not prevalent in current literature. The novelty also comes from the determination of the methods by which heavy metals are adsorbed onto the given adsorbate as literature does not focus on the mechanisms themselves. The work presented sheds light on the specific adsorption mechanisms, with the aim of elucidating how a given material's surface can be enhanced to target a specific analyte. This work focused on the use of microwave plasma atomic emission spectroscopy (MP-AES), x-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller theory (BET) to obtain the necessary data required for the determination of adsorption mechanisms, adsorption capacities, and surface characterization of the materials. MP-AES is used for the determination of the adsorption capacity of the materials produced. Surface characterization of the materials was done using XPS, and surface area and pore size distributions were determined using BET for surface area determination and nitrogen adsorption measurements following density functional theory for pore size distribution determination. XPS of the activated carbon post-chromium and post-arsenic adsorption show a reduction of the metals from chromium (VI) to chromium (III) and from arsenic (V) to arsenic (III). By increasing the amount of hydroxyl functional groups on the AC surface through a simple thermal-treatment, the chromium adsorption was increased from 17.0 mg/g to 22.4 mg/g. By loading a reducing agent onto the activated carbon surface, an increased number of potential binding sites for the arsenic are loaded onto the AC surface and the adsorption of arsenic increased from 8.1% to 51%.

Author Keywords: Activated Carbon, Adsorption, Adsorption Mechanisms, Arsenic, Chromium, Petroleum Coke

This thesis presents the design, synthesis, and evaluation of activated carbon polyacrylamide (AC-PAM) composites for oil sands tailings remediation, integrating flocculation and adsorption functionalities. Surface-initiated atom transfer radical polymerization (SI-ATRP) was employed to graft high molecular weight PAM brushes onto petroleum coke and commercial activated carbon, with SARA-ATRP yielding the most uniform architecture (Mn ≈ 5.2 kg/mol, Đ ≈ 1.25). Flocculation tests using mature fine tailings (MFT) revealed superior sedimentation and dewatering with SARA-ATRP composites, outperforming conventional PAM at lower dosages. Adsorption studies using benzoic acid and model naphthenic acids showed selective uptake governed by polymer brush morphology and molecular structure, with Dubinin–Radushkevich isotherms best capturing the behavior of ARGET-ATRP composites. Post-flocculation assays confirmed reduced metal and polymer contamination, validating dual-function efficacy. These findings underscore petcoke's viability as a sustainable substrate and highlight controlled polymerization as a critical driver for tuning composite performance in industrial water treatment.

Author Keywords: Activated Carbon, Adsorption, Atom Transfer Radical Polymerization, Dubinin–Radushkevich, Isotherm, Polyacrylamide