The mortality rate of cancer establishes it as a leading global health concern, prompting significant investment into cancer research. While the effects of cancer are well known, the understanding of specific sources of cancer therapy resistance are not. In this study, our goal was to develop innovative methods to address current shortcomings in cancer treatment and understanding. To do this, we studied exosome-mimetic nanovesicles as an immunotherapeutic platform and fluorescence lifetime imaging as a means to measure cancer-associated enzyme activity at a single cell level.

Through the use of a novel method of production, we generated nanovesicles from dendritic cells in high yields and leveraged the antigen-presenting and costimulatory properties of dendritic cells for induction of a T cell immune response. We demonstrate that these nanovesicles are able to present antigens in functional immune stimulatory complexes and retain parental ability to activate CD8+ T cells. Additionally, these nanovesicles were shown to mediate activation of T cells through indirect means. Here, nanovesicles are taken up by bystander dendritic cells, thereby delivering antigen to the dendritic cell and conferring T cell stimulatory capability. Next, we investigated the application of fluorescence lifetime imaging to measure cancer-associated cytochrome P450 enzyme activity at the single-cell level. We demonstrated this approach provides detailed insights into cellular heterogeneity and localized enzyme activity. Additionally, we showed that sensitivity and dynamic range can be tuned to enzyme activity and levels by altering excitation and emission wavelengths.

These advancements offer new and promising avenues to enhance nanoparticle-based immunotherapy and understanding of the role of enzyme activity and cellular heterogeneity in cancer progression. Ultimately, the methods developed contribute to improving therapeutic strategies and personalized medicine.

Metal halide perovskites have gained interest in optoelectronic applications such as photovoltaics, lasers, LEDs, transistors, and photodetectors due to their excellent semiconducting properties considering their low cost. Metal halide perovskite (HP) photovoltaics have rapidly increased in power conversion efficiency (PCE), which now exceeds 25%. HPs have gained attention in these applications due to their high tolerance towards defects, long charge carrier diffusion lengths, high charge carrier mobility, high optical absorption, and bandgaps that are tunable over a large range. Even though HP photovoltaic PCEs are improved these are still not commercially available due to them showing lower stability and energy loss due to severe charge recombination at the surface and interfaces in the device . Treating the HP surface with surface ligands has become a promising approach to improve photovoltaic performance, defect passivation, and interfacial energetics. In this dissertation,  the influence of ammonium functionalized p – conjugated ligands on MAPbI3 perovskite energetics, photovoltaic performance, and interfacial charge transfer is investigated. With the thiophene ligands, a drastic PCE drop was observed for p-i-n devices, and improved PCE was obtained for n-i-p devices. With PDI surface ligands no significant change was observed for photovoltaic performance.  Two-dimensional metal halide perovskites (2D HP) have captured interest in the field due to their improved stability against air, moisture, and light relative to their 3D counterparts. 2D HPs have a layered structure, where the organic spacer cations are sandwiched between layers of inorganic octahedra. This organic layer in 2D HPs adds additional protection against moisture and oxygen ingression and other degradation pathways . These materials are used as the active layer in LEDs and solar cells and as capping layers in 3D HPs. 2D perovskites demonstrate remarkable structural variabilities, where the properties can be modified by changing the layer thickness, the halide anion, and the spacer cation. To make devices with 2D perovskites we need to understand the influence of the organic spacer cations on the optoelectronic properties of these materials . In this work, we  investigate the influence of the dipole magnitude and the direction of a series of functionalized PEAI derivatives as organic spacer cations on the ionization energy and the electron affinity of 2D tin halide perovskites. However, determining ionization energy and electron affinity in HPs could be quite difficult as several methods are being used in data interpretation for HPs . In this work, we propose a method to assign the energy levels in 2D HPs by correcting for the instrumental resolution in ultraviolet and inverse photoemission spectroscopy.

The current standard of care (platinum-based drugs) for the treatment of different forms of malignancy have been very effective in the clinic, however the negative side effects associated with the administration of these platinum based-drugs remains an unsolved problem. Gold based molecules are among a few metal complexes that have been developed over the years in search for better chemotherapy drugs. While the anticancer mechanism of action of platinum-based drugs is well known to involve DNA damage, the mechanism of action of gold based small molecules remains a subject of debate. It is understood that gold-based complexes exhibit non-cisplatin like anticancer mechanism of action, hence the potential to overcome resistance seen in patients with recurrent tumors after initial remission with platinum-based drugs. Herein, we report efforts to elucidate the mechanism of action of novel gold-based anticancer agents with very potent inhibitory effect against triple negative breast cancers and ovarian cancer. A recurring observation from the mechanism of action studies is the perturbation of mitochondria physiology by these complexes. These includes; perturbation of mitochondria bioenergetics, depolarization of mitochondria membrane potential of the cells, increased mitochondria ROS production, depletion of mitochondria DNA, and disruption of mitochondria dynamics. Modified versions of the lead molecules were developed as probes to monitor in vitro localization of the complexes and facilitate elucidation of the mechanism of action. Target identification studies with a biotinylated lead complex unveiled heme oxygenase 2 (HMOX2) as a novel target in gold medicinal chemistry. Preliminary target validation studies revealed for the first time, HMOX2 as an upstream regulator of the MYC proto-oncogene. These findings uncover a new strategy for targeting tumor cells and reinforces the belief that small molecules can serve as probes to interrogate the complex cancer biology system and unveil new strategies for development of better chemotherapeutic agents.

Anaerobic bacteria and archaea thrive in seemingly inhospitable environments because they are extremely energy efficient. Their efficiency is based in large part on their ability to conduct electron transfer bifurcation ('bifurcation') at strongly reducing potentials, thereby producing extremely potent reducing agents able to fix nitrogen and make molecular hydrogen. This chemistry is made possible by the use of a flavin as the site of bifurcation, supported by a specialized protein environment and mechanisms that control the flow of individual electrons.

Bifurcating electron transfer flavoproteins (Bf-ETFs) are versatile protein modules that provide the bifurcating capability associated with several metabolic functions. Bf-ETFs enable use of low-energy electron reserves such as NADH to charge the carriers ferredoxin and flavodoxin with high-energy electrons. Bf-ETFs possess two flavin adenine dinucleotide (FAD) cofactors. The bifurcating FAD (Bf-FAD) receives two electrons from NADH, and distributes them through two distinct pathways. One pathway involves exothermic electron transfer to a high- potential acceptor via the second FAD, the ET-FAD (electron transfer FAD). This provides the driving force to send the second electron to a lower potential (higher-energy) acceptor.

Investigations described herein elucidated the crystal structure and internal dynamics of flavodoxin (Fld), a high-energy acceptor in the bifurcation process. 19F NMR was used to examine conformational heterogeneity and dynamics of Fld free in solution, to characterize the flexibility of a 20-residue stretch of Fld's peptide chain that is believed to mediate interaction between Fld and ETF. Temperature-dependent NMR studies, alongside paramagnetic relaxation investigations comparing Fld in both its oxidized and semi-reduced forms, detailed internal dynamics pivotal to Fld's interactions with diverse partner proteins.

Complementary research explored conformational dynamics of ETF, employing small-angle neutron scattering (SANS). This revealed notable divergence from published structures, demonstrating presence of a more extended conformation in solution. Significant reduction- triggered conformational change was also discerned via SANS by comparing the fully oxidized and reduced states of ETF. Molecular dynamics simulations-based data modeling suggests coexistence of multiple ETF conformations, ranging from extended to compact, in solution.

Finally, conformational consequences of complex formation between ETF and a partner protein were examined. We demonstrated isolation of a complex between ETF and its high- potential acceptor butyryl CoA dehydrogenase (BCD). Innovative application of segmental deuteration of BCD in combination with SANS, enabled comprehensive insights into the conformational adaptations made by ETF upon complex formation. Contrast variation SANS, utilizing 80% deuterated BCD, was used to identify the match point, paving the way for advanced analysis of the complex's structural dynamics.

This work enriches comprehension of the roles played by dynamics in bifurcation, and advances new technical approaches for future explorations of conformational changes within multidomain proteins.

Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs in recent years, cancer continues to be a leading cause of mortality in the United States. Metallodrugs, especially gold complexes, have played a prominent role in the search for the next generation chemotherapeutic agents. Herein, I report on the synthetic strategies proffered towards rational design of stable gold-based agents, studied their reactivity in biological environment and proffer insights into the cytotoxic mechanism of action in diseased and normal cells. Stable gold complexes exist mostly in +I or +III oxidation states. Research into Au(I) complexes has overshadowed Au(III) complexes due to the reemergence of auranofin for treatment of other conditions including cancer. 

Despite been isoelectronic to cisplatin, Au(III) complexes exhibit different chemistry, reactivity, and molecular target compared to their platinum counterpart. My work has developed synthetic tools exploring the use of chiral bisphosphine ligands (Quinox P*) to synthesize cytotoxic Au(III) bisphosphine enantiomers that show similar response when administered to cancer cells. Further studies on chiral bisphosphine ligands using R-DuPhos ligands (where R is methyl or isopropyl) identified for the first-time products from the speciation studies of chiral Au(III) complex with L-glutathione (L-GSH), a biological reductant in cells. Furthermore, I carried out structure activity relationship studies with bisphosphine ligands. Thus, reacting different bisphosphines with di-µ-chlorido biphenyl digold(III), gold(III) bisphosphine complexes were obtained with the phosphine backbone or side chains dictating stability and reactivity. The complexes showed very high physiological stability in L-glutathione while also demonstrating serum stability for 24 h. Further mechanism studied showed that compared to cisplatin, these complexes act as mild mitochondria uncoupler comparable to other protonophores such as FCCP. This, to the best of my knowledge is the first Au(III) mitochondria uncoupling agent. Also, I studied the impact of degree of cyclometallation on two set of cyclometalated gold(III) complexes bearing either a phenylpyridine (C^N) or biphenyl (C^C) Au(III) backbone. While the neutral C^C complexes showed improved electrochemical and biological stability (in L-glutathione), they showed lower cellular responses in cancer cells when compared to the C^N counterpart. Furthermore, longer alkyl chain complexes were not soluble in biological media. To overcome physicochemical barriers encountered in long alkyl chain gold(III) dithiocarbamate, encapsulation with bovine serum albumen was carried out. This resulted in improved solubility, cytotoxicity, and cellular uptake of the drug into cancer cells

Nanomaterials are widely used in a variety of applications such as opto-electronics, energy production and storage, and bio-medical applications due to their unique optical, catalytic, electronic, and mechanical properties. Most of the nanomaterials offer a plethora of modifications in their structure, composition, morphology, and dimensionality that can lead to the manipulation of their physiochemical properties. Thus, this dissertation presents insight into two types of compelling nanomaterials: carbon nanodots (CNDs) and transition metal dichalcogenides (TMDs), investigating their optical and electrocatalytic properties respectively.   Carbon nanodots (CNDs) are a promising class of photoluminescent nanomaterials that hold a significant potential in many optoelectronic applications. The photoluminescence behavior of CNDs highly depends on their structure and chemical composition. The complexity of the structure and chemical composition of CNDs makes it difficult to uncover the origin and behavior of the photoluminescence of these materials. Hence, this work first provides fundamental insight into the photoluminescence of low-oxygen-content CNDs derived from polycyclic aromatic hydrocarbon pyrene. In this study, the formation of bright emitting molecular fluorophore was identified through a rigorous separation scheme using column chromatography and solvent-induced extraction. Further, the distinct structure and optical properties of the molecular fluorophore  and CNDs were identified using different structural and morphological characterization techniques and bulk fluorescence measurements.  Transition metal dichalcogenides (TMDs) are another intriguing class of nanomaterials that are abundant and cost-effective alternatives to expensive and precious electrocatalysts for various electrochemical reactions. 

TMDs can be modified by changing their phase and dimensionality, and their layered nature makes them suitable for heterostructures. Consequently, TMD nanostructures have gained attention as electrocatalysts for hydrogen evolution reactions (HER) due to the increasing demand for low-cost green hydrogen production. Thus, secondly, a greener and reliable top-down synthesis approach for producing highly exfoliated ultrathin crystalline WS2 nanosheets using a modified liquid phase exfoliation is presented in this work. The ultrathin pristine WS2 nanosheets showed a promising electrochemical activity for HER, and the correlation between the structure and the electrocatalytic activity was carried out through Operando Raman spectro-electrochemical measurements. Further, TMD nanostructures are excellent candidates to use as support materials for metal single atom catalysis (SACs). Pt single atom catalysts (SACs) supported on transition metal dichalcogenides (TMDs) are promising electrocatalysts in the green hydrogen production by proton exchange membrane (PEM) water electrolysis. Hence, thirdly this study presents a novel and a convenient synthesis of Pt SACs and clusters supported on WS2 (Pt/WS2) using photonic curing, with improved efficiency for hydrogen evolution reaction (HER). This catalyst design constitutes enhanced atomic utilization, higher number of accessible active sites and catalytic activity modulation of Pt through electronic metal support interactions (EMSI). This work as a whole provides insight on the fundamental aspects of intricate properties of two types of nanomaterials in unveiling the correlation between structure, properties, and application.

The increasing atmospheric CO₂ concentration causes significant concern about global warming and its environmental impact. Industrial sectors, including power generation, transportation, and production factories, contribute most of the anthropogenic sources of CO₂ emissions. Researchers search for methods to mitigate these CO₂ emissions without compromising the benefits of industrial processes, including CO₂ capture, utilization, and sequestration (CCUS). Post-combustion carbon capture (PCCC) by amine scrubbing is the most technology ready CCUS, with various pilot-scale projects worldwide showing small-scale to fully operational plants. While researchers have made significant progress in amine scrubbing, they strive to improve the efficiency and economics of these plants. One challenge they face includes solvent degradation due to flue gas constituents and temperature effects. 

            This dissertation focuses on the degradation byproducts' impact on the parent amine solvent. It explores knowledge about degradation byproducts in amine solvents used in carbon capture, including what degradation products, how much, how they form, and what impact these products have on the capture process. The dissertation splits into three sections where the first focuses on three thermal degradation byproducts of ethanolamine (MEA): oxazolidine-2-one (OZD), N-(2-hydroxyethyl)-ethylenediamine (HEEDA), and N-(2-hydroxyethyl)-imidazoline-2-one (HEIA) interactions in the solvent. The second focuses on O₂ solubility and the role O₂ plays in oxidative degradation. The final section discusses some initial degradation results of a new class of amine carbon capture solvents called water-lean (WL) solvents. 

            The discussion of the thermal degradation byproducts began by describing thermal degradation byproducts that react with CO₂ with and without the parent amine present. The species found were explored further at the liquid-vapor barrier to explain how the species interact with each other. The degradation byproducts with unhindered primary or secondary amines, such as HEEDA, create a pseudo-blended solvent that could improve the solvent's capture performance as it improves the CO₂ solubility in the amine solvents. In contrast, hindered structures like HEIA and OZD will minimally impact the speciation in the amine solvents. However, these species revert to the carbamate at lower CO₂ concentrations or higher temperatures and further react with CO₂ concentrations. 

            The discussion on O₂ solubility in the different amine solvents and the role O₂ plays in oxidative degradation began by validating a dissolved oxygen (DO) electrochemical probe by redox titrations following the Winkler method. The validated probe then measured the DO or O₂ solubility in different amine solutions under various conditions found in CO₂ capture. It also explored how additives used in advanced amine solvents impact the O₂ solubility in the solution. The redox titration measured the DO slightly higher than the probe, validating the electrochemical probe for amine solvents. However, solvents with transition metals that can oxidize iodine cannot use this method to measure the DO in the solvents. In the amine solvents, the diamines measured higher O₂ solubility than the alkanolamines, and the alkanolamines measured higher O₂ solubility than the amine diols. In addition, as the number of hydrogens bonded to nitrogen decreased, the O₂ solubility decreased. The ionic effect on O₂ was also demonstrated, where the DO decreased with increased CO₂ loading. However, there was still DO, indicating that the solvents will undergo oxidative degradation at high loadings. Furthermore, the solvents minimally impacted the O₂ solubility except those that can react with CO₂. The additive 2-mercaptobenzathiazole (MBT) decreased the DO concentration until it exhausted its capacity to react with O_2, and then the DO rose back to the levels at equilibrium. The additive sodium metavanadate increased the DO concentration because metavanadate can react with O₂, increasing the oxidative potential in the solution. The final section described the initial findings of degradation byproducts of WL solvents and what the organic cosolvent does in the system, including some initial discussions on how the organic cosolvent impacts an amine solvent, how the solvent phase separates at higher loadings due to an ionic effect in the cosolvent, and what compounds were found during oxidative degradation experiments.

KEYWORDS: Carbon Capture, Amine Scrubbing, Degradation, Amine Oxidative Degradation, Amine Thermal Degradation, Water Lean Solvents

The long-anticipated implementation of using renewable sources such as solar and wind to meet the world’s energy demand is still limited by not having appropriate grid-level energy storage systems on a global scale. When considering grid-scale energy storage solutions, environmental concerns, and techno-economic viability play a crucial role in the practical implementation of such technology. To address this, redox-active organic molecules (ROMs) have been explored for many uses including serving as redox-active molecules in redox flow batteries (RFBs) and providing overcharge protection in lithium-ion batteries (LIBs). Nevertheless, in order to be a major player in electrochemical energy storage, further optimization of ROMs with respect to performance and stability is required. Achieving optimum performance and stability mandates a molecular-level understanding of the interactions between chemical compounds, solvent molecules, and any other supporting solutes in the medium. Hence we approached this research question in the context of redox-active organic molecules for non-aqueous redox-flow batteries (NARFBs) by narrowing down the chemical space to a few classes of molecules. Herein, we extensively studied it from multiple perspectives such as; (1) Examining the correlation of molecular structure of redox-active organic molecules (ROMs) to solubility at different states of charge using quantitative structure-property relationships (QSPR), (2) Investigating the effect of electrolytes (counter-anions) on the solubility of ROMs using molecular dynamics (MD) simulations interfacing with experiments and multiple linear regression, (3) Exploring the concentration dependence of electrolytes with MD to explain experimental behavior at very high concentrations and to identify optimum concentration ranges for NARFBs, and (4) Probing Bulk and Interfacial Interactions of ROMs in complex solutions under an applied potential using classical MD simulations. This multi-approach endeavor has informed us of the strengths and limitations of predictive modeling in non-trivial molecular systems with limited data and high variability and boundaries related to improving the solubility of ROMs using structural modifications. Thus, in our continued efforts, we discovered that the solubility of these ROMs can be dramatically improved up to three-fold by switching the counter-anion due to the flexibility and size of the counter-anions. Our exploration of high-concentrated electrolytes implies that changes to supporting electrolyte concentration are significantly more impactful to the solution’s transport properties with the crowding of electrolytes leading to non-Newtonian fluid-like regimes. Expanding classical MD simulations to capture bulk and interfacial properties opens up a new paradigm of using computationally less-expensive methods for high-throughput simulations. To address the limitations we encountered in this effort, we also developed systems to automate similar MD simulations and analyses with the goal of producing large datasets that may pave the path to generating machine-learning models to predict different performance matrices efficiently in the future. In summary, the results and theoretical insights gained through these collective efforts would set the foundations for optimizing the performance and stability of ROMs thus helping experimentalists design better materials for electrochemical energy storage.

Conjugated polymers (CPs) are an emerging class of materials that are attractive for many applications due to their low cost, flexibility, and ease of processing. Both chemical and electrochemical doping of CPs is done to alter important properties such as their electrical conductivities and optical absorbances. This ability to tune their properties allows for their use in devices such as organic electrochemical transistors (OECTs) for biosensing and bioelectronics, electrochromic devices for color changing windows, as well as wearable thermoelectrics to use body heat to power wearable electronics. There are several factors that can influence the properties of doped CPs including doping level, film morphology, and the dopant or counterion used in the process. One disputed topic is what influence the ion size within the electrolyte has on the properties of electrochemically doped CPs. These ions balance the positive or negative charges on the backbones of doped CPs and their size can influence their interactions with the charge carriers and the overall morphologies of the films, therefore influencing their optical and electronic properties. This dissertation focuses primarily on understanding the influence of anion size on the properties of doped CPs as a function of their respective doping level. 

            The work presented here first focuses on the electrochemical doping ability of two benchmark CPs regioregular and regiorandom poly(3-hexylthiophene), rr- and rra-P3HT respectively, in electrolytes with anions of different sizes. Films of rr-P3HT are semicrystalline while those for rra-P3HT are amorphous allowing us to probe anion size as a function of CP morphology. Measured oxidation potentials and UV-vis data suggest that the larger anions are positioned further from the backbone of the polymer with two distinct polaron/bipolaron transitions apparent for rr-P3HT and only one for rra-P3HT. Further investigation into these materials as a function of doping level shows two distinct regimes that are important to consider. In the low doping regime, Coulombic interactions with the CP backbone and counterion largely contribute to the film’s properties with the larger anion having a higher electrical conductivity and lower Seebeck coefficient than the smaller and more Coulombically bound anion. Alternatively, in the high doping regime all charges are essentially “free” and CP morphology has the largest impact on film properties. In this case, the larger anion is more disruptive to the film morphology granting a lower electrical conductivity but higher Seebeck coefficient. At all measured doping levels, the films with the larger anions display higher thermoelectric power factors, proving that counterion size is an important consideration for these devices. 

According to the center for disease control (CDC), an estimated 1.7 to 2.2 million persons die from waterborne diseases annually. The majority of individuals dying from diseases resulting from unsafe drinking water, such as diarrhea and gastroenteritis, are children. This has in turn created a global water crisis. Different methods have been developed to treat contaminated water in response to the global water crisis such as adsorption, filtration, ozonolysis, catalysis, etc. Of the methods available, filtration via polymeric membranes has been one of the most successfully applied. A membrane is a thin semi-permeable barrier (often made of a polymer) used to separate differing phases in a media under pressure. Membrane filtration is ideal for water treatment due to high rejection and throughput, as well as ease of integration into other water treatment systems. Unlike other methods of water treatment, membrane filtration can be easily tuned to target specified contaminant at different size and pressure levels.