The health of our communities depends on the effective treatment of both solid and liquid waste to eradicate hazardous pollutants before they can interact with living organisms or contaminate the environment. Daily, society generates solid waste (commonly destined for landfills) and liquid waste, (commonly discharged into wastewater systems) and without proper treatment, these wastes can release hazardous primary secondary pollutants. Industries producing wastewater with high pollutant concentrations, especially those utilizing lignin-based biomass, face complex challenges because each facility may require a tailored treatment approach. In response, this work investigates the use of ozonolysis to transform lignin monomers into smaller, less hazardous components that can be more efficiently managed by public wastewater systems. Furthermore, while conventional wastewater treatment systems are effective for common water quality issues, they can inadvertently allow complex compounds, such pollutants from hospital effluent, to pass through. Under simulated treatment conditions incorporating sunlight and chlorination, a pollutant released from medical facilities is degraded, but this process may also lead to the formation of carcinogenic disinfection by-products (DBPs) that pose direct toxicological risks to nearby communities. The implications extend to solid waste management as well. Chemical phenomena, such as those occurring in poorly understood elevated temperature landfills (ETLFs), can compromise treatment methods and increase community exposure to harmful pollutants. By monitoring hazardous components, such as volatile organic compounds (VOCs), over time, this work aims to elucidate the chemical reactions occurring both during treatment and in the environment thereafter. Ultimately, this research underscores the need for fundamental, innovative approaches to pollution transformation. Bridging the gap between existing practices for solid and liquid waste treatment will be critical to safeguarding environmental and public health.

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Biorefineries play a vital role in reducing dependence on fossil fuels and addressing global warming concerns. Unfortunately, investment in biorefineries remains limited due to economic sustainability concerns. One approach to enhance the economic viability of biorefineries is by fully utilizing the potential of feedstocks, particularly lignocellulosic biomass, which is commonly used in these processes. Traditional processing methods often alter the lignin portion of biomass, making it unsuitable for further utilization. However, when retained in its native form, lignin can serve as a valuable source of chemicals that contribute to the economic sustainability of biorefineries.

The lignin-first approach, which removes lignin from the cellulosic portion before biofuel conversion, allows for the recovery of value-added chemicals from lignin and enhances the sustainability of biorefineries. One common method for implementing this approach is organosolv, which removes the lignin from biomass. This research developed an organosolv pretreatment method to isolate syringaresinol (S-β-β'-S), a lignin-derived dimer with various biomedical and industrial applications, from oak sawdust as the source biomass. The method incorporated a heat treatment step to increase syringaresinol yields, and key treatment parameters were optimized for maximum output. This approach was then applied to other biomass types: hardwood, softwood, and grass. Poplar and hemp were identified as alternative sources of syringaresinol. The method also revealed the presence of several other potential value-added compounds in the biomass types investigated.

Additionally, this research established a linear retention index (LRI) for the gas chromatographic (GC) analysis of 25 common lignin-derived monomers and dimers, which are frequently detected in biomass chromatograms after pretreatments like organosolv. LRI values are independent of column characteristics, enabling unambiguous identification of analytes and ensuring reproducibility in experimental results. These calculated values were validated with a second GC system. The LRI facilitates the identification and confirmation of compounds without the need for mass spectrometric (MS) analysis, allowing for comparison of chromatographic results across multiple GC systems and aiding in the prediction of retention times for these compounds.

While extracting value-added compounds like syringaresinol from biomass is the first step, recovering them from complex reaction mixtures presents additional challenges. This study explored the use of cyclodextrins (CDs) as potential recovery materials for syringaresinol. CDs are conical molecules with a hydrophilic exterior and a hydrophobic cavity, which can selectively capture lignans through guest-host complex interactions. Initial high-performance liquid chromatography (HPLC) analysis with a commercial β-CD column revealed that lignans, particularly syringaresinol and pinoresinol interact more strongly with β-CD than with most other monomeric lignin decomposition products. Furthermore, the study suggested that γ-CD might be a better recovery material for syringaresinol compared to β-CD. To test this hypothesis, a modified frontal analysis continuous capillary electrophoresis (FACCE) method was developed and validated as an inexpensive, simple approach to estimate the binding constants of lignans to CDs. The FACCE method provided insights into the interactions between lignans and CDs, facilitating the selection of the potentially suitable CD-type for recovery.

Gold(I) complexes typically bond in a linear fashion; however, an increased valence can be achieved via ligand modulation. The most prevalent therapeutic gold complex, auranofin, contains a linear Au(I) center and has shown great potential in several diseases and conditions. On the other hand, the potential of three-coordinate Au(I) complexes have scarcely been probed as therapeutics. Reported here are the synthesis, characterization, and applications of novel three-coordinate Au(I) complexes. The degree of asymmetry varies between complexes depending on the Au-X ancillary ligands. This insight suggests that the degree of asymmetry influences the potency when incubated in various cancer cell lines. In addition, the coordination of bidentate phenanthroline ligand derivatives effect the symmetry by inducing varying degrees of distortion in the crystal structure. When the center Au(I) is bound to an N-Heterocyclic Carbene (NHC), the compound shifts from a distorted trigonal planar geometry to a distorted linear geometry. These complexes were used to probe glioblastoma, an aggressive head-and-neck cancer. When the center Au(I) is bound to biaryl dialkyl phosphine ligands, the geometry varies in symmetry, but the distorted trigonal planar geometry remains intact. Structure activity relationship studies were performed on these complexes in triple negative breast cancer cell lines. Previous research shows a disruption of mitochondrial dynamics when cancer cells were treated with three-coordinate Au(I) complexes, and the novel Au(I)-NHC library indeed disrupts mitochondrial dynamics. Mitochondria are the main energy production centers in the cell and are desirable therapeutic targets due to their implication in aging, inflammation, and cancer. The Au(I)-P library shows little mitochondrial disruption; instead, these complexes induce significant stress in the endoplasmic reticulum. The endoplasmic reticulum transports and folds proteins that allow the cell to function properly and synthesizes lipids and cholesterols. When the endoplasmic reticulum undergoes stress, the several signaling pathways, known as the unfolded protein response, activate, which can lead to lipid accumulation. Both a disruption of mitochondrial dynamics and an induction of endoplasmic reticulum stress can lead to apoptotic cell death. These effects were characterized by several in vitro and in vivo experiments. 

Carboranes are electron-delocalized clusters containing as few as five and as many as fourteen boron and carbon atoms, the majority of which contain two cage carbons. The carbons in the cluster can be easily functionalized with alkyl and aryl phosphines for coordination to metal complexes. Described here is the synthesis of phosphine-functionalized carborane (DPPCb) containing three-coordinate Au(I) complexes. Taken as a whole, this work expands on the current three-coordinate gold(I) libraries and evaluates their in vitro and in vivo biological efficacy.

Organic metal halide perovskites (HPs) are attractive materials for a variety of electronic applications due to their low cost, tunable band gaps, excellent charge transport properties, and high photoluminescence efficiency. As such, HPs are being investigated for use in solar cells, photodetectors, X-ray detectors, light emitting diodes, field effect transistors, lasers, resistive random-access memory, etc. Currently the most popular metal used in HPs is lead, but the use of lead comes with the potential for heavy metal exposure. Tin-based perovskites offer a less hazardous alternative, but their optoelectronic properties lag behind those of lead and less work has been done to characterize them. In this work, we investigate Ruddlesden-Popper Phase (RPP) tin perovskites with phenethylammonium and its derivatives to determine how the structure of the A*-site cation impacts the optical and electronic properties.

Lignin is a complex aromatic biopolymer and an important constituent in plant cell walls. The process of lignin biosynthesis, known as lignification, is poorly understood and challenging to study but has important implications in a variety of fields including sustainable energy, bioengineering, and materials science and is therefore of interest to pursue. In the final stage of lignification, H-, G-, and S-monolignols are oxidized by laccase and peroxidase enzymes to generate radical species that couple to form dimers and further oligomeric species to ultimately produce the lignin polymer. Biomimetic lignin model systems utilize in vitro oxidative coupling reactions as an important tool to further develop our understanding of this complex process. The goal of the first portion of this dissertation was to explore several aspects of monolignol oxidative coupling using high performance liquid chromatography (HPLC). These aspects included the study of relative reaction rates, both with respect to monolignol conversion and product formation, and the effects of solvent composition on product distribution. Electrospray ionization mass spectrometry (ESI-MS) was an important analytical tool for characterizing many coupling products, especially higher oligomeric compounds. The insights acquired from these experiments contributed valuable information towards a fuller understanding of the lignification process.

Plant secondary metabolites are a vital source of medicinally relevant compounds. These metabolites are involved in the plants’ highly dynamic chemical defense against environmental stressors such as UV light, predators, and pathogens. Elicitation is a process in which changes in plant secondary metabolism are induced by specific stressors to understand metabolic pathways involved in plant defense. The second portion of this dissertation focused on the study of metabolism, known as metabolomics. Methods development for sample preparation and data processing in untargeted metabolomics was applied to study elicitation of secondary metabolites in Lobelia Cardinalis hairy root cultures. This study specifically explored the potential of nanoparticles as a delivery system to enhance the elicitation effects of jasmonic acid. In this work, UHPLC-MS with high resolution accurate mass was used to evaluate the secondary metabolic response of L. Cardinalis hairy root cultures to jasmonic acid-loaded nanoparticles.

With the continuing rise in demand for energy, it is becoming increasingly necessary to invest more effort into the research and development of new materials that generate or harvest energy. One avenue of materials science is continued research into perovskites, a class of materials having a similar structure to its namesake mineral, which has seen use in piezoelectrics, photovoltaics, and sensors. An adaptation of perovskites; hybrid organic-inorganic materials/metalates, referred to here as HOIMs or just simply as halometalates, have been promising alternatives to traditional perovskites. Derived from the perovskite A2+B4+(X-2)3 formula, HOIMs following the A2+Bn+Xn+2 format where A represents the organic cation, B the metal cation, and X the halide anion are synthesized from a combination of organic and inorganic components which allows for deviations from the stricter crystal structure of the perovskites. These organic components allow for lower temperature requirements and solution processability, making them promising materials with a low barrier of entry. Because of this versatility in synthesis and structure, the corresponding tunability of their constituents provides an excellent avenue of approach for the development of novel, task-specific HOIMs the physical, optical and electronic properties of which could be carefully controlled for. While there has been and currently is research being done to elucidate the tuning of individual changes to the various cation and anion sites within halometalate materials there remains a need to combine these various approaches together into a cohesive manual for the design and fabrication of these materials for future use. The hypothesis upon which this work is structured lies in that tying together of the disparate structures which have been shown to exhibit tunability before. That is the ability to individually yet cotemporally alter specific structural characteristics of an HOIM in such a way as to select for a unique combination of performant traits, and in so doing show a verifiable, reproducible methodology. This work investigates several promising halometalate materials whose similar structures allow for simple, stepwise alterations with the intent of measuring the effect these changes have on their physical arrangement and nonlinear properties.

Graphene and other two-dimensional (2D) materials exhibit remarkable electronic, thermal, and optical properties that can be tailored by material selection, structural design, and the incorporation of transition metals. This study explores graphite intercalation compounds (GIC) via sonication techniques and extends the approach to alternative carbon allotropes. This work also highlights our advancements on hexagonal boron nitride (hBN), a wide band gap insulator structurally related to graphene, and advancement of intercalation via sonication at ambient temperature.

Additionally, the manipulation of ferromagnetic 2D materials, including chromium (III) iodide and chromium sulfur bromide, is demonstrated through electron beam patterning, highlighting advancements in artificial spin lattices and spin ices.

These works are characterized using PXRD, TEM, and STEM coupled with EDS analysis. This comprehensive research underscores the potential of 2D materials for innovative applications in nanoelectronics and material science.

Bacterial vesicles hold immense potential in various biomedical fields, including vaccines, antimicrobial agents, drug delivery systems, and cancer immunotherapy. Among these, outer membrane vesicles (OMVs) produced by Gram-negative bacteria are among the most extensively studied. While the exact mechanism of OMV production remains unclear, numerous environmental factors have been shown to influence both the yield and composition of OMVs. In this study, we investigated the effect of three different antimicrobial families on OMV production by E. coli. Interestingly, antimicrobials within the same family did not provide the same effects on OMV yield, suggesting that OMV production may not directly correlate with the antimicrobial mechanism of action.

OMVs have demonstrated tumor-inhibitory activity in multiple mouse tumor models. However, their potential toxicity poses a significant challenge, as OMVs have been shown to cause mortality in mice. To address this limitation, we developed bacterial-engineered vesicles (BEVs) as a safer alternative to OMVs. Proteomic analysis revealed that BEVs contained fewer outer membrane proteins compared to OMVs. In vitro assays, BEVs effectively repolarized pro-tumor macrophages (M2) to the anti-tumor phenotype (M1) and promoted dendritic cell maturation. Additionally, BEVs were shown to serve as a versatile platform for antigen peptide display, with the displayed peptides not interfering with BEVs' inherent immunomodulatory activity.

We further evaluated the anti-tumor efficacy of BEVs in a B16F10 melanoma model. The intravenous administration of BEVs significantly inhibited tumor growth and elicited robust immune responses. Flow cytometry analysis of spleen and lymph node samples from BEV-treated mice revealed an elevated M1/M2 macrophage ratio and an increased population of CD8+ T cells. To explore combination therapies, we generated cancer cell-derived vesicles (PD-1 CEVs) using PD-1-transfected B16F10 cells. Interestingly, while BEVs alone inhibited tumor growth effectively, the co-administration of BEVs and PD-1 CEVs resulted in comparable tumor suppression but attenuated immune responses. However, a significant decrease in regulatory T cell percentages was monitored among all vesicle-treated groups compared to the PBS control group. This unexpected immune modulation warrants further investigation to understand the mechanisms underlying PD-1 CEV-mediated immune suppression.

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Small molecule metal complexes have diverse applications including usage as catalysts, single molecule magnets, photosensitizers and pharmaceuticals. Nature itself frequently takes advantage of such complexes for fundamental biological processes. For example, heme-based iron complexes provide O₂ for cellular respiration, while the active site of carbonic anhydrase catalyzes the hydration of CO₂. Now it is our turn to define and exploit the chemical characteristics of such metal complexes. This body of work is specific to the development and application of novel aminated ligands that, when coordinated to various metal centers, can be used for an assortment of applications. The first research project in this work reports a new benzimidazole-based ligand, which dimerizes upon coordination to afford a trinuclear Cu(I) complex. Due to the linear geometry of the Cu(I) metal centers, paired with the strong nitrogen coordinating groups, the resulting complex is resistant to oxidation in both air and water, even in the presence of strong oxidants. The complex is shown to be efficient in the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction and used to tag anticancer drug candidates in vitro. The complex is fully characterized, and a catalytic cycle is proposed. The next project focuses on a series of amidine-based ligands featuring chiral functional groups proximal to the coordinating site. In doing so, the reaction of achiral substrates may be influenced to promote the formation of one enantiomeric product over the other. The ligands are shown to be active in catalyzing the hydroxymethylation of silyl enol ethers in the presence of bismuth chloride in aqueous solutions. The reaction is optimized and yields are reported. In the final research project, Ni(II) dimer complexes are investigated for their magnetic behavior. For octahedral Ni(II) dimers bridged by a common anion, it has previously been established that the ferromagnetic superexchange between the Ni(II) metal centers can be enhanced as the angle of the bridging anion approaches 90 degrees. Novel imidazole and pyridine-based ligands are synthesized to add to the catalogue of chlorine-bridged complexes in the literature. Further, their bromine-bridged analogues are synthesized in order to determine the effect the identity of the halide bridge has on the magnetic properties of the complex. These three projects, while functionally different with individual aims, fundamentally share the goal of probing the chemical space that influences intrinsic properties of unique metal complexes.