This dissertation focuses on the diverse use of chemical synthesis. Herein, I will discuss the use of synthetic organic chemistry for the modification surfaces and the synthesis of small molecules. Chapter One is an introduction to the realm of surface chemistry. I have highlighted some key methods for surface modification. Additionally, methods to characterize the as-formed thin films are also outlined. In Chapter Two, I discuss the use of visible-light photoredox catalysis in the nanoscale lithography of Au(111) surfaces. Blue LED irradiation of solutions of NBDT in the presence of Ru(bpy)32+ results in the formation of p-nitrophenyl radicals that graft onto Au. Further reaction of the grafted arenes with aryl radicals results in oligomerization to polyphenylene structures with resulting film thicknesses that are dependent on both the initial concentration of diazonium salt and the duration of the grafting procedure. Grafting onto Au(111) coated with SiO2 mesospheres (d = 500 nm) prior to mesospheres removal results in the production of nanopatterned surfaces wherein each nanopore represents the former location of a mesosphere. Chapter Three focuses on the a novel use of visible light photoredox catalysis for organic thin film formation with nanoscale lithography of Au(111) surfaces. Irradiation of solutions of phthalimide esters with blue LEDs in the presence of the Ru(bpy)3Cl2 results in the formation of carbon centered radicals that form organic thin films. We propose that a series of additional reactions of the grafted aliphatic chains with alkyl radicals results in oligomerization and the formation of multilayers. Chapter Four is a brief discussion of the significance of oligosaccharide synthesis. The development of efficient and stereoselective methods for glycosylation is a synthetic challenge. Thioglycosides are inert to many glycosylation methods and are bench top stable. Their stability to common carbohydrate protecting group manipulations makes thioglycosides ideal glycosyl donors or acceptors. Traditionally, the activation of thioglycosides requires heavy metals, halogen electrophiles, or stoichiometric thiophilic reagents. In contrast, our method discussed in Chapter 5 requires catalytic Bronsted acid for the remote activation of a thioglycoside donor. Under these conditions, O-glycosylation formation and release of a tetrahydrothiophene aglycon is swift and high yielding.

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High performance polyamides containing the 4,4’-disubstituted-2,2’-bipyridyl moiety were synthesized by phosphorylation polycondensation from 2,2’-bipyridyl-4,4’-dicarboxylic acid and a series of primary aromatic diamines with triphenylphosphite and pyridine as the agents to facilitate condensation. Polyamides exhibiting improved solubility in organic solvents and strong acids, melting transitions at low temperatures and good thermal properties were prepared by introducing bulky methyl and fluoro groups, flexible ether and propyl linkages, and by using monomers with reduced symmetry. Solutions of the polyamides with rigid mainchains (II, III, IV, V, VI, and VIII) showed birefringence (colorful spherulites) at concentrations of 5, 10, and 15% w/v polymer/solvent. The immobilization of the bipyridyl units in the polymer matrix increases the metal ion sensing of the polymer by promoting a chelating interaction between the polyamides and metal ions. The chelation of nickel (II) ions caused extensive crosslinking within the polymeric systems immediately precipitating insoluble metallopolymers. Ultra violet-visible data of the chromium (III) and zinc (II) extract yielded inconclusive evidence of metal ion chelation. The optical spectroscopic studies of the extraction of ruthenium ions by the 2,2’-bipyridyl containing polyamides revealed the formation of distinct ruthenium (II) complexes [RuII(poly)L4] (λmax=530nm), [RuII(poly)2L2] (λmax=584nm), and [Ru(poly)3]2+ (λmax=476nm), while iron (II) ions formed only one complex (λmax=569nm). The diverse functional features of the polymer repeat unit directly influences the chelation of metal ions. Subsequently, the chelation of ruthenium (II) ions resulted in the preparation of directional metallopolyamides systems based on the geometrically favorable tris(2,2’-bipyridyl)ruthenium (II) complex. The three-dimensional polyamides, which absorbed at λmax of 476nm and emitted at λmax of 620 nm, exhibited high thermal stability and improved solubility making them suitable candidates for compressive strength studies and cyclic voltammetry studies as part of an effort to address the corrosion of graphite-fiber reinforced composites.

Magnetic resonance imaging (MRI) has become a powerful clinical modality in diagnostic medicine. It is non-invasive and offers high spatial and temporal resolution. The goal of molecular imaging is to reveal the pathophysiology underlying the observed anatomy and diagnose diseases. The detection of pathological biomarkers can lead to early recognition of diseases and improved monitoring for recurrence. Clinically available contrast agents are limited in their discrimination of contrast between tissues and they tend to have very high detection limits. Because biomarkers are very low in concentration there is a need for high payload deposition of contrast agent (CA) and targeted imaging. Encapsulating discrete Gd3+ chelates in nano assembled capsules (NACs) is a simple and effective method of preparing an MRI contrast agent capable of delivering a large payload of high relaxivity imaging agent. The preparation of contrast agent containing NACs had previously focused on preparations incorporating GdDOTP5- into the internal aggregate. In this report we demonstrate that other Gd3+ chelates bearing overall charges as low as 2- can also be used to prepare NACs. This discovery opens up the possibility of using Gd3+ chelates that have inner-sphere water molecules that could further increase the relaxivity enhancement associated with the long rotational correlation time (TR) that arises from encapsulation. However, encapsulation of the q = 1 chelate GdDTPA2- afforded the same increase in relaxivity as the outer-sphere chelate GdTTHA3-. This leads us to the conclusion that in the NAC interior proton transport is not mediated by movement of whole water molecules and the enhanced relaxivity of Gd3+ chelate encapsulated within NACs arises primarily from second sphere effects. The nano assembled capsule platform has been further expanded by an alternative coating method, a new cross linked peptidic shell reported in this work affords robust capsules and exceptionally high per Gd3+ relaxivities (70.7 mM-1s-1). The availability of free amines on the surface of these capsules can be exploited to attach targeting moieties. This was demonstrated through the reaction of fluorescein isothiocyanate (FITC), an intense green emitting dye, with these amines. Green emission from the capsules indicated that surface amines were accessible to FITC. Unlike T1-shortening contrast agents, paraCEST agents can be switched on and off by the imaging scientist by turning on and off a pre-saturation pulse. This affords the ability to acquire both pre- and post-contrast images even after administration of a paraCEST contrast agent. This could potentially eliminate problems co-registering pre- and post-contrast images. A reverse NAC may allow a cationic paraCEST contrast agent to be incorporated in a high payload NAC. We were successful in synthesizing a reverse capsule using DyDOTAM3+, a paraCEST agent, and the negatively charged polymer polyacrylate and encapsulated with SiO2 nanoparticles. These initial preparations of reverse NACs were not able to generate CEST contrast however.

Corrosion is a spontaneous process that causes irreversible damage to nearly all metals, which has world-wide implications for architectural and artistic metalwork, such as bridges, buildings, airplanes and sculptures. Protective coatings such as wax, paint, or polymeric clear coatings are used to prolong the lifetime of metals such as steel and bronze. Unfortunately, these coatings fail over time due to oxidative damage by UV rays and by failure to exclude water that can carry salts and pollutants that cause corrosion of the underlying substrate. The current method of coating assessment is visual inspection but when coating failure is detected at this stage, irreversible damage has already occurred to the metal substrate. Diagnosing coating quality on artistic metalwork is a unique challenge as it requires a method that is non-destructive as to not alter the aesthetic of the piece. A non-destructive technique or device that can detect early signs of coating failure in the field (such as at a sculpture park) does not currently exist. The aim of this thesis is to develop a method that can be readily used in the field by a conservator to quickly diagnose the protective state of a coating on a sculpture in order to provide localized treatment. Electrochemical impedance spectroscopy (EIS) is a method currently used to study protective coatings in the lab. The technique itself is non-destructive but the most common electrochemical cell used with it must be used on a planar substrate and requires that a portion of coating be removed. Not only is the current method destructive, but the data produced by EIS is complicated and time consuming to analyze. These issues provide the foundation for this project. This thesis first proposes multiple methods to quickly analyze the complicated data traditionally collected through EIS. Three quick analysis methods, including the estimation of the derivative at one single frequency in EIS spectra, was successfully used to categorize coating quality of five different coating types. Using this quick analysis can aid conservators in assessing coating condition without the need for extensive training in EIS data interpretation. This thesis also proposes a method to measure early warning signs of coating degradation through a co-planar hydrogel electrochemical cell paired with EIS. The configuration of this co-planar hydrogel cell negates the need for the removal of the coating and can be used on multiple types of surfaces because of its flexibility, therefore overcoming the drawbacks of the traditional EIS electrochemical cell. Data provided demonstrates that this co-planar hydrogel provides similar information, when compared to the standard electrochemical cell, about the bulk of the protective coating. Unique to the co-planar hydrogel cell, information about surface degradation is provided during EIS measurements. This provides a warning sign before bulk degradation of the coating and therefore before any damage to the underlying substrate has occurred.

The purpose of the research in this dissertation was to elucidate the intrinsic properties of how nanoparticles are different from bulk materials. This was done by mechanical and electronic studies of the properties of designed nanoparticles using advanced modes of atomic force microscopy. Information relating to the work functions, contact potential difference, Youngs Moduli, elasticity, and viscoelasticity can be investigated using state-of-the-art atomic force microscope (AFM) experiments. Subsurface imaging of polystyrene encapsulated cobalt nanoparticles was achieved for the first time using Force Modulation Microscopy (FMM) in conjunction with contact mode AFM. Previously prepared sample of polystyrene coated cobalt nanoparticles were studied. Tapping-mode AFM was used to evaluate the size of coated nanoparticles. Force modulation microscopy was used to visualize details of the outer polystyrene coating. Differences between the softer polystyrene outer coating and the harder cobalt nanoparticle core was visualized based upon the elastic and viscoelastic properties. Variances in sample elasticity were monitored via the amplitude channel that monitors the oscillation amplitude of the cantilever while scanning. Viscoelastic differences were mapped by the phase channel which provides information of the phase lag of the probe. The identification of designed nanoparticles based upon electrochemical properties was evaluated using the Kelvin Probe Force Microscopy (KPFM) mode of AFM. The contact potential difference between the tip and the sample is measured using an AC bias that is offset with a compensating DC bias while operating in either tapping-mode or non-contact mode AFM. The contact potential difference is more commonly referred to as the difference in work function between the tip and the sample. The work function of a material can be calculated using a reference material with a known work function. Cobalt nanoparticles and gold nanoparticles were imaged using KPFM and baseline experimental contact potential difference values were obtained. Thus far, co-deposition of a mixed nanoparticle solution led to inconclusive results as the experimental and theoretical contact potential difference values were calculated. However, future studies relating to this experiment are planned.

G protein-gated inwardly rectifying potassium (GIRK) ion channels are part of a larger family of inwardly rectifying potassium channels (Kirs) that regulate diverse biological processes. Kirs regulate solute balance in the kidneys, cardiac rates and rhythms, and neuronal excitability. Specifically, dysfunction in GIRKs expressed throughout the central nervous system (CNS) have been linked to schizophrenia, pain perception, drug addiction, and epilepsy. In the heart and adrenal glands, dysfunctional GIRKs have demonstrated arrhythmia phenotypes and have been linked to adrenal carcinoma. The gathering of valuable information on cellular processes, such as the function and regulation of ion channels will benefit greatly from the development of small molecule probes and fluorescent dyes. Recently, we conducted a high-throughput thallium (Tl+) flux assay and identified a series of small molecules that modulate GIRK1-containing GIRK channels. From these compounds, we developed ML297, a diaryl urea with a potency of 160 nM on GIRK1/2 channels. Further structure-activity relationship studies identified remarkably selective GIRK1/4 (heart-localized) inhibitors and selective GIRK1/2 (CNS-localized) activators. Our current efforts are directed towards further increasing the selectivity and potency of our scaffolds. In parallel, we are also interested in latent fluorescent dyes that are selectively activated by exogenous enzymes expressed in GIRK-containing cell lines. This pro-dye/enzyme system would optimize the signal-to-noise ratio of Tl+ flux assays, which we use extensively to study GIRK channels. Our understanding of function and regulation of GIRK channels will improve with better chemically-synthesized products; potent and selective small molecules and improved dyes will guide the therapeutic potential of modulating GIRK channels.

Analyte-membrane and analyte-membrane receptor interactions are related to drug absorption through transmembrane diffusion and cellular signal transduction, respectively. Therefore, the study of these interactions plays key roles in new drug development. Membrane-based chromatography using artificial phospholipid vesicles as stationary phases provides a high-throughput approach to screen analyte-membrane interactions. Additionally, by incorporating membrane receptors into the vesicle stationary phases, analyte-membrane receptor interactions can be studied. However, the inherent instability of artificial phospholipid vesicles limits their application. This work has explored the utilization of polymerized phospholipid vesicles in developing highly stable separation and sensing platforms based on analyte-membrane or analyte-membrane receptor interactions. The processes of vesicle polymerization using polymerizable lipids and polymer scaffolding are also characterized and optimized.In order to improve the stability of stationary phases in membrane-based chromatography, polymerized phospholipid vesicles made of polymerizable bis-SorbPC lipids were covalently immobilized on the inner wall of silica capillaries to serve as stationary phases. The polymerized vesicle stationary phases showed enhanced stability against drying/rehydration and shear forces compared to non-polymerizable counterparts. Aliphatic amines were separated using the polymerized vesicle stationary phases based on their different interactions with the vesicle membranes in both open-tubular capillary liquid chromatography (CLC) and capillary electrochromatography (CEC) formats. This application broadens the range of membrane-based stationary phases to include polymerized phospholipid vesicles, which provide enhanced stability. Biosensors that detect ligands based on ligand-receptor interactions using artificial phospholipid vesicles generally do not allow ligand identification. A pull-down assay was developed using novel silica core-polymerized vesicle shell particles combined with MALDI-MS for the simultaneous detection and identification of peptide/protein ligands that bind to membrane receptors. The polymerized vesicle shell survived MS vacuum conditions and showed higher stability against organic solvent treatment compared to non-polymerizable counterparts. As a proof of concept, cholera toxin binding subunit (CTB) was successfully detected using ganglioside GM1-functionalized core-shell particles. The assay has the potential to differentiate among multiple ligands that bind to the same receptor and identify unknown ligands in a complex ligand mixture.In addition to using polymerizable lipids, polymer scaffolding is also used to stabilize phospholipid vesicles, although the formation of polymer scaffolds in nanometer-sized vesicles is difficult to characterize. Polymer scaffolds were successfully synthesized inside vesicles composed of non-polymerizable DOPC lipids (100-200 nm in diameter), by doping small molecule linear monomers and cross-linkers into the vesicle lamellar region followed by photochemical initiation. It was found that DOPC vesicles containing polymer scaffolds formed by different linear monomers showed similar stability against surfactant treatment. This study adds new insights to the current understanding and characterization of the polymer scaffolding process.

The Mississippi River high water levels in 2011 and 2016 resulted in the opening of the Bonnet Carré Spillway (BCS), introducing nutrients and terrestrial sourced dissolved organic matter (DOM) into Lake Pontchartrain Estuary. The resulting dynamic change in concentration and composition of the DOM was measured using ultraviolet visible (A254, A350, SUVA254, and S275-295) and fluorescence spectroscopy (excitation emission matrices and fluorescence and biological indices). Additionally, the analysis was enhanced and individual fluorophores of DOM were determined using multi-way parallel factor analysis (PARAFAC). Through comparing the results of the 2011 dataset and 2016 dataset, similarities in the DOM composition during diversions were determined and variations of the overall DOM composition were identified and predicted to be the result in variations of temperature, sunlight, and rain fall.

<p>Nanomaterials are increasingly being used in consumer products due to their unique optical, electronic, and antibacterial properties. However, proliferated use of nanomaterials will lead to increased entrance into the environment where toxicity can occur to plants and other organisms. The focus of this research is to understand the origin of nanomaterial organismal toxicity and methods for its reduction through engineering. Nano silver, nano carbon, and nano copper were chosen as the subjects of study due to their prevalent use in consumer products, and likely entrance into the environment during use and disposal. </p><p>The majority of the research focuses on silver nanomaterials (AgNMs). In the first part of this work, Chapters 2-5, the toxicity of AgNMs with three different shapes (i.e. silver nanoparticles, silver nanocubes, and silver nanowires) was examined in environmentally relevant and model organisms including Lolium multiflorum, Danio rerio, Caenorhabditis elegans, and the bacterial strains Escherichia coli, Pseudomonas aeruginosa, and Bacillus cereus to determine if the shape of the AgNM affected its toxicity. Shape was shown to affect the toxicity of silver nanomaterials to L. multiflorum; silver nanoparticles (AgNPs) were more toxic than silver nanocubes (AgNCs) and silver nanowires (AgNWs). However, this shape-based toxic effect was not found in the other species examined. </p><p>To further understand the shape-specific toxicity, dissolution and physical contract were studied. While dissolution is often assumed to be the cause of silver nanomaterial toxicity, we concluded that dissolution alone did not account for all of the toxicity shown. Instead, physical contact between the nanomaterial and plant was found to be necessary for shape-based phytotoxicity. The surface reactivity was experimentally calculated for each nanomaterial to determine if different surface reactivity between different AgNM shapes could further explain phytotoxicity. It was shown that this value correlated to phytotoxicity, suggesting surface reactivity might be related to nanomaterial toxicity in environmentally relevant organisms.</p><p>Since AgNMs are likely to undergo chemical and physical transformations after entrance into the environment, the effect of sulfidation on shape-based phytotoxicity was studied. Sulfidizing the AgNMs resulted in an increase in size due to the formation of a silver sulfide shell. Sulfidation was found to decrease AgNM toxicity toward L. multiflorum, D. rerio, and C. elegans. However, it was determined that shape still affected the AgNM toxicity after sulfidation.</p><p>Due to their lack of phytotoxicity as compared to bacterial toxicity, AgNCs were chosen as a precursor for a novel silver-antibiotic hybrid surface coating. Silver nanocubes were functionalized with a sub-monolayer of gold (Au@AgNC) to increase the ease of covalent attachment of functional moieties. The Au@AgNCs were then covalently functionalized with gentamicin, a commonly used antibiotic. The gentamicin-Au@AgNCs showed increased bacterial toxicity to Staphylococcus aureus compared to a mixed gentamicin and Au@AgNC composite. Phytotoxicity of the gentamicin-Au@AgNC compound was found to be minimal in L. multiflorum, Lactuca sativa, and Solanum lycopersicum. In this work the physical and chemical properties of nanostructures were tuned to reduce environmental toxicity while retaining desired functional properties. </p><p>The research was also extended to other nanomaterials. In Chapter 7, the effect of copper nanowire (CuNW) diameter on phytotoxicity was studied in the plant species L. multiflorum, L. sativa, and S. lycopersicum. L. multiflorum and S. lycopersicum did not show any diameter-based toxicity, though L. sativa did. Smaller diameters correlated to increased toxicity in L. sativa, and all CuNWs were more toxic than ionic copper. CuNWs were aged to simulate more realistic plant exposures. After aging, CuNWs were less toxic, though the diameter-based toxicity trend was still present. To further understand the diameter-based toxicity, dissolution was studied. It was determined that dissolution alone could not account for the phytotoxicity shown.</p><p>In Chapter 8, the recently synthesized material soluble graphitic nanofiber (SGNF) was studied for its phytotoxicity to plants using the environmentally relevant and model plant species L. multiflorum, L. sativa, and S. lycopersicum. SGNFs consist of a carbon nanotube (CNT) core wrapped with sheets of graphene oxide (GO). As both of these materials are toxic, it was hypothesized that their toxicity would be additive in SGNFs. In plant growth assays, GO was the most phytotoxic and CNTs were the least phytotoxic. SGNFs were between the GO and CNTs for toxicity. It was determined that pH of the solution played a minor effect on the decreased growth shown. The majority of toxicity could be attributed to agglomeration of SGNFs onto the surface of the plant root.</p><p>Additionally, four zero-dimensional carbon nanomaterials (CNMs) were studied to determine if chemical bonding properties affected their phytotoxicity to the plant species L. multiflorum, L. sativa, and S. lycopersicum. Nanodiamond, onion-like carbon, partially graphitized nanodiamond, and carbon dots were all studied to determine if exposure resulted in decreased germination, root, or shoot growth. Generally, all four CNMS resulted in similar or increased growth compared to the control. This data suggests that differences in chemical bonding are unlikely to cause toxicity at environmentally relevant concentrations.</p><p>Finally, graphene oxide was studied as a surface coating for ceramic pot water filtration devices (CPWFDs). GO was covalently attached to the ceramic membrane surface using linker chemistry. The ceramic membranes were challenged with Esherichia coli to determine their bacterial removal efficiency. Hydraulic conductivity was also measured to determine the water flux of the ceramic membranes as a proxy for measuring membrane fouling.</p><p>The results from these studies show that a greater understanding of how physico-chemical properties affect toxicity toward environmentally relevant organisms is necessary to better engineer nanomaterials with increased desired properties while reducing unintended consequences. Additionally, this work showed collaborations among scientists from different disciplines were necessary to better understand the complex scientific question of environmental fate and toxicity of nanomaterials.</p> / Dissertation