Gradient surfaces exhibit a variation in functionality along the length of the surface. One method for preparing gradients is controlled-rate infusion (CRI). In Part 1 of this work, CRI was used to prepare gradients for the purpose of separating transition and heavy metals. Initial work on this project was focused on controlling the retention of the metal ions by varying the number of amine groups, aminoalkoxysilane concentration, and the infusion time. The retention factors of four metal ions varied predictably with increasing number of amine groups, increasing aminoalkoxysilane concentration, and increasing infusion time, producing small but useful changes in the retention factors. The continuation of this project involved the preparation of two-dimensional multi-component gradients on TLC plates, which were used to separate six transition and heavy metals. The retention, and thus the separation, was affected by the presence or absence of a gradient and the direction of the gradient. Part 2 of this work focused on understanding the factors that motivated instructors in the early and late stages in the process of change. Instructors who attended the POGIL-PCL (Process-Oriented Guided Inquiry Learning in the Physical Chemistry Laboratory) workshops were asked to complete online surveys. The goals of the first survey were to understand the factors that initially interested instructors in POGIL-PCL, to determine if instructors enter the implementation stage, and to understand the factors that affect how instructors implement POGIL-PCL. Later surveys were designed to explore the development of the POGIL-PCL network and assess whether implementation is sustained over time.

The most abundant biological thiols, homocysteine (Hcy), cysteine (Cys) and glutathione (GSH) have been the subject of intense research due to their association with a wide range of diseases. They play a key role in maintaining the redox status of biological systems. Selective detection methods for these thiols are challenging due to their similar structures and properties. Current commercially available detection methods use separations, fragile and expensive enzymatic or immunogenic materials and complex instrumentation. This has led to a global effort towards developing simple and inexpensive optical probes and indicators selective for specific biological thiols. Highly selective chemical probes and simple methods for detection and potential quantification of Hcy and GSH in their natural biological media have been developed. These indicators and methods are relatively simple and inexpensive for potential application at point of care. The selective detection of Hcy using novel asymmetric viologen chemical probes at room temperature is described as well as the use of commercially available materials under photochemical conditions. These probes respond linearly proportional to increasing Hcy concentrations, potentially enabling the monitoring of Hcy levels in human plasma. Additionally, new methods for the selective determination of GSH in human plasma, as well as its quantification in whole blood deposited on filter paper (dried blood spots), is also presented herein.

In vitro protein selection has had major impacts in the field of protein engineering. Traditional screens assay individual proteins for specific function. Selection, however, analyzes a pool of mutants and yields the best variants. Phage display, a successful selection technique, also provides a reliable link between variant phenotype and genotype. It can also be coupled with high throughput sequencing to map protein mutations; potentially highlighting vital mutations in variants. We propose to apply this technique to cancer therapy. RAF, a serine/threonine kinase, is critical for cell regulation in mammals. RAF can be activated by oncogenic RAS, found in over 30% of cancers, to drive cancer proliferation. Rigosertib, a benzyl styryl sulfone in phase III clinical trials for myelodysplastic syndrome (MDS), is an inhibitor of the RAS binding domain (RBD) in RAF. Phage display can be used to select RAF mutants for RAS binding affinity, in the presence of Rigosertib. High-throughput sequencing of these variants can provide a means of anticipating, and mapping resistance to this anti-cancer drug.

Hemimicelles and admicelles are well-investigated wonders in modern science; they are surfactant monolayers and surface adsorbed micelles, respectively. Capacitance measurements for monitoring the formation of dodecyl sulfate (DS) surfactant monolayer on positively charged gold substrates (planar gold) and the adsorbance of 2-naphthol onto DS surfactant monolayer were performed. The investigation of the electrical control of DS at various concentrations (4, 6, 16, and 32 mM) below and above the critical micelle concentration (CMC= 8 mM) on gold surfaces for analyte preconcentration, prior to chromatographic analysis, is presented. Charged ionic surfactants, such as DS, drawn to a surface of opposite charge (porous nickel substrates coated with gold) serve as a stationary phase to trap organic analytes. It is believed that these DS assemblies gain stability through surfactant chain–chain interactions. The attachment and the removal of the surfactant are controlled using an electric field. Due to the fact that the surfactantanalyte association is released by electrical control, organic solvents, which are used in conventional solid phase extraction, are not required, making this procedure environmentally friendly. Electrical Impedance Spectroscopy was used to investigate the formation of the DS layer and the preconcentration of 2-naphthol in the presence of an applied electric field. High performance liquid chromatography was used to determine 2- naphthol concentrations. Anthracene and 9-anthracenecarboxylic acid were substituted as additional test molecules as well. Presented are the results of the preconcentration of 2-naphthol, anthracene and 9-anthracenecarboxylic acid using the DS layer with various concentrations of sodium dodecyl sulfate on a gold electrode surface.

The discovery of a method by which proteins of interest can selectively be labeled with a probe of choice intracellularly is a longstanding goal in chemical biology research. Conventional labeling techniques have utilized large domain tags but despite the development of small labeling molecules there have been no short peptide sequences known to covalently label a small molecule without the aid of an enzymatic process or metal chelation. We aimed to find a sequence of nucleophilic peptides that reacted covalently and specifically with electrophilic small labeling molecules using mRNA display. Our goal was to show that an electrophilic small labeling molecule that is brought in proximal distance to a protein of interest via affinity can result in nucleophilic attack by a neighboring nucleophilic amino acid to covalently label the protein of interest. Utilizing affinity between a small labeling molecule and a protein of interest to bring them spatially close to one another maximizes the chance that a covalent reaction can take place and provides selectivity between two components in a complex mixture. Towards this goal, we developed several electrophilic fluorescent small molecules. Covalent labeling was achieved using electrophilic bait in the form of sulfonate esters, a polyethylene oxide linker provided structural flexibility, and a fluorescent affinity tag containing a rhodamine backbone served as the potential binding site to a key peptide sequence encoded within a protein of interest. The synthetic routes to access our electrophilic rhodamine B and sulforhodamine 101 fluorophores were optimized. Key intermediates were produced and served as flexible points of modification to make various analogs of our desired electrophilic fluorophores. The affinity between proteins containing the peptide sequence and the fluorescent electrophiles were determined by fluorescence polarization. Covalent labeling was determined to be both time and concentration dependent. The expected published affinity between the peptides and fluorophore was not high enough to produce selective labeling. However, our small labeling molecules were found to be effective at labeling various proteins in vitro. In addition, our electrophilic fluorophores have been found superior to sulforhodamine 101 in live cell imaging of astrocytes.

The ever increasing demand for more efficient and environmentally benign routes for synthesizing target compounds, has led to the use of organometallic catalysts. This demand has created the need to understand the mechanistic details that are at work in these organometallic catalytic cycles. Along with this, there is a demand for new organometallic catalysts that are tailored for specific transformations. This presents a myriad of challenges for organometallic chemists. Unfortunately, it is often difficult to gain an understanding of the reaction mechanisms at work when the intermediates are too short lived to be observed in the condensed phase. It is also very time consuming to synthesize, purify, and characterize organometallic catalysts following standard condensed phase methods. Therefore, it would be beneficial to probe organometallic reactions in a way that the inherent reactivity of the organometallic complex can be uncovered and where purity is not a prerequisite. Using an ion-trap mass spectrometer that has been modified to allow introduction of neutral reagents to the buffer gas, organometallic ion-molecule reactions can be probed in an environment free from solvation effects. This enables the study of the inherent reactivity of the complexes and also provides insight into reaction mechanisms by allowing reactive intermediates to be probed. In addition, organometallic complexes probed in this manner do not need to be pure due to ability of the ion trap to function as a mass filter. This results in a quick and efficient method. This dissertation presents results found during the investigation of the reactions and mechanistic details of gold, silver, and iridium complexes using a modified ion-trap mass spectrometer.

This work presents heuristics for searching large sets of molecular structures for low-energy, stable systems. The goal is to find the globally optimal structures in less time or by consuming less computational resources. The strategies intermittently evaluate and rank structures during molecular dynamics optimizations, culling possible weaker solutions from evaluations earlier, leaving better solutions to receive more simulation time. Although some imprecision was introduced from not allowing all structures to fully optimize before ranking, the strategies identify metrics that can be used to make these searches more efficient when computational resources are limited.

The objective of this study was to evaluate the chemical resistance of common shoe materials regularly worn in undergraduate chemistry laboratories by subjecting the materials to hydrochloric acid and sodium hydroxide. The materials tested were leather, canvas cotton, and polyester. Due to the lack of restriction on undergraduate laboratory footwear, the research discussed in this thesis is important to undergraduate universities. Currently, many universities across the nation only require undergraduate students to wear close-toed, close-heeled shoes in chemistry laboratories, and often the resistance of the shoe material to acids and bases may not be taken into careful consideration. Overall, the results of this experiment revealed that exposure to the different chemical concentrations of NaOH and HCl did not appear to negatively affect the structural integrity of the fabrics, but according to the mass spectrometry results gathered in this experiment, the three fabrics differed in individual complexities as well as in the compounds extracted following acid and base treatments.

Bromoarenes are important aromatic building blocks that are commonly used to synthesize various functional compounds in pharmaceutical, agrochemical and related industries.1,2 This great demand for bromoarenes makes their preparation a widely studied area of synthetic organic chemistry. However, further understanding of the reactivity and regiochemistry of aromatic functionalization reactions is still necessary, as much about the secondary substitution and solvent effects remain unknown. Resonance Theory is a widely used theoretical model to predict the regiospecifity and reactivity of the bromination of various aromatic compounds.3 The reactivity and regiospecificity of many substituted aromatic compounds is well explained using resonance theory.4 However, kinetic understanding of the p-bromination of halosubstituted aromatic compounds has not been investigated to the best of our knowledge.5,6In this thesis, the reactivity and regiospecifity of the p-bromination of activated secondary substituted aromatic compounds as well as media effects on the process will be discussed. Synthesizing bromoarenes has been accomplished using many different experimental setups.7-11 N-bromosuccinimide is the most highly utilized electrophilic aromatic brominating agent. Many of the NBS- based aromatic bromination reactions have been reported using strong acids, strong bases, halogenated solvents, nonpolar solvents and polar solvents alike.12 The bromination reactions reported herein were performed using two different solvents, acetonitrile and acetone, to investigate the effects of solvent polarity on p-bromination. Although acetonitrile is one of the most commonly used solvents in the p-bromination of aromatic compounds, acetone has not been investigated.

The effect of Mg++ ion on the solubility of calcium carbonate was determined using P. K. Weyls "carbonate saturometer." The amount of calcium carbonate precipitated or dissolved was measured for five series of waters when equilibrated with solid carbonate. It was found that the effect of Mg++ ion on solubility depend upon the nature of the solid phase: surface area, coprecipitated Mg++, minerology, etc. Pure low area calcite showed an increase in solubility which could be explained by ion-pair formation, while its other carbonates departed from this behavior.