Organizational Unit:

School of Chemistry and Biochemistry

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https://hdl.handle.net/1853/70752

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College of Sciences

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https://finding-aids.library.gatech.edu/agents/corporate_entities/153

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Now showing 1 - 10 of 79

Surface Modification of Hard PVC by Molecules with Antibacterial Activity

(Georgia Institute of Technology, 2019-12-09) Pigliautile, Lucrezia

In this work, we present an analysis of different PVC surface modifications, attempted with the intention of attaching antibacterial small molecules, polymers, and oligomers on the plastic. These modifications allowed us to obtain intrinsically antibacterial PVC, which can be potentially applied in healthcare and medical devices. The modification was performed with two procedures, copper-catalyzed azide-alkyne cycloaddition, and nucleophilic substitution. In the first case, the surface of PVC was initially treated with sodium azide to obtain partially azidated PVC, followed by treatment with alkyne-bearing small molecules and polymers. In the second method, the surface was treated with amine-bearing small molecules and polymers, directly substituting the chlorine atoms on PVC. We concluded that the hydrophilicity, the size of the molecule, and the reaction conditions, are the main factors that influence the success of these modifications. Bacteria viability tests were performed on differently-substituted PVC samples, showing good antibacterial activities for PVC surfaces treated with quaternary ammonium salts and acceptable activities for samples modified with polyethyleneimine and oligoethylene glycol.
Development of biocompatible dextran-oxanorbornadiene hydrogels

(Georgia Institute of Technology, 2019-07-23) Lloyd, Jessica

Hydrogels have garnered much attention over the past few decades for their ability to deliver therapeutics with spatial and temporal control. However, many of these systems can exhibit burst release and are not easily adjusted to realize different release kinetics. The research reported in this thesis aims to develop tunable degradable hydrogels from oxanorbornadiene linkers, which have been shown to have programmable fragmentation rates that can be tuned over an exceptionally wide range of time. OND hydrogels of different crosslinking compositions were all able to form robust gels in as little as seconds and release of entrained cargo was found to be tunable over 0.5 to 25 days by changing the OND substitution or crosslinking system. Oxanorbornadiene hydrogels were then applied to in vivo models seeking to improve healing in chronic wounds where it was found that OND hydrogels were able to deliver therapeutic cargo at the expected preprogrammed rates to improve wound healing. Degradable hydrogels comprised of OND cleavable linkages continue to show great promise as simple drug delivery systems that can be widely useful to applications requiring controlled release over hours or months.
Ligand design for developing f-element photochemistry

(Georgia Institute of Technology, 2019-04-30) Yik, Brandon J.

Overall, this thesis describes the synthesis and characterization of ligand architectures to study f-element photochemistry. Chapter 1 provides a general overview of photocatalysis and uses and need to develop photochemistry in the lanthanides. Chapter 2 describes efforts into developing new lanthanide starting materials to advance the field in general, but to also provide a wider set of materials available to use in facilitating discoveries across the f-block. These new starting materials involve the synthesis and characterization of diethyl ether adducts of trivalent lanthanide iodides. Chapter 3 of this thesis describes the work done on the synthesis of an anionic phenylpyridine ligand to develop lanthanide analogs of commonly used photocatalysts and photosensitizers in the organic methodology community. The synthesis and characterization of the ligand salt and metalation to yield Cp*2Sm(ppy) is described. Two appendices are also included which describe synthesis and metalation studies of two other ligand sets, a triamine pincer ligand and an imidophosphorane ligand, that will be used in studying the photochemistry of the lanthanides.
Contributions of active site residues to substrate binding and catalysis of 5-nitroanthranilic acid aminohydrolase

(Georgia Institute of Technology, 2019-04-30) Tao, Xingjian

Synthetic and naturally occurring nitroaromatic compounds are recalcitrant to degradation and they are toxic/mutagenic. The symbiont Bradyrhizobium sp. JS329 is the first microbe found to degrade a biological nitroaromatic compound, 5-nitroanthralinic acid (5NAA), which is secreted by the bacterium responsible for potato scabs, Streptomyces scabies. The first enzyme in the degradation pathway is 5NAA-aminohydrolase (5NAA-A), a metalloprotease family member that has evolved to hydrolyze 5NAA to 5-nitrosalicylic acid. 5NAA-A is the first characterized metalloenzyme to utilize nucleophilic aromatic substitution. Here, I used isothermal titration calorimetry, enzyme activity assays, and X-ray crystallography to dissect contributions of individual active site and second-shell residues for assisting substrate transport. My studies demonstrate the interplay between substrate binding and catalysis requirements for this unusual metalloenzyme. Knowledge of the 5NAA-A structure and mechanism informs potential bioremediation and biocatalytic approaches to mitigate the environmental and ecological impact of nitroaromatic and other challenging substrates.
Hemoprotein discovery through proteomic techniques

(Georgia Institute of Technology, 2018-12-11) Stapleton, Cole S.

Heme is an essential cofactor and signaling molecule. Due to hydrophobicity and toxicity, heme must be tightly regulated to prevent cellular dysfunction. Despite this fact, the manner by which heme is regulated is not well known. Understanding the molecules and mechanisms required to maintain heme homeostasis would be greatly beneficial in understanding heme regulation in health and disease. Historically, hemin-agarose resin has been utilized to identify new hemoproteins. However, this approach is susceptible to the non-specific binding of a large number of proteins in the proteome, making the identification of new hemoproteins difficult. In order to improve upon this technique, we have utilized biorthogonally tagged heme analogs to enrich heme-binding proteins. These heme analogs, which contain an azide, can be fed to cells and distributed using the cell’s own trafficking machinery. Then, through phosphine-azide copper-free click chemistry, biotin can be conjugated to the azide-tagged heme analogs for subsequent enrichment on streptavidin-resin. We demonstrate that these azide-linked heme analogs can enrich model hemoproteins in vitro and can be imported by cells. We also were able to optimize the method of hemoprotein enrichment in Saccharomyces cerevisiae. This technique could be extended to many cell types, in numerous contexts to gain a more thorough understanding of the heme-binding proteome in health and disease.
Rapid characterization of poor-quality medicines using mass spectrometry

(Georgia Institute of Technology, 2018-11-19) Donndelinger, David Vincent

Communities worldwide, especially in the developing world, are afflicted with poor-quality medicines disguised as genuine medicines used for treatment of common infections. Poor-quality medicines range from expired genuine tablets to placebos containing toxins created by criminals. Numerous patients are left with untreated conditions, financial losses, and little confidence in the health system. The developing world struggles to identify and quantitate poor-quality antimalarial and antibiotic medicines. Portable devices employing robust laboratory techniques have the potential to turn the tide in this fight. Vast regions in the developing world lack laboratory analysis capabilities and therefore need portable instruments to perform medicinal quality evaluations. The portable devices lack the demonstrated capability to analyze all classes of poor-quality medicines. Results from tested devices reveal a significant gap in demonstrating the critical ability to distinguish poor-quality from genuine medicines. This study evaluated the Waters QDa mass spectrometer in identifying and quantitating common antimalarial and antibiotic medicines. This instrument correctly identified all poor-quality medicines among 7 common pharmaceutical treatments. Using a high-throughput easily customizable method, the QDa characterized all poor-quality medicines, both falsified and substandard. This capability is unparalleled among portable instruments. The QDa possesses the ability to become an instrumental asset in the fight against poor-quality medicines.
Organic syntheses: Modular divergent formation of anti-malarial natural products

(Georgia Institute of Technology, 2018-01-22) Osborne-Benthaus, Kymberlee Alana

Callophycus serratus, a Fijian red macro alga, is the source of an interesting family of macrolides which have been elusive to the synthetic community. Sesquiterpene bromophycolides P, Q U, and related callophycolide A have highly conserved structural motifs which can be accessed through similar transformations therefore allowing for the application of a modular strategy. Formation of the modules features an expansion of electrophilic π-cyclizations with bromodiethylsulfonium bromopentachloroantimonate(V) (BDSB), and stereoselective Sharpless epoxidation and dihydroxylation conditions. Connection of the modules entail optimization of a magnesate assisted aryl-allyl coupling and a sulfone stabilized anion epoxide ring opening. The strategies explored can be applied to access a family of approximately 30 molecules. The development of a synthetic strategy is desirable due to notable anti-bacterial (MRSA and VREF), anti-malarial properties, and low natural abundance. Herein, I report results for the progress towards the total synthesis of bromophycolides P, Q, U, and callophycolide A utilizing a modular strategy.
Synthesis and structure of N-heterocyclic carbene gold sulfide complexes

(Georgia Institute of Technology, 2018-01-12) Sato, Christopher M.

The synthesis and structures of gold(I) sulfide and hydrosulfide complexes, supported by N-heterocyclic carbene (NHC) ligands are described. The trigold(I) sulfide cations, {[(ICy)Au]3(μ3-S)}+ and {[(IMes)Au]3(μ3-S)}+, terminal hydrosulfide gold(I) complex and the hydrosulfide-bridged gold(I) complex with IPr as a supporting ligand, were characterized by NMR spectroscopy and X-ray diffraction crystallography.
Label-free bioanalytical methods for investigating bimolecular interactions: A review

(Georgia Institute of Technology, 2017-05-23) Ingram, Rena

Interactions between biological molecules such as DNA, RNA, protein, lipids, and carbohydrates are critical to the understanding of all biological, physical, and chemical processes such as protein function, disease diagnosis, and drug discovery.1 Most of the techniques currently used to detect and quantify biomolecular interactions are assisted by foreign molecules that are either permanently or temporarily attached to the molecule of interest; such labels most often fluorescence, luminescence, are radioactive, or are large enough to be easily detected (nanoparticles).2 Fluorescent labeling detection methods, the most common and convenient, are attractive due to their stability, easy manipulation, and high sensitivity and dynamic range.2 However, label-free and real-time detection methods are of high demand due to a number of potential disadvantages of the labels or the methods used to attach them: 1) altering the structure, conformation, or functional properties of the biomolecule of interest, 2) occupying the active site(s) of biomolecules thereby changing their binding affinity, 3) producing false-positive results by interacting with unanticipated components, 4) loss of sample during the labeling and purification process, 5) high sensitivity to changes in environmental conditions, and 6) potential to be tedious and expensive.
Towards the elucidation of the mechanism of the antibiotic activity of tamoxifen

(Georgia Institute of Technology, 2017-04-24) Levinson, Nathanael Simeon

Antibiotic resistance is increasingly a health and financial burden on the global population. Use and misuse of antibiotics has led to increased frequencies of antibiotic-resistant infections worldwide, leading to fatalities as well as greatly increasing healthcare costs. To combat this, researchers have done much work to expand to the field of antibiotics, delving back into old compounds and testing massive libraries of compounds with rapid screening techniques. Tamoxifen is one such compound that is primarily used as an anticancer agent, but displays many useful other characteristic, including antibacterial effects. However, the mechanism of the antibacterial effects of tamoxifen are poorly documented. My research was aimed at both improving the effectivity of tamoxifen as an antibacterial and elucidating the mechanism of action of tamoxifen.