Physical Sciences and Mathematics Commons^™

Synthetic Amphiphiles As Antibiotic Potentiators, Helena Spikes

Dissertations

Antibiotic resistance has become a massive threat to modern medicine. Bacteria acquire resistance either through genetic mutations or mobile genetic elements, such as plasmids. The growing resistance crisis is exacerbated by over-prescription of antibiotics and improper use. As antimicrobial resistance becomes more widespread, superbugs (bacteria resistant to more than one class of drug) have evolved. Since few new drugs reach clinical trials and even fewer are approved by the FDA, we must find a way to make existing drugs more potent. One technique to accomplish this is by using combination therapy. By administering two or more drugs at a time, …

Ferrocenium Salt Aided Substitution Reactions And Synthesis Of Glycosylated Curcumin Derivatives, Deva Saroja Talasila

Dissertations

Organic synthesis has been significantly advanced with the employment of transition metal complexes. The discovery of transition metal catalysts provided the synthetic community with powerful tools for accelerating reactions and making them more selective and efficient. Many chemical reactions do not happen without a catalyst.

Iron-based catalysts have several advantages for the chemical industry because it is a non-toxic and ecologically friendly metal. Our group previously found that ferrocenium cations with a 3+ oxidation state of iron-catalyzed propargylic substitution reactions at low temperatures. The sandwich structure of ferrocenes allows substituents to be introduced on the cyclopentadienyl rings, which allows for …

Novel Thioglycosides As Versatile Glycosyl Donors For Oligosaccharide Synthesis, Ganesh Shrestha

Dissertations

This thesis is dedicated to the development of new methodologies for efficient synthesis of carbohydrate building blocks and their application to chemical glycosylation. S-Indolyl (SIn) anomeric moiety was investigated as a new leaving group. Understanding of the reaction pathways for the SIn moiety activation was achieved via the extended mechanistic study. The activation profile of indolylthio glycosides required large excess of activators. This drawback was partially addressed by the development of N-alkylated SInR derivatives. The activation process was studied by NMR and the increased understanding of the mechanism led to a discovery of different activation pathways taking place with …

Synthesis Of Novel Dna-Binding Polyamides To Prevent Cancer-Related Gene Overexpression, Huy Q. Nguyen

Dissertations

Pyrrole-imidazole polyamides (PIPs) are nanomolecular compounds designed to fit in the tight space of DNA minor grooves. As analogs of Netropsin and Distamycin A, PIPs are specifically designed to recognize the base pairs of DNA sequences. PIPs have many biological applications, such as regulating gene expression, biochemistry pathway regulations, and suppressing the development of cancer cells. SETMAR gene is the chimeric fusion of the SET domain with the mariner transposase. Its protein (Metnase) has functions involving DNA repairs in the NHEJ pathway, regulating gene expression, DNA decatenation, etc. Despite not having an active transposable element, SETMAR still has an unknown …

Mechanism Of Sila- And Germafluorenes For Biological Applications, Shelby Jarrett

Dissertations

2,7-disubstituted silafluorenes and germafluorenes, originally designed for OLED applications, are a class of fluorescent dyes that have gained recent interest as probes for bioimaging and as biosensors to monitor cellular dynamics and interactions. Desirable biological probes absorb in the visible region, have high extinction coefficients, high quantum yield and excellent photostability. Here, their spectral properties are investigated under aqueous conditions for relevant biological applications. These molecules display intense blue fluorescence in the solid state and in solution, have high extinction coefficients, and exhibit appreciable solubility in aqueous solution. To better understand potential applications, the mechanism of fluorescence was investigated. It …

Bis(Tryptophan) Amphiphiles: Design, Synthesis And Efficacy As Antimicrobial Agents, Michael Mckeever

Dissertations

Amphiphiles play important roles in nature. These molecules contain both hydrophilic and hydrophobic regions, leading to some astonishing properties. The lipid bilayer of the cell membrane is a fascinating organization of amphiphilic phospholipids. Natural and synthetic amphiphiles, such as antimicrobial peptides, interact with the cell membrane. Such interactions can impact transport of molecules across the cell membrane, disrupting cell functions. In this work, a library of tryptophan-containing amphiphiles was synthesized and their antimicrobial properties were explored.

First, a library of bis(tryptophan) amphiphiles was synthesized. Preparation included a coupling reaction of a diamine with tryptophan residues, via their carboxy-termini, at …