Physical Sciences and Mathematics Commons^™

Part 1: Design, Synthesis, And Evaluation Of Novel Gram-Positive Antibiotics Part 2: Synthesis Of Dihydrobenzofurans Via A New Transition Metal Catalyzed Reaction Part 3: Design, Synthesis, And Evaluation Of Bz/Gabaa Α6 Positive Allosteric Modulators, Christopher Michael Witzigmann

Theses and Dissertations

Part 1. Lead compound SK-03-92 represents a new scaffold for antibiotic drug discovery. Development of a new process for the synthesis of analogs has led to the development of a number of new ligands with even more potent activity against gram-positive bacteria, including drug-resistant strains of S. aureus. Compounds 36 and 38 represent some of the most potent analogs developed thus far, and preliminary results indicate that they are also not cytotoxic. Research into a Heck-mediated transition metal catalyzed pathway towards electron-rich stilbenoid analogs has greatly expanded the scope of future SAR studies. This development has led to 14 new …

Corrosion Of Aluminum Current Collector In Cost Effective Rechargeable Lithium-Ion Batteries, Shengyi Li

Theses and Dissertations

Rechargeable lithium ion batteries (LIB) have been widely used as commercial energy storage systems for portable equipment, electronic devices and high power applications (e.g. electronic vehicles). One issue with the commercialized LIB is that expensive, highly toxic and flammable organic solvents are used in the electrolyte and the fabrication process of electrodes. The toxic organic based solvents increase the production cost and lead to significant safety concerns in the event of a battery overcharge or short circuit. The recent development of “green manufacturing” technology allows manufacturers to replace the organic solvents used in the cathode coating process by aqueous based …

Experimental Methods In Cryogenic Spectroscopy: Stark Effect Measurements In Substituted Myoglobin, Bradley Michael Moran

Theses and Dissertations

Dawning from well-defined tertiary structure, the active regions of enzymatic proteins exist as specifically tailored electrostatic microenvironments capable of facilitating chemical interaction. The specific influence these charge distributions have on ligand binding dynamics, and their impact on specificity, reactivity, and biological functionality, have yet to be fully understood. A quantitative determination of these intrinsic fields would offer insight towards the mechanistic aspects of protein functionality. This work seeks to investigate the internal molecular electric fields that are present at the oxygen binding site of myoglobin.

Experiments are performed at 1 K on samples located within a glassy matrix, using the …

Development Of An Automated Detection System For Nitrite In Aquatic Environments, Tim Schierenbeck

Theses and Dissertations

The main objective of the project is to develop an automated nitrite sensor for use in aquatic environments, and more specifically for use in recirculating aquaculture systems (RAS), where monitoring can help sustain a controlled environment, protect against nitrite intoxication, and promote fish health. Detecting nitrite manually with semi-quantitative colorimetric test kits, although inexpensive and simple, is prone to inter-user variability and poor sensitivity. An automated nitrite sensor has potential to provide higher resolution measurements at both concentration and time scales and can serve as a research tool for the study of filtration systems essential in maintaining a healthy RAS …

Seasonal And Spatial Variations In Chemical Composition And Fluxes Of Dissolved Organic Matter And Nutrients In The Lower Milwaukee River, Tarek A. Teber

Theses and Dissertations

Physical, chemical and biological processes directly influence the transport, composition, and fluxes of dissolved organic matter (DOM) in river watersheds. Changes in the abundance and composition of DOM and nutrients (P&N) in the watershed should reflect changes in hydrological cycle, effluent discharge, land-use and land-cover, and anthropogenic activities in the river basin, especially in rivers that run through metropolitan areas such as the Milwaukee River. Despite the importance of DOM to ecosystem health and function, a literature search to date finds no comprehensive accounting of DOM in the Milwaukee River. To examine DOM dynamics, monthly water samples were collected between …

Development Of Cellular High Throughput Assays To Determine The Electrophysiological Profile Of Gaba(A) Receptor Modulators For Neurology And Immunology, Nina Yina Yuan

Theses and Dissertations

Gamma (γ) -aminobutyric acid (GABA) is the major inhibitory neurotransmitter found in

the mammalian central nervous system. Its effect stems from its ability to cause the opening of ion channels which causes an influx of negatively charged chloride ions or an efflux of positively charged potassium ions. This hyperpolarization of the neuron lowers the threshold for neuronal firing. This has an overall inhibitory effect on neurotransmission, decreasing the excitability of the neuron and diminishing the likelihood of a successful action potential occurring. There are two classes of GABA receptor: ligand-gated GABAA receptor (GABAAR) and metabotropic GABAB receptor (GABABR). The GABAAR …

Molecular Recognition In Water: Design, Synthesis, And Characterization Of Rigid Molecular Receptors And Enzymatic Mechanistic Probes, Robert William Hoppe

Theses and Dissertations

Molecular recognition can be defined as a selective and reversible binding between two or more molecules through non-covalent interactions. Multiple weakly attractive intermolecular forces work in concert to achieve selectivity in association. Such discrimination is critical to the physiological processes of catalysis, transport, antigen recognition, and storage. To better understand this phenomenon, acyclic synthetic molecular receptors also known as “molecular tweezers” were made to study the inclusion of small molecule guests from water. Three anionic tweezers derivatives with syn¬- cofacial orientation were constructed from a 1,2:4,5-bis-Trӧger’s Base skeleton that differed in the amount and distribution of negative charge about the …

The Role Of Proteome In Cellular Zn2+ Trafficking And In The Ability Of The Fluorescent Zinc Sensors To Image Intracellular Zn2+, Mohammad Rezaul Karim

Theses and Dissertations

Zinc is an essential biological trace metal used in as many as 3000 Zn-proteins, about 10% of the eukaryotic proteome, as either a structural constituent or a catalytic cofactor. These proteins include the zinc fingers, the most prevalent transcription factors that bind a wide range of gene promoters and thus regulate gene expression. A eukaryotic cell contains several hundred micromolar of Zn2+- almost all of it is bound to specific Zn-proteins. Recently, Zn2+ has been reported to serve as a regulatory signal and a neurotransmitter, suggesting that there also exists a dynamic Zn2+ pool in cells. These findings led to …

Structural And Functional Characterization Of Acetoacetate Decarboxylase-Like Enzymes, Lisa Mueller

Theses and Dissertations

The acetatoacetate decarboxylase-like superfamily (ADCSF) is a largely unexplored group of enzymes that may be a potential source of new biocatalysts. Bioinformatic analysis has grouped these approximately 2000 enzymes into seven different families based on comparison of predicted active site residues. To date, only the prototypical ADCs (Family I) that catalyze the decarboxylation of acetoacetate have been studied. Analysis of gene context suggests that Family V contains predominantly enzymes predicted to be involved in secondary metabolism. On average, these share about 20% sequence identity to the true ADCs. To learn more about the diversity of chemistries performed by members of …

The Synthesis Of Fluorescent 3, 6-Dihydroxyxanthones: A Route To Substituted Fluoresceins, Surajudeen Omolabake

Theses and Dissertations

ABSTRACT

THE SYNTHESIS OF FLUORESCENT 3, 6-DIHYDROXYXANTHONES:

A ROUTE TO SUBSTITUTED FLUORESCEIN

by

Surajudeen Omolabake

University of Wisconsin-Milwaukee, 2016

Under the Supervision of Professor Alan W Schwabacher

Xanthones belong to the family of compounds of the dibenzo-γ-pyrone framework. Naturally occurring xanthones have been reported to show a wide range of biological and medicinal activities including antifungal,19 antimalarial,20 antimicrobial,21 antiparasitic,22 anticancer,23 and inhibition of HIV activity in cells.24 Xanthones have also been used as a turn on fluorescent probe for metal ions,32 including use as pH indicators, metal ion sensors, in molecular biology, medicinal chemistry and in the construction of other …

Synthesis Of Subtype Selective Bz/Gabaa Receptor Ligands For The Treatment Of Anxiety, Epilepsy And Neuropathic Pain, As Well As Schizophrenia And Asthma, Michael M. Poe

Theses and Dissertations

The α2/α3 subtype selective Bz/GABAA receptor positive allosteric modulator HZ-166 (3) has been shown to be a nonsedating anxiolytic with anticonvulsant and antihyperalgesic activity. However, instability in vitro and in vivo has hindered its advancement into clinical trials. A series of ligands based off HZ-166 (3) were synthesized. Many of these ligands were designed to increase metabolic stability, while others were synthesized to study the effects that electronics and sterics have on the efficacy exerted when bound to the GABAA receptor. The α3 subtype selective methyl ester MP-III-024 (19) was shown to have increased resistance to metabolism in in vitro …

Electrical Measurements And Attenuated Total Reflection Infrared Spectroscopic Study Of Aromatic Isocyanides And Thiols On Gold, Rasha Khaled Abuflaha

Theses and Dissertations

In 1947, Bell Laboratories produced an amplifier design in which an electric field would enhance the flow of electrons near the surface of a layer of silicon, it was called the “point-contact transistor”, the world’s first semiconductor amplifier. In order to minimize the electronic circuit elements (device miniaturization), the ability to utilize single molecules that function as self-contained electronic devices (molecular electronics) has motivated researchers around the world. Molecular electronics investigates single molecules and collections of molecules assembled into electronic circuits. Currently, semiconductor devices are fabricated using a “top-down” approach that employs lithographic and etch techniques to pattern a substrate, …

The Function Of Renalase, Brett Allen Beaupre

Theses and Dissertations

Renalase was originally reported to be an enzyme secreted into the blood by the kidney to lower blood pressure and slow heart rate. Despite multiple reports claiming to confirm this activity in vivo there has been considerable discord in regards to the reaction catalyzed by renalase. The structural topology of renalase resembles that of known flavoprotein oxidases, monooxygenases and demethylases, but the conserved active site residues are unique to renalase. It has been reported that the catalytic function of renalase is to oxidize circulating catecholamines, however in vitro studies have failed to demonstrate a catalytic activity in the presence of …

Synthesis And Performance Analysis Of Polyurethane Foam Nanocomposite For Arsenic Removal From Drinking Water, Faten Bakri Hussein

Theses and Dissertations

Water contamination by various heavy metal pollutants such as, Lead, Arsenic, Cadmium, and Mercury, have severe toxic effects on living organisms and humans. High concentrations of arsenic in drinking water cause serious damage to the central and peripheral nervous systems, as well as, the dermal, cardiovascular, gastrointestinal, and respiratory systems. Arsenic contamination of ground water poses a substantial concern in many countries throughout the world, including the United States.

Considerable research work, aimed at finding and developing various separation and treatment techniques, has been conducted over the past few decades. The conventional treatment methods of arsenic involve coagulation with ferric …

Variable Pathlength Cavity Spectroscopy Development Of An Automated Prototype, Ryan Schmeling

Theses and Dissertations

ABSTRACT

VARIABLE PATHLENGTH CAVITY SPECTROSCOPY

DEVELOPMENT OF AN AUTOMATED PROTOTYPE

by

Ryan Andrew Schmeling

The University of Wisconsin-Milwaukee, 2016

Under the Supervision of Professor Joseph H. Aldstadt III

Spectroscopy is the study of the interaction of electromagnetic radiation (EMR) with matter to probe the chemical and physical properties of atoms and molecules. The primary types of analytical spectroscopy are absorption, emission, and scattering methods. Absorption spectroscopy can quantitatively determine the chemical concentration of a given species in a sample by the relationship described by Beer’s Law. Upon inspection of Beer’s Law, it becomes apparent that for a given analyte concentration, …

Encapsulation Of Cationic Fluorescent Dyes And Photosensitizers Into The Nanoscopic Domains Of Poly(Ethylene Glycol)-B-Poly(Ε-Caprolactone) Micelles, Zhe Cao

Theses and Dissertations

This study describes an initial systematic investigation on the molecular determinants associated with the effective encapsulation (or lack thereof) of small cationic molecules into the nanoscopic domains of Poly(ethylene glycol)-b-poly(ε-caprolactone) micelles. Out of the seven model dyes investigated here (methylene blue, crystal violet, rhodamine 123, styryl 9M, HITC, DIR and Cardiogreen) only DiR and Cardiogreen were found to partition into the core region of the respective polymeric micelles with a high degree of efficiency. Evidences of weak interactions between styryl 9M and HITC with the corona region of these micelles were also found. No experimental evidences indicating any significant interaction …