Physical Sciences and Mathematics Commons^™

Studies Of The Reaction Of Rongalite With Epoxides, Anuj Aryal

Theses, Dissertations and Culminating Projects

Reactions between Rongalite (Na⁺O^-SOCH₂OH) and epoxides were studied with the aim of developing new synthetic routes for the procurement of sulfone diols. This class of compounds contains essential building blocks in the construction of sulfur heterocycles, which have been implied in the development of several medicinal compounds. Thus far, the desired diols have not been isolated. During control experiments with bromo alcohols, an unknown product was isolated but remains to be identified.

Design Of Block Copolymer With Tunable Hydrophobic/Hydrophilic/Fluorophilic Interactions, Tatiane De Fatima Dutra

Theses, Dissertations and Culminating Projects

Block copolymers (BCP) with balanced interactions and their resultant bulk-phase self-assembly have become increasingly important in advancing nanotechnology, separation, and energy applications. However, a few reports have addressed the synthesis challenge and bulk-phase self-assembly of such triblock copolymers. This thesis presents a facile route for preparing triblock copolymer via controlled radical and organocatalytic ring-opening polymerization that allows precise control over the incorporation of individual moieties in resultant polymer, responsible for balanced hydrophilic, hydrophobic/lipophilic, and fluorophilic interactions. Synthesized polymer with suggested self-assembled 2D lamellar nanostructure exhibits high-temperature stability. The long-term goal of this work is to selectively use this polymer class …

A Computational Study Of The Copper-Catalyzed Trifluoromethylation Of Boronic Acids, Kevin Nyhuis

Theses, Dissertations and Culminating Projects

This work is a computational study of a reaction mechanism for the trifluoromethylation of boronic acids. Three steps of the proposed reaction mechanism are studied, •CF₃ addition to a copper catalyst center, base promoted transmetalation between copper and aryl boronic acid, and bond forming reductive elimination in which the CF₃ and aryl substituent form a bond. Limited information is known about this mechanism. This study uses computational methods to attempt to elucidate the mechanism and provide the groundwork for potential improvement. Quantum chemical methods in conjunction with tight-binding based conformational sampling methods are used to investigate the possible …

An Investigation Towards The Synthesis Of A Novel Conformationally Restricted Ethylenediamine Scaffold, Fanny Mai

Theses, Dissertations and Culminating Projects

This study reports the synthesis of a novel conformationally restricted ethylenediamine scaffold that can be explored for drug discovery. There was significant progress in synthesizing the target scaffolds, but future studies are needed to finish this synthesis. This potential ethylenediamine compound may offer new scaffolds for exploration in drug design and orexin receptor antagonists with improved selectivity for OX1R and OX2R.

Cyclic Sulfones From Double Conjugate Addition Of Rongalite, Hao Zong

Theses, Dissertations and Culminating Projects

We report a cyclic sulfone synthesis method from the addition of sodium hydroxymethanesulfinate to doubly electrophilic dienone substrates. The novel synthesis of the cyclic sulfone thus avoided the using the toxic and odorous sulfides, and also oxidizing reagents. We prepared both the symmetrical and unsymmetrical substrates, and then used the substrate for the synthesis of cyclic sulfone.

Vertical Metal Distributions In Brownfield Soils Drive Enzyme Activities And Plant Success, Eshariah N. Dyson

Theses, Dissertations and Culminating Projects

The distribution of contaminants in polluted soils can vary through depth. We measured the vertical distributions of heavy metals and enzyme activities in the top 10 cm of side-by-side, vegetated and barren brownfield soils. The data showed metals significantly accumulated in the top 2 cm of barren soil and uniformly distributed through vegetated soil. When planted, germination rate was significantly lower in the previously barren soil, with the metal layer intact, compared to mixed barren soil. These data suggest a feedback loop in which plant roots redistribute metals, diluting metal-rich regions, yet germination remains initially limited by a metal cap. …

Investigating The Effects Of Catalytic Activity In Mycobacterium Tuberculosis Indole-3-Glycerol Phosphate Synthase In Wildtype, N189l, And E57d Variants, Sarah S. Cho

Theses, Dissertations and Culminating Projects

Indole-3-glycerol phosphate synthesis (IGPS) is an enzyme that catalyzes the ring closure in 1-(o-carboxylphenylamino)-1-deoxyribulose 5-phosphate (CdRP). Multiple steps are expected to be involved in formation of the pyrrole ring including dehydration, decarboxylation, cyclization, and condensation. IGPS is an essential protein in the pathogen Mycobacterium tuberculosis and a potential target in the treatment of drug-resistant tuberculosis. In order to better understand the function of Mycobacterium tuberculosis IGPS (mtIGPS), we introduced single-point mutations into active site residues. This was based on the hypothesis that introducing mutations would affect the catalysis in a way where we would be able to obtain more information …

Determining The Relative Activities Of Wild-Type Mycobacterium Tuberculosis Indole-3-Glycerol Phosphate Synthase And Mutants E57a And E219a With An Investigation Into The Relationship Between Wild-Type Mycobacterium Tuberculosis Igps Activity And Ph, Thomas Emmanuel Candela

Theses, Dissertations and Culminating Projects

The relationship between wild-type protein indole-3-glycerol phosphate synthase (IGPS) activity and pH was investigated through the formation of pH activity profiles, and the relative catalytic activities of wild-type Mycobacterium tuberculosis and mutants E57A and E219A were also deduced in this work. The activity of each enzyme variant was determined by reacting native substrate 1-(o-carboxyphenylamino)-1-deoxyribulose-5-phosphate with enzyme buffered at pH 7.5 in a cuvette and using a fluorometer to detect the increase in fluorescent signal produced by the formation of fluorescent product indole-3 glycerol phosphate. Work with wild-type IGPS showed the enzyme to have a kcat of 1.26 ± 1.75 (s …

Characterizing Functions Of Two Regulatory Proteins In The Parasitic Nematode Brugia Malayi And Their Potential As Drug Targets In Treating Lymphatic Filariasis, Brittany Amber Hart

Theses, Dissertations and Culminating Projects

Lymphatic filariasis (LF) is a debilitating disease caused by parasitic nematodes that affect millions of people in largely tropical environments. While drugs are available for treating LF, they suffer from a lack of efficacy against adult parasites, toxicity, and emergence of resistance. Here, we describe two novel potential drug targets within the filarial parasite, Brugia malayi (B. malayi). These two proteins, bm9350, a predictive MAPK stress response protein, and bm2032, a potential histone modifying enzyme, have little or no annotation or experimental evidence of function. Using predictive analysis and tools, we examined potential functions of these proteins and their potential …

Studies Toward The Synthesis Of A Novel Diamine Scaffold, Joseph Edward Quinlan Iii

Theses, Dissertations and Culminating Projects

The orexin system in humans contains receptors Orexin 1 (OX1) and Orexin 2 (OX2). These receptors are involved in numerous physiological processes including wake/sleep cycling, energy homeostasis, and motivation/reward. In scientific literature, it is known that antagonism of these receptors exhibits therapeutic effects in the realm of cocaine and alcohol addiction, as well as sleep disorders. On the market today exist drugs for treatment of sleep disorders through orexin receptor antagonization. Here we report a synthesis toward novel conformationally rigid antagonists of the orexin receptor system that may provide improved affinity and/or selectivity compared to known compounds. We report the …

Discovery Of Single-Stranded Dna Aptamers For The Detection Of Ranavirus, Allyssa Angel

Theses, Dissertations and Culminating Projects

A key problem when developing molecular diagnostic techniques is procuring target detection probes. The need of a stable and selective probe is necessary for accurate target identification in disease detection. Antibodies are widely used but they are unstable at ambient temperatures and are expensive and time consuming to develop. The use of aptamers (short singlestranded DNA) as molecular probes provides several advantages over protein-based methods because they are more stable, easily selected and modifiable. The need of a reliable and stable probe is necessary for accurate detection tests in the field for disease monitoring. Currently, field methods are limited in …

Synthesis Of Amide And Sulfonamides As Pde11 Inhibitors, Noor Abouchakra

Theses, Dissertations and Culminating Projects

With increasing age, individuals begin to experience cognitive decline, especially memory deficits. Given the lack of effective treatments for memory loss, a new promising approach includes targeting second messenger systems that play a critical role in cognitive processes by inhibiting phosphodiesterases (PDEs), specifically PDE11A since its expression is restricted to the brain. PDE11A is responsible for regulating levels of second messengers, such as cyclic AMP and cyclic GMP, which participate in several biochemical processes relating to long term memory function. Since these signaling cascades are controlled by PDEs that result in turning off the signaling pathway, inhibiting phosphodiesterases will lead …

A Study And Synthesis : Bronze Compounds, Patricia Rose Olsen

Theses, Dissertations and Culminating Projects

The focus of this thesis is the investigation of ternary and quaternary reduced metal oxide compounds termed “bronzes.” The name bronze originally arose from the metallic-like luster of these compounds. Examples of these compounds range from sodium tungsten oxides to the more complex potassium cesium molybdenum oxides. These compounds are crystalline solids at room temperature.

The “bronzes” are compounds that have been studied since their initial synthesis by Wohler in 1824. These compounds belong to a class of compounds that are known as “nonstoichiometric” compounds. The general formula for reduced ternary transition metal oxides is AxMyOz. In this general formula, …

A Comparative Study Of Drug Affinities Determined By Thermofluor And Kinetic Analysis, Oruba Shatnawi

Theses, Dissertations and Culminating Projects

Determining the binding affinity and potency in vitro is one of the significant steps that can give a clue for a new candidate drug during the drug discovery process. Thermofluor is a method used in measuring binding affinity (Kd) of protein-ligands interaction through determining the change in thermal denaturation temperature of protein using real time PCR (RT-PCR). Kinetic analysis assay is used to screen a library of compounds to calculate their potencies (IC50) and inhibition constants (Ki) and it can be performed by spectrophotometer technique. In this study, we used bovine carbonic anhydrase II (BCA II) enzyme, and four of …

Preparation And Crystal Structures Of Racemic And Quasiracemic Imidazole Or N-Methyl Imidazole Copper Complexes Containing Substituted N-Benzoylalanines, Emily Catherine Chong

Theses, Dissertations and Culminating Projects

A quasiracemate is the cocrystallization of two similarly shaped but chemically distinct molecules of opposite handedness. There has been limited to no work regarding quasiracemates in the field of inorganic chemistry. The goal of this study was to prepare various metal based enantiomers, racemates, and quasiracemates using N-benzoylalanines with imidazole or N-methylimidazole as ligands bound to copper to form a metal complex. In this study, we developed a method to prepare substituted N-benzoylalanines and its copper complexes. We also prepared one co-crystal between two differently substituted N-benzoylalanines.

This work reports the successful synthesis and crystal structure analysis of an organic …

The Effects Of Active Site And Allosteric Residues On Catalysis And Inhibitor Selectivity In The Bacillus Stearothennophilus Dihydrofolate Reductase, Tyler Eck

Theses, Dissertations and Culminating Projects

In drug discovery, building a comprehensive picture of the binding events between a drug and its enzyme target can be useful, especially in the development of new drugs or predicting the effect of a drug on a similar target from the same protein family. It is well known that a drug's selectivity is influenced by its interactions with amino acid residues within the active site, but contributions from residues situated away from (distal to) the active site are less well understood. Using a novel predictive approach PAnPredictor that employs sequence alignments, we have previously predicted residue positions in the dihydrofolate …

Indole-3-Glycerol Phosphate Synthase Ligand Binding Interactions, Oshane Thomas

Theses, Dissertations and Culminating Projects

Indole-3-glycerol phosphate synthase (IGPS) catalyzes the irreversible ring closure of 1-(ocarboxyphenylamino)- 1-deoxyribulose 5- phosphate (CdRP) into indole-3-glycerol phosphate (IGP) during the fourth step in tryptophan biosynthesis. Analysis of the crystal structure of IGPS from Mycobacterium tuberculosis (MtIGPS) hinted the importance of Lys119 for binding or catalysis. Lys110 from sulfolobus sulfataricus IGPS (ssIGPS) that aligns with Lys119 from MtIGPS, was proposed to be a general acid for the proton transfer that initiates the ring closure and decarboxylation of CdRP. To study the importance of Lys119 in the chemical mechanism for MtIGPS, an amino acid change was made at this position to …

Light Addressable Electrode For Neurotransmitter Sensing, Irina Michelle Terrero Rodríguez

Theses, Dissertations and Culminating Projects

Electrochemical sensors are important for a variety of applications. However, they suffer from physical constraints, as each electrode requires a dedicated wire. Although arrays of 500 electrodes have been reported, achieving high-density electrochemical measurements is still difficult.

In a light-addressable electrode, electrochemical processes occur only when the electrode is illuminated. Light-addressable electrodes could potentially solve many of the drawbacks of traditional electrode arrays, as light is used to spatially confine the redox process to only a small part of the electrode and only one connection is needed. It could also allow for new imaging techniques.

Light-addressable electrodes require a semiconductor …

Inhibition Of Hsv-1 Binding By Egcg-Stearate, Valerie Paschalis

Theses, Dissertations and Culminating Projects

Herpes simplex virus type 1 (HSV-1) is the causative agent of oral herpes, and is able to establish lifelong latent infection along with painful, recurring symptoms. Epigallocatechin-3- gallate (EGCG) is the most abundant polyphenol derived from green tea (Camellia sinensis), whose anti-inflammatory, antioxidant, anti-cancer, and antiviral properties have been widely studied. Although EGCG is not chemically stable and has poor hydrophobicity, lipophilic derivatives of EGCG have shown increased stability as well as increased antiviral efficacy against HSV. Previous studies have demonstrated that EGCG stearate (EGCG-S), a derivative of EGCG esterified at the 4’ position with stearic acid, is able to …

Elucidation Of Substrate Binding To Photolyase From Sulfolobus Solfataricus Using Isothermal Titration Calorimetry, Amanda Rose Kuerzi

Theses, Dissertations and Culminating Projects

DNA photolyase is a DNA repair enzyme commonly found across the kingdom of life. Binding studies for the hyperthermophilic photolyase derived from Sulfolobus solfataricus (SsPL) may serve to illuminate how DNA photolyase can adapt over a large temperature range. In the first section of this study, the thermodynamics of substrate binding for SsPL in a choline chloride buffer were determined using isothermal titration calorimetry. Using the Counter-Ion Condensation Concept as a model, ionic strength studies were performed to separate the binding interactions into electrostatic, and nonelectrostatic components. The electrostatic interactions do not appear to make a significant contribution to the …

Presence Of Cofactor Nadph Slows Down The Dissociation Of Methotrexate From Dihydrofolate Reductase From Bacillus Stearothermophilus, Ryan Seamus Foley

Theses, Dissertations and Culminating Projects

The goal of this project was to study the effect of the presence or absence of the cofactor NADPH on the binding and release of ligand methotrexate (MTX) to/from Bacillus stearothermophilus (Bs) dihydrofolate reductase (DHFR). A previously developed, fluorescently-labeled Bs DHFR (C73A/S131CMDCC DHFR) was used to investigate the kinetics and protein conformational motions associated with the binding of NADPH and the binding of methotrexate to the holoenzyme. This Bs DHFR contains a distal cysteine where the fluorophore, N-[2-(1-maleimidyl)ethyl]-7-(diethylamino)coumarin-3-carboxamide (MDCC) can be covalently attached. This probe is sensitive to the local molecular environment, reporting on changes in the protein conformation associated …

Crispr/Cas9 In Leishmania Genome Editing : Towards A Proof Of Concept, Zein Kasbo

Theses, Dissertations and Culminating Projects

Leishmaniasis is a parasitic Neglected Tropical Disease (NTD) that affects mostly poor countries of the third word due to their limited access to clean water and health care. The disease is transmitted through the bite of a sand fly of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Historically, NTDs have not been given adequate attention or research funding and finding curative treatments has been slow. However, the fact that the insect vector and the parasite can live and thrive in any ecological system in the world, and under the current circumstances …

A Computational Study Of C-Cn Bond Activation Through Nickel Catalysis Using The Random Phase Approximation, Craig Waitt

Theses, Dissertations and Culminating Projects

This study evaluates the performance of a computational method known as the Random Phase Approximation (RPA) for a Nickel catalyst that activates the C-CN bond of benzonitrile. The reaction mechanism contains two distinct processes. The first process describes the cleavage of the C-CN bond of benzonitrile. The latter describes the fluxionality of benzonitrile about the Nickel atom. Many popular computational methods would struggle to properly describe either or both processes, because they may not perform consistently for transition-metal complexes, are computationally expensive, or have a strong dependence on orbital energy gaps. The RPA provides results with an excellent balance of …

The Mechanism Of Inhibition Of Botulinum Neurotoxin Type A By Two Quinolinol Compounds, Yacoba Vroom Teschemaker Minnow

Theses, Dissertations and Culminating Projects

Quinolinol-based compounds are a promising starting point for discovery o f effective inhibitors o f the clostridial neurotoxin, botulinum neurotoxin type A light chain (BoNT/A LC). Insights into the mechanism o f inhibition by quinolinol compounds facilitate interpretation o f docking data and inhibitor optimization. In this study, a fluorogenic substrate o f BoNT/A, SNAPtide, was used to study the mechanism by which two new quinolinol compounds, MSU58 and MSU84, with IC₅₀ values of 3.3 uM and 5.8 uM, respectively, inhibit BoNT/A LC. Kinetic studies and model discrimination analysis showed both compounds to be competitive inhibitors o f BoNT/A …

Investigation Of Hsp90 Structure-Activity Relationships In Epigallocatechin Gallate, Arpita Patel

Theses, Dissertations and Culminating Projects

(-)-Epigallocatechin gallate (EGCG) is a polyphenolic natural product that inhibits the key chaperone protein Hsp90 by binding to the carboxy terminal portion of the protein. The natural product has modest activity as an Hsp90 inhibitor and there is little information in the literature on structure activity relationships for EGCG analogs. Previous studies from this laboratory provided initial data on the effect of a limited range of changes associated with functional groups, substituents and stereochemistry. The focus of this research is to explore these initial results in more detail with a focus on the synthesis of EGCG analogs with more drug …

The Effects Of Heavy Metals And Microbes On Extracellular Enzyme Activity At Liberty State Park, Eleanor Urenna Ojinnaka

Theses, Dissertations and Culminating Projects

The overall goals of this research were to 1) understand the influence of microbes and heavy metals on extracellular enzyme activity in soil environments and 2) explore the possibility of using living organisms, such as microbes, to improve the enzyme activity of contaminated, poor-functioning soil—bioremediation. Microbes exude enzymes into the soil, which are vital in the cycling of nutrients in soil communities. Thus, measuring extracellular enzyme activity can be used to quantify the health of soil. In this experiment, phosphatase enzyme was measured as a proxy for enzyme activity. The study site is a closed-off section of Liberty State Park …

Modeling The Formation Of Tetrahydropyranyl Radicals Via Hydrogen Abstraction, Robert Booth

Theses, Dissertations and Culminating Projects

A computational analysis was performed on the reaction between tetrahydropyran (THP) and atomic bromine in order to gain a better understanding of the energetics of the addition-elimination mechanism as compared to similar chemical reactions. Prior to the reaction energetics study, a separate analysis was performed on substituted tetrahydropyran derivatives in order to optimize the computational methods being used, to understand the extent of the anomeric effect in tetrahydropyran, and to understand solvent contributions to the energies of the tetrahydropyran derivatives. Trial calculations were performed using Hartree-Fock (HF) theory, Density Functional theory (DFT), and second-order Moller-Plesset perturbation (MP2) theory, and it …

Expression, Purification, Enzymatic And Inhibition Profile Of Brugia Malayi Dihydrofolate Reductase, Romy Perez-Abraham

Theses, Dissertations and Culminating Projects

Dihydrofolate reductase (DHFR) is an essential enzyme that plays an important role in the production of cofactors that are required in deoxyribonucleic acid (DNA) synthesis. The literature suggests that DHFR is a potential drug target for the elimination of the parasitic worm, B. malayi. B. malayi is one of the causative parasites of lymphatic filariasis, a globally neglected tropical disease. In this study, we expressed and purified B. malayi DHFR. Expression was carried out in E. coli with a His6-tagged construct, and purification was achieved through affinity chromatography using a special strain of E. coli cells called “LOBSTR.” The resulting …

Ionic Liquid Based Fluorescent Sensors For Cations, Jaelene M. Torres

Theses, Dissertations and Culminating Projects

The development of novel fluorescent sensors for cations is an area of current interest. Most of these sensors are large organic molecules that have a low solubility in water and are not suitable to be used as sensors in water. The goal of this study is to develop a new sensor by attaching an ionic liquid group to make it water-soluble. We have used a well-known photoinduced electron transfer (PET) sensor for protons as our first test. This sensor is based on a chromophore-spacer-receptor design that is based on an anthracene chromophore and a morpholine proton receptor. The sensor is …

Effects Of Allosteric Mutations On Dihydrofolate Reductase, Marian Okondo

Theses, Dissertations and Culminating Projects

Dihydrofolate reductase (DHFR) is an essential enzyme necessary in the synthesis of DNA precursors. DHFR acquires resistance to numerous known anti-folates and this has led to the continuous need to discover novel and selective DHFR inhibitors. Allosteric mutations on Bacillus stearothermophilus (Bs.) DHFR were previously found to alter inhibitor binding and specificity. In this work, we investigate how these mutations affect the conformational motions of DHFR associated with inhibitor binding. Two distal allosteric mutations, isoleucine at position 86 to alanine (I86A) and tyrosine at position 127 to alanine (Y127A) were separately introduced to C73A/S131C, a previously modified wild type DHFR …