Chemistry Commons^™

Cariporide Prodrugs: Targeting Brain Cancer Cells Through Sodium-Proton Exchange Inhibition, Jacob Vervynckt, Johnathan Brantley, Jessica Moore, Mark Graves Ii, William Harley, Fredric A. Gorin, Hasan Palandoken

Chemistry and Biochemistry

More than 200,000 people in the United States are diagnosed with a primary or metastatic brain tumor annually. The life expectancy for these individuals is approximately 9-12 months from the time of diagnosis. This poor prognosis is due to the ineffectiveness of existing therapies (i.e., chemotherapy and radiotherapy) against brain cancer, where the primary problem is the inability to differentiate cancer cells from healthy brain cells.

Relative to healthy brain tissue, the heightened metabolism of cancer cells increases their reliance on the ion transport proteins NHE (sodium-proton exchanger) and NCX (sodium-calcium exchanger). Inhibition of these proteins disrupts the intricate pH …

Removal Of Benzaldehyde From Methanol Using Alkoxyamine Functionalized Silica Gel, Dino Sulejmanovic, Carrie Jo Pruitt, Eric Conte, Hasan Palandoken, Shing-Yi Suen

Chemistry and Biochemistry

Alkoxyamines (RONH₂) react readily with aldehydes and ketones to form stable oxime ethers, and, thus are expected to be excellent scavengers of these compounds. We installed alkoxyamines on silica gel surface to remove benzaldehyde from methanol. Silica gel was immersed in H₂O₂/H₂SO₄ solution to activate the surface. Activated silica gel was then reacted with 3-chloropropyltrichlorosilane. Displacement of the chloride with N-hydroxyphthalimide and subsequent treatment with hydrazine provided alkoxyamines on the surface of silica gel. The resulting silica gel surface with alkoxyamine functional groups was immersed in a 100 ppm benzaldehyde solution …

The Effects Of A Networked Data Acquisition System On Student Learning In General Chemistry Laboratories, Stuart C. Burris, Les L. Pesterfield, Darwin Dahl, Hasan Palandoken, Jacqueline Pope-Tarrence

Chemistry and Biochemistry

We have recently incorporated a networked data acquisition and analysis system into in our second semester general chemistry laboratories. Our investigation team has conducted a study to evaluate the effects of the networked data acquisition system on student performance on a Beer's Law laboratory. We focused on two specific phenomena: the effect of the networked data acquisition system on 1) student learning of specific content material and 2) student comfort level with laboratory work and data analysis. The study involved a networked data acquisition group (employing a UV-Vis spectrometer and colorimeters) and a control group (employing traditional, single wavelength spectrometers). …

Photocycloaddition Of Allenes, Crystal Ward

Theses and Dissertations

For the past ten years the Fleming research group has been involved in the research of allene compounds. We have explored the synthesis of allenes as well as several reactions involving allenes, such as oxidation and nitrene addition. Recently, we have explored the synthesis and photochemistry of allenic alcohols tethered to silicon. There are literature examples using allenes in synthesis, but very few examples exist using allenes in photochemical cycloaddition reactions. We have found that a diisopropylallenyloxy(cinnamyloxy)silane derivative undergoes [2+2] photochemical cycloaddition to produce a cyclobutylsilane product when irradiated for 60-75 minutes.

Simple Inhibitors Of Histone Deacetylase Activity That Combine Features Of Short-Chain Fatty Acid And Hydroxamic Acid Inhibitors, Jessica L. Tischler, Basel Abuaita, Sierra C. Cuthpert, Christopher Fage, Kristi Murphy, Andrew Saxe, Edward B. Furr, Jamie Hedrick, Jennifer Meyers, David Snare, Ali R. Zand

Chemistry & Biochemistry Publications

Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds' ability to inhibit rat-liver HDAC using a fluorometric assay. In keeping with previous structure-activity relationships, the most effective inhibitors consisted of longer …

Phosphorylation Of P27kip1 Regulates Assembly And Activation Of Cyclin D1-Cdk4, Michelle D. Larrea, Jiyong Liang, Thiago G. Da Silva, Feng Hong, Shan H. Shao, Kathy Han, D. Dumont, Joyce M. Slingerland

Chemistry and Physics Faculty Articles

p27 mediates Cdk2 inhibition and is also found in cyclin D1-Cdk4 complexes. The present data support a role for p27 in the assembly of D-type cyclin-Cdk complexes and indicate that both cyclin D1-Cdk4-p27 assembly and kinase activation are regulated by p27 phosphorylation. Prior work showed that p27 can be phosphorylated by protein kinase B/Akt (PKB/Akt) at T157 and T198. Here we show that PKB activation and the appearance of p27pT157 and p27pT198 precede p27-cyclin D1-Cdk4 assembly in early G₁. PI3K/PKB inhibition rapidly reduced p27pT157 and p27pT198 and dissociated cellular p27-cyclin D1-Cdk4. Mutant p27 allele products lacking phosphorylation at …

Molecular-Orientation-Dependent Ac Stark Effect And Its Impact On Multiphoton Processes, Xi Chu

Chemistry and Biochemistry Faculty Publications

We study the dependence of the ac Stark shifts of electronic energies on the molecular orientation relative to the polarization direction of an incident intense laser field, using a three-dimensional non-Hermitian Floquet method and H(2)+ as a model system. Simultaneously, we also study the orientation-dependent high-order harmonic generation (HHG) and multiphoton ionization (MPI). We find that with the presence of near-one-photon resonance, the Stark effect strongly mixes electronic states of different symmetries to create quasienergy states (QESs). The orientation dependence of multiphoton processes, in which these QESs play an important role, becomes complex. Population transfer is better achieved with aligned …

Oriented Cell Growth On Self-Assembled Bacteriophage M13 Thin Films, Jianhua Rong, L. Andrew Lee, Kai Li, Brandon Harp, Charlene M. Mello, Zhongwei Niu, Qian Wang

Faculty Publications

Fibrillar M13 bacteriophages were used as basic building blocks to generate thin films with aligned nanogrooves, which, upon chemical grafting with RGD peptides, guide cell alignment and orient the cell outgrowth along defined directions.

Non-Canonical Binding Of Calmodulin To Aquaporin-0: Implications For Channel Regulation, Steve Reichow, Tamir Gonen

Chemistry Faculty Publications and Presentations

Aquaporins (AQPs) are a family of ubiquitous membrane channels that conduct water across cell membranes. AQPs form homo-tetramers containing four functional and independent water pores. Aquaporin-0 (AQP0) is expressed in the eye lens where its water permeability is regulated by calmodulin (CaM). Here we use a combination of biochemical methods and NMR spectroscopy to probe the interaction between AQP0 and CaM. We show CaM binds the AQP0 C-terminal domain in a calcium dependent manner. We demonstrate that only two CaM molecules bind a single AQP0 tetramer in a non-canonical fashion, suggesting a form of co-operativity between AQP0 monomers. Based on …

I. Thermodynamics And Magnetism Of Cu2ocl2 Ii. Repairs To Microcalorimeter The "2"S Are Subscripts, And The Second 2 Is Preceded By A Lower Case L, Not A One, Thomas J. Parry

Theses and Dissertations

Adiabatic calorimetry provides accurate and precise specific heat (Cp) data. From this data, thermodynamic functions may be calculated. Cu2OCl2, melanothallite, became of interest as part of a study of a particular thermochemical cycle. The experimental specific heat data and the calculated thermodynamic functions are reported here. Free energies of formation, calculated from the thermodynamic functions, suggest the particular cycle of interest with this compound as an intermediate is not feasible; uncertainty as to the accuracy of CuO and CuCl2 data used in the calculations indicate further study may be necessary. Upon collection of the specific heat data, an antiferromagnetic transition …

A Radical Conjugate Addition Approach To The Total Synthesis Of Celogentin C, Steven G. Capps

Theses and Dissertations

The synthesis of five chiral DBFOX (dibenzofuran-oxazoline) ligands with either aryl or benzyl substituents will be presented. The requisite amino alcohols were obtained with high enantioselectivity either commercially (DBFOX/Bn), via Sharpless asymmetric aminohydroxylation (DBFOX/Nap, DBFOX/t-BuPh, DBFOX/Pip), or via phase-transfer catalyzed asymmetric alkylation (DBFOX/MeNap). These ligands, complexed with Mg(NTf2)2, were used as Lewis acid promoters of enantioselective radical conjugate additions to α/β-unsaturated nitro-amides/esters. A summary of these results is presented and discussed. These findings led us to believe that our initial binding model between metal, ligand, and substrate was flawed. Thus, we figured that if we started with a functionality known …

Regulators Of G-Protein Signaling, Rgs13 And Rgs16, Are Associated With Cxcl12-Mediated Cd4+ T Cell Migration, Lijin Xia

Theses and Dissertations

Chemokines are important chemical signals that guide lymphocyte movement within the immune system and promote the organization and functions of germinal centers (GCs) in the secondary lymphoid tissues. Previous studies have shown that GC T cells exhibit high expression of chemokine receptor 4, CXCR4, but that these cells are unable to migrate to the ligand for this receptor, the chemokine CXCL12. This “migratory paralysis” to CXCL12 was found to be correlated with the expression of two Regulators of G-protein Signaling, RGS13 and RGS16 in the GC T cells. The objective of my research was to determine whether RGS13 and RGS16 …

A Fluorescent Photoinduced Electron Transfer (Pet) Sensor For Cations With A Separate Pet Channel To Suppress Proton Signals, Supun Pathirana

Theses, Dissertations and Culminating Projects

This thesis presents A-((10-((2-methoxy-4-methylphenoxy)methyl)anthracen-9- yl)methyl)(pyridin-2-yl)-A-((pyridin-2-yl)methyl)methanamine, 1, a photoinduced electron transfer (PET) sensor that acts as a fluorescent ‘Off-On’ switch in the presence of Zn ions and not sensitive to protons.

Spectroscopic Study Of Compressible Mobile Phase And Stationary Phase Behavior In Chromatography, Lawrence R. Baker

Theses and Dissertations

Raman spectroscopy, laser-induced fluorescence, and sum-frequency generation (SFG) spectroscopy are used to investigate the behavior of compressible mobile phases and stationary phases under a variety of chromatographic conditions. Efforts to understand and optimize separations employing compressible mobile phases have been limited by a lack of understanding of the mobile phase density gradient. Mobile phase compressibility leads to gradients in linear velocity and solute retention and affects separation speed and efficiency, especially in packed columns. This work describes on-column density measurement of CO2, a common carrier fluid for SFC and SGC, in packed capillary columns using Raman microspectroscopy. On-column detection by …

Genetic Analysis Of The Role Of Smpb In Establishing The Reading Frame On Tmrna, Talina Christensen Watts

Theses and Dissertations

Ribosomes translate the genetic information encoded by mRNA into proteins. Defective mRNAs can cause stalling of translating ribosomes. The molecule tmRNA (transfer-messenger RNA) rescues stalled ribosomes in eubacteria. Together with its protein partner SmpB, tmRNA mimics a tRNA by entering the ribosomal A site and linking an alanine residue to the growing polypeptide chain. The ribosome then abandons the defective mRNA template and resumes translation on tmRNA, adding ten more amino acids to the nascent polypeptide. As a result of tmRNA action, stalled ribosomes are released and recycled, the defective mRNA is destroyed, and the aborted protein product is tagged …

Ion Permeation Through Membrane Channels: Molecular Dynamics Simulations Studies, Morad Mustafa

Theses and Dissertations

Molecular dynamics simulation was used to study ion permeation through different membrane proteins embedded in a lipid bilayer (DMPC) with different saline solutions. The potential of mean force (PMF) for ion transport was obtained by umbrella sampling simulations. A revised MacKerell force field for tryptophan residues was studied using gramicidin A (gA) channel as a test model. The revised force field contribution to the Na+ PMF was consonant with the prediction from the experimental results, but in stark contrast to the prediction of the CHARMM force field, version 22, for the tryptophan side-chain. A new grid-based correction map algorithm by …

Electron Crystallography Of Aquaporins, Simeon Andrews, Steve Reichow, Tamir Gonen

Chemistry Faculty Publications and Presentations

Aquaporins are a family of ubiquitous membrane proteins that form a pore for the permeation of water. Both electron and X-ray crystallography played major roles in determining the atomic structures of a number of aquaporins. This review focuses on electron crystallography, and its contribution to the field of aquaporin biology. We briefly discuss electron crystallography and the two-dimensional crystallization process. We describe features of aquaporins common to both electron and X-ray crystallographic structures; as well as some structural insights unique to electron crystallography, including aquaporin junction formation and lipid-protein interactions.

The Role Of Upstream Sequences In Selecting The Reading Frame On Tmrna, Allen R. Buskirk, Mickey R. Miller, David W. Healey, Jonathan D. Dewey, Stephen G. Robison

Faculty Publications

tmRNA acts first as a tRNA and then as an mRNA to rescue stalled ribosomes in eubacteria. Two unanswered questions about tmRNA function remain: how does tmRNA, lacking an anticodon, bypass the decoding machinery and enter the ribosome? Secondly, how does the ribosome choose the proper codon to resume translation on tmRNA? According to the -1 triplet hypothesis, the answer to both questions lies in the unique properties of the three nucleotides upstream of the first tmRNA codon. These nucleotides assume an A-form conformation that mimics the codon-anticodon interaction, leading to recognition by the decoding center and choice of the …

Foundations And Interpretations Of Quantum Mechanics, Cory Johnson

Honors Theses

The first famous thought experiment of Einstein gives rise to his theories of relativity, the bedrock of modern astrophysics and cosmology. His second famous thought experiment begins the investigation into the foundations of quantum mechanics. It leads to a paradox, inspiring various 'no-go' theorems proven by Bell, Kochen, and Specker. Physicists and philosophers worldwide become increasingly dissatisfied with the probabilistic complementarity interpretation (Born-Bohr) and eventually offer their own accounts of the theory. By the end of the 20th century two alternative approaches stand out as the best candidates: Both the hidden variables interpretation (de Broglie-Bohm) and the many worlds interpretation …

Effects Of Context Of Natural And Artifactual Objects On Categorization, Linsey Walker

Honors Theses

Categorization of animals and vehicles in different contexts was investigated in three experiments using event related potentials (ERPs). The presence of a background and congruency of the background in relation to the object were both manipulated in order to determine the effects of context on visual processing. In Experiment 1, adults were presented with images of animals and vehicles in two conditions: situated in a congruent context (e.g. an animal in a field) and in the absence of a context (an animal in a white homogeneous background). In experiment 2, adults were presented with images of animals and vehicles in …

Identification Of Guanylate Cyclases And Related Signaling Proteins In Sperm Tail From Sea Stars By Mass Spectrometry, Mia Nakachi, Midori Matsumoto, Philip M. Terry, Ronald L. Cerny, Hideaki Moriyama

Hideaki Moriyama Publications

Marine invertebrates employ external fertilization to take the advantages of sexual reproduction as one of excellent survival strategies. To prevent mismatching, successful fertilization can be made only after going though strictly defined steps in the fertilization. In sea stars, the fertilization process starts with the chemotaxis of sperm followed by hyperactivation of sperm upon arriving onto the egg coat, and then sperm penetrate to the egg coat before achieving the fusion. To investigate whether the initiation of chemotaxis and the following signaling has species specificity, we conducted comparative studies in the protein level among sea stars, Asterias amurensis, A. forbesi …

Optimization Of Expression And Purification Of Acetoacetyl-Coa Thiolase From Sunflower, Anthony Muriithi Maina

Theses, Dissertations and Culminating Projects

The [beta]-oxidation system in sunflower (Helianthus annuus L.) cotyledons is distinguished by the existence of two different thiolase isoforms, Thiolase I (acetoacetyl-CoA thiolase, EC 2.3.1.9 AACT) and Thiolase II (3-oxoacyl-CoA thiolase, EC 2.3.1.16 OACT). Glyoxysomal AACT is the last enzyme in the p-oxidation of fatty acids in plant glyoxysomes. Glyoxysomal AACT has been successfully cloned, expressed and purified from sunflower cotyledons (Dyer et al., 2006). In this paper we investigate the optimal conditions for both expression and purification. These include the choice of vector, the growth conditions and the purification parameters for the maximum possible yield of AACT protein.

Identification Of Metallo-Ss-Lactamase Inhibitors Via Enzyme Assay And Hplc-Ms Monitoring, Peggy Ann Sanchez

Theses, Dissertations and Culminating Projects

The vast overuse of antibiotics along with extrachromosomal gene insertion between different bacterial species has led to the Darwinian consequence of antibiotic resistance. Amongst the contributing factors to the rise of bacterial resistances are the production of ß-lactamases, which pose a major impediment to treatment with ß-lactam drugs such as penicillins and carbapenems. SPM-1 is a metallo-ß-lactamase (MBL) that confers antibiotic resistance to bacteria through zinc-mediated hydrolysis of ß-lactams. Bacteria that express the SPM-1 metalloenzyme show reduced sensitivity to ß-lactam drugs. One method to defeat this form of resistance is to administer a ß-lactam antibiotic with a potent ß-lactamase inhibitor …

Iron(Iii)-Salophene: An Organometallic Compound With Selective Cytotoxic And Anti-Proliferative Properties In Platinum-Resistant Ovarian Cancer Cells, Thilo S. Lange, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Carolyn Mccourt, Laurent Brard

Chemistry Faculty Publications and Presentations

Background: In this pioneer study to the biological activity of organometallic compound Iron(III)-salophene (Fe-SP) the specific effects of Fe-SP on viability, morphology, proliferation, and cell-cycle progression on platinum-resistant ovariancancer cell lines were investigated.

Methodology/Principal Findings: Fe-SP displayed selective cytotoxicity against SKOV-3 and OVCAR-3 (ovarian epithelial adenocarcinoma) cell lines at concentrations between 100 nM and 1 μM, while the viability of HeLa cells (epithelial cervix adenocarcinoma) or primary lung or skin fibroblasts was not affected. SKOV-3 cells in contrast to fibroblasts after treatment with Fe-SP revealed apparent hallmarks of apoptosis including densely stained nuclear granular bodies within fragmented nuclei, highly condensed …

A Comparison Of The Surface Adsorption Characteristics Of Reduced And Oxidized Cytochrome C On A Fused Silica Surface Via Attenuated Total Internal Reflection Spectroscopy, Casey M. Kraning

Undergraduate Honors Thesis Collection

No abstract provided.

Dioxidobis(2-Oxo-1,2-Dihydropyridin-3-Olato)­Molybdenum(Vi), Manoj Trivedi, Daya Pandey, Nigam Rath

Chemistry & Biochemistry Faculty Works

In the title compound, [Mo(C5H4NO2)2O2], the MoVI atom exhibits a distorted octa­hedral coordination geometry formed by two terminal oxo ligands and two monoanionic O,O-bidentate pyridinone ligands. The two terminal oxo ligands lie in a cis arrangement, the ketonic O atoms of the pyridinone ligands are coordinated trans to the oxo ligands and the deprotonated hydroxyl O atoms are located trans to each other. The crystal structure contains inter­molecular N-H...O hydrogen bonds, C-H...O contacts and face-to-face [pi]-[pi] stacking inter­actions with an inter­planar separation of 3.25 (1) Å.

Diethyl 2-[(4-Nitro­Phen­Yl)(4-Phenyl-1,2,3-Selenadiazol-5-Yl)Meth­Yl]Malonate, A. Marx, S. Saravanan, S. Muthusubramanian, V. Manivannan, Nigam Rath

Chemistry & Biochemistry Faculty Works

In the title compound, C22H21N3O6Se, the heterocyclic ring makes dihedral angles of 50.03 (11) and 67.75 (11)°, respectively, with the benzene and phenyl rings. The terminal C atoms of the ester groups are disordered over two positions: the site occupancies for the C atoms are 0.62 (3)/0.38 (3) and 0.48 (3)/0.52 (3). In the crystal structure, weak intra- and inter­molecular C-H...O inter­actions are observed.

Progress Toward Cariporide Analogs For Sodium-Proton Exchange Inhibition, Jessica Moore, Mark Graves Ii, Jacob A. Vervynckt, William Harley, Fredric Gorin, Hasan Palandoken

Chemistry and Biochemistry

The sodium proton exchanger (NHE) is particularly important in maintaining the intracellular pH in human heart and brain. Under anaerobic conditions (i.e., ischemia), a shift from oxidative to nonoxidative glycolysis occurs. The resultant decrease in the intracellular pH activates NHE, which increases the intracellular sodium, initiating the sequence of physiological events that lead to cell death. Thus, there has been great interest in the development of compounds that inhibit NHE. Indeed, potent NHE inhibitors are available. However, a fundamental impediment to the field is the delivery of these compounds to poorly vascularized tissues during the early phases of ischemia when …

The Effects Of Pc-Based Laboratories On Student Learning, Lester L. Pesterfield, Stuart Burris, Darwin B. Dahl, Hasan Palandoken, Jacqueline Pope-Tarrence

Chemistry and Biochemistry

The Department of Chemistry at Western Kentucky University recently incorporated a net-worked MeasureNet data acquisition and analysis system into in the second semester General Chemistry laboratories. Our investigation team has conducted a study to evaluate the effects of the MeasureNet system on student learning and performance on a Beer's Law laboratory. We focused on two phenomena: the effect of the MeasureNet system on 1) student learning of specific content material and 2) student interest in chemistry and science in general. The study involved a MeasureNet system group (employing a UV-Vis spectrometer and colorimeters) and a control group (employing traditional Spectronic …

Volume 01, Jessica Fields, Stephanie Neeley, Derek W. Hambright, Mary E. Lehman, Andrew R. Grzankowski, Zachary Johnson, Boone M. Prentice, Ashley M. Swandby, Victoria Morgan, Katie Williamson, Kristine G. Bender, Katelyn N. Romaine, D. Nicole Swann, Jessica Fox, Mike Mcateer, Alex Grabiec, Laura Nodtvedt, Nick Costa, Rachel Wolfe, Zack Dalton

Incite: The Journal of Undergraduate Scholarship

Introduction from Dean Dr. Charles Ross

Three Decades of Digging: Undergraduate Archeology at Longwood by Jessica Fields and Stephanie Neeley

Interactions of Allelopathy and Heat Stress in Plants by Derek W. Hambright and Mary E. Lehman

Inertial Electrostatic Confinement D-D Fusion Device: Construction and Simulation by Andrew R. Grzankowski

Shackled Nim by Zachary Johnson

Development of GC-MS and Chemometric Methods for the Analysis of Accelerants in Arson Cases by Boone M. Prentice

A Comparison of Image Analysis Methods in cDNA Microarrays by Ashley M. Swandby

Perceived Sexual Activity of Short and Long-Term Relationships by Victoria Morgan and Katie Williamson

Elderly …