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Organization, Structure, And Assembly Of Alpha-Carboxysomes Determined By Electron Cryotomography Of Intact Cells, Cristina V. Iancu, Dylan M. Morris, Zhicheng Dou, Sabine Heinhorst, Gordon C. Cannon, Grant J. Jensen

Faculty Publications

Carboxysomes are polyhedral inclusion bodies that play a key role in autotrophic metabolism in many bacteria. Using electron cryotomography, we examined carboxysomes in their native states within intact cells of three chemolithoautotrophic bacteria. We found that carboxysomes generally cluster into distinct groups within the cytoplasm, often in the immediate vicinity of polyphosphate granules, and a regular lattice of density frequently connects granules to nearby carboxysomes. Small granular bodies were also seen within carboxysomes. These observations suggest a functional relationship between carboxysomes and polyphosphate granules. Carboxysomes exhibited greater size, shape, and compositional variability in cells than in purified preparations. Finally, we …

Open Notebook Science Challenge Solubilities Of Organic Compounds In Organic Solvents, Andrew Lang, Jean-Claude Bradley, Cameron Neylon, Rajarshi Guha, Antony J. Williams, Bill Hooker, Brent Friesen

College of Science and Engineering Faculty Research and Scholarship

The Open Notebook Science Solubility Challenge Solubility is an important consideration for many chemistry applications. Synthetic chemists usually use a solvent to perform reactions and knowledge of the solubility of the starting materials or products can be very useful to pick an appropriate solvent. Analytical chemists can use solubility to design separation techniques and factor in dynamic range considerations. Physical chemists can create and evaluate their models of how molecules interact in the solubilization and precipitation processes. Solubility data can be obtained from a variety of online and offline sources. As with all chemical data, it can be a challenge …

Dual-Action Hygienic Coatings: Benefits Of Hydrophobicity And Silver Ion Release And Surface Analysis, Niall Stobie, Brendan Duffy, John Colreavy, Patrick Mchale, Steven Hinder, Declan Mccormack

Articles

Coatings that demonstrate reduced attachment of crystalline precipitates and the medical device colonising Staphylococcus epidermidis were prepared by the immobilisation of silver doped perfluoropolyether–urethane siloxane thin films on glass substrates. The presence of stratified hydrophobic perfluoropolyether groups protects the coating surface from the attachment of crystalline hydrophilic species such as chlorides and phosphates, whilst silver ion release inhibited attachment of S. epidermidis and subsequent biofilm formation in vitro. The release of silver ions protects the perfluoro groups from the hydrophobic interactions of S. epidermidis cells, which can reduce the hydrophobicity of the protective coating. These coatings also exhibited significant antibacterial …

Methods And Kit For Determination Of Prostacyclin In Plasma, Sylvia Daunert, Michael Poon, Urvee Desai, Sapna K. Deo

Chemistry Faculty Patents

A solid-phase immunoassay for 6-keto-Prostaglandin F_1α, the stable hydrolysis product of prostacyclin (Prostaglandin I₂) is disclosed. Prostacyclin, a potent vasodilator with anti-platelet and anti-proliferative properties is an effective treatment for primary pulmonary hypertension and pulmonary arterial hypertension associated with scleroderma and scleroderma-like syndrome. Levels of 6-keto-Prostaglandin F_1α can be directly correlated with levels of prostacyclin. Therefore, 6-keto-Prostaglandin F_1α has become the indicator of choice to measure prostacyclin levels. The single step immunoassay for 6-keto-Prostaglandin F_1α uses the bioluminescent protein, aequorin as a label. Analyte-label conjugates were constructed by linking the carboxyl group of …

Development Of Novel Synthetic Methodologies And Their Use In Approaches For The Preparation Of Lactacystin, Lepadiformine And A Giardia Lamblia Fructose-1,6-Bisphosphate Aldolase Inhibitor, Jiwen Zou

Chemistry and Chemical Biology ETDs

The investigations carried out in my doctoral studies focus on (1) applications of pyridinium salt photochemical and tandem ene-yne-ene metathesis reactions to the synthesis of the natural products (+)-lactacystin and lepadiformine C, and (2) the preparation of a novel inhibitor for the class II Giardia lamblia fructose-1,6-bisphosphate aldolase. New developments in the area of pyridinium salt photochemistry were explored in the context of approaches to the natural product (+)-lactacystin. The results of this effort show that irradiation of a substituted 1,2-cyclopenta-fused pyridinium salt in aqueous solution followed by treatment with sodium bicarbonate leads to selective production of an unusual, structural …

Development Of Novel Fluorescent Sensors For The Detection Of Functional And Bio-Interesting Small Molecules And Metal Ions, Wei Jiang

Chemistry and Chemical Biology ETDs

As one important kind of sensitive analytical technology, fluorescence method is widely applied in environmental science, materials, medicine pharmacy and nowadays much popularly in cellular biological science, which requires the development of diverse fluorescent sensors to meet various analytical and researching demands. During my Ph.D. study, my work focuses on the development of novel fluorescent sensors for the detection and specific recognition of functional and bio-interesting small molecules and metal ions, and the contents are described in this dissertation using three sections. In the first part, novel fluorescent sensors for the specific recognition of bio-toxic thiophenols have been developed based …

Investigation Of Co2 Insertion Into Lanthanide Amides, Alkoxides, And Mixed Amide/Alkoxides, Leigh Anna M. Ottley

Chemistry and Chemical Biology ETDs

A novel set of lanthanide (Ln) alkoxycarbonates, [Ln(μ-CO₂-DBP)(DBP)₂]₂ where Ln = lanthanide; and DBP = OC₆H₃-2,6-C(CH₃)₃, were isolated from a systematic study of the insertion of CO_2(g) (referred to as CO₂) into the Ln-O bonds of a series of new lanthanide alkoxides, Ln(OR)₃. This study was undertaken to determine if the deleterious metal carbonate [M(CO₃)_y] formation that promotes higher thermal budgets during processing could be avoided. While processing controls can reduce the formation of the M(CO₃) …

Mesoporous Silica Microparticles Enhance The Cytotoxicity Of Anticancer Platinum Drugs, Zhimin Tao, Bonnie Toms, Jerry Goodisman, Tewodros Asefa

Chemistry - All Scholarship

We report on the endocytosis and the time-dependent enhanced cytotoxicity of anticancer platinum drugs when the drugs are combined with (or loaded into) one of the two most common types of mesoporous silica materials, MCM-41 or SBA-15. The anticancer drug cisplatin and its isomer transplatin, when loaded on MCM-41 and SBA-15 microparticles, were less cytotoxic to leukemia cells than the drugs alone after 12 h exposure. However, the drug-loaded microparticles exhibited unprecedented enhanced cytotoxicity to the cancerous cells after 24 h of exposure. This cytotoxicity of the drug-loaded microparticles was even higher than of the pure drugs in solutions, suggesting …

The Heat Capacity And Thermodynamic Properties Of The Iron Oxides And Their Relation To The Mineral Core Of The Iron Storage Protein Ferritin, Claine Lindsey Morton Snow

Theses and Dissertations

The iron oxides are a group of materials with geological, biological, and technological importance. A thermodynamic understanding of these materials is important because it provides information about their relative stabilities, chemical reactivity, and transformations. This study provides the heat capacity of a nanocrystalline magnetite (Fe3O4) sample, bulk hematite (α-Fe2O3), nanocrystalline hematite, akaganéite (β-FeOOH), and lepidocrocite (γ-FeOOH) at temperatures as low as 0.5 K. These measurements were fit to theoretical functions at temperatures lower than 15 K, and the respective thermophysical properties of these materials are discussed. Also the molar entropies of bulk hematite and hydrous nanocrystalline hematite as well as …

A Novel Choline Cotransporter Sequestration Compartment In Cholinergic Neurons Revealed By Selective Endosomal Ablation, Michael T. Ivy, Robert F. Newkirk, Yilun Wang, James G. Townsel

Biology Faculty Research

The sodium-dependent, high affinity choline transporter – choline cotransporter – (ChCoT, aka: cho-1, CHT1, CHT) undergoes constitutive and regulated trafficking between the plasma membrane and cytoplasmic compartments. The pathways and regulatory mechanisms of this trafficking are not well understood. We report herein studies involving selective endosomal ablation to further our understanding of the trafficking of the ChCoT. Selective ablation of early sorting and recycling endosomes resulted in a decrease of ∼75% of [3H]choline uptake and ∼70% of [3H]hemicholinium-3 binding. Western blot analysis showed that ablation produced a similar decrease in ChCoTs in the plasma membrane subcellular fraction. The time frame …

A Natural Missing Link Between Activated And Downhill Protein Folding Scenarios, Feng Liu, Caroline Maynard, Gregory E. Scott, Artem Melnykov, Kathleen B. Hall, Martin Gruebele

Chemistry and Biochemistry

We propose protein PTB1:4W as a good candidate for engineering into a downhill folder. PTB1:4W has a probe-dependent thermal unfolding curve and sub-millisecond T-jump relaxation kinetics on more than one time scale. Its refolding rate in denaturant is a non-linear function of denaturant concentration (curved chevron plot). Yet at high denaturant concentration its unfolding is probe-independent, and the folding kinetics can be fitted to a single exponential decay. The domain appears to fold via a mechanism between downhill folding and activated folding over several small barriers, and when denaturant is added, one of these barriers greatly increases and simplifies the …

Spectrophotometric And Colorimetic Methodology To Detect And Quantify Hydrazide Based Chemotherapeutic Drugs, Ronald Bartzatt

Chemistry Faculty Publications

Pharmaceuticals having the hydrazide functional group are an important division within anti-tuberculosis, anti-parasitic, anti-cancer, and anti-radiation chemotherapeutics. This work presents a colorimetric methodology to detect and quantify hydrazide based pharmaceuticals. Processes for rapid spot test, qualitative colorimetric assay, and spectrophotometric quantitative assay are presented. The reagent 2,6-dichloroquinon-4-chloroimine (Gibb's reagent) is utilized to accomplish the various analytical objectives. The rapid spot test and qualitative colorimetric assay enables a detection of hydrazide drugs to a level of 0.0037 grams per milliliter. Quantitative spectrophotometric detection of hydrazide drugs is sensitive to a level of 128.2 micrograms permilliliter. The molar absorptivity () is calculated …

Carboxysomal Carbonic Anhydrases: Structure And Role In Microbial Co2 Fixation, Gordon C. Cannon, Sabine Heinhorst, Cheryl A. Kerfeld

Faculty Publications

Cyanobacteria and some chemoautotrophic bacteria are able to grow in environments with limiting CO₂ concentrations by employing a CO₂-concentrating mechanism (CCM) that allows them to accumulate inorganic carbon in their cytoplasm to concentrations several orders of magnitude higher than that on the outside. The final step of this process takes place in polyhedral protein microcompartments known as carboxysomes, which contain the majority of the CO₂-fixing enzyme, RubisCO. The efficiency of CO₂ fixation by the sequestered RubisCO is enhanced by co-localization with a specialized carbonic anhydrase that catalyzes dehydration of the …

Effects Of Metal Compounds With Distinct Physicochemical Properties On Iron Homeostasis And Antibacterial Activity In The Lungs: Chromium And Vanadium, Mitchell D. Cohen, Maureen Sisco, Colleen Prophete, Kotaro Yoshida, Lung-Chi Chen, Judith T. Zelikoff, Jason Smee, Alvin A. Holder, Jacqueline Stormhuerner, Debbie C. Crans, Andrew J. Ghio

Faculty Publications

In situ reactions of metal ions or their compounds are important mechanisms by which particles alter lung immune responses. The authors hypothesized that major determinants of the immunomodulatory effect of any metal include its redox behavior/properties, oxidation state, and/or solubility, and that the toxicities arising from differences in physicochemical parameters are manifest, in part, via differential shifts in lung iron (Fe) homeostasis. To test the hypotheses, immunomodulatory potentials for both pentavalent vanadium (V(V); as soluble metavanadate or insoluble vanadium pentoxide) and hexavalent chromium (Cr(VI); as soluble sodium chromate or insoluble calcium chromate) were quantified in rats after inhalation (5 h/day …

Development Of Pharmacophore And Comfa Study Of Rigid And Flexible Sigma 2 Receptor Ligands, Hemantbhai Patel

Theses

In the present study a pharmacophore and CoMFA model was derived for sigma 2 (62) receptors by using Sybyl 7.2 Software Package. The CoMFA studies used 22 bioactive molecules as a training set and 4 molecules as a test set for the o2 receptor ligands. The geometries and electrostatic charges of all molecules were calculated using various levels of calculations. The geometry optimization and electrostatic charges of all 26 molecules were performed by using semiemprical AM1, ab initio HF/6-31G* and density functional B3LYP/6-31G* in Gaussian 98. The pharmacophore model was derived by using Distance Comparisions (DISCOtech) from 4 partially to …

Identification And Quantitation Of 3,4-Methylenedioxy-N-Methylamphetamine (Mdma, Ecstasy) In Human Urine By 1h Nmr Spectroscopy. Application To Five Cases Of Intoxication, Jonathan Liu, John Decatur, Gloria Proni, Elise Champeil

Publications and Research

Identification of 3,4-methylenedioxy-N-methylamphetamine (MDMA, ecstasy) in five cases of intoxication using nuclear magnetic resonance (NMR) spectroscopy of human urine is reported. A new water suppression technique PURGE (Presaturation Utilizing Relaxation Gradients and Echoes) was used. A calibration curve was obtained using spiked samples. The method gave a linear response (correlation coefficient of 0.992) over the range 0.01–1 mg/mL. Subsequently, quantitation of the amount of MDMA present in the samples was performed. The benefit and reliability of NMR investigations of human urine for cases of intoxication with MDMA are discussed.

Conformations Of A Model Protein Revealed By An Aggregating Cuᴵᴵ Porphyrin: Sensing The Difference, G. De Luca, A. Romeo, L. M. Scolaro, Robert F. Pasternack

Chemistry & Biochemistry Faculty Works

Aggregated t-CuP binds to poly-L-glutamate through supramolecular interactions, revealing itself to be an extremely sensitive probe for the major conformations of the polymeric scaffold.

Construction, Figures Of Merit And Testing Of A Single-Cell Fluorescence Excitation Spectroscopy System, Laura S. Hill, Tammi L. Richardson, Louisa T.M. Profeta, Timothy J. Shaw, Christopher J. Hintz, Benjamin S. Twining, Evelyn Lawrenz, Micheal L. Myrick

Faculty Publications

Characterization of phytoplankton community composition is critical to understanding the ecology and biogeochemistry of the oceans. One approach to taxonomic characterization takes advantage of differing pigmentation between algal taxa and thus differences in fluorescence excitation spectra. Analyses of bulk water samples, however, may be confounded by interference from chromophoric dissolved organic matter or suspended particulate matter. Here, we describe an instrument that uses a laser trap based on a Nikon TE2000-U microscope to position individual phytoplankton cells for confocal fluorescence excitation spectroscopy, thus avoiding interference from the surrounding medium. Quantitative measurements of optical power give data in the form of …

Phase Transition Enthalpy Measurements Of Organic And Organometallic Compounds. Sublimation, Vaporization And Fusion Enthalpies From 1880 To 2010, William Acree, James Chickos

Chemistry & Biochemistry Faculty Works

No abstract provided.

Homocystamides Promote Free-Radical And Oxidative Damage To Proteins, Martha Sibrian-Vazquez, Jorge O. Escobedo, Soojin Lim, George K. Samoei, Robert M. Strongin

Chemistry Faculty Publications and Presentations

Elevated levels of homocysteine are associated with several major diseases. However, it is not clear whether homocysteine is a marker or a causative agent. The majority (ca. 80%) of the homocysteine present in humans is protein bound. The study of the posttranslational modification of proteins by homocysteine and its cyclic congener, homocysteine thiolactone, is emerging as an area of great current interest for unraveling the ongoing “mediator/marker controversy” [Jacobsen DW (2009) Clin Chem 55:1–2]. Interestingly, many of the pathologies associated with homocysteine are also linked to oxidative stress. In the current study, chemical evidence for a causal relationship between homocysteine-bound …

Role Of Small Oligomers On The Amyloidogenic Aggregation Free-Energy Landscape, Xianglan He, Jason T. Giurleo, David Talaga

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

We combine atomic-force-microscopy particle-size-distribution measurements with earlier measurements on 1-anilino-8-naphthalene sulfonate, thioflavin T, and dynamic light scattering to develop a quantitative kinetic model for the aggregation of β-lactoglobulin into amyloid. We directly compare our simulations to the population distributions provided by dynamic light scattering and atomic force microscopy. We combine species in the simulation according to structural type for comparison with fluorescence fingerprint results. The kinetic model of amyloidogenesis leads to an aggregation free-energy landscape. We define the roles of and propose a classification scheme for different oligomeric species based on their location in the aggregation free-energy landscape. We relate …

High Magnetization Aqueous Ferrofluid: A Simple One-Pot Synthesis, Kyler J. Carroll, Michael D. Schultz, Panos P. Fatouros, Everett E. Carpenter

Chemistry Publications

A one-step polyol method was utilized to prepare a stable aqueous iron/iron oxide ferrofluid. The dried powders were characterized by x-ray diffraction, electron microscopy, x-ray absorption spectroscopy, and vibrating sample magnetometry for the determination of phase, morphology, and magnetic properties. To show its potential for imaging applications, the ferrofluid was also investigated as a magnetic resonance imaging contrast agent.

Kinetic Analysis Of Prodrug Activation And Atp/Utp Substrate Preference Of Nine Human Deoxycytidine Kinase Mutants, Breanna Wentz, Jaclyn Einspahr, Michael H. Godsey

CUP Undergraduate Research

Deoxynucleoside analogues are prodrugs that canfunction as inhibitors of both viral and cellular DNA replication processes. They are important in anti-cancer therapy because they hinder DNA synthesis and cellular mitosis. Within the cell, deoxyribonucleotides are synthesized using the salvage pathways by converting the unphosphorylated nucleosides to their mono, di- and tri-phosphate forms using a phosphoryl donor: ATP or UTP. Human deoxycytidine kinase (dCK) is the first and rate-limiting enzyme in this process. The dCK protein uses nucleotide triphosphates to phosphorylate several clinically important nucleoside analogue prodrugs in addition to its natural substrates. The preferred physiological phosphoryl donor for dCK is …

Novel Photochemical Methodologies For Diversity Oriented Synthesis And Screening Of Combinatorial Libraries, Roman Askatovich Valiulin

Electronic Theses and Dissertations

The main goal of this project was to develop an efficient methodology allowing rapid access to structurally diverse scaffolds decorated with various functional groups.

Initially, we discovered and subsequently developed an experimentally straightforward, high-yielding photoinduced conversion of readily accessible diverse starting materials into polycyclic aldehydes and their (hemi)acetals decorated by various pendants. The two step sequence, involving the Diels-Alder addition of heterocyclic chalcones and other benzoyl ethylenes to a variety of dienes, followed by the Paternò-Büchi reaction, was described as an alkene-carbonyl oxametathesis. This methodology offers a rapid increase in molecular complexity and diversity of the target scaffolds.

To develop …

The Analysis Of Cyanide And Its Breakdown Products In Biological Samples, Brian A. Logue, Diane M. Hinkens, Steven I. Baskin, Gary A. Rockwood

Chemistry and Biochemistry Faculty Publications

Cyanide is a toxic chemical that may be introduced into living organisms as a result of natural processes and/or anthropogenic uses (legal or illicit). Exposure to cyanide can be verified by analysis of cyanide or one of its breakdown products from biological samples. This verification may be important for medical, law-enforcement, military, forensic, research, or veterinary purposes. This review will discuss current bioanalytical techniques used for the verification of cyanide exposure, identify common problems associated with the analysis of cyanide and its biological breakdown products, and briefly address the metabolism and toxicokinetics of cyanide and its breakdown products in biological …

Electrochemical Sensing In Paper-Based Microfluidic Devices, Zhihong Nie, Christian A. Nijhuis, Jinlong Gong, Xin Chen, Alexander Kumachev, Andres W. Martinez, Max Narovlyansky, George M. Whitesides

Chemistry and Biochemistry

This paper describes the fabrication and the performance of microfluidic paper-based electrochemical sensing devices (we call the microfluidic paper-based electrochemical devices, μPEDs). The μPEDs comprise paper-based microfluidic channels patterned by photolithography or wax printing, and electrodes screen-printed from conducting inks (e.g., carbon or Ag/AgCl). We demonstrated that the μPEDs are capable of quantifying the concentrations of various analytes (e.g., heavy-metal ions and glucose) in aqueous solutions. This low-cost analytical device should be useful for applications in public health, environmental monitoring, and the developing world.

Structure-Reactivity Relationships Of L-Proline Derived Spirolactams And A-Methyl Prolinamide Organocatalysts In The Asymmetric Michael Addition Reaction Of Aldehydes To Nitroolefins., Fintan Kelleher, Sinead Kelly, John Watts, Vickie Mckee

Articles

L-Proline derived spirolactams and a-methyl prolinamides act as organocatalysts for the asymmetric conjugate addition of aldehydes to nitroolefins in excellent yields, with good diastereoselectivity and enantioselectivity. Furthermore, low catalyst loadings (5 mol%) and a low aldehyde molar excess (1.5 molar equivalents) were achieved.

Mechanistic Importance Of Redox Potentials And Conformational Flexibility In Electron-Transferring Flavoproteins, Michael Anthony Swanson

Electronic Theses and Dissertations

The mitochondrial matrix flavoproteins electron transfer flavoprotein (ETF) and electron transfer flavoprotein-ubiquinone oxidoreductase (ETF-QO) are responsible for linking fatty acid β-oxidation with the main mitochondrial respiratory chain. Electrons derived from flavoprotein dehydrogenases are transferred sequentially through ETF and ETF-QO to ubiquinone and then into the respiratory chain via complex III. In this study, the effects of changes in ETF-QO redox potentials on its activity and the conformational flexibility of ETF were investigated.

ETF-QO contains one [4Fe-4S]^2+,1+ and one flavin adenine dinucleotide (FAD). In the porcine protein, threonine 367 is hydrogen bonded to N1 and O2 of the flavin ring …

Mechanistic And Computational Studies Of Oxidatively-Induced Aryl-Cf3 Bond Formation At Palladium, J. Brannon Gary

Faculty Publications

This article describes the rational design of 1st generation systems for oxidatively-induced Aryl– CF3 bond-forming reductive elimination from PdII. Treatment of (dtbpy)PdII(Aryl)(CF3) (dtbpy = di-tert-butylbipyridine) with NFTPT (N-fluoro-1,3,5-trimethylpyridium triflate) afforded the isolable PdIV intermediate (dtbpy)PdIV(Aryl)(CF3)(F)(OTf). Thermolysis of this complex at 80 °C resulted in Aryl–CF3 bond-formation. Detailed experimental and computational mechanistic studies have been conducted to gain insights into the key reductive elimination step. Reductive elimination from this PdIV species proceeds via pre-equilibrium dissociation of TfO− followed by Aryl–CF3 coupling. DFT calculations reveal that the transition state for Aryl–CF3 bond formation involves the CF3 acting as an electrophile with the …

Towards The Total Synthesis Of Haplomyrtin, Nora Ellen Hunter

Browse all Theses and Dissertations

Haplomyrtin, a 1-aryl-2,3-naphthalide lignan obtained from Turkish Haplophyllum myrtifolium and Haplophyllum telephioides offers a number of synthetic challenges with the incorporation of two aromatic hydroxyl groups at positions C4 and C7 on the naphthalene ring system and regiospecific condensation of the γ-lactone ring. Improvements towards the total synthesis of haplomyrtin were pursued with commercially available vanillin and piperonal in a total of 8 separate steps. All steps have excellent reproducibility. This strategy includes bromination of protected vanillin to yield 2-(4-(4-methoxybenzyloxy)-2-bromo-5-methoxyphenyl)-1,3-dioxolane and 2-(4-(benzyloxy)-2-bromo-5-methoxyphenyl)-1, 3-dioxolane in 48% and 88% yield respectively, and incorporation of the fully functionalized pendant aryl ring through a …