Chemistry Commons^™

Decoding The Double Helix: Frederick Sanger And Sanger Sequencing, Creighton A. Jackson

Natural Sciences Student Research Presentations

This is a poster presented at the Natural Sciences Poster Session at Parkland College, which summarizes the work of Frederick Sanger, a British biochemist and the only recipient of two separate Nobel Prizes in the field of chemistry. His first prize was awarded for his work deciphering the structure of the protein insulin. This discovery would go on to influence research on proteins and DNA as it determined that proteins had definite structures and led to the theory that DNA directed the construction of proteins. His second was awarded for this work on the Sanger method of DNA sequencing and …

Facile Synthesis Of Tertiary Aliphatic Amine– Containing Cyclic Motif Via Neutral Aminyl Radical Cyclization, Heng Chen

Wayne State University Theses

Tertiary amine–containing cyclic motifs are prevalent in natural products and pharmaceutical lead targets. Inspired by these biological active molecules, one focus in our lab is the development of neutral aminyl radical chemistry in the synthesis of tertiary aliphatic amine–containing cyclic compounds. In this project, I investigated the mono- and tandem cyclization of aminyl radical with different types of olefins (terminal olefin, enone, and styrenyl). The effect of the hydrogen atom donor and the limitation of the reaction will be discussed.

Decarbonylative Cross Coupling Of Phthalimides With Diorganozinc Reagents—Efforts Toward Catalysis, Kimberly S. Deglopper, Sarah K. Fodor, Thomas Bd Endean, Jeffrey B. Johnson

Faculty Publications

The decarbonylative coupling of phthalimides with diorganozinc reagents to form o-substituted benzamides has been previously demonstrated as a viable process, but only with stoichiometric nickel(0). Investigations into a number of reaction variables, including solvent, ligand, and substrate substitution, have yielded multiple sets of conditions capable of achieving up to 10 catalyst turnovers, most successfully with the use of electron withdrawing nitrogen substituents on the phthalimide. In addition, these investigations have provided insight into the intermediates within the catalytic cycle and have revealed new approaches to the development of a general catalytic methodology.

A General Valence-Length Correlation For Determining Bond Orders: Application To Carbon-Carbon And Carbon-Hydrogen Chemical Bonds, F. D. Hardcastle

Journal of the Arkansas Academy of Science

A quantum-mechanical LCAO approach was used to derive Pauling’s popular empirical bond valencelength relationship s = exp((R₀-R)/b), where s is the bond order or bond valence associated with bond length R, and R₀ and b are fitting parameters. An expression for the b “empirical” fitting parameter is derived in terms of atomic orbital exponents. The b parameters calculated from the atomic orbital exponents are consistent with optimized b parameters. In general, atomic orbital exponents may be used to determine bond valence-length relationships for any chemical bond regardless of valence state, oxidation number, physical or chemical environment. In this study, almost …

Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite T. cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) with sera from patients with chronic ChD, revealing the disaccharide Galα(1,3)Galβ as the immunodominant glycotope (Chapter 2). This disaccharide comprises the two terminal sugars of the known immunodominant glycotope Galα(1,3)Galβ(1,4)GlcNAcα, which is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-α-Gal antibodies (Abs) in infected …

Single Nanoparticle Plasmonic Spectroscopy For Study Of The Efflux Function Of Multidrug Abc Membrance Transporters Of Single Live Cells, Lauren M. Browning, Kerry J. Lee, Pavan K. Cherukuri, Prakash D. Nallathamby, Seth Warren, Jean-Michel Jault, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

ATP-binding cassette (ABC) membrane transporters exist in all living organisms and play key roles in a wide range of cellular and physiological functions. The ABC transporters can selectively extrude a wide variety of structurally and functionally unrelated substrates, leading to multidrug resistance. Despite extensive study, their efflux molecular mechanisms remain elusive. In this study, we synthesized and characterized purified silver nanoparticles (Ag NPs) (97 ± 13 nm in diameter), and used them as photostable optical imaging probes to study efflux kinetics of ABC membrane transporters (BmrA) of single live cells (B. subtilis). The NPs with concentrations up to …

Anticancer, Biophysical And Computational Investigations Of Half-Sandwich Ruthenium(Ii) Thiosemicarbazone Complexes: The Effect Of Arene Versus Thiacrown Face-Cap, Floyd A. Beckford, Alyssa Stott, P. Canisius Mbarushimana, Marc-Andre Leblanc, Kinsey Hall, Samantha Smith, Jimmie L. Bullock, Dennis J. Houghton, Alvin A. Holder, Nikolay Gerasimchuk, Antonio Gonzalez-Sarrías

Chemistry & Biochemistry Faculty Publications

A series of half-sandwich ruthenium complexes, two containing an arene face-cap and the other a thiacrown ether face-cap were synthesized to investigate the necessity of the arene for anticancer activity in this class of compounds. The complexes are formulated as [(h⁶-p-cymene)Ru(dmabTSC)Cl]PF₆, [(h⁶-benzene)Ru(dmabTSC)Cl]PF₆ (arene complexes), and [([9]aneS₃(dmabTSC)Cl]PF₆ (dmabTSC = dimethylaminobenzaldehye thiosemicarbazone). It was observed that none of the complexes showed good anticancer activity in vitro against HCT-116 and Caco-2 (colon adenocarcinoma) cells. All three complexes can bind strongly to calf-thymus DNA with binding constants on the order of 10 …

Gravimetrically Characterizable Common Alkali Reducing Agents And Ligand Design Of A New Electron Rich Guanidinate, Efrain Maximiliano Castillo

Open Access Theses & Dissertations

SynThesis, isolation and characterization of 12 new alkali arenides was performed by the addition of the chelating base 18-crown-6. Electrochemistry, UV-vis/NIR spectroscopy and XRD studies were performed.

The incoorporation of an imidazolin-2-iminato group to the background of a guanidinate showed that this kind of ligand is electronically flexible and metal dependent. It was found that is more electron donating than some previously reported guanidinates and ketimine guanidinates.

Synthesis, Characterization, And Properties Of Peroxo-Based Oxygen-Rich Compounds For Potential Use As Greener High Energy Density Materials, Nipuni-Dhanesha Horadugoda Gamage

Wayne State University Dissertations

One main aspect of high energy density material (HEDM) design is to obtain greener alternatives for HEDMs that produce toxic byproducts. Primary explosives lead azide, lead styphnate, and mercury fulminate contain heavy metals that cause heavy metal poisoning. Leaching of the widely used tertiary explosive NH4ClO4 into groundwater has resulted in human exposure to ClO4– ions, which cause disruptions of thyroid related metabolic pathways and even thyroid cancer. Many research efforts to find replacements have gained little success. Thus, there is a need for greener HEDMs. Peroxo-based oxygen-rich compounds are proposed as a potential new class of greener HEDMs due …

Adsorption Of Antibiotics By Vermiculite, Mosa J. Ferdous

Dissertations and Theses

The occurrence of residual antibiotics in the environment has been a worldwide issue and warrants the development of inexpensive yet effective methods for antibiotics removal from contaminated water. In this thesis work, the adsorption of four antibiotics, namely chlorotetracycline (CTC), oxytetracycline (OTC), ofloxacin (OFL), and enrofloxacin (ENR), onto natural vermiculite has been studied using batch (static) and column (dynamic) adsorption techniques. The Langmuir and Freundlich isotherm models were initially used to explain the adsorption processes. The separation factor (RL) values derived from the Langmuir model and the 1/n values derived from Freundlich model in the present investigation were less than …

Quantitative Model For Rationalizing Solvent Effect In Noncovalent Ch-Aryl Interactions, Bright C. Emenike, Sara N. Bey, Brianna C. Bigelow, Srinivas V.S. Chakravartula

Publications and Research

The strength of CH–aryl interactions (ΔG) in 14 solvents was determined via the conformational analysis of a molecular torsion balance. The molecular balance adopted folded and unfolded conformers in which the ratio of the conformers in solution provided a quantitative measure of ΔG as a function of solvation. While a single empirical solvent parameter based on solvent polarity failed to explain solvent effect in the molecular balance, it is shown that these ΔG values can be correlated through a multiparameter linear solvation energy relationship (LSER) using the equation introduced by Kamlet and Taft. The resulting LSER …

Organometallic Materials: Ferroceno[C]Thiophenes And 1,2-Bisthienylmetallocenes, Surya R. Banks

Theses and Dissertations--Chemistry

Development of synthetic routes toward two general organometallic frameworks was undertaken. The first project involved synthetic attempts of substituted and unsubstituted ferroceno[c]thiophene while the second one was the synthesis of 1,2-dithienylmetallocenes. The long-term goal of this work is to lay the foundations for study of electronic, electrochromic, redox, and optical properties of thiophene-based materials integrated with organometallic systems such as ferrocene, ruthenocene and cymantrene. The synthetic pathway for the target molecule in the first project involved converting 1,2-bis(hydroxymethyl)ferrocene to 1,2-bis(thiouroniummethyl)ferrocene with thiourea under acidic conditions. Refluxing the salt in base followed by acidification resulted in 1,2-bis(mercaptomethyl)ferrocene, which is …

The Development Of Colorimetric Assays To Determine The Identity And Frequency Of Specific Nucleobases In Dna Oligomers, Elizabeth Marie Thomas

Theses and Dissertations--Chemistry

Colorimetric methods combined with color-changing chemical probes are widely used as simple yet effective tools for identifying and quantifying a wide variety of molecules in solution. For nucleic acids (DNA and RNA), perhaps the most commonly used colorimetric probe is potassium permanganate, which can be used to identify single-stranded pyrimidines (thymine and cytosine) in polymers. Unfortunately, permanganate is not an effective probe for identifying purines (adenine and guanine), especially in the presence of the more reactive pyrimidines. Therefore, robust methods for discriminating between the purines remain elusive, thereby creating a barrier toward developing more complex colorimetric applications. In this dissertation, …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Synthesis Of Medicinally Relevant Thiazolyl Aryl Ketones Under Mild Conditions, Danielle M. Gardner

Health, Human Performance and Recreation Undergraduate Honors Theses

Purpose: The growing amount of clinical resistance observed in current antifungal drugs and in anti-HIV pharmaceuticals is a concern in the medical community. The purpose of this study is to develop a mild synthetic process for biomedically relevant thiazolyl aryl ketones that can be used to develop antifungal and anti-HIV drugs. We hypothesized that the proposed synthetic technique would be more efficient, produce fewer unwanted byproducts, and be more tolerant of functional groups than existing methods.

Methods: Prior to each of the ketone reactions, the necessary salt was synthesized by mixing thiazole and 9-bromofluorene neat in a reaction tube heated …

Toward The Probing Of Dhqs Activity By Protein Engineering Through The Introduction Of Unnatural Amino Acids And The Selection Of Trna/Trna Synthetase Pairs, Shaina E. Ives

Department of Chemistry: Dissertations, Theses, and Student Research

Protein engineering is a valuable tool that allows scientist to explore how an enzyme works by mutation of key residues. This method has been used to improve function or stability of enzymes, thus allowing their use in both the lab and in industry to be expanded. Genetic incorporation of unnatural amino acids (unAA) can be used with protein engineering to exceed the current limitations, due to the limited number of functional groups of the 20 common amino acids.

The majority of this thesis will discuss the progress on incorporating the various unAA into the active site of the enzyme, Dehydroquinate …

Asymmetric Synthesis Of Cα-Methyl-Γ- And Δ-Amino Acids From A Common Synthon And Evaluation Of Thionyl Chloride Assisted Peptide Esterifications, Emily Rose Vogel

Dissertations

C^α-methyl-γ- and δ-unnatural amino acids (UAAs) are important class of biomolecules used extensively as structural scaffolds, peptidomimetics, and in the development of pharmaceuticals. Due to steric congestion surrounding the quaternary center, asymmetric preparation of α,α-disubstituted UAAs are synthetically challenging. Herein, two methods for the synthesis of chiral synthons to prepare C^α-methyl-γ- and -δ-UAAs are reported. A crucial step in both strategies includes an enzymatic hydrolysis of prochiral malonic esters with pig liver esterase (PLE). The first method utilizes the Meyer Schuster rearrangement to prepare α,β-unsaturated diesters synthons, but the preparation of the precursor propargyl alcohol decomposes …

Influence Of Shelling Temperature And Time On The Optical And Structural Properties Of Cuins2/Zns Quantum Dots, Colette Robinson

Graduate Theses and Dissertations

CIS/ZnS core/shell QDs are an important class of nanomaterials for optoelectronic, photovoltaic and photoluminescence applications. They consist of lower toxicity materials than the prototypical II-VI Cd-based QDs and show long fluorescence lifetimes, which generates prospective in biological imaging applications. It is vital to develop reproducible synthetic methods for this new class of nanomaterials in order to maintain small sizes with high QYs. CIS core QDs have been shelled with ZnS at various temperatures from 90-210°C for reaction times ranging from 20-140 minutes to examine the role of thermodynamics and kinetics on the shell growth. Using HR-TEM and ICP-MS, it was …

Production And Harvest Of Microalgae In Wastewater Raceways With Resource Recycling, Alexander Colin Roberts

Master's Theses

Microalgae can be grown on municipal wastewater media to both treat the wastewater and produce feedstock for algae biofuel production. However the reliability of treatment must be demonstrated, as well as high areal algae productivity on recycled wastewater media and efficient sedimentation harvesting. This processes was studied at pilot scale in the present research.

A pilot facility was operated with nine CO₂-supplemented raceway ponds, each with a 33-m² surface area and a 0.3-m depth, continuously from March 6, 2013 through September 24, 2014. The ponds were operated as three sets of triplicates with two sets continuously fed …

Synthesis Of Agents For The Treatment And Analysis Of Tropical Diseases, Jeanine Yacoub

USF Tampa Graduate Theses and Dissertations

Toxoplasmosis is an opportunistic disease caused by the protozoan parasite Toxoplasma gondii. The parasite is usually staved off by a healthy immune system and remains dormant in the body. In immunocompromised patients, the parasite can become active and spread throughout the body causing symptoms such as encephalitis, cognitive disorders, seizures, and death. Combination drug therapy is the usual treatment for toxoplasmosis; however, patients suffer from problems of intolerance, allergic reactions, and cytotoxicity. In an effort to identify new drug targets for toxoplasmosis, a series of compounds have been synthesized that can be used as tools to probe the unique …

Synthesis And Characterization Of Neo-Confused Porphyrins And Related Systems, Arwa Salem Almejbel

Theses and Dissertations

Carbaporphyrins have been the focus of many studies, and a wide variety of related carbaporphyrinoid systems have been reported. N-confused porphyrins are a class of carbaporphyrins where one pyrrole unit has been inverted. In this work, a newly discovered family of porphyrin isomers where one of the pyrrolic subunits is connected to the meso-bridges in a 1,3-fashion, called neo-confused porphyrins, has been investigated.

Reaction of pyrrole-3-carbaldehydes with acetoxymethylpyrroles and NaH in DMF gave neo-confused dipyrrylmethane dialdehydes. The resulting dialdehydes underwent an acid catalyzed condensation with a dipyrrylmethane to give neo-confused phlorins, and following oxidation with FeCl3 afforded new neo-confused porphyrins. …

Progress Toward A Structure-Function Relationship For Novel, Small-Molecule Inhibitors Of Plasminogen Activator Inhibitor-1, Sarah Burke

Master's Theses and Doctoral Dissertations

Plasminogen activator inhibitor-1 (PAI-1) is a serpin protein whose function is to inhibit tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), and hence, fibrinolysis. This inhibition leads to decreased plasminogen to plasmin conversion, which results in deleterious effects on the organism, such as blood clots. Elevated levels of PAI-1 are implicated in a variety of diseases and conditions. We have synthesized a variety of novel, small-molecule PAI-1 inhibitors in order to establish a structure-function relationship throughout the compounds. This goal was accomplished through an iterative process in which only one aspect of the molecule was altered at a time. …

Viral Infection Causes A Shift In The Self Peptide Repertoire Presented By Human Mhc Class I Molecules, Charles T. Spencer, Jelena S. Bezbradica, Mireya G. Ramos, Chenoa D. Arico, Stephanie B. Conant, Pavlo Gilchuk, Jennifer J. Gray, Mu Zheng, Xinnan Niu, William Hildebrand, Andrew J. Link, Sebastian Joyce

Chemistry Faculty Research

Purpose

MHC class I presentation of peptides allows T cells to survey the cytoplasmic protein milieu of host cells. During infection, presentation of self peptides is, in part, replaced by presentation of microbial peptides. However, little is known about the self peptides presented during infection, despite the fact that microbial infections alter host cell gene expression patterns and protein metabolism.

Experimental design

The self peptide repertoire presented by HLA-A*01;01, HLA-A*02;01, HLA-B*07;02, HLA-B*35;01, and HLA-B*45;01 (where HLA is human leukocyte antigen) was determined by tandem MS before and after vaccinia virus infection.

Results

We observed a profound alteration in the self …

Selective Iodination Using Diaryliodonium Salts, William H. Miller Iv

Department of Chemistry: Dissertations, Theses, and Student Research

Aryl iodides have become widely recognized as versatile synthetic intermediates, owing to aromatic iodine’s excellent ability to participate in oxidative addition reactions. Iodoarenes readily undergo a variety of synthetic transformations including metal catalyzed cross-coupling reactions, diaryliodonium chemistry, formation of organometallics through reduction or metal-halogen exchange, as well as classical S_N2 type chemistry. Because a wide array of transformations are available for aryl iodides, organic molecules containing this moiety often serve as vital precursors to highly desirable pharmaceuticals.

This thesis describes a simple and selective two-step approach to the formation of aryl iodides. This method proceeds through an easily …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Bis(Spirolactam) 1,3-Double-Armed Calix[4]Arene Compounds And Their Application As Extractants For The Determination Of Heavy Metal Ions, Fintan Kelleher, Mary Deasy, James Ward, Li Li, Fiona Regan

Articles

A number of double-armed calix[4]arene compounds, with proline-derived spirolactam ligating groups on the lower rim, have been synthesised and investigated as extractants of toxic heavy metal ions from aqueous solution. Pedersen’s extraction technique was employed to determine the capability of these new 1,3-distal derived calix[4]arene spiroalactams to extract selected heavy metal ions (e.g. Pb²⁺, Cd²⁺, Zn²⁺, Cu²⁺, Ni²⁺, Co²⁺) from an aqueous phase into an organic phase. The percentage extraction was calculated using UV-vis spectroscopy. All of the compounds synthesised demonstrated good selectivity for the heavy metals selected …

Temporal Variation In Optical Properties Of Chromophoric Dissolved Organic Matter (Cdom) In Southern California Coastal Waters With Nearshore Kelp And Seagrass, Catherine D. Clark, Warren J. De Bruyn, Paige Aiona

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Optical properties of chromophoric dissolved organic matter (CDOM) were measured in surf zone waters in diurnal field studies at a Southern California beach with nearshore kelp and seagrass beds and intertidal plant wrack. Absorption coefficients (aCDOM(300 nm)) ranged from 0.35 m21 to 3.7 m21 with short-term variability<1 h, increases at ebb and flood tides and higher values (6 m21) during an offshore storm event. Spectral slopes (S) ranged from 0.0028 nm21 to 0.017 nm21, with higher values after the storm; S was generally inversely correlated with aCDOM(300 nm). 3-D excitation–emission matrix spectra (EEMs) for samples with lower S values had humic-type peaks associated with terrestrial material (A, C), marine microbial material (M) and protein peaks, characteristic of freshly produced organic material. Samples with high S values had no or reduced protein peaks, consistent with aged material. Fluorescent indexes (f450/f500 >2.5, BIX>1.1) were consistent with microbial aquatic sources. Leachates of senescent kelp and seagrass had protein and humic-type EEM peaks. After solar simulator irradiation (4 h), protein peaks rapidly photochemically degraded, humic-type peak C increased in intensity and peak M disappeared. Optical characteristics of kelp leachates were most similar to field samples, …

Small Molecule Inhibitor Design For Anaplastic Lymphoma Kinase Inhibition, Theodore D. Hansel, David J. Grabovsky

Interface Compendium of Student Work

The Anaplastic Lymphoma Kinase (ALK) gene has been linked to tumorigenesis in a number of human cancers, including anaplastic large cell lymphoma (ALCL) and neuroblastoma. While ALK mutations in ALCL and many other cancers occur as a result of gene fusions with wild type kinase domains, those in neuroblastoma stem from single nucleotide polymorphisms (SNPs) in the kinase domain. These lead to autophosphorylation and constitutive signaling by ALK for cell growth and division, ultimately causing cancer. Crizotinib, an ATP-competitive ALK inhibitor, has proven to be an effective inhibitor of both ALKWT and ALKMutant kinase domains, and is in the middle …

Oxidative Cyclization Of Tertiary Pentenol Derivatives Forming 2,5,5-Trisubstituted Thf Rings And The Total Synthesis Of Cyclocapitelline, Geoffrey A. Phillips, Cory Palmer, Andrew C. Stevens, Mattew L. Piotrowski, Daryyl Sr Dekruyf, Brian Pagenkopf

Chemistry Publications

The synthesis of 2,5,5-trisubstituted tetrahydrofuran rings was accomplished via the Mukaiyama aerobic oxidative cyclization of tertiary 5-pentenols employing the Co(nmp)₂catalyst. A variety of THFs were formed in moderate to good yield and diastereoselectivity. The method developed herein was successfully applied to an enantioselective total synthesis of cyclocapitelline.

Asymmetric Transfer Hydrogenation Of Secondary Allylic Alcohols, Christopher Olugbenga Olusegun Shoola

Seton Hall University Dissertations and Theses (ETDs)

This dissertation highlights the developments and optimization of a new reaction method that transforms racemic secondary allylic alcohols into optically active secondary alcohols. The key step in this methodology occurs through a ruthenium catalyzed tandem isomerization and asymmetric transfer hydrogenation reaction. This reaction is a one pot, two-step process, which utilizes the unique ability of a transition metal catalyst to effect a combined reduction of the C-C double bond and the carbonyl group in a selected class of secondary allylic alcohols.

With a-vinyl benzyl alcohol as substrate, the optimal catalyst for this reaction was generated in situ from a …