Chemistry Commons^™

Dodecanedioic Acid Treatment In Vlcad Fibroblasts, Igor Radzikh

Undergraduate Research Posters 2018

Very-long-chain acyl-CoA dehydrogenase deficiency is the second most common disorder of fatty acid oxidation in the USA, with an incidence of 1:25,000-1:100,000 newborns (Tucci, Floegel, Beermann, Behringer, Spiekerkoetter, 2017, pg. 196). The current dietary therapeutic strategies are designed to avoid long chain fatty acids, instead providing carbohydrates and medium chain triglycerides as an energy source. Despite the controlled and biochemically balanced diet, it has a limited success in treatment of clinical symptoms and metabolic decompensations in VLCAD affected individuals. It has been proposed that defect in long chain fatty acids catabolic pathway leads to the severe energy deficiency, that primary …

Tmco1 Is A Novel Target For Cancer Chemotherapy, Ashley Przybylowicz, Ruhan Wei, Qiaoyun Zheng

Undergraduate Research Posters 2018

Transmembrane and coiled-coil domains 1 (TMCO1) is a protein of 22 KDa highly conserved in amino acid sequence among mammalian species and functions as an endoplasmic reticulum (ER) Ca2+load-activated Ca2+channel. Homozygous frameshift mutation in TMCO1 causes distinctive craniofacial dysmorphism, skeletal anomalies, and mental retardation. However, its physiological functions are largely unknown. In this study, we found that TMCO1 was co-localized with microtubules as determined by immunohistostaining and a co-sedimentation assay. Interestingly, TMCO1 was highly expressed in the invasive front of high grade lung cancer and metastatic cancer cells of clinical specimens. To further investigate the biological role of TMCO1 in …

Off Targets Toxicological Investigation Of Anti-Cancer Tubulin Inhibitors, Abbound Sabbagh, Yaxin Li

Undergraduate Research Posters 2018

We have developed a class of novel tubulin inhibitors based on NSC751382 (Figure 1), Benzo[1,3]dioxole-5- carboxylic acid [3-(2,5-dimethyl- benzyloxy)-4- (methanesulfonyl-methyl-amino)-phenyl] -amide, as the lead compound. This compound showed potent tubulin polymerization inhibitory activity by binding at the colchicine’s binding domain, and suppressed cancer cell growth with an IC50 of 200nM. It has molecular weight of 482, logP of 4.1, only one hydrogen bond donor, and eight hydrogen bond acceptors. The compound meets the Lipinski's Rule of Five and is a highly drug-like molecule. In addition, NSC751382 significantly inhibited the growth of Taxol resistant cancer cells, suggesting it is not a …

Increasing The Efficacy Of Doxorubicin Against Breast Cancer, Jovana Hanna, Jung-Suk Choi

Undergraduate Research Posters 2018

In the United States, breast cancer accounts for one in three cancer diagnoses in women, making it the most common type of cancer in women. One important chemotherapeutic agent used to treat breast cancer is doxorubicin, an anthracycline compound that causes cell death by damaging DNA in addition to producing reactive oxygen species. Previously, the Berdis lab developed an artificial nucleoside analog designated 5-NIdR that improves the efficacy of DNA damaging agents used against brain cancer. This nucleoside works by inhibiting the replication of damaged DNA created by certain chemotherapeutic agents. In this project, we tested the ability of 5-NIdR …

Synthesis Of Sialic Acid Derivative For Modifying Cell Surface Sialylation, Isaac Turan, Joseph Keil

Undergraduate Research Posters 2018

The exterior of cell surfaces express a dense layer of glycans which are often terminated by sialic acid (SA). SA is an acidic monosaccharide whose presence is found on the terminal ends of glycans of either glycoproteins or glycolipids. Due to its hydrophilic and electronegative nature, SA is often involved in both physiological and pathological processes, such as in regulating cellular interactions with ligands, microbes and neighboring cells. In addition to these functions, SA is also implicated in controlling cellular activation, differentiation, transformation and migration. Cell surface glycometabolic engineering provides a useful tool to remodel cell surface SA. In this …

Crystallographic,Vibrational Modes And Optical Properties Data Of Α-Dipabcrystal, Ahmad Alsaad, Chris M. Marin, Nabil Alaqtash, Hsien-Wen Chao, Tsun-Hsu Chang, Chin Li Cheung, A. Ahmad, I. A. Qattan, Renat F. Sabirianov

Department of Chemistry: Faculty Publications

The Crystallographic data of the α-DIPAB sample was measured using powder X-ray diffraction (PXRD). The crystal structure was also optimized using density functional based method. The calculations were performed both including vander Waals (vdW) interactions and excluding them to quantify the effects of vdW interaction on the crystal formation. The vibrational modes of DIPAB crystal corresponding to the Bromine deficient samples are calculated and presented. These show the origin of drastic change in dielectric response in Br deficient samples as compared to the ideal stoichiometric DIPAB crystal (Alsaad et al. 2018) [4]. Optical properties of an ideal α-DIPAB were calculated …

The Investigation Of Lactoferrin Nitration: Quantification, Function, And Inhibition, Amani Yahya Alhalwani

Electronic Theses and Dissertations

Lactoferrin (LF) is an iron-binding glycoprotein of molecular mass ca. 80 kDa that is predominantly found in mammalian body fluids. Lactoferrin is a multifunctional protein that has a wide range of properties such as antibacterial, antiviral, anti-inflammatory, and anti-allergic functions. Tyrosine residues in the protein play a part in many lactoferrin functions. Protein tyrosine nitration modification represents an oxidative and nitrosative stress process which can be caused by the exposure of proteins to oxidants from air pollution or disease. Understanding the way nitrated lactoferrin interacts with the biochemical environment of the body is thus important to the broader goal of …

Catalyst Design And Mechanism Study With Computational Method For Small Molecule Activation, Muqiong Liu

Electronic Theses and Dissertations

Computational chemistry is a branch of modern chemistry that utilizes the computers to solve chemical problems. The fundamental of computational chemistry is Schrödinger equation. To solve the equation, researchers developed many methods based on BornOppenheimer Approximation, such as Hartree-Fock method and DFT method, etc. Computational chemistry is now widely used on reaction mechanism study and new chemical designing. In the first project described in Chapter 3, we designed phosphine oxide modified Ag3, Au3 and Cu3 nanocluster catalysts with DFT method. We found that these catalysts were able to catalyze the activation of H2 by cleaving the H-H bond asymmetrically. The …

The Periodical Winter 2018, Southern Adventist University

the Periodical – Chemistry Department Newsletter

Volume 5, issue 2 of the Periodical includes articles about new faculty member Matthew Duffy, diversity within the department, a student missionary feature, and a listing of May 2018 graduates.

Uniform Electron Gas Limit Of An Exact Expression For The Kohn–Sham Exchange-Correlation Potential, Viktor N. Staroverov

Chemistry Publications

Previously, we derived an exact formula for the Kohn–Sham exchange-correlation potential corresponding, in the basis-set limit, to the Hartree–Fock electron density of a given system. This formula expresses the potential in terms of the occupied Hartree–Fock and Kohn–Sham orbitals and orbital energies. Here, we show that, when applied to the Hartree–Fock description of a uniform electron gas, the formula correctly reduces to the exchange-only local density approximation.

Dialkynylborane Complexes Of Formazanate Ligands: Synthesis, Electronic Properties, And Reactivity, Alex Van Belois, Ryan R. Maar, Mark S. Workentin, Joe Gilroy

Chemistry Publications

Dialkynylborane complexes of N-donor ligands have received significant attention due to their application in biological imaging, as light-harvesting materials, and as the functional component of organic photovoltaics. Despite these advances, relatively few types of N-donor ligands have been explored in this context. To this end, we prepared a series of dialkynylborane complexes of formazanate ligands and explored their electronic properties and reactivity. In doing so, we demonstrated that: 1) The nature of the alkynyl substituents has little influence over the UV-vis absorption properties of the title complexes, but does affect the potentials at which they are electrochemically oxidized …

Polymer Assembly Encapsulation Of Lanthanide Nanoparticles As Contrast Agents For In Vivo Micro-Ct, Charmainne Cruje, Joy Dunmore-Buyze, Jarret P. Macdonald, David W. Holdsworth, Maria Drangova, Elizabeth R. Gillies

Chemistry Publications

Despite recent technological advancements in microcomputed tomography (micro-CT) and contrast agent development, pre-clinical contrast agents are still predominantly iodine-based. Higher contrast can be achieved when using elements with higher atomic numbers, such as lanthanides; lanthanides also have x-ray attenuation properties that are ideal for spectral CT. However, the formulation of lanthanide-based contrast agents at the high concentrations required for vascular imaging presents a significant challenge. In this work, we developed an erbium-based contrast agent that meets micro-CT imaging requirements, which include colloidal stability upon redispersion at high concentrations, evasion of rapid renal clearance, and circulation times of tens of minutes …

Microencapsulation By In Situ Polymerization Of Amino Resins, Olivier Nguon, Francois Lagugne-Labarthet, 3m Company Canada, Elizabeth R. Gillies

Chemistry Publications

By surrounding small droplets with a coating, one can obtain micrometer-size capsules (microcapsules), and combine multiple properties into a single system. This technology has allowed the design of advanced and functional materials. Amino resins are composed principally of urea and/or melamine and formaldehyde, and exhibit advantages as wall-forming materials, such as high mechanical strength and chemical resistance. In this review, a general description of the encapsulation process by in situ polymerization of amino resins is given. Characterization methods, and the influence of the physical and design parameters are discussed. A mechanistic description, and some of the promising avenues of research …

Applications Of Molecular And Quantum Mechanical Methods For Studying The Chemical Reactions Of Inorganic And Organic Systems, Yi-Jung Tu

Wayne State University Dissertations

Computational studies can assist chemists to interpret experimental observations and to predict the properties and behaviors of molecules. The work presented in this dissertation applies different computational methods to study the molecular properties and reaction paths for various inorganic and organic systems. The second and third chapters discuss the force field development using “Gaussian Electrostatic Model (GEM)” and its amenability for use in the AMOEBA force field. The forth and fifth chapters discuss the density functional theory (DFT) studies of photodissociation behaviors for inorganic molecules. The sixth chapter explores the oxidation mechanisms of ascorbic acid and its antioxidant properties in …

Quantitative Analysis Of Bleomycin In Rat Plasma By Lc-Ms/Ms, Huawen Li

ETD Archive

Bleomycin is the most commonly used compound in its group of antineoplastic drugs. It works on tumor cells by single and double stranded DNA cleavage after its activation, in which it blocks tumor cells’ DNA replication or transcription activities to inhibit tumor cells’ growth. Bleomycin sulfate (Blenoxane) is the most popular preparation used in clinical research, and contains Bleomycin fractions of A2 and B2, which causes difficulties in quantitative analysis. This work uses the metal chelating property of Bleomycin as an advantage to simplify and improve sensitivity of existing quantitative methods. Copper was spiked in excess to plasma samples, followed …

Synthesis And Biological Evaluation Of Small Molecular Drug Candidates For The Treatment Of Her2 Overexpressed Breast Cancer, Anran Zhao

ETD Archive

In the US breast cancer is the most common cancer after skin cancer. Currently in the US the average risk of a woman to develop breast cancer in her life is roughly 12%. About 25-30% of breast cancer patients have HER2 overexpressed tumor, and the growth of tumor cell is depend on HER2 pathway. It has been well-documented that patients with over-expressed HER2 are associated with increased disease recurrence, worse prognosis and lower survival. Currently there are two type of HER2 targeting drug. The first group is HER2 monoclonal antibody drugs such as trastuzumab approved by FDA in 1998; the …

Development Of Bioanalytical Methods For Quantitative Measurement Of Anticancer Agents, Sandeep R. Kunati

ETD Archive

The ever-growing need to develop new anticancer agents due to increased incidence of cancer and its recurrence has led to a broad range of investigational efforts in anticancer research. Drug discovery and development processes involve evaluations of pharmacokinetic and pharmacodynamic parameters of potential drug candidates in order to assess their safety, toxicity, and efficacy profiles. By providing sensitivity, assay precision, reliability, and high-throughput, mass spectrometry has become an indispensable tool in quantitative and qualitative analysis, from early-stage drug discovery and development processes to routine laboratory analysis. Development of bioanalytical methods requires knowledge of separation science with instrumentation, data interpretation and …

Computational Investigation Of Protein Assemblies, Sm Bargeen Alam Turzo

ETD Archive

Selective nitrosylation of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) at Cys-247 affects gene regulation through the interferon-gamma (IFN- γ) activated inhibitor of translation (GAIT) complex. Oxidized low-density lipoprotein (LDL_ox) and INF-γ induce assembly of the nitrosylase complex composed of inducible nitric oxide synthase (iNOS), S100A8, and S100A9 proteins. Crystal structure of the complex of GAPDH and S100A8A9 is not known, structural prediction method were employed by protein-protein docking and binding energy calculation with PatchDock and FIREDock respectively. Candidate models were selected, based on a weight factor calculated, from the computational method developed from the "artificial protease" cleavage mapping Fe(III) (s)-1-(p- …

Model Chemistry Study Of Choline And Urea Based Deep Eutectic Solvents, Libby Nicole Kellat

ETD Archive

Gaussian and GaussView software were utilized to characterize interactions between choline salts and urea, which form a deep eutectic solvent (DES). The initial system studied was choline chloride and urea, at a 1:2 molar ratio, which is also known as reline. Subsequent systems, substituting the chloride anion with other anions (fluoride, bromide, and hydroxide), were studied to show that the system with greater calculated strength of interaction will have more non-ideal physical properties, such as melting point (found in literature). Observations regarding structure related to counterion electron density and hydrogen bonding were made throughout the studies.

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Progress Toward The Synthesis Of Aminomethyl-Substituted Qpt-1 Bacterial Topoisomerase Inhibitors, Riley Scoville, Michael Barbachyn

Summer Research

Bacterial resistance to antibiotics is a growing public health threat. Each year, ~2 million infections and 23,000 deaths are caused by antibiotic resistance in the US.1 Developing antibiotics for treating Gram-negative bacteria is especially challenging because they utilize two membranes, an outer membrane that is hydrophilic, and an inner membrane that is lipophilic, features that make cellular entry a challenge. These bacteria also have antibiotic de-activating enzymes and RND efflux pumps that work to remove the antibiotics from the cell. These features make targeting of Gram-negative organisms very difficult. Agents targeting the essential bacterial type II topoisomerases DNA gyrase and …

Progress Toward The Synthesis Of Novel Bacterial Topoisomerase Inhibitors Derived From Fluoroquinolones. N-1 Alkyne Derivaties, Sara Biel, Michael Barbachyn

Summer Research

Bacterial resistance continues to be a growing threat throughout the world. In the US alone, 2 million people are infected by, and 23,000 die from antibiotic-resistant bacteria each year. 1 Developing antibiotics to treat infections caused by Gram-negative and Gram-positive bacteria has become the focus of research efforts worldwide. Fluoroquinolones are a large, marketed class of antimicrobial agents that are effective against both types of bacteria. They target DNA Gyrase and Topoisomerase IV, type II topoisomerase enzymes that are involved in DNA replication, specifically negative supercoiling and decatenation, respectively.

As fluoroquinolones have been clinically used since the mid 80’s, their …

Hydroxylamines And Hydrazines As Surrogates Of Sp3 Carbons In Medicinal Chemistry, Sandeep Dhanju

Wayne State University Dissertations

Current compound libraries that are used in high-throughput screening (HTS) are populated by low molecular weight and relatively planar compounds with high sp2 character and little stereochemical complexity. Unfortunately, such planar compounds cover only a very small corner of chemical space. In order to increase the diversity, structurally complex molecules with high fractions of sp3-hybridized atoms should be included in compound libraries. However, generating a large number of architecturally complex molecules using the current organic synthesis toolbox is considered tedious due to the requirement of multi-step synthesis. Recognizing this need, several creative strategies, like diversity-oriented synthesis, have been developed with …

Computational Study Of Transition Metal Complexes For Solar Energy Conversion And Molecular Interaction With Strong Laser Fields, Xuetao Shi

Wayne State University Dissertations

There are two topics in this dissertation: ground state and excited state modeling of a few series of transition metal complexes that facilitate solar energy conversion, and Born-Oppenheimer Molecular Dynamics (BOMD) simulations of molecular cations interacting with intense mid-infrared laser light.

In Chapter 2 and 3, a few series of transition metal complexes that facilitate solar energy conversion are studied computationally. Metal-to-ligand charge-transfer (MLCT) excited states of several (ruthenium) (monodentate aromatic ligand, MDA) chromophore complexes are modeled by using time-dependent density function theory (TD-DFT). The calculated MLCT states correlate closely with the heretofore unknown emission properties that were observed experimentally. …

Toward Better Keys For Lectin Locks: Glycoconjugates Versus Glycomimetics, Peng Wen

Wayne State University Dissertations

As one of the four major classes of macromolecule in living systems, the roles of carbohydrates as energy storage substances and structural components have long been recognized. However, the unique role of carbohydrates in cellular recognition processes has only been scrutinized since the 1960s, thanks to the progress in the research in both cell surface carbohydrates and carbohydrate-binding proteins (lectins). The advances in the research of such process demand the use of carbohydrates as basic tools. Therefore, the primary goal of glycochemistry has been to obtain complex carbohydrates and their analogs effectively. One common approach to the problem involves the …

Cation Clock Reactions For The Determination Of Relative Reaction Kinetics In Glycosylation Reactions, Philip Adero

Wayne State University Dissertations

This dissertation presents the development of cyclization reactions as clocks for the determination of the molecularity of glycosylation reactions in individual pyranoside systems and extends it to the arabinofuranoside systems. It also describes the development of selective hydrogenolytic cleavage of naphthylmethyl ethers in the presence of sulfides.

The first part of chapter one gives an overview of the significance of glycochemistry and the challenges involved. The second part describes some selected glycosylation methods and extends this to the general mechanistic studies of glycosylation. This is followed by the discussion of the general clock reactions in literature which initiates a further …

3d Momentum Imaging Spectroscopy Probing Of Strong-Field Molecular And Surface Dynamics, Lin Fan

Wayne State University Dissertations

Electron-ion coincidence measurements in combination with 3-dimensional (3D) momentum imaging can provide comprehensive 3D-momentum information to unravel multichannel photoionization/dissociation processes, and thus is an effective tool to investigate atomic/molecular dynamics. A camera-based 3D coincidence momentum imaging system and the velocity mapping imaging (VMI) based machine were introduced in Chapter 2. Studies of strong field dissociative single and double ionization of relatively large molecules camphor and 2-phenylethyl-N, N-dimethylamine (PENNA) were carried out and illustrated in Chapter 3. We demonstrated the main products of double ionization of PENNA were singlet diradicals. In Chapter 4, a novel angle resolved-photoemission spectroscopy based on VMI …

Design, Synthesis, And Reactivity Of Homo- And Heterobimetallic Complexes Bridged By A Xanthene Linker, Thilini Samangi Hollingsworth

Wayne State University Dissertations

Cooperative reactivity of bimettalics can be is observed in many different areas of chemistry and have been increasingly investigated because of the advantageous reactivity when compared to the corresponding mononuclear systems. The focus of my dissertation is on (1) investigation of the homobimetallic cooperativity in lactide polymerization catalysis; (2) investigation of the heterobimetallic cooperativity in the biomimetic studies of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme in order to make a functional model of its active site.

Three new main group bis(alkoxide) complexes Mg(OR)2(THF)2, Zn(Cl)(μ2-OR)2Li(THF) and In(OR)2(μ2-Cl)2Li(THF)2 featuring bulky alkoxide [OCtBu2Ph] were synthesized serve as metal alkoxide precursors for bimetallic lactide …

Design And Synthesis Of Oligo-(3,5-Dithio-Β-D-Glucopyranoside) As Β-(1→3)-Glucan Mimetics, Xiaoxiao Liao

Wayne State University Dissertations

This dissertation presents the design and synthesis of oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics. The synthesized dimeric, trimeric and tetrameric mimetics were tested for their binding affinities to Dectin-1 and CR3 and their abilities to activate phagocytosis and pinocytosis.

The first chapter gives an introduction of β-(1 → 3)-D-glucan. It gives an introduction about the structure and origin of β-(1 → 3)-D-glucan as well as the immunostimulating effect of natural β-(1 → 3)-D-glucan. The study of interaction between β-(1 → 3)-D-glucan and the receptors leads to a conclusion that the hydrophobicity of β-(1 → 3)-D-glucan is crucial to its immunostimulating …