Author Archives: Rebecca Joy Ulrich

Elahson Swanson–Small Molecule Iron Chelation for Parkinson’s Disease Therapy

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Abstract: “One of the hallmarks of Parkinson’s disease (PD) is the death of dopaminergic neurons, which is suggested to be caused by oxidative stress due to increased levels of iron present in the brain. Furthermore, the brains of Parkinson’s patients have been found to contain intracellular protein deposits, known as Lewy Bodies, that are comprised of alpha-synuclein (αS) and contain a relatively high concentration of iron. As a result of these observations, a complex that could chelate iron, thereby sequestering it in solution, and decrease the aggregation of αS was proposed as a therapeutic agent against Parkinson’s disease. The target complex, C1, was synthesized via click chemistry with a design centered on the incorporation of a sugar molecule, due to the brain’s affinity for glucose, and a pyridine as the coordinator for the targeted metal ion. Once synthesized, C1 was evaluated for its ability to prevent the metal-associated aggregation of αS. Treatment of αS with C1 in the presence of either Fe(II) or Fe(III) saw a reduction in the relative aggregation of the protein. Moreover, when the samples were analyzed using dynamic light scattering (DLS) and transmission electron microscopy (TEM), smaller particles were consistently observed when C1 was included. Taken together, the overall decrease in fluorescence and smaller particle size of αS and iron containing solutions when C1 was added indicates a decrease in αS aggregation, making iron a potential therapeutic target for PD.”

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Paul Grocki–Chemometric Analysis of Urinary Volatile Organic Compounds Discriminates Murine Breast Cancer Presence and Progression Over Time

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Abstract: “Previous studies demonstrated that volatile organic compounds (VOCs) in urine are potential biomarkers of breast cancer. An unanswered question is how urinary VOCs change over the course of tumor progression. To explore this, urine samples were collected from female Balb/c mice injected with 4T1.2 murine tumor cells in the tibia prior to tumor injection (20 samples) and over the next three weeks (12, 15, and 18 samples collected during weeks 1, 2, and 3 respectively). Samples were analyzed by headspace solid phase microextraction coupled to GC-MS QTOF. Univariate analysis showed many VOCs dysregulated by cancer, with some varying significantly during cancer progression and others not. PCA using panels of VOCs could distinguish both Cancer Weeks 1-3 from Control and Cancer Week 1 from Cancer Week 3 with > 90% sensitivity and specificity. Forward feature selection and linear discriminant analysis identified a unique panel of five VOCs that could distinguish Cancer Weeks 1 and 3 from Control with a fivefold cross validated (CV) area under the receiver operator characteristic (AUROC) equal to 0.95. The same model could also distinguish Cancer Week 1 from Cancer Week 3 with a fivefold CV AUROC equal to 0.97. The results of this study show that VOCs can be used to monitor breast cancer progression in mice models.

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Omar Kazi–Direct Electrochemically Grown Thick Energy Dense Lithium Manganese Oxide Cathodes for Lithium-Ion Batteries

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Abstract: “We demonstrate for the first time an intermediate temperature (250-350°C) molten hydroxide mediated electrodeposition process to grow ternary lithium manganese oxide chemistries (Li2MnO3, LiMnO2, and LiMn2O4). State-of-the-art synthesis routes for such cathodes for lithium-ion batteries involve prolonged high temperature (over 700°C) processing for long reaction times under high oxygen pressure, followed by slurry casting after mixing with binders and additives. Our electrodeposited oxide cathodes are synthesized with the lowest reported temperature and reaction times, yet still retain the key structural and electrochemical performance observed in the high-temperature bulk synthesized analogs. The binder-and-additive- free, tens of microns thick, greater than 80% dense electrodeposits exhibit near theoretical gravimetric capacities and reversible areal capacities up to 1.5 mAh/cm^2.”

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Thy Nguyen–Donor-Acceptor Characterization of Homoleptic Cobalt Dithione Complexes

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Abstract: “Metallodithiolene complexes are well known for their charge transfer properties that great promise towards the development of material science due to the non-innocent nature of the dithiolene ligand. Dithione (Dt0) ligands exhibit significant charge delocalization across their thioamide moiety, making them redox-active ligands. The ability for Dt0 ligands to participate in redox processes, in conjunction with transition metalcore, grants such complexes potential access to additional redox states. In this project, octahedral cobalt Dt0 complexes, [Co(Me2 Dt0)3][PF6]3 (1) and [Co(iPr2 Dt0)3][PF6]3, (2) have been thoroughly characterized utilizing elemental analysis, mass spectroscopy, IR, UV-Vis, NMR, cyclic voltammetry, and DFT calculations. The excited state transitions of 1 and 2 were determined with TD-DFT calculations and visualized using electronic density difference maps (EDDMs). Low energy charge transfers for 1 and 2 are determined to be MLCT, while higher energy transitions are assigned as Dt0-based p → p* LL’CT.”

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Ryan Baker–Computational Adsorption Dynamics of Halogenated Disinfection Byproducts on Graphenic Surface

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Abstract: “Modern wastewater treatment procedure often results in the creation of halogenated methanes and other disinfection byproducts (DBP). Many of these, namely chloroform and dichloromethane, are known carcinogens, and their removal from municipal water supply is paramount to public safety. Many techniques have been developed to combat this issue, such as the widespread use of activated carbon as an adsorbent. This method is effective, but the nature of the adsorptive interaction is largely understudied. In this study, the adsorption of all chlorine, bromine, and iodine derivatives of methane to a model graphenic structure, circumcoronene, are studied relative to unaltered methane. This adsorption was studied computationally, considering potential starting and final conformers to approximate realistic adsorption at standard temperature.”

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Kylie Smith–Inorganic Chemistry Lab Development: Iron Solubility

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Abstract: “The electronic configuration and chemistry of iron allows for a variety of coordination compounds and complexes to be formed. These complexes consist of the metal ion bound to ligands, which can be nonmetal ions, small molecules such as H2O, NH3, or large molecules including organic ligands. Metal complexes are important to the function of proteins. For example, heme is a coordination complex of an iron ion coordinated to a porphyrin. Heme is a precursor to hemoglobin which can bind oxygen in the blood. Another example is nitrogenase, an enzyme in cyanobacteria that is important in nitrogen fixation. We are developing an inorganic chemistry lab experiment that introduces students to the coordination chemistry of iron by allowing them to relate complex formation to color changes and solubility. The objectives of the experiments presented here are: i) Observe and understand the chemistry of transition metal complexes. ii) Correctly calculate and prepare solutions of known concentrations. iii) Determine and explain changes in color and solubility in terms of metal-ligand interactions. iv) Analyze metal-ligand formation and generate evidence-supported conclusions. Students explore several concepts related to transition metal chemistry, coordination chemistry, oxidation-reduction reactions, and solubility.”

 

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Mercedes DeMoss–In Vivo Screening of Indenoisoquinoline compounds

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Abstract: “The MYC oncogene is a promising drug target for cancer research due to its overexpression in a majority of cancers. However, the MYC protein is considered undruggable. The G-quadruplex structure formed in the promoter region of the MYC oncogene is a transcription inhibitor. Stabilizing the MYC promoter G-quadruplex with small molecules decreases MYC levels in cancer cells causing cell death. Indenoisoquinoline compounds have been shown to induce and stabilize the MYC promoter G-quadruplex and inhibit MYC expression. Currently, there is no commercially available DNA-targeted small molecule compound library. In this study we first establish a DNA-targeted molecule compound library with over 2000 indenoisoquinoline compounds and analogs. We created a physical library with electronic data to easily access the information about each compound. We screened the library in vitro for binding of each compound to the MYC promoter G-quadruplex. Then we used in vivo cellular assays with two different cancer cell lines to determine the compounds’ toxicity to cancer cells and their ability to stabilize the MYC promoter G-quadruplex and downregulate MYC. With these results we discovered 270 hit compounds. Currently we are conducting more detailed studies of these hit compounds to better determine their MYC promoter G-quadruplex binding and MYC inhibition in cancer cells to ultimately develop an in-depth structure-activity relationship for indenoisoquinolines at this promising cancer target.”

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Matthew Martin–Synthesis, Characterization, and Anticancer Activity of Arsenoplatin-4

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Abstract: “The FDA approved anticancer drug arsenic trioxide (As2O3) is highly efficient for treatment of acute promyelocytic leukemia, but due to its rapid renal clearance in the form of arsenous acid, As(OH)3, it has been ineffective in the treatment of solid cancers. A new class of potent anticancer agents that contain As(OH)2 moiety bound to platinum(II) center, arsenoplatins [Pt(µ-NHC(R)O)2XAs(OH)2] (R=CH3 or CH3CH2), X=Cl-, SCN-), have been synthesized. A high Pearson correlation coefficient (r = 0.96) was obtained while comparing anticancer activity of Arsenoplatin-2 (R = CH3CH2, X=Cl- ; AP-2) to As2O3 in the NCI-60 screen, suggesting the two compounds act in a similar manner. This project aims to synthesize, characterize, and test the anticancer activity of an iodide analog of AP-2, labeled AP-4. X-ray, NMR, and elemental analysis have been completed to determine the structure and purity of this new compound. The cytotoxicity of AP-4 in the triple negative breast MDA-MB-231 cancer cell line has been evaluated by MTS cell proliferation assay. Interaction of AP-4 with the biologically important molecule glutathione (GSH) was assessed by fluorescent detection assay. GSH depletion has been shown to sensitize cancer cells that are resistant to platinum drugs. The effect of AP-4 concentrations on the GSH level is discussed. Based on current results, AP-2 and AP-4 may act as a delivery vehicle for As2O3, overcoming one of the primary limitations of As2O3 as a drug for solid cancers.”

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Ji Seon “Lucy” Shon–Single-Chain Nanoparticle Delivers a Partner Enzyme for Concurrent and Tandem Catalysis in Cells

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Abstract: “In biological environment, enzymes catalyze reactions at extremely high efficiency and selectivity. The polypeptide scaffolds of enzymes selectively bind substrates to the catalytic to increase the efficiency. Single-chain nanoparticles have been developed with Ru(bpy)3 as enzyme mimic photocatalyst. They have been shown to penetrate the cell membrane and perform the reactions inside cells. More importantly, the nanoparticles can co-deliver an exogenous enzyme (beta-galactosidase) into cells and reside in endosomes. The SCNP-enzyme complex preserves their activity and perform concurrent or tandem reactions intracellularly. Therefore, the endosomes are engineered as artificial organelles, which efficiently producing fluorescent compounds or bioactive agents intracellularly.”

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Vennela Mannava–Carbon Dioxide Utilization in Plastic Production: Development of a Nickel Catalyst

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Abstract: “Carbon dioxide emissions, known to exacerbate climate change, have been increasing rapidly over the past century. One strategy to alleviate this issue is carbon capture and utilization (CCU), in which atmospheric CO2 is used to produce more valuable compounds. An attractive target is sodium acrylate, the building block of superabsorbent polymers found in many common goods. Researchers have sought a reaction coupling CO2 and ethylene, which would produce acrylate from sustainable starting materials. Nickel catalysts have been able to facilitate this coupling but suffer from low efficiency, due to the formation of a nickelalactone intermediate. This has a very stable ring structure that resists the release of acrylate from the catalyst. My project aims to develop supporting ligands for the catalyst that provide appropriate steric bulk and electron density to the nickel center to promote efficient nickelalactone ring-opening. Current work focuses on N-heterocyclic carbene (NHC) ligands, which are very electron-donating and highly modular. Preliminary experiments on a simple bis(NHC) nickelalactone and computational investigation of other ligand systems with varying properties predicts that strong electronic asymmetry and broad steric bulk are vital to ligand design for destabilizing nickelalactones. These NHC ligands could be the key to efficient nickel catalysts coupling CO2 and ethylene for sodium acrylate production, thus contributing to global CCU efforts.”

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