2017 Program
The conference begins in the morning with registration, breakfast, and laptop setup followed by the opening address at in room 1001 in Giedt Hall. Oral presentations by undergraduates are then scheduled in three parallel sessions in rooms 1001, 1002, and 1003. Sessions will be moderated by a faculty member who also facilitates a brief discussion after each presentation. The keynote address and the awards ceremony are scheduled for the early afternoon.
Congratulations to the winners of the Best Presentation Awards!
Best presentation in Chemical Biology ($200) : Ardavan Farahvash
Best presentation in Organic/Inorganic ($100 each): Navteg Singh Grewal and Ming Yin Kong
Best presentation in Physical/Analytic ($100 each): Jessi Hartman and Alec Tyra
Morning Session A (room 1001) 10:00 am – noon
A1. The Impact of Mutations to Residues Surrounding the [4Fe-4S]2+ Cluster of the Adenine Glycosylase MutY on DNA Repair
Holly Vickery, Chandrima Majumdar, and Sheila David
A2. Calmodulin Mutations Impair Ryanodine Receptor 2 Function in Cardiac Arrhythmias
Gillian K. Rexroad, David E. Anderson, James B. Ames
A3. Defining the Structure of a Major Groove Nucleobase Click Modification in RNA
Madeline Mumbleau, Scott Suter, Andrew J. Fisher, Peter Beal
A4. Evolution of Isobutyl Acetate Tolerance in Escherichia coli
Tram (Kelly) Nguyen, Anna Case, Shota Atsumi
A5. Epigenetic lesions are bound but not cleaved by glycosylase hNEIL1
Taylor McCart, Brittany Anderson-Steele, Sheila David
A6. Synthesis of Small Molecule Inhibitor Analogs of Bacterial Cell Division Protein FtsZ
Tony Moreno, Nicole Cooper, and Jared Shaw
A7. The Neuroprotective Potential of Psychedelics
Sina Soltanzadeh Zarandi and David E. Olson
A8. One-Pot Multi Enzyme Synthesis of Galβ1-4(Fucα1-3)GlcβProN3
Natalie DeForest, Abhishek Santra, and Xi Chen
Morning Session B (room 1002) 10:00 am – noon
B1. Advances in Ruthenium Chemistry
Michael M. Aristov, Xian B. Powers, Kamran B. Ghiassi, Marilyn M. Olmstead, and Alan L. Balch
B2. Synthesis and Redox Reactivity of Gallium(III) Isoindoline Complexes
Shiela S. Angulo, Cody R. Carr, and Louise A. Berben
B3. Synthesis and Characterization of the Novel Lithium Amide Ligand Transfer Agent LiN(SiMeCy2)2 [Cy = cyclohexyl] and its Transition Metal Bisamido Derivatives
Skylar Osler and Philip P. Power
B4. Synthesis, Structure and Thermoelectric Properties of the Type-I Clathrates K8A8Ge38 (A = Al, Ga, and In)
Victor Bates, Chris Perez, and Susan Kauzlarich
B5. Stereoselective Synthesis of Indolines via Intramolecular C-H Bond Insertion
Dashiel Barrett, Rich Squitieri, Lucas Souza, and Jared Shaw
B6. Synthesis of Malonamides with Methallylsilanes and Analysis of their Photophysical Properties
Alayna Nguyen, Julia Jennings, and Annaliese K. Franz
B7. Synthesis of BaNixFe2-xAs2 via the Hydride Route
Ming Yin Kwong, Julia V. Zaikina, and Susan M. Kauzlarich
B8. Exploring New Anion-Binding Catalysts for the Synthesis of Quinoline Products
Noreen Brar, Kayla Diemoz, and Annaliese Franz
Morning Session C (room 1003) 10:00 am – noon
C1. Study of Rh2-yCryO3 loaded Al:SrTiO3 nanoparticles as photocatalysts for solar water splitting
Emma Willard, Zeqiong Zhao, and Frank E. Osterloh
C2. Interaction of Water with N-Doped Graphene by First Principles Simulations
Jessi Hartman, Svenja Johanna Wörner, Davide Donadio
C3. Reduction of Silica Sea Sponge Spicules for Synthesis of useful Silicon Semiconductors
Wai Lone Jonathan Ho and Kristie J. Koski
C4. X-ray Induced Singlet Oxygen Generation by Quantum Dot-Nanoporphyrin Conjugates for Photodynamic Therapy
Yuting Ma, Jennifer Lien, Xiangdong Xue, Yuanpei Li, and Ting Guo
C5. Photophysical Characterization of Substituted Spiropyrans as Novel GSH Sensors using Ultraviolet-Visible Spectrophotometry
Stephen Z. Liu and Angelique Y. Louie
C6. The Effect of Co-Catalysts on Copper Tungstate for Photo-Induced Water Oxidation Under Visible Light
Ghunbong Cheung, Zongkai Wu, and Frank Osterloh
C7. Observing Changes in Cell Surface N-glycans and O-glycans during Intestinal Epithelial Cell Differentiation
Zhi Cheng, Gege Xu, Dayoung Park, and Carlito B. Lebrilla
C8. DFT study of Zintl Phase Thermoelectrics Ca2CdSb2 and Yb2CdSb2
Matthew Han, Shruba Gangopadhyay, Joya Cooley, Susan M. Kauzlarich, Warren E. Pickett, Davide Donadio
Afternoon Session A (room 1001) 1:00 – 2:45 pm
A9. Evaluation of the MUTYH Associated Polyposis Variant V217F in the Mus Musculus Homolog Mutyh
Kelsey Mifflin, Katie Bradshaw and Sheila David
A10. Structural Insights for Fe(II) Binding to Retinal Guanylyl Cyclase Activator Protein-5 (GCAP5): a Redox Sensor in Zebrafish Photoreceptors
Grace Manchala, Sunghyuk Lim, and James B. Ames
A11. Investigating a Missing Link in the Mechanism of Cytochrome c Oxidase: Prediction and Analysis of Internal Water Chains
Ardavan Farahvash, Alexander Morozenko, Alexei Stuchebrukhov
A12. Synthesis of Gyramide-Bound Photoaffinity Reagents and Analogs for DNA Gyrase
Ada J. Kwong, Lucas C. Moore, Jared T. Shaw
A13. Chemoenzymatic Synthesis of 2-keto-3-deoxynononic(Kdn)-containing Gangliosides Using Bacterial Sialyltransferase
Jeyxa Faustorilla, Wangqing Li, Abhishek Santra, and Xi Chen
A14. Expression, Purification, and Crystallography of CysK2
Jiahui Lu, Nicholas Hurlburt, Andrew Fisher
A15. Functional Conversion of Anthranilate Synthase to Aminodeoxychorismate Synthase using Janus Predicted Mutations
Sarah C. Potter, Dong hee Chung, Saheli Chatterjee, Michael D. Toney
Afternoon Session B (room 1002) 1:00 – 2:45 pm
B9. Synthesis and Characterization of Monomeric Heavier Main Group 14 Element Diaryls EAriPr62 (AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2) (E = Ge, Sn, Pb)
Kelly L. Gullett, Madison L. McCrea-Hendrick, James C. Fettinger, Philip P. Power
B10. Lewis and Brønsted Acid-catalyzed Allylsilane Oligomerization
Benjamin Wigman, Brittany Armstrong, Annaliese Franz
B11. Direct Spark-Plasma Sintering Synthesis and Thermoelectric Properties of Yb14Mn1-xTexSb11
Dashiel J. Barrett, Elizabeth L. Kunz Wille, and Susan M. Kauzlarich
B12. Synthesis of novel indole-containing malonamides and potential HDAC inhibitors
Blanca Gomez, Julia Jennings, and Annaliese Franz
B13. Synthesis and Characterization of Yb14-x-yCaxBayMgSb11 for Potential Thermoelectric Applications
Navtej Singh Grewal, Elizabeth L. Kunz Wille, and Susan M. Kauzlarich
B14. The Effect of Precursor Concentration on the Synthesis of Germanium Nanoparticles
Joey N. Kingstad, Kathryn A. Newton, and Susan M. Kauzlarich
B15. Compounds to Increase Neuroplasticity
Alexandra Greb, Calvin Ly and David Olson
Afternoon Session C (room 1003) 1:00 – 2:45 pm
C9. Investigating Photochemical Charge Transfer Processes in Thin Films of Organic Dyes
Brian Roehrich, Ruirui Han, and Frank E. Osterloh
C10. Structural Insights for Sequence Specific DNA Binding by the Homeodomain Protein, HoxD13
Martin Esparza Sanchez, Matthew Turner, David Anderson, and James B. Ames
C11. Development of a Rapid High-Throughput Mass Spectrometry-Based Method for the Quantification of Monosaccharides in Food
Thai-Thanh Vo, Ace G. Galermo, Matthew J. Amicucci, Carlito B. Lebrilla
C12. Association of dynamic changes of osteopontin concentrations in human milk
Allison Lee, Rulan Jiang, and Bo Lonnerdal
C13. Deriving Paleotemperatures from the Speleothem Record: past climate change in the Western Sierra Nevada
Alec Tyra, Barbara Wortham, and Sujoy Mukhopadhyay
C14. Activatable Manganese-Based Contrast Agent Sensitive to GSH
Xinzhe Li and Angelique Louie
Keynote Address (room 176) 3:15 – 4:10 pm
Prof. Kevin Gardner (CUNY Advanced Research Center)
“Environmentally-switched protein/protein interactions: Studying nature’s switches to make scientists’ tools”
Abstracts
A1. The Impact of Mutations to Residues Surrounding the
[4Fe-4S]2+ Cluster of the Adenine Glycosylase MutY on DNA Repair
Holly Vickery, Chandrima Majumdar, and Sheila David
MutY is a DNA base excision repair (BER) enzyme that catalyzes the excision of adenine (A) base paired opposite the damaged DNA base 8-oxo-7,8-dihydroguanine (OG), formed by the oxidation of the natural DNA base guanine (G). If OG:A mispairs are left unrepaired, replication will result in a G:C to T:A point mutation. The accumulation of OG:A mutations in the genome is associated with cancerous growth, and mutations in the MUTYH (human homolog of MutY) gene have been associated with a form of colorectal cancer called MUTYH-Associated Polyposis. An interesting structural feature of MUTYH/MutY is the presence of a [4Fe-4S]2+ cluster in the N-terminal domain. Two of the cysteine ligands of this cluster anchor a solvent exposed loop called the [4Fe-4S]2+ loop (FCL) motif of the enzyme. This loop contains a high density of positively charged, basic amino acid residues that aid in binding the negatively charged DNA backbone. Previous studies have shown that mutating these residues to alanine results in compromised binding of the enzyme to DNA containing OG:A, but the rate of glycosylase activity with OG:A shows no measurable difference, and G:A containing DNA substrates show a reduced rate of glycosylase reaction. In order to further explore the effects of these mutations in a cellular context, we are using a plasmid based cellular assay with E. coli as the host organism to determine the overall extent of repair of OG:A lesions in vivo by these variants. The results obtained will provide insight into the role of these residues and the effect of decreased binding on the in vivo repair ability of the glycosylase in a cellular context.
A2. Calmodulin Mutations Impair Ryanodine Receptor 2 Function in Cardiac Arrhythmias
Gillian K. Rexroad, David E. Anderson, James B. Ames
Ryanodine receptor 2 (RyR2), a Ca2+ release channel in the sarcoplasmic reticulum (SR) membrane of cardiac myocytes, promotes Ca2+ influx from the SR into the cytosol that causes cardiac muscle contraction. Calmodulin (CaM), an EF-hand calcium-sensor protein, binds to RyR2 and confers Ca2+-induced inactivation (CDI) of channel activity. Electrically stimulating a cardiac myocyte leads to plasma membrane depolarization that in turn causes RyR2 channel opening, resulting in a 10-fold increase in cytosolic Ca2+ levels. Under such high intracellular calcium concentrations, Ca2+-bound CaM binds to and inactivates RyR2, resulting in muscle relaxation. CaM mutations (N54I, D96V, and N98S) are genetically linked to various cardiac arrhythmias. These CaM mutations interfere with normal CDI by altering calmodulin’s binding affinity for Ca2+, RyR2, or both. I performed fluorescence polarization binding assays to measure CaM binding to three separate sites in RyR2: site 1 (residues 1942-1966), site 2 (3581-3607), and site 3 (4246-4276). The CaM mutation N54I decreased CaM binding to RyR2 sites 2 and 3 by more than 10-fold, but had little effect on CaM binding to site 1. The CaM mutation D96V decreased CaM binding to both sites 2 and 3 by 3-fold, and abolished CaM binding to site 1. Finally, the CaM mutation N98S decreased CaM binding to site 2 by 8-fold, and abolished CaM binding to site 1. The differential effects of each CaM mutant suggest that the multiple RyR2 sites may have different functions that act independently. We propose that CaM binding to the multiple RyR2 sites may separately control Ca2+-dependent activation and inactivation of RyR2 channel activity.
A3. Defining the Structure of a Major Groove Nucleobase Click Modification in RNA
Madeline Mumbleau, Scott Suter, Andrew Fisher, Peter Beal
Copper-catalyzed azide/alkyne cycloaddition (CuAAC), or ‘click’ reactions on terminal alkynes allow for a variety of modifications of ethynyl containing RNAs. Previously in our group, an N-ethylpiperidine substituent was incorporated via a click reaction with 7-ethynyl-8-aza-7-deazaadenosine (7-EAA) to better understand the impact of this unique ribonucleoside modification in the major groove of an RNA duplex. The crystal structure of the double stranded RNA was solved, however a well-defined electron density for the triazole substituent was inconclusive. To obtain a better defined crystal structure, new rigid modifications were introduced via click reactions involving 7-EAA with either 4-azidoaniline or 1-azido-4-bromobenzene. Successful results were obtained with the bromobenzene modification yielding a 1.6Å resolution crystal structure. This work also comments on the optimized approach for clicking 1-azido-4-bromobenzene, which offers unexpected byproducts in reducing conditions.
A4. Evolution of isobutyl acetate tolerance in Escherichia coli
Tram (Kelly) Nguyen, Anna Case, Shota Atsumi
The Atsumi group has constructed an efficient isobutyl acetate (IBA) production pathway (~18 g/L) in Escherichia coli, a chemical used as a flavoring agent, solvent, and fuel. IBA is one of few renewable fuel alternatives to have been produced in industrially relevant concentrations by engineered microorganisms. One of the greatest challenges in microbial chemical production is separation and purification of the product from the culture. One advantage of IBA production is that it has a relatively low water solubility limit (only 6 g/L) when compared with other chemical feed-stocks (isobutanol is soluble up to 71 g/L). This would allow for the formation of a natural bilayer at concentrations greater than 6 g/L, however, the toxicity limit of IBA is relatively low (1.5 g/L). This prevents production in high enough titers for bilayer formation and necessitates the use of a second layer (in this case hexadecane) to remove IBA from the culture layer and alleviate toxicity effects. Improving the tolerance of E. coli to IBA up to the solubility limit would eliminate the need for a hexadecane layer and would improve separation efficiency of the system. Directed evolution techniques have been utilized to improve the tolerance of the strain to IBA from 1.5 g/L to 3 g/L. In addition, it has been confirmed that IBA production in the IBA tolerance mutant is comparable with that in the parent strain.
A5. Epigenetic lesions are bound but not cleaved by glycosylase hNEIL1
Taylor McCart, Brittany Anderson-Steele, Sheila David
Epigenetic lesions are prevalent in DNA and can result in changes in phenotype without change in DNA sequence. One such lesion is methylcytosine (mC) where methylation of the cytosine can act as an on or off switch for gene expression. mC can be further oxidized by Ten Eleven Translocation (TET) enzymes producing the lesions hydroxymethylcytosine (hmC), formylcytosine (fC), and carboxycytosine (caC). TET enzymes play a role in the repair of mC by transforming it into substrates for base excision repair (BER) enzymes. Indeed, the hNEIL1 BER glycosylase, which is known to remove a variety of oxidized bases has been previously implicated in pull-down studies to one of the BER enzymes involved in this process. Surprisingly, we found that hNEIL1 is not able to remove these epigenetically modified DNA bases from DNA duplexes in vitro. We hypothesized that the DNA glycosylase hNEIL1 may participate in gene regulation by binding to these lesions, without mediating base cleavage. Moreover, there are two forms of hNEIL1 resulting from RNA editing that may exhibit differential affinity to the epigenetic lesions. To determine the binding affinity of hNEIL1 to the epigenetic lesions and nonspecific DNA, a fluorescence polarization binding assay was utilized. In the binding assay, both the edited and unedited forms of hNEIL1 were used, and these forms only differ by a single amino acid change from lysine to arginine at position 242. We found that hNEIL1 binds to fC and caC in a similar fashion to that of nonspecific DNA, whereas both forms of hNEIL1 bind to hmC tighter than nonspecific DNA.
A6. Synthesis of Small Molecule Inhibitor Analogs of Bacterial Cell Division Protein FtsZ
Tony Moreno, Nicole Cooper, and Jared Shaw
Due to the increase of antibiotic resistant bacteria, the world is in desperate need of antibiotics with novel mechanisms of action. In effort to possibly answer this need, current research involves investigating the structural-activity relationship (SAR) of a new potential antibiotic target. Temperature sensitive filamenting protein Z (FtsZ) was found to play a central role in bacterial cell division. A class of molecules, named Zantrins, were discovered that selectively interact with FtsZ of Escherichia coli to inhibit its function. The Shaw lab has done work with a particular Zantrin, Z3, by modifying three different areas of its structure and studying the SAR between these analogs and their inhibitory capabilities of FtsZ. A Z3-inspired core structure was functionalized with a phosphonate ester at area 3 so that analogs could readily be made using a Horner-Wadsworth-Emmons reaction. Current efforts involve building a library of these analogs and measuring their IC50 of FtsZ through in-vitro biological assay. Zantrin Z3 inhibits FtsZ isolated from Escherichia coli at a IC50 of 50 µM. Future work involves building a substantial library of analogs, and measuring their IC50’s with the goal of reducing the IC50 into the nanomolar range. If successful, this small molecule inhibitor could be a potential antibiotic target that bacteria have no current resistance to.
A7. The Neuroprotective Potential of Psychedelics
Sina Soltanzadeh Zarandi and David Olson
Stroke is the third leading cause of death in the United States and a major cause of disability in adults that may lead to physical impairment or cognitive deficits. During a stroke, the brain degenerates rapidly due to lack of oxygen that ultimately results in cell death. Neuroprotective agents such as brain-derived neurotrophic factor (BDNF) have the capacity to prevent irreversible injury of ischemic neurons. However, BDNF does not readily cross the blood-brain barrier which necessitates elaborate drug delivery methods. My research has focused on studying compounds such as N,N-dimethyltryptamine (DMT), ketamine and lysergic acid diethylamide (LSD) that readily cross the blood-brain barrier, can potentially increase the production of BDNF, and achieve neuroprotection. To test for this, in vitro cortical neurons were treated with glutamate or hydrogen peroxide to model a stroke. Thereafter, the cell cultures were treated with either DMT, LSD, or Ketamine and the extent of cell survival was quantified by using a colorimetric assay for assessing cell metabolic activity. Thus far, the use of LSD and Ketamine appear promising in achieving neuroprotection. Further work will include testing these compounds at varying concentrations and testing for BDNF-independent mechanisms of neuroprotection.
A8. One-Pot Multi Enzyme Synthesis of Galβ1-4(Fucα13)GlcβProN3
Natalie DeForest, Abhishek Santra, and Xi Chen
Lewis x (Lex) is an antigen found within glycoconjugates on the human cell surface that plays an integral role in preventing immune detection by the host of the pathogenic bacterium. Alterations in the structure of Lex have been observed to show biological importance, thus making them attractive synthetic targets. Here, we utilize chemoenzymatic synthesis methods to selectively obtain complex carbohydrates. The one-pot multi-enzyme (OPME) system was implemented to synthesize the oligosaccharide Galβ1-4(Fucα1-3)GlcβProNH-FMOC, which closely resembles Lex. First, the acceptor was synthesized by protecting Galβ1-4GlcβProN3 using FMOC. The OPME system then uses guanosine 5’-triphosphate (GTP), adenosine 5’-triphosphate (ATP), and L-fucose with the enzymes L-fucokinase/GDP-fucose pyrophosphorylase (FKP), inorganic pyrophosphatase (PmPpA), and Hpα1-3Δ66. These enzymes are responsible for driving the reaction forward energetically and catalyzing the transfer of the fucose moiety from GDP-Fuc to Galβ1-4(Fucα1-3)GlcβProNH-FMOC. This protocol prevents the use of high cost sugars and avoids loss of product between steps.
A9. Evaluation of the MUTYH Associated Polyposis Variant V217F in the Mus Musculus Homolog Mutyh
Kelsey Mifflin, Katie Bradshaw and Sheila David
In the presence of reactive oxygen and nitrogen species (RONS), DNA can undergo oxidative damage, which can be problematic for proper replication of the genome. RONS commonly reacts with a susceptible guanine resulting in a chemical transformation to 8-oxo-7, 8-dihydro-2’-deoxyguanosine (OG). OG is particularly dangerous due to its dual coding ability, where the damaged base can form a stable base pair with cytosine, as well as adenine when OG is in the syn conformation. The DNA repair glycosylase, Mutyh, removes the mismatched adenine creating an abasic site for other enzymes in the repair pathway to reintroduce a correct cytosine base opposite OG. Inheritance of biallelic mutations in the MUTYH gene has been clinically shown to result in MUTYH-Associated Polyposis (MAP), which significantly increases the risk of developing colorectal cancer. Several variants surrounding the [4Fe-4S]2+cluster of Mutyh were selected for the project due to the cluster’s established role in the enzyme’s affinity and binding abilities to damaged DNA. My results showed that the V217F variant of Mutyh does not show a decline in the percent activity but rather a dramatic increase. For the STOs, the V217F variant resulted in a k2 = 1.1 ± 0.2. From the current data, this variant is indeed active and shows a similar kinetics profile to WT; however, further kinetic evaluation and repair are needed to establish the variant’s true implication in MAP.
A10. Structural Insights for Fe(II) Binding to Retinal Guanylyl Cyclase Activator Protein-5 (GCAP5): a Redox Sensor in Zebrafish Photoreceptors
Grace Manchala, Sunghyuk Lim, and James B. Ames
GCAP5, a retinal calcium sensor protein, confers both Fe2+- and Ca2+-sensitive activation of retinal guanylyl cyclase (RetGC) in zebrafish retinal cone cells. Fe2+-induced activation of RetGC is functionally important for replenishing cGMP levels to promote the recovery phase of phototransduction in vision. Previous studies have shown that GCAP5 has increased capacity to activate RetGC activity under reducing conditions caused by high metabolic activity in photoreceptor cells. Thus, relatively high Fe2+ levels present under reducing conditions may bind to GCAP5 and control its ability to activate RetGC. To test this hypothesis, I performed NMR spectroscopy to probe the binding of Fe2+ to GCAP5 by recording NMR HSQC spectra of 15N-labeled GCAP5 as a function of added Fe2+. The NMR spectra showed Fe2+-induced structural changes in GCAP5, indicating that GCAP5 forms a dimer that binds to Fe2+ with a one to two binding stoichiometry of iron to protein. To determine the location of iron binding, two notable cysteine residues, C15 and C17 were mutated to alanine. The NMR spectrum of the C15A/C17A mutant no longer exhibits any Fe2+-induced spectral changes, indicating that high affinity Fe2+ binding was abolished. I propose that sulfhydryl sulfur atoms from the two Cys residues in GCAP5 each form a coordinate covalent bond with a bound Fe2+.
A11. Investigating a missing link in the mechanism of cytochrome c oxidase: prediction and analysis of internal water chains
Ardavan Farahvash, Alexander Morozenko, Alexei Stuchebrukhov
Cytochrome c oxidase (CcO) is the terminal enzyme in the respiratory electron transport chain; its bi-nuclear center (BNC) catalyzes the reduction of oxygen to water. Key to understanding the mechanism of this catalysis is the question of how protons are transported to the BNC – presumably by water chains in the enzyme, which have not been resolved in experimental X-ray structures so far. Here we present an analysis of the hydration of CcO near the BNC, and a potential solution to the problem of missing water chains in the X-ray structures. Through analysis of the BNC with the hydration software Dowser++, recently developed in our group, it was shown that there are several energetically favorable hydration sites near the BNC, and that these sites could account for the missing water chains leading to the BNC, particularly in the K-channel. Molecular dynamics (MD) simulations were performed to investigate the dynamic nature of water molecules in these predicted hydration sites, and the results suggest a consistent explanation as to why they would be missing in experimental structures.
A12. Synthesis of Gyramide-Bound Photoaffinity Reagents and Analogs for DNA Gyrase
Ada J. Kwong, Lucas C. Moore, Jared T. Shaw
Antibiotic resistant bacteria are on the rise, and it is imperative that new drugs be developed to fight them. Unexploited targets that cause bacterial death are an important area of study for such development. We are targeting DNA gyrase, a protein that helps uncoil DNA during replication and transcription in bacteria because it can be distinguished from the analogous human protein, Topoisomerase II. Gyramides are small molecules that have been shown to successfully inhibit DNA gyrase. Previously, our group synthesized and screened an initial batch of gyramides that showed good inhibition activity, but they were cytotoxic to human cell lines. To tailor the gyramide analogs to target bacterial cells exclusively, we can utilize photoaffinity reagents to gather a better understanding of the approximate location and shape of the binding site. Presented here is our recent progress towards synthesizing and studying the gyramide-bound photoaffinity reagents as well as our work towards various analogs.
A13. Chemoenzymatic Synthesis of 2-keto-3-deoxynononic(Kdn)-containing Gangliosides Using Bacterial Sialyltransferase
Jeyxa Faustorilla, Wangqing Li, Abhishek Santra, and Xi Chen
Sialic acids occupy the terminal position of gangliosides and are involved in intracellular signaling. Its role in cellular communication are linked to diseases including influenza and cancer. To further investigate its function, libraries of gangliosides will be synthesized. One-pot three-enzyme approach was utilized to synthesize Kdnα2,3LacβProN3 and Kdnα2,3GalNacαProN3 from chemically synthesized LacβProN3 and GalNacαProN3. Formation of sialic acid Kdn from mannose was catalyzed using sialic acid aldolase. Using the CMP-sialic acid synthetase N. meningitidis, Kdn was activated for glycosylate transfer to the acceptor sugar residues. Bacterial sialyltransferase PmSTI M114D from Pasteurella multocida catalyzed the Kdn transfer. The specific activity of PmSTI M114D for α2,3-linkage transfers led to the formation of Kdnα2,3LacβProN3 and Kdnα2,3GalNacαProN3.
A14. Expression, Purification, and Crystallography of CysK2
Jiahui Lu, Nicholas Hurlburt, Andrew Fisher
The biosynthesis of Cysteine is a crucial metabolic pathway supplying the building blocks for protein synthesis and serves in first-line defense mechanisms against oxidative stress imposed by macrophages. CysK2, annotated as a cystathionine beta-synthase, catalyzes the reaction of L-serine with L-homocysteine to form L-cystathione, and is a pyridoxal 5'-phosphate(PLP) dependent enzyme. Our goal is to understand its catalytic mechanism and structure-function relationships. We cloned the CysK2 gene from Mycobacterium tuberculosis and inserted it into expression vector pET-28b and pMAL, and expressed the protein with Kanamycin selection in E. coli. We then purified the protein expressed by pET-28b through an Ni-NTA column with an imidazole step gradient, and purified the protein expressed by pMAL through an amylose column, then further purified with HPLC. The single protein band was analyzed and identified by Coomassie-stained SDS–PAGE. Various concentrations of purified CysK2, and CysK2 with its substrate OPS (O-phosphoserine) were used in hanging-drop vapor-diffusion crystallization trays with screens MCSG1, MSCG2, and MCSG3. Potential crystals grew, however they did not diffract X-rays. Future work encompasses crystal screening under different conditions for CysK2-MBP, such as adding in L-cysteine, or buffer with different pHs as well as trying additional crystallization screens.
A15. Functional Conversion of Anthranilate Synthase to Aminodeoxychorismate Synthase using Janus Predicted Mutations
Sarah C. Potter, Dong hee Chung, Saheli Chatterjee, Michael D. Toney
Anthranilate synthase (AS) (EC 4.1.3.27) is a chorismate-utilizing enzyme encoded by the trpE gene in E. coli. It catalyzes the conversion of chorismate into anthranilate, the precursor to tryptophan. Because tryptophan is essential for bacterial growth and AS is absent in mammals, this enzyme is an attractive antibacterial target. Aminodeoxychorismate synthase (ADCS) is a highly structurally similar chorismate-utilizing enzyme encoded by the pabB gene in E. coli, and catalyzes the first step of folate biosynthesis. The bioinformatics tool Janus, developed in the Toney lab, was used to predict mutations that functionally interconvert these two enzymes. ADCS was previously converted into AS to identify amino acid residues that are essential for pyruvate elimination (aromatization) specificity. Current work focuses on the reverse conversion of AS into ADCS to understand how the structural context influences which mutations are essential for interconversion. Multi-pot-PCR, a novel PCR-based library generation procedure, was used to incorporate the top 15 Janus-predicted mutations into AS. Library sequencing showed that all 15 desired mutations are present, and no extraneous mutations occur. The library has been transformed into an ADCS knockout cell line, and a selection process has been developed in order to isolate mutants with functional ADCS activity. This selection process will allow isolation and characterization of functional mutants to better understand reaction specificity.
B1. Advances in Ruthenium Chemistry
Michael M. Aristov, Xian B. Powers, Kamran B. Ghiassi,
Marilyn M. Olmstead, Alan L. Balch
In recent work, coordination complexes synthesized via reactions of hydrazine monohydrate (N2H4•H2O) or carbon disulfide with tris(triphenylphosphine)ruthenium(II) dichloride (RuCl2(PPh3)3) were analyzed using infrared spectroscopy, phosphorus-31 nuclear Magnetic resonance, and single crystal X-ray diffraction. From this analysis, RuCl2(PPh3)3 was observed displaying a binding preference for ligands with accessible sulfur, nitrogen, or oxygen atoms. Based on these reactivities, RuCl2(PPh3)3 was proposed to form coordination complexes with various thiocyanates (-SCN-), isothiocyanates (-NCS-), or quinone derivatives, and efforts were made to analyze these potential complexes. Reactions involving hydroxylamine (NH2OH) and RuCl2(PPh3)3 were also studied due to interest in comparing the reactivities of the isoelectronic reagents N2H4 (aq) and NH2OH (aq) with RuCl2(PPh3)3. From the above proposed work, several novel complexes were obtained, and the results of these exploratory reactions will be presented here.
B2. Synthesis and Redox Reactivity of Gallium(III) Isoindoline Complexes
Shiela S. Angulo; Cody R. Carr, and Louise A. Berben
“Non-Innocent Ligands”, classified as either actively involved in bond-making and -breaking processes or redox-reactive, are of great interest in coordination and organometallic chemistry. Their active involvement in redox reactions and bond-making and -breaking processes offer great implications to various fields, such as catalysis, chemical biology and materials science. We have investigated the coordination chemistry and redox activity of the ligand 1,3-Bis((5-methylpyridyl)imino)isoindoline (IsP2) complexed to gallium. A reaction between HIsP2 and GaCl2H(THF) afforded (IsP21-)GaCl2. The reduced form (IsP22-)GaCl was synthesized via the addition of one equivalent of Na to (IsP21-)GaCl2. Characterization of (IsP22-)GaCl using 1H-NMR and IR suggests a paramagnetic compound consistent with our proposed structure. NMR spectroscopy utilizing the Evans Method to measure magnetic susceptibility and effective magnetic moment further supports the presence of an unpaired electron. Initial CV runs indicate reversible redox couples of (IsP21-)GaCl2 with E1/2 at -1.02 V and -1.42 V supporting the notion that -IsP2 can undergo stable one electron reduction events.
B3. Synthesis and Characterization of the Novel Lithium Amide Ligand Transfer Agent LiN(SiMeCy2)2 [Cy = cyclohexyl] and its Transition Metal Bisamido Derivatives
Skylar Osler and Philip P. Power
The new amine HN(SiMeCy2)2 was synthesized from NH3 and ClSiMeCy2 and lithiated using nBuLi to afford LiN(SiMeCy2)2, which was characterized using X-ray crystallography. Reaction of this reagent with FeCl2, CoCl2, and NiCl2(DME) in diethyl ether yielded the bisamido complexes Fe{N(SiMeCy2)2}2, Co{N(SiMeCy2)2}2, and Ni{N(SiMeCy2)2}2. These metal derivatives were characterized spectroscopically and by X-ray crystallography. The iron-amido complex was found to have a nearly linear geometry [N-Fe-N = 177.79(6)°] and relatively short Fe-N bond lengths [Fe-N = 1.899
]. The geometry of the open-shell complex is thought to be enforced by attractive dispersion forces between the ligands’ cyclohexyl substituents. The stabilizing nature of the novel amide ligand is being exploited to form two-coordinate vanadium and titanium complexes.
B4. Synthesis, Structure and Thermoelectric Properties of the Type-I Clathrates K8A8Ge38 (A = Al, Ga, and In)
Victor Bates, Chris Perez, and Susan Kauzlarich
Thermoelectric materials are of interest due to their ability to convert heat into electricity. The efficiency of thermoelectric materials is defined by zT, the thermoelectric figure of merit. zT is maximized by materials with high electrical conductivity and low thermal conductivity. Clathrates are a class of compounds composed of group 13 and 14 elements which form polyhedral cages with guest atoms such as alkali metals residing in the center. Clathrates have attracted interest for thermoelectric applications because the bonding within the cage structure can be tuned, leading to a high electrical conductivity. The structures also allows for the atom at the center of the cage to rattle, leading to a low thermal conductivity. The high electrical conductivity and low thermal conductivity of Clathrates make them ideal candidates for thermoelectric applications. A series of group 13 metal containing compounds with Type-I Clathrates, K8A8Ge38 (A = Al, Ga, and In) were synthesized and measured by X-ray diffraction. Thermal and electrical conductivity were measured by a Physical Properties Measurement System.
B5. Stereoselective Synthesis of Indolines via Intramolecular C-H Bond Insertion
Corinne Penrod, Rich Squitieri, Lucas Souza, Jared Shaw
Developing new reaction methods to assemble densely functionalized heterocyclic cores is critical to increasing the accessibility of pharmacophores. The ability to functionalize carbon-hydrogen bonds allows for the synthesis of such cores in a relatively inexpensive and efficient manner. Furthermore, excellent control over regio-, diastereo-, and enantioselectivity proves to be an important aspect in the synthesis of compounds. A three-step synthesis was developed to produce molecules containing an indoline core through intramolecular C–H bond insertion with high stereoselectivity. This method first involves the substitution of an amine for fluorine on 2-fluorobenzophenone in a nucleophilic aromatic substitution reaction. The ketone of benzophenone is reacted with hydrazine to form hydrazone in the second step. In situ oxidation of hydrazone to diazo and subsequent catalyst addition creates a rhodium carbenoid which can insert intramolecularly into an N-substituted aniline. Herein I present the results of the scope study used to determine which types of N- substituents yield indolines with high stereoselectivity.
B6. Synthesis of malonamides with methallylsilanes and analysis of their photophysical properties
Alayna Nguyen, Julia Jennings, Prof. Annaliese K. Franz
Malonamides are generally known to serve as ligands for copper and lanthanides, as medicinal compounds and in nuclear waste sequestration. We have developed a new class of malonamides with interesting photophysical properties. Investigating these properties can further expand the utility of these compounds. Potential applications of fluorescent molecules include biochemical imaging, material science, and medicinal purposes. Fluorescent indolylmalonamides were synthesized through a lanthanum(III)-catalyzed multi-component reaction by combining coumarin-3-carboxylates, indoles, and amines. Indoles and their derivatives have long been studied for their photophysical properties, in addition to their role in many natural products and pharmaceutical cores. The fluorescent properties of these malonamides are studied by investigating different substituents on the various components; most notably at nucleophile as shown in the figure below. While indoles are known for their photophysical properties, the use of other nucleophiles can give us insight into its role in the fluorescence of malonamides. We hypothesize that the indole component is a major contributor to the fluorescent properties of the malonamide. My goal is to incorporate other nucleophiles, specifically allylsilanes, in lieu of the indole to study the effect of this component on the photophysical properties of the compound. These novel malonamides will then be analyzed using UV/vis spectroscopy and spectrophotometry to quantify their quantum yields and other photophysical properties for comparison and characterization. Preliminary results show that the methallylmalonamide is fluorescent, comparable to the indolylmalonamide.
B7. Synthesis of BaNixFe2-xAs2 via the Hydride Route
Ming Yin Kwong, Julia V. Zaikina, Susan M. Kauzlarich
Superconductors containing iron arsenide were discovered in 2008, and they are known to have high Tc. Compounds like BaNixFe2-xAs2, where Ni is substituting Fe, have been studied extensively. However, there are still synthetic challenges in making these compounds. In our work, we use the hydride route, which involves using barium hydride instead of barium metal. Because barium hydride is a fine powder, it provides better mixing of the reactants and more surface area available for reaction, yielding more rapid preparation. The goal of this project is to optimize the synthesis of BaNixFe2-xAs2 using this hydride route. Samples with different stoichiometry ranging from x=0.02 to x=0.18 are synthesized and analyzed by x-ray powder diffraction. The superconducting properties are also measured. It is shown that the optimal x is 0.12, with the highest Tc at 20K and the most superconducting fraction at about 75%. This is consistent with literature and confirms that BaNixFe2-xAs2 can be successfully synthesized using the hydride route, with only a small amount of impurities produced.
B8. Exploring New Anion-binding Catalysts for the Synthesis of Quinolone Products
Noreen Brar, Kayla Diemoz, and Annaliese Franz
The catalytic activities of silanols, disiloxanediols and montmorillonite clay have been investigated for developing sustainable catalysts for the synthesis of organic molecules, such as medicinally relevant quinolone heterocycles.My project is focused on exploring the anion-binding and hydrogen-bonding catalysis of different reactions in order to synthesize N-acylated quinolone products. The goal is to compare the catalytic activity of four different catalysts for the synthesis of phenyl-1-(2-methylallyl)isoquinoline-2(1H)-carboxylate. The three silanol containing catalysts investigated in this study include tetraphenyldisiloxanediol, trisilanolphenyl POSS and trisilanolisobutyl POSS. Polyoctahedral silsesquioxanes, or “POSS”, is an organosilicon compound that participates in hydrogen-bonding and/or anion-binding catalysis similar to tetraphenyldisiloxanediol catalysts. The hydroxy group of the silanol was able to activate the electrophile while effectively lowering the activation energy barrier for the allylic additions of allylsilanes to an acylated isoquinoline. This study investigated the catalytic activation of anion-binding interactions via the stabilization of the intermediate iminium ion. Good product yields were obtained using the tetraphenyldisiloxanediol catalyst compared to montmorillonite clay. Although the anion-binding abilities have been observed previously, there is currently no evidence reporting the catalytic ability of the incompletely condensed silsesquioxanes POSS structures. Initial results show a higher conversion to product using trisilanolisobutyl POSS compared to the tetraphenylisobutyl POSS. Analysis of hydrogen-bonding interactions using 1H NMR spectroscopy and mass spectrometry have been performed to gain insight into catalytic ability of these POSS compounds.
B9. Synthesis and Characterization of Monomeric Heavier Main Group 14 Element Diaryls EAriPr62 (AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2) (E = Ge, Sn, Pb)
Kelly L. Gullett, Madison L. McCrea-Hendrick, James C. Fettinger, Philip P. Power
The reaction of two equivalents of AriPr6Li(OEt2)1 (AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2) with GeCl2•dioxane, SnCl2, or PbBr2 in diethyl ether afforded the monomeric, colored bis aryl tetrylenes E{C6H3-2,6-(C6H2-2,4,6-iPr3)2}2 (where E = Ge, Sn, Pb). The stannylene has been characterized by 1H, 13C{1H} and 119Sn{1H} NMR spectroscopy as well as by UV-VIS and FT-IR spectroscopy. The synthesis of the germanium and lead analogues were also completed, however, they have yet to be fully characterized.
B10. Lewis and Brønsted acid-catalyzed allylsilane oligomerization
Benjamin Wigman, Brittany Armstrong, Annaliese Franz
Silicon containing oligomers and polymers have a wide range of applications. We have observed allylsilane oligomerization using either Lewis acidic metal salts such as Sc(OTf)3 or a Brønsted acid such as H3PO4 as a catalyst where sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBArF) is present as an activator. Several trisubstituted allylsilanes have been observed to oligomerize with full consumption of the allylsilane monomer, as determined using 1H NMR spectroscopy. Further characterization of the oligomeric products has been performed using MALDI-TOF mass spectrometry. Investigations have been performed with the addition of α-pinene as a proton scavenger to determine the role of the metal salts either as Lewis or Brønsted acids. Various allylsilanes with different silyl substituents including triisopropyl, trimethyl, diisopropyl, chlorodimethyl, cyclohexadienyldimethyl, and benzhydryldimethyl, have been investigated. Depending on the structure of the silyl group, further transformations of these silane oligomers are possible, such as conversion to alcohols and silanols. The modified oligomers containing multiple silanols or alcohols can greatly change the properties of the oligomer. These unique oligomers have potential usage in copolymers, and the available transformations of the oligomers could yield a wide variety of desirable properties.
B11. Direct Spark-Plasma Sintering Synthesis and Thermoelectric Properties of Yb14Mn1-xTexSb11
Dashiel J. Barrett, Elizabeth L. Kunz Wille, and Susan M. Kauzlarich
Thermoelectric (TE) materials convert heat energy to electrical power in the presence of a temperature gradient via the Seebeck effect. Yb14MnSb11 is a p-type TE material currently under investigation for high temperature applications due to a high TE figure of merit (zT) of ~1.3 at 1275K. The performance indicated by the zT values of Yb14MnSb11 can be attributed to a complex Zintl structure that conducts electrical energy well while impeding thermal energy from transferring within the crystal structure. While powder metallurgical synthesis of Yb14MnSb11 has been previously reported, the intermediate heat treatment stage results in a time- and resource-intensive synthesis. Through optimization of parameters for powder production (ball milling) and consolidation (spark-plasma sintering), direct synthesis of both Yb14MnSb11 and Te-doped Yb14MnTe0.05Sb10.95 was achieved. Results were verified via Rietveld refinement of powder X-ray diffraction patterns and electron microprobe analysis. Comparing Seebeck coefficient, electrical resistivity, thermal conductivity, and zT between samples prepared with and without a furnace anneal indicates that direct synthesis of Yb14MnSb11 is a viable process chain for fully dense TE materials and a more economical and environmentally friendly approach.
B12. Synthesis of novel indole-containing malonamides and potential HDAC inhibitors
Blanca Gomez, Julia Jennings, Dr. Annaliese Franz
Histone deacetylases, or HDACs, play a key role in various biological pathways involved in gene expression. Disruption of this process can result in changes in the growth of cells and cell death. For this reason, HDAC inhibitors have been considered recently as potential anticancer treatments and as therapeutics for neurological diseases. Certain classes of HDACs contain a zinc atom in their binding sites. Therefore, one strategy for inhibition of these classes of HDACs is chelation of the zinc atom with a binding group such as hydroxamic acids. Potential HDAC inhibitors in our lab are currently being synthesized (Scheme 1) which contain an indole core and the important hydroxamic acid functional group. Many current HDAC inhibitors have little selectivity and inhibit multiple classes of HDACs. The goal of this project is to design and synthesize complex, highly functionalized compounds which can impart both specificity and activity toward a single class of HDACs.
B13. Synthesis and Characterization of Yb14-x-yCaxBayMgSb11 for Potential Thermoelectric Applications
Navtej Singh Grewal, Elizabeth L. Kunz Wille, Susan M. Kauzlarich
The Zintl phase p-type thermoelectric compound Yb14MnSb11 has been investigated and modified through elemental substitution and doping for many years in order to improve its thermoelectric efficiency. Powder metallurgic synthesis of Yb14-x-yCaxBayMgSb11 (x+y = 4) was performed using both traditional furnace annealing methods as well as simultaneous synthesis and consolidation via spark plasma sintering with phase purity compared and verified using powder x-ray diffraction in order to assess the viability of these synthetic routes. These materials are isostructural with Yb14MgSb11 in the I41/acd space group with the triple cation system of Yb2+, Ca2+, and Ba2+ theoretically reducing carrier concentration due to greater electron donation and increasing phonon scattering due to unit cell distortion. Initial characterization and analysis of sample composition indicates that high excesses of Mg, 100% excess, are necessary to produce phase pure samples of Yb10Ca3BaMgSb11. Comparisons between samples produced via both synthetic avenues show that greater excesses of Mg are necessary to produce samples of the same purity when circumventing furnace annealing; however, this comes at the cost of structural integrity of consolidated pellets due to oxidation of Mg at the grain boundaries. Further investigation was performed to determine a balance between promotion of product formation and the maintenance of pellet integrity in order to perform physical properties measurements. Thermal conductivity, electrical resistivity, and Seebeck coefficient were measured for compounds of x = 0, 1, 2, and 3 from room temperature to 1073K to quantify the potential of Ba containing analogues as p-type thermoelectric materials..
B14. The Effect of Precursor Concentration on the Synthesis of Germanium Nanoparticles
Joey N. Kingstad, Kathryn A. Newton, Susan M. Kauzlarich
Germanium nanoparticles can be synthesized by microwave heated reaction of germanium(II) iodide with oleylamine. To determine the effect of precursor concentration on the synthesis, various concentrations of GeI2 (0.4, 0.6, 0.8mol) in oleylamine were reacted via microwave heating at 250°C for 30 minutes. Following this, particles were removed from solvent by centrifugation and suspended in toluene. Ligand exchange is done to better protect the surface of nanoparticles from oxidation, making them more stable in ambient conditions. Germanium nanoparticles were treated with 5 molar hydrazine to remove the oleylamine ligand. Particles were then microwaved with dodecanethiol to recap the surface. FT-IR spectroscopy and powder x-ray diffraction are used to determine if concentration has an effect on crystallite size and resistance to ligand exchange.
B15. Compounds to Increase Neuroplasticity
Alexandra Greb, Calvin Ly and David Olson
Many neuropsychiatric diseases are characterized by deficits in neuroplasticity, and therefore, agents capable of promoting neuroplasticity have enormous therapeutic potential. Neurotrophic factors—a class of biomolecules that are produced naturally in the brain—are one such class of molecules. The goal of my research is to identify medicinal compounds that enhance plasticity by increasing the brain’s production of neurotrophic factors. We anticipate that these compounds will play a key role in treating certain neuropsychiatric diseases, such as depression, addiction, and post-traumatic stress disorder. To evaluate the effects of compounds on plasticity, cortical rat neurons were treated, fixed, and stained so that we could visualize changes in dendritic morphology using microscopy. We discovered that classical psychedelics (e.g., LSD, DMT, and DOI) are capable of increasing neuronal branching in vitro through a neurotrophic factor-dependent mechanism. We hypothesize that this increase may be the underlying cause of their clinical effects on neuropsychiatric diseases. Ultimately, we hope to identify better-tolerated compounds capable of promoting plasticity and to elucidate the basic biology responsible for their mechanisms of action.
C1. Study of Rh2-yCryO3 Loaded Al:SrTiO3 Nanoparticles as Photocatalysts for Solar Water Splitting
Emma Willard, Zeqiong Zhao, and Frank E. Osterloh
With fossil fuels largely contributing to the decay of our atmosphere, it is vital to find renewable and environmental-friendly energy resources. Hydrogen gas obtained from the carbon-free pathway of solar water splitting can be one of these resources. This process can be operated with the help of semiconductor nanoparticles as photocatalysts. Al doped SrTiO3 microparticles with Rh2-yCryO3 co-catalysts possess 30% apparent quantum efficiency at 360 nm, which is the highest value reported so far. The goal of this work is to test the photocatalytic activity of Al:SrTiO3 nanoparticles with different Al dopant amount to study the effect of Al dopant amount and the particle size. Al:SrTiO3 nanoparticles with different Al dopant amount were synthesized from a hydrothermal synthesis with an average size of 40 nm. Al:SrTiO3 nanoparticles with Rh2-yCryO3 are capable of overall water splitting under Xe lamp irradiation. In addition, the photocatalytic activity of Al:SrTiO3 will increase first with increased Al dopant amount while too much dopant amount will decrease its activity, with the highest hydrogen evolution rate being 53 μmol per hour. One hypothesis is that the aluminum dopant could increase the conductivity of the semiconducting material and increase the photocatalytic activity. Too much Al dopant will cause more defects in the crystal and decrease the photocatalytic activity. In conclusion, we successfully synthesized Al:SrTiO3 nanoparticles and performed photocatalytic tests. Results showed the aluminum dopant will increase the photocatalytic activity of SrTiO3 for overall water splitting; the activity shows a volcano-like dependence on the Al dopant amount.
C2. Interaction of Water with N-Doped Graphene by First Principles Simulations
Jessi Hartman, Svenja Johanna Wörner, Davide Donadio
Nitrogen-doped graphene (N-doped graphene) has shown promise as a catalyst for the oxygen reduction reaction (ORR) in fuel cells, approaching or even surpassing the efficiency of platinum catalysts. Graphene itself does not exhibit such catalytic performance, so activity must be due to defects related to nitrogen atoms. Because ORR occurs in aqueous environment, it is important to examine the interaction of water with N-doped graphene. Here we study the interaction of water with three different nitrogen defects using electronic structure calculations and first-principles molecular dynamics simulations based on density functional theory. The static calculations showed pyridine defects decorating a vacancy or divacancy were not only more likely to occur but also adsorb water more favorably. MD simulations showed that water readily enters the exclusion zone near such vacancy-related defects, forming relatively stable hydrogen bonds with nitrogen.
C3. Reduction of Silica Sea Sponge Spicules for Synthesis of useful Silicon Semiconductors
Wai Lone Jonathan Ho and Kristie J. Koski
Sea sponge of Classes Demospongia and Hexactinellida sponges, which are composed of micro and nano-scale SiO2 particles, will be processed to generate silicon and silicon telluride materials. Current industrial processes of producing pure Si utilize high temperature carbon-based reduction of SiO2 to form bulk Si which lack nanostructure. As sea sponge spicules are covered by layers of organic material, we can potentially reduce the SiO2 with the carbon present in its spongin fibers to form Si via a simple redox reaction. Experimental trials with varying temperature and lengths have been carried out to determine the feasibility of this approach. The effects of carbon content on the reaction will also be studied. A second approach we will pursue is to reduce SiO2 using Al via a redox reaction to form silicon. Once again, the temperature, lengths, and amounts of reactants would be varied to determine the most feasible method of production. Products will be characterized using Scanning Electron Microscopy (SEM) and Energy Dispersive X-ray Spectroscopy (EDS) to determine structure and chemical composition. Future work will be concentrated on investigating the most efficient methods of reducing SiO2 into Si. Due to the complexity of organic materials, focus will also be placed on obtaining pure Si whilst maintaining its nanostructure. Once the production of silicon is successful, it may then be used to synthesize useful silicon compounds, such as silicon telluride.
C4. X-ray Induced Singlet Oxygen Generation by Quantum Dot-Nanoporphyrin Conjugates for Photodynamic Therapy
Yuting Ma, Jennifer Lien, Xiangdong Xue, Yuanpei Li, and Ting Guo
Singlet oxygen is a cytotoxic agent for photodynamic therapy (PDT). In PDT, photosensitizers such as porphyrins produce singlet oxygen upon light excitation in the presence of oxygen molecules. However, PDT applications are limited because of the small penetration depth of light in human tissues. This shortcoming can be overcome by X-ray excitation. Furthermore, while porphyrins are shown to be good photosensitizers for single oxygen generation, nanoporphyrins (NPs) may offer improvement over their molecular counterparts. In this work, we load organic-soluble CdTe quantum dots (QDs) into the hydrophobic NPs core to form QD@NPs. Upon relaxation, excitons can transfer energy from QDs via FRET to NPs, which can generate singlet oxygen in the presence of molecular oxygen. Cadmium and tellurium are effective X-ray absorbers due to their high-Z, attributing to the use of CdTe QDs in this study. Upon X-ray absorption, photoelectrons and Auger and secondary electrons are emitted that can then interact with QDs to generate excitons. Single oxygen generation is quantified by a fluorescent probe molecule, Singlet Oxygen Sensor Green (SOSG). As a control, we measure the singlet oxygen yield in a mixture of water-soluble QDs with NPs. No FRET is expected between these NPs and QDs. The new QD@NPs system combines QD constructs with X-ray irradiation, showing efficient singlet oxygen generation and demonstrating potential for PDT in deep tissues.
C5. Photophysical Characterization of Substituted Spiropyrans as Novel GSH Sensors using Ultraviolet-Visible Spectrophotometry
Stephen Z. Liu and Angelique Y. Louie
Chronic pathologies such as cancers, cardiovascular diseases, and diabetes are strongly associated with oxidative stress. The overproduction of oxidative radicals in arterial endothelium, for example, can promote cellular damages and atherosclerosis that ultimately facilitate development of ischemic strokes. A previous population study has shown that plasma concentrations of a biologically active antioxidant called glutathione (GSH) are 17.4% ± 4.6% lower among 134 stroke patients than the control group, which indicates that GSH level is significantly decreased in stroke. A GSH sensor could therefore allow identification of stroke-risk patients. Spiropyrans (SPs) were recently reported to undergo a reversible structural isomerization with GSH present. Characteristics of GSH-induced switching, meanwhile, could be structurally and electronically influenced by changing the type and placement of SP’s substituents. In my work, properties including switching reversibility, selectivity over confounding biothiols, isomerization rate constant, and association constant of SP with GSH were characterized for a series of nine substituted SPs using ultraviolet-visible spectrophotometry. Absorbance data showed that the incorporation and position differences of electron-donating methoxy (-OCH3) drastically influence SPs’ sensitivities towards GSH. For example, the presence of methoxy at the chromene position improves the sensitivity by accelerating the isomerization rates and promoting SPs’ associations with GSH. Interference of electron-withdrawing nitro (-NO2), in contrast, completely suppresses SPs’ molecular switching abilities with GSH present. This spectroscopic study demonstrates the implication of substituent effects to GSH-sensing using spiropyrans. Understanding characteristics of substituted SPs is essential for future clinical applications as in vivo diagnostics for early-staged ischemic strokes.
C6. The Effect of Co-Catalysts on Copper Tungstate for Photo-Induced Water Oxidation Under Visible Light
Ghunbong Cheung, Zongkai Wu, Frank Osterloh
The solution to the world's energy problems lie within the completely sustainable solar energy. Artificial photosynthesis is the splitting of water into hydrogen and oxygen, and it converts solar energy directly into chemical energy. Copper tungstate is a suitable n-type semiconductor capable of photo-induced water oxidation. This photocatalyst has a band gap of 2.2 eV as found through UV-Vis, which falls ideally within the visible light spectrum. CuWO4 particles were synthesized using a solid state reaction. The morphology was characterized using SEM, and the composition was confirmed by XRD. To test the photocatalyst’s activity, the CuWO4 particles were dispersed in water with sodium periodate as the sacrificial reagent. The amount of oxygen produced under visible light was then measured using gas chromatography. Various co-catalysts were added to the CuWO4 particles to explore their effects on oxygen evolution rate. The co-catalysts were proven to enhance the rate of oxygen production.
C7. Observing Changes in Cell Surface N-glycans and O-glycans during Intestinal Epithelial Cell Differentiation
Zhi Cheng, Gege Xu, Dayoung Park, Carlito B. Lebrilla
Intestinal epithelial cells (IEC) differentiation is widely correlated with many Gastrointestinal (GI) tract diseases including cancer. The cell surface glycans of IEC contains both N-glycans and O-glycans. By analyzing the changes of N-glycans and O-glycans on cell surface over the course of cell differentiation, we can potentially find new biomarkers of GI diseases. In this study, we have developed methods to characterize cell surface N-glycans and O-glycans. Both the N-glycan and O-glycan samples were analyzed using an Agilent nano-LC/ESI QTOF MS system. The results showed that for N-glycans, the amount of high mannose and fucosylated glycans deceased significantly. In contrast, sialylated N-glycans increased. For O-glycans, however, total sialylation decreased during cell differentiation, while fucosylated glycans increased. Fucosylation increased in both N-glycans and O-glycans. The different trends of changes in N-glycans and O-glycans indicate different regulation mechanisms of N-glycan and O-glycan synthesis in the cell. Our methodologies enabled rapid identification of changes in cell surface glycans and provided a better understanding of the correlation of differentiation and cell surface glycosylation.
C8. DFT study of Zintl Phase Thermoelectrics Ca2CdSb2 and Yb2CdSb2
Matthew Han, Shruba Gangopadhyay, and Davide Donadio
Optimal thermoelectric materials ideally have a structure that allows high electron mobility while minimizing lattice thermal transport. This is achieved in numerous ways, but Zintl phase compounds, in particular, are of great interest because of their complex crystal structures and balance among ionic and covalent bonds. Ca2CdSb2 and Yb2CdSb2 are isoelectronic Zintl phase compounds with Ca2+ and Yb2+ ions being almost identical in size. Despite their expected similarities, the compounds have significantly different symmetry, which yield diverse transport properties. We use density functional theory (DFT) to determine the electronic structure of the two compounds, revealing Ca2CdSb2 has a wider direct bandgap of 0.357 eV while Yb2CdSb2 has a smaller indirect bandgap of 0.077 eV. The two compounds also demonstrate different electronic density of states. Ca2CdSb2 has an almost pure Sb p-orbital density of state with no hybridization, while Yb2CdSb2 has Yb d-orbitals hybridizing with the Sb p-orbitals. These differences affect the thermoelectric properties of the materials. Boltzmann transport calculations are in good agreement with experimental measurements for the Seebeck coefficient of Yb2CdSb2, while Ca2CdSb2 has yet to be measured. Our calculations, however, suggest that the latter compound has much higher Seebeck coefficients than the former, thus proposing Ca2CdSb2 as a viable high performance thermoelectric material.
C9. Investigating Photochemical Charge Transfer Processes in Thin Films of Organic Dyes
Brian Roehrich, Ruirui Han, and Frank E. Osterloh
Solar energy offers a promising, green alternative to the current dependence on fossil fuels. Key to the development of new photoelectrochemical energy conversion methods is understanding the underlying charge transfer mechanics. Prior work has largely focused on understanding inorganic semiconducting materials as candidates for photochemical energy conversion, but organic dyes play a very important role in dye-sensitized solar cells. In this study, thin films of several organic dyes were prepared, and their photochemical charge separation processes were investigated using ultraviolet- visible light spectroscopy and surface photovoltage spectroscopy (SPS), a technique which has been developed to study photogenerated charge in semiconductors. It was found that features in the surface photovoltage spectrum of a dye closely corresponded to features in the UV/Vis spectrum and in the calculated density of states plot. Overall, these findings show that charge generation in films of organic dyes is highly dependent on the electronic structure of the dye.
C10. Structural Insights for Sequence Specific DNA Binding by the Homeodomain Protein, HoxD13
Martin Sanchez, Matthew Turner, David Anderson, and James B. Ames
Human homeobox genes consist of four groups (A, B, C, and D) that control the expression of genes during embryonic morphogenesis. Mutations in the homeodomain protein, HoxD13 have been found to cause synpolydactyly, the fusion of digits. HoxD13 is more than 70% identical in sequence to HoxA13 that causes both Hand-Foot-Genital syndrome and Guttmacher syndrome. Here, I present the NMR structure of the DNA-binding domain of HoxD13 (residues 265-338) bound to a 10-base pair DNA duplex that overall looks similar to the previous NMR structure of HoxA13 bound to its target DNA (RMSD < 1.0 Å). Both structures contain a three helix bundle flanked by an N-terminal arm (residues 266-278). The C-terminal helix (residues 315-335) makes conserved hydrophobic contacts with methyl groups of thymine DNA bases in the major groove. Although, the target DNA sequences for HoxA13 and HoxD13 are somewhat different, the conserved thymine nucleotides in the major groove make nearly identical contacts with both HoxA13 and HoxD13. This structurally conserved binding interaction is confirmed by DNA binding studies that show the DNA binding domains of HoxA13 and HoxD13 both bind to the HoxD13 target DNA sequence with nearly the same affinity. We propose that sequence specific DNA binding exhibited by the full-length HoxD13 protein is NOT conferred by the DNA binding domain, but instead may involve DNA contacts with the N-terminal regulatory domain (residues 1-260).
C11. Development of a Rapid High-Throughput Mass Spectrometry-Based Method for the Quantification of Monosaccharides in Food
Thai-Thanh Vo, Ace G. Galermo, and Carlito B. Lebrilla
Although carbohydrates are the predominant biomolecule, their landscapes of common foods remain largely unknown. When not digested by the host, carbohydrates are involved in a symbiotic relationship with the gut microbiota which holds an important role in immune development and nutrient absorption. To fully understand the bioactivity of carbohydrates, it is necessary to obtain the complete determination of their composition and structure, however, due to the nature of their large size, there are no known methods that rapidly and accurately elucidate a polysaccharide’s structure. This project aims to develop a robust and high-throughput method to quantify and characterize the monosaccharide compositions of foods with the ultimate goal of generating a database of foods’ unique monosaccharide profiles. Foods such as rice, flour, and fruits were lyophilized, pre-cooked, and broken down to their monosaccharide components via hard acid hydrolysis with trifluoroacetic acid (TFA). Samples then underwent derivatization with 3-methyl-1-phenyl-2-pyrazoline-5-one (PMP) and analysis was carried out using ultra-high performance liquid chromatography paired with triple quadrupole mass spectrometry (UHPLC/QqQ-MS). This robust, rapid, and highly sensitive method will further our knowledge of the unique sugars in food, aid in the advancement of food science, and eventually generate modified food that target specific health problems.
C12. Association of dynamic changes of osteopontin concentrations in human milk and infant plasma
Allison Lee, Rulan Jiang, Bo Lonnerdal
Osteopontin (OPN) is a highly acidic phosphorylated glycoprotein that is involved in many biological activities, such as immune modulatory functions. OPN is abundantly present in human milk (~ 138 mg/L) in comparison to bovine milk (~18 mg/L). A clinical trial conducted by our group showed that infants fed formula supplemented with bovine milk OPN (130 or 65 mg/L) exhibited outcomes more similar to breast-fed infants and compared to infants fed regular formula, judged by days with fever, immune profile, and cytokine responses. To understand the function of milk OPN in different lactation stages and the effects of milk OPN on the plasma OPN concentration, OPN concentrations in human and infant plasma (breast-fed, regular formula-fed, OPN-formula-fed) from the clinical trial were evaluated by an OPN ELISA. Our results show that the concentration of OPN in breast milk peaks in early lactation, significantly decreases until after 4 months and remains stable from 4-12 months. Consistently, the plasma OPN concentration in 1 month old breast-fed infants was higher than that in formula-fed infants at the same age. In summary, the OPN concentration in milk changes dynamically, and milk OPN can be absorbed into the circulatory system, possibly playing a role in infant development.
C13. Deriving Paleotemperatures from the Speleothem Record:
Past Climate Change in the Western Sierra Nevada
Alec Tyra, Barbara Wortham, and Sujoy Mukhopadhyay
The Western Sierra Nevada, between the Last Glacial Maximum 20K years ago and the Younger Dryas 11K years ago, experienced dramatic changes to the climate and temperature. Understanding how the region responded to the changing climate allows us to predict how futures changes in temperature will affect the region. Speleothems are formed from the precipitation of calcium carbonate in cave drip water. Trapped water and air in speleothems contain noble gases that depend on the temperature at the time the inclusion formed. To extract the noble gas concentrations from the speleothems , we crushed billets along their growth axis and the air and water are released into an ultra-high vacuum line. We measured amounts of noble gases by a Nu Noblesse mass spectrometer and the water is measured manometrically. To determine the relative contribution of noble gases from the water inclusions, a software package in Matlab was used to separate the measured values into an atmospheric noble gas component and an air saturated water component. Preliminary results show levels of noble gas abundances that can be measured precisely (Ne between 1.04x10-10 - 3.91x10-8 cc, Ar between 5.64 x10-8 - 2.83 x10-6 cc, Kr between 9.70 x10-12 - 4.61 x10-10 cc, and Xe between 1.23 x10-12 - 6.93 x10-12 cc). The preliminary temperatures that are derived from the speleothem record indicate an average temperature in the region at 10˚C. Producing accurate temperatures from the paleorecord provides an understanding of how temperatures changed in the Western Sierra between the Last Glacial Maximum and the Younger Dryas, which will provide insight to how the region will respond to climate change in the future.
C14. Activatable Manganese-Based Contrast Agent Sensitive to GSH
Xinzhe Li and Angelique Louie
The Louie research group is working on synthesizing manganese- based glutathione (GSH) sensitive Magnetic Resonance contrast agent which is believed to be safer and more functional than the clinically used gadolinium contrast agent. Recent reports have indicated that the introduction of gadolinium based contrast agent causes the accumulation of gadolinium in the brain as well as nephrogenic systemic fibrosis for patients who have poor renal systems. These findings have indicated undesired side effects when using a gadolinium based contrast agents. Therefore, efforts have been directed towards designing a manganese based contrast agent as a safer option to gadolinium. The research team is also developing a spiropyran based probe sensitive to GSH, due to the short comings of modern medicine at measuring GSH concentration. GSH is an antioxidant produced by the body that prevents the buildup of oxidative stress, which may lead to cell death and cell damage. Recent reports indicated that tumor cells have 4 folds higher GSH level than normal tissue. As a result, there will be a clear contrast between normal tissue and the tumor tissue, which in turn help us to localize the tumor. I am currently synthesizing the spiropyran probe that is linked to the contrast agent that can change its structure to adopt a more open shape in the presence of GSH. The hydration site of the contrast agent also decreases from 2 to 1 which gives a contrast in the MRI image. This engineered chemical compound will provide us a non-invasive and accurate means to measure the GSH levels in a specific region of the body, thus allowing us to differentiate normal tissue and a tumor.