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Chemistry

Watch Michael Gormally '11 Discuss His Research

A QCM-D Study of the Oriented Immobilization of Anti-hCG Using Functionalized Self-Assembled Monolayers

Natalie Chung ('11); Rebecca Hamlin ('10); Mentor: Malkiat S. Johal

Abstract: This work utilizes the quartz crystal microbalance with dissipation monitoring (QCMD) to design an immunosensor, utilizing functionalized self-assembled monolayers, that monitors the binding of human chorionic gonadotropin (hCG) onto an immobilized layer of anti-hCG. Previous studies have shown that the use of immunosensors with positively or negatively charged surfaces for electrostatic surface interactions between the antigens and their corresponding antibodies is not a sufficient method to promote the proper antibody orientation for antigen binding. In order for an immunosensor to be sensitive and specific for hCG, it must employ a chemical surface modification, making the antibody irreversibly bound by covalent bonding. Furthermore, the sensor should be devised for immobilizing the antibody in the proper orientation for maximum availability of antigen binding sites. This can be accomplished using a chemical crosslinker that binds the lysine residues found on an antibody’s Fc fragment, so that the antigen binding sites on the Fab.
Funding provided by Rose Hills Foundation (NC)

Structural Investigations of the N2-IQ-dG adduct in an Extended NarI Recognition Sequence

Andrew de Jong ('13); Kallie Stavros*; Michael P. Stone*
*Center for Structural Biology, Vanderbilt University, Nashville, TN

Abstract: Heterocyclic amines (HCA) were discovered in the 1980s as potent mutagens and carcinogens found in browned meat, fish, poultry, and cigarette smoke. One of the most mutagenic HCAs, 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), once enzymatically activated, efficiently bonds to the C8- and N2- positions of deoxyguanosine. The NarI restriction enzyme recognition sequence containing the GC reiteration is considered a hotspot for HCA mutagenesis. This summer we progressively purified and characterized samples of our unmodified oligonucleotides using a variety of methods such as Nuclear Magnetic Resonance spectroscopy (NMR), High-performance Liquid Chromatography (HPLC), and Capillary Zone Electrophoresis (CZE) in order to establish a reference structure for the unmodified duplex. Future work for assessing the dietary risk factors of this specific adduct will require deeper structural analysis employing NMR spectroscopy and X-Ray crystallography and involve investigations into the adduct’s effect on mutagenesis and DNA repair with respect to human DNA polymerases.
Funding provided by CA-55678; ES-016561

The Surface Activity of Organic Films on Atmospheric Aerosols

Erika Falsgraf ('12); Veronica Vaida*; Elizabeth Griffith*; Molly Larsen*; Mentor: Malkiat Johal
*Colorado University, Boulder, CO

Abstract: Aerosols are small solid or liquid suspensions distributed in the Earth’s atmosphere. Many aerosols contain organic compounds that are surface active, requiring an understanding of the processes occurring at the air-water interface. This project utilized a Langmuir-Blodgett trough to model environmental organic films by designing monolayers of stearic acid on aqueous subphases and subjecting them to changes in pressure. The first significant finding was that the presence of phenylalanine in the subphase caused stearic acid to disperse from the surface, indicating micelle or vesicle formation or the formation of some chemical bond. This line of research has implications for the study of peptide bond formation on prebiotic and contemporary marine surfaces. The second focus was the effect of dissolving various dicarboxylic acids in ammonium nitrate. The largest, azelaic acid, removed stearic acid from the surface upon compression. Future dynamic light scattering experiments propose to identify any vesicles or micelles.
Funding provided by The Fletcher Jones Foundation

Synthesis of Novel Oligopeptides with C!-Tetrasubstituted Amino Acid Residues

Ari Filip ('12); Mentor: Daniel J. O'Leary

Abstract: While 310-helical preference in peptides is promoted by tetrasubstituted amino acid residues, namely aminoisobutyric acid (aib), hydrophobic side chains typically compromise water solubility. With the aim of synthesizing a short, water-soluble peptide with 310-helical structure, incorporation of #-hydroxymethylserine (HmS) residues and isopropylidene (Ipr) protected derivates was examined. Multiple HmS protection strategies were evaluated to develop a system for efficient and orthogonal protections, deprotections, and couplings. Liquid-phase synthesis was begun on a target tetrapeptide consisting of O-allylated #-methyl-L-Serine (MeS-al) and HmS residues, MeS(al)-HmS-HmSMeS( al). Unwanted side reactions during Nterminal deprotection of FMOC-HmS(Ipr)- MeS(al)-OMe halted conventional C!N elongation. In the future, the peptide will be approached by an alternate synthetic pathway involving creation of an HmS(Ipr) homodipeptide, followed by N- and C-terminal additions of MeS(al). Intramolecular ring closing metathesis (RCM) by Grubb's catalyst will be performed to stabilize the secondary structure of the final peptide while promoting in-vivo resilience.
Funding provided by The Fletcher Jones Foundation

Measuring Glucose in Tears Using Electrochemical Glucose Sensors

Amanda Ghassaei ('11); Babak Parviz*; Angela Shum*; Melissa Cowan*; Ilkka Lahdesmaki †; Mentor: Mal Johal
*Electrical Engineering Dept (UW); †Chemistry Dept (UW), University of Washington, Seattle, WA

Abstract: With an estimated 23.6 million cases nationwide and 1.6 million new cases diagnosed annually, diabetes management is a prevalent topic in American medicine. Regular blood glucose monitoring helps avoid complications such as nerve damage, blindness, kidney disease, and death. By measuring the concentration of glucose present in tears, electrochemical glucose sensors micro-fabricated on contact lenses offer a sensitive, cost effective, and non-invasive alternative to "finger-prick" tests. An indium tin oxide surface immobilizes glucose oxidase, an enzyme which catalyzes the formation of hydrogen peroxide from glucose, near three platinum electrodes. Standardization of the current response from the electrochemical oxidation of hydrogen peroxide gives quantizable measurements of the glucose concentration in solution. Characterization of the device showed detectable glucose concentrations as small as 125μM, the lower bound of glucose concentrations found in human tears. Further investigation of strategies to block interfering agents is needed before these devices are ready for clinical testing.
Funding provided by University of Washington

Potential of the Quartz Crystal Microbalance as a Light Transducer and Monitor of Light- Dependant Processes

Mike Gormally ('11); Matthew C. Dixon; Mentor: Malkiat Johal

Abstract: There is a growing need for new technologies to quantitatively measure the properties of material interfaces. One technique in particular, the Quartz Crystal Microbalance with Dissipation Monitoring (QCM-D), fulfills the need for capturing real-time dynamic adsorption and desorption phenomena. Capable of operating in both gas and liquid environments, QCM-D provides a powerful approach to analyze the thickness, structural, and viscoelastic properties of both film formation and reactions within the film itself. Here we introduce the application of QCMD to monitoring light dependent processes. We found that the QCM-D sensor exhibits a unique frequency response that is dependent on the wavelength and intensity of the incident light. This allowed us to monitor changes of surface bound material due to light irradiation. As a demonstration, we measured the rate and extent of degradation of several polymer films upon exposure to UV light. Based on control experiments we were able to correlate incident
Funding provided by The Dale N. Robertson Fund

Synthesis of a parallel helix bundle: a novel stabilized peptide structure

Kasey Grewe ('11); Mentor: Daniel O'Leary

Abstract: Peptides are attractive candidates for the development of novel therapeutics, yet their effectiveness is limited by rapid proteolysis and loss of bioactive structure in vivo. Past research has focused on stabilizing single peptide fragments through ring-closing olefin metathesis (RCM) with ruthenium-based catalysts. The focus of this research is to use RCM to crosslink Oallylated #-methyl-serine side chains of two parallel hexapeptides, thus creating a macrocyclic parallel helix bundle or "peptide ladder." Oallylated Boc-Ala-(#Me)Ser(OAll)-Ala-OMe tripeptide units will be coupled to an O-bridged tripeptide homodimer, forming a hexapeptide homodimer comprised of two Boc-Ala- (#Me)Ser(O*)-Ala-Ala-(#Me)Ser (OAll)-Ala- OMe fragments linked by an alkene at the O* position. The allylated #-methyl-serine residues at position five will be linked by RCM, forming the macrocyclic ladder. This summer Boc-Ala- (#Me)Ser(OAll)-Ala-OMe units, a Boc-Ala- (#Me)Ser(OAll)-Ala-Ala-(#Me)Ser(OAll)-Ala- OMe hexapeptide, and an O-linked #-methylserine homodimer were synthesized with reasonable coupling efficiencies through solution phase methods. Future work will include RCM closure and CD studies to determine helicity.
Funding provided by The Craddock-McVicar Award

Microbial Community Analysis of Three Geoevironmentally Unique Sites: Hydrothermal Mud Volcano Effluent, Hypersaline Pools Adjacent to the Mud Volcanoes, and Thiolploca Mats from the Soledad Basin

Danny Lawrence ('11); Mentor: E.J. Crane

Abstract: In this study, three distinct environments were characterized by microbial community analysis using 16S rRNA gene cloning. Although the methods used to examine these three environments are extremely similar, the differing nature of each environment requires that each be considered independently. The first of these samples was collected from the anaerobic ocean sediment of the Soledad Basin, west of Baja California, with the aim to identify the presence of Thioploca and support a proposed symbiotic relationship with anammox bacteria. The second sampling site includes samples from the 1) anaerobic mud expelled by the Salton Sea geothermal mud volcanoes and 2) the hypersaline pools that lie within feet of the mud volcanoes. Initial results show extensive diversity between Soledad Basin clones, though neither Thioploca nor anammox bacteria were found. Mud Volcano clones included a variety of anaerobic bacteria, including possible sulfur-respiring bacteria.
Funding provided by The Fletcher Jones Foundation

Mechanistic Implications of Phe161 in NADHdependent Persulfide Reductase from Shewanella loihica PV-4

Kyu Hyun Lee ('11); Scott Humbarger ('12); Emily Brotman ('13); Megan Warner ('10); Vinita Lukose ('08); Mentors: E.J. Crane, Matthew Sazinsky

Abstract removed upon request.

Chemical Vapor Deposition of Vanadium (V) Oxide Using Two Different Precursors: Effects of Precursor Chemistry on Film Morphology

Heidi Leonard ('12); Levi Moore ('11); Morgan Ingemanson ('13); Mentors: Charles Taylor, Tyler Moersch

Abstract: Vanadium oxide thin films are relevant to the field of environmental chemistry because of their ability to act as in-situ chemical sensors. One approach to creating the thin films needed for such environmental sensors is chemical vapor deposition. The sensing properties of vanadium oxide thin films can be enhanced by appropriate choice of ligand chemistry in the precursor molecule. For this reason, thin films of vanadium oxide were deposited via chemical vapor deposition from two chemically distinct molecular precursors—vanadium (V) oxynitrate and vanadium (V) oxy-tri-propoxide. Films were grown on oxidized single-crystal silicon substrates in the temperature range of 300 °C - 500 °C and evaluated by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Raman spectroscopy. XRD patterns revealed that both molecular precursors generated the same crystalline phase of V2O5 (shcherbinaite), but each precursor led to a distinct preferred growth direction.
Funding provided by The Fletcher Jones Foundation (HL), Pomona College Chemistry Dept, NASA, NIST

Optical and piezoelectric methods for probing the Solid-Liquid Interface: Investigation of Binding Events and the Development of Novel Bio-recognition Elements

Jenny Lin ('11); Theodore Zwang ('11); Mentor: Malkiat Johal

Abstract: Lipid membranes are essential for cellular function, acting both as a selective barrier between the cell interior and its environment as an interface for cell signaling responses and cell communication. Creating model membranes allow for the complexities of membranes to be characterized in hopes of further understanding lipid membrane functions and physiology. In this research, we have used acoustic and optical techniques to study a self-assembling membrane system. Our study of membranes focuses on the interactions between the lipid membrane and the support on which it is formed, as well as the factors that govern the self assembling mechanism. Specifically, our research includes analyzing the water layer underneath a supported membrane, manipulating the lipid-support interactions through changing the chemical environment, and observing how varying osmotic pressure can facilitate the membrane formation process.
Funding provided by Rose Hills Foundation (JL), Howard Hughes Medical Institute (TZ)

Synthesis of Triazine Derivatives as Inhibitors of Dihydrofolate Reductase (DHFR) in Plasmodium falciparum

Albert Liu ('12); Mentor: Cynthia Selassie

Abstract: Plasmodium falciparum (Pf) causes one of the most virulent forms of malaria in humans today. Treatments for Pf induced malaria include antifolates that inhibit critical folate synthesis in the organism. However, drug-resistance to current antifolates is becoming widespread. Our primary goal is to synthesize a series of novel, small heterocyclic molecules with triazine pharmacophores that selectively target plasmodial DHFR, a key enzyme in folate synthesis, and to assess their anti-malarial effectiveness using the Quantitative Structure Activity Relationships (QSAR) approach. Synthesis involves a Schiff base reaction of m-nitro-benzaldehyde and a substituted aniline, followed by reduction with NaBH4 and subsequent catalytic hydrogenation. The amine hydrochloride intermediate is then condensed with cyanoguanidine and acetone in a cyclization reaction to form the desired triazine molecule. Variations of the substituents on the aniline were made in order to determine effects of hydrophobic and electronic characteristics on activity. Preliminary syntheses of two molecules will be discussed.
Funding provided by Rose Hills Foundation

Creating a Protocol for Tracing Phylogeny of Acanthaceae via Analysis of Sugars in Nectar

Thuy Ly ('12); Erin Tripp (RSABG); Mentor: Charles Taylor

Abstract: This protocol studies of Acanthaceae in a phylogenetic context, concentrating on phylogenetic relatedness to test whether nectar evolves due to shared ancestry via phylogenetic constraint or in response to pollinator selection. The final protocol separates sugar standards with six carbons from those with twelve carbon chains to have different amounts of Trifluoroacetic Acid (TFA) and Hexamethyldisiloxane (HMDS) and to have different times in the waterbath. The four sugar standards of HPLC and GC-MS grade used were glucose, fructose, sucrose, and maltose. The procedure starts with the sugar and reacts to become a sugar oxime, TMS. The analysis of this oxime, TMS first went through HPLC with little result due to many column errors. The analysis was, then, changed to GC-MS analysis to give unique peaks. The next step from this protocol is to apply the procedure to nectar collected the Rancho Santa Ana Botanic Garden to gather phylogenic data.
Funding provided by The Andrew W. Mellon Foundation (TL), Rancho Santa Ana Botanic Garden

Calculating and Extrapolating the Average Walklength of Random Molecular Diffusion Across Quasicrystals

Johan Martinez ('13); Kevin Wang ('13); Ian Chua ('12); Gustavo Ruiz ('13); Joshua Rodriguez ('13); Jonathan Adusah ('13); Mentor: Roberto A. Garza

Abstract: The average walklengths of random molecular diffusion in quasicrystals and multi-fold lattices are calculated using an algorithm involving the use of matrices and large systems of equations. Although quasicrystals exhibit glaring symmetry, their non periodic structure makes extrapolation of average walklengths near impossible. Hence, the data collected through manual calculations are discussed for possible linear and exponential trends, along with the kinetic efficiency of such lattices.
Funding provided by The Fletcher Jones Foundation (JM, IC), Howard Hughes Medical Institute (JA), Pomona College Chemistry Dept.

Overexpression, Kinetics and Crystallization of NFeoB from S. oneidensis MR-1

Justin Moser ('11); Mentor: Matthew Sazinsky

Abstract removed upon request.

An Examination of the HO2-Acetaldehyde Reaction

Eric Newenhouse ('11); Aileen Hui*; Stan Sander†; Mentor: Fred Grieman
*CalTech, Pasadena, CA; †Jet Propulsion Laboratory, Pasadena, CA

Abstract: In an effort to understand tropospheric ozone, various sinks of HO2 (a major contributor to tropospheric ozone production) have been identified. One sink is acetaldehyde (CH3CHO), a hydrocarbon present in significant amounts in the upper troposphere. The HO2-acetaldehyde reaction is being examined via a two-pronged approach: first, by computer models created using FACSIMILE software and second, through the direct measurement of reactant and product concentrations as a function of time through infrared kinetic spectroscopy (IRKS). Various reaction mechanism models have been created with increasing amounts of complexity in an effort to determine initial reactant concentrations necessary for the measurements of species of interest (HO2, OH, O3) to be feasible using the IRKS method. Once the IRKS apparatus is operational, experimental data can be obtained. The modeling suggests that the HO2-acetaldehyde chemistry compares well with similar, previously studied HO2-acetone chemistry, giving indication that examination via the IRKS method should be rewarding.

Effects of Para-Substituted Phenols on Saccharomyces cerevisiae Apn1/Apn2 Double Mutant in Comparison to the Effects in S. cerevisiae Wildtype

Isabelle Nguyen-Quoc ('11); Clarissa Valdez ('10); Mentors: Tina Negritto, Cynthia Selassie

Abstract: The purpose of this project is to test whether base excision repair (BER) is involved in DNA damages induced by para-substituted phenols. AP endonucleases, encoded by the Apn1 and Apn2 gene, are enzymes that play an integral part in BER. Therefore, to determine whether BER is involved in repairing phenol-induced DNA damages, growth assays for X88 yeast strains (Apn1/Apn2 knockouts) and for X70 strains (wildtype) are performed. From the growth assays, the inhibitory concentrations (IC) 50, concentrations indicating 50% cell death, are obtained from the X88 and X70 strains. Comparing the X88 and X70 growth curves and their IC values indicate whether Apn1 and Apn2 genes in the BER pathway are involved in the repair mechanism.
Funding provided by The Norris Foundation (INQ)

Cross Metathesis of Allylated Alpha-O-Methyl Mannoside Using Second-Generation Ruthenium-Based Grubbs Catalyst

Chase Olsson ('12); Tom Vasquez; Mentor: Daniel O'Leary

Abstract: Surface Plasmon Resonance (SPR) biosensors can be used to monitor protein binding events on the surface of cells. By labeling a thin gold sheet with a test molecule, and monitoring changes in the reflectively profile on the back of the gold, one can detect biomolecular interactions in real-time. The synthetic preparation of the target molecule begins with benzylation of the hydroxyl groups of Alpha-O-Methyl Mannoside. The C-Glycoside is then prepared by allylating the protected sugar. Using the second-generation ruthenium-based Grubbs catalyst (which fuses together terminal alkenes), the terminal double bond of the C-glycoside will then undergo cross metathesis with another alkene. While the prepared C-glycoside crossed easily with a test substrate, cis-2-butenediol diacetate, crossing the C-glycoside with dimerized hexenyl tosylate had very low yields. Further research efforts will involve displacing the tosylate with a phthalimide prior to cross metathesis.
Funding provided by The Paul K. Richter and Evalyn E. Cook Richter Award

Diffusion-Controlled Reactions Across Mineral Crystals

Kevin Y. Wang ('13); Johan Martinez ('13); Gustavo Ruiz ('13); Joshua Rodriguez ('13); Kimberley Africa*; Joseph Anzora*; Tewa Kpulun*; Phu Lam*; Christofer Rodelo*; Mentor: Roberto Garza
*Pomona College Academy for Youth Success

Abstract: The average walklengths of random molecular diffusion in crystals and are calculated using an algorithm involving the use of matrices and large systems of equations. This project establishes the foundations for further utilizing crystals as industrial catalysts. Catalytic sites were emulated as trap sites in the calculations.
Funding Provided by: The Fletcher Jones Foundation (JM), Hirsch (RG), Department of Chemistry

Fabrication of Hydrophobic Silica Aerogel Thin Films

Ellen Yang ('11); Mentor: Malkiat S. Johal

Abstract: Hydrophobic silica aerogels are low density, porous solid networks that have potential as oil absorbent material. My goal this summer was to fabricate a silica aerogel thin film layer suitable for subsequent oil experiments with quartz crystal microbalance with dissipation monitoring (QCM-D). Gels were initially derived with tetraethoxysilane using the sol-gel technique, followed by surface silylation with trimethylchlorosilane. After sonication, fluid sols were spin-coated onto substrates and dried under ambient pressure. Samples were characterized using scanning electron microscopy (SEM) and found to contain pores as small as 50 nm. With a few modifications, the method described can be used to reproduce aerogel thin films on QCM-D sensor crystals.
Funding provided by Pomona College SURP

Do Differences in Siderophore Binding Cause Increased Infection Rates in Diabetics?

Theodore Zwang ('11); Mike Gormally ('11); Mentors: Malkiat Johal, Matt Sazinsky

Abstract removed upon request.

Research at Pomona