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Chemistry

Click to watch Michael Haber '13 discuss his research project.

Using VOCs to Diagnose Tuberculosis

Lauren Budenholzer; ('12); Kelly Park ('12); Angelika Niemz*; Peter Vandeventer*; Mentor: Charles Taylor, Tyler Moersch
*Keck Graduate Institute of Claremont, CA

Abstract: Volatile organic compounds (VOCs) present in exhaled breath can be useful for clinical diagnoses. Solid phase microextraction (SPME) has been used to concentrate and identify VOCs produced in the headspace above growing cultures of M. tuberculosis – BCG and E. coli. Analyses were performed using gas chromatography with mass spectrometric detection (GCMS). The data indicate that bacterial pathogens M. tuberculosis – BCG and E. coli can be distinguished based on their chromatograms. These results will be used to guide experiments for the development of a Raman-based breath test for active tuberculosis. Future work includes performing SPME and GCMS analysis on other bacterial pathogens and confirming the identities of suspected VOCs found using authentic standards.
Funding Provided by: Pomona College Chemistry Dept. (LB) Rose Hills Foundation (KP)

Structural Determination of Phenylacetaldehyde Dehydrogenase, an Enzyme of the Pseudomonas Putida Styrene Degradation Pathway

Anders Crabo ('12); George T. Gassner*; Mentor: Matthew Sazinsky
*Chemistry and Biochemistry Dept, San Francisco State University, San Francisco, CA

Abstract removed upon request.

Emerging Solar Cell Technology: Advances in Solid-state Polymer-hybrid Dye-sensitized Solar Cells

Andrew deJong ('13); Mentor: Malkiat Johal

Abstract: Dye-sensitized solar cells are quickly becoming the most well-known “third generation” photovoltaic technology due to their promise of cheap materials and low energy processing. The polymer hole-transport material poly(3-hexylthiopene) (P3HT), most widely known for its use in polymer bulk-heterojunction solar cells, has recently been studied regarding its potential as both light absorber and hole-transporter in solid-state dye-sensitized solar cells. Here, the compatibility of P3HT with several porphyrin dyes is explored as well as the effect of ionic additives such as tert-butyl pyridine and lithium bis(trifluoromethylsulfonyl)imide (Li-TFSI). Through an investigation of external quantum efficiencies (EQEs) of working solar cells fabricated under either ambient or nitrogen-rich atmospheric conditions, it has been determined that the effect of oxygen-doping on P3HT drastically alters the origin of the cell’s photocurrent. A predicted pathway for Forster Resonant Energy Transfer (FRET) from P3HT to the porphyrin dye is not found.
Funding Provided by: Andrew W. Mellon Foundation Grant to the Claremont Colleges Environmental Analysis Program

Synthesis of Stapled Analogues of the Peptide Antibiotic Temporin-SHf

Ari Filip ('12); Ellen McCormack ('12); Mentor: Daniel O'Leary

Abstract: While short peptide sequences can be useful substitutes for more complex bioactive molecules or larger proteins, they may be limited by unstable secondary structure, susceptibility to proteolytic enzymes, and cost. Problems of structure stabilization and in vivo resilience may be ameliorated by "peptide stapling", the incorporation of a hydrocarbon bridge via olefin metathesis. Using this technique, we have begun synthesis on stapled analogues of an 8-residue peptide antibiotic candidate, temporin-SHf. Though synthesis of the linear peptide precursors has been successful, we have been so far unsuccessful in performing microwave-assisted olefin metathesis and isolating the final peptides. Our immediate goals are to diagnose obstacles to the metathesis step and explore alternative synthetic strategies, namely performing reactions in solution phase.
Funding Provided by: Corwin Hansch Summer Undergraduate Research Fellowship (Underwritten by Dr. Emil Kakkis, '82)

The Bilayer-modifying Potential of Limonene and its Metabolites

Will Fletcher ('12); Mentor: Malkiat Johal

Abstract: Membrane protein function depends on the surrounding bilayer, which may account for undesired effects of hydrophobic drugs that modify bilayer properties. I assessed the extent to which D-limonene, perillyl alcohol, perillaldehyde, and perillic acid alter lipid bilayer properties by means of fluorescence-quenching and electrophysiological experiments. To quantify the changes in bilayer properties, I used gramicidin (gA) channels which have previously been established as molecular force probes. In the fluorescence assay, large unilamellar vesicles were prepared using 1,2-Dierucoyl-sn-glycero-3-phosphocholine (DC22:1PC), filled with the fluorophore 8-aminonaphthalene-1,3,6-trisulfonate (ANTS), doped with gramicidin, and finally exposed to the quenching agent Tl+. Limonene decreased gA channel activity, whereas perillyl alcohol and perillaldehyde increased activity; perillic acid had no apparent effect. Two molecules, limonene and perillyl alcohol, were selected for analysis using single-channel electrophysiology, which can distinguish between gA channel appearance rate and lifetime. Results from the electrophysiological technique were in agreement with the fluorescence assay findings.
Funding Provided by: Dale N. Robertson Fund

The synthesis of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3’-(4’’-X-anilinomethyl)phenyl)-s-triazines as Potential P. falciparum DHFR Inhibitors

Ulysses Gomez ('11); Mentor: Cynthia Selassie

Abstract:  Malaria has been a major threat throughout the history of human civilization.  Every year about 300-660 million people around the world are diagnosed with malaria, of which 1-3 million die.  In order to develop a new antimalarial drug against the most virulent malaria-causing protist, Plasmodium falciparum, it is imperative to understand where and how to target it.  Since dihydrofolate reductase (DHFR) plays a crucial role in the synthesis of essential biological chemicals responsible for cell growth and proliferation, its inhibition results in cell death.  Given that there is enough homological difference between human and protozoal DHFR, the development of a pharmaceutical that is only selective to P. falciparum is possible.  Due to the recent increase in drug resistance, we hope the synthesis of a series of 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(3’-(4’’-X-anilinomethyl)phenyl)-s-triazines will guide us toward the identification of a new, potent and nontoxic antimalarial agent.
Funding Provided by: Rose Hills Foundation

The Effects of Protein Glycation on Iron Homeostasis and Immune Response in Diabetics

Michael Haber ('13); Theodore Zwang ('11); Mentor: Malkiat Johal, Matthew Sazinsky

Abstract removed upon request.

The Electrophoretic Mobility Shift Assay (EMSA) of FeoC and the Effects of Mutant Feo Operons on E.Coli Iron (Fe2+) Uptake and Cell Growth

Jixi He ('12); Rachel Allan ('10); Mentor: Matthew Sazinsky

Abstract removed upon request.

Quantifying the Effects of BSA Binding Hemin in the Presence of Various Glycated Sugars

Gabriella Heller ('14); Theodore Zwang ('11); Liz Sarapata* ('13 HMC); Marco Lobba ('13); Mentor: Malkiat Johal, Matthew Sazinsky, Ami Radunskaya

Abstract removed upon request.

Synthesis of Mannose Conjugate for use in Carbohydrate Microarrays

Tera Jones ('12); Daniel Ratner*; Mentor: Daniel O'Leary*
Chemical Engineering Dept, University of Washington

Abstract:  Synthetic glycans can be used for functionalization of surfaces to create carbohydrate microarrays.  This research project aimed to develop a method for creating one of these glycans. The target glycan of this synthesis can be used as a substrate in surface modification experiments that monitor protein binding. The synthetic preparation of the target began with the creation of a tetra-O-benzyl protected mannose, starting with α-O-methyl mannoside. The mannosyl coupling partner was completed by Schmidt glycosidation with trichloroacetonitrile to create a trichloroacetimidate mannoside intermediate. The coupling was done by acid-catalyzed Fischer glycosidation via an immobilized sulfuric acid catalyst with a carboxybenzyl protected aminobutanol. The final target was synthesized in good yield and characterized by 1H-NMR.
Funding Provided by: Pomona College SURP  

Growth Kinetics and Film Morphologies of Vanadium (V) Oxide Thin Films Prepared via Chemical Vapor Deposition

Heidi Leonard ('12); Daniel Mendes ('14); Mentor: Charles Taylor, Tyler Moersch

Abstract:  Vanadium oxide thin films may be used as the active element in gas sensors.  One approach to creating the thin films needed for such environmental sensors is chemical vapor deposition.  The sensing properties of these films can be enhanced by appropriate choice of temperature and deposition time of the precursor.  Thin vanadium oxide films were grown on silicon substrates with vanadium (V) oxynitrate precursor in the temperature range of 275 °C - 650 °C and evaluated by scanning electron microscopy (SEM) for both changes in film thickness and crystal morphologies.  Arrhenius plots of growth rate versus temperature revealed unique kinetics plots for various partial pressures of the precursor.  Films grown with the precursor kept at the lowest temperature of 7 °C, and hence lowest partial pressure, were the most uniform in their morphologies and exhibited the slowest growth rates overall.
Funding Provided by: Norris Foundation (HL) Pomona College Chemistry Dept (DM) 

Blue/White Screening Methods of FeOB

Art Li ('14); Mentor: Matthew Sazinsky

Abstract removed upon request.

Investigating the Membrane Stability of Isolated Lipid Vesicles

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

Abstract:  Cell membranes are studied to gain a greater understanding of all living organisms. Unfortunately, cell membranes are difficult to study in solution, so a solid supported lipid bilayer model is used to characterize membrane properties. This project investigates membrane structural stability by constructing a system of isolated solid supported vesicles. It focuses on the vesicle-support interactions, vesicle-vesicle interactions, and intravesicular interactions, all of which contribute to vesicular deformation. Specifically, the difference in osmotic pressure inside and outside of the vesicle affects the stability of the membrane, causing membrane to bend and vesicle to rupture. By varying the osmotic gradient, one gains insight into the vesicle rupture process and the solution conditions at which it takes place. By extension, the isolated vesicle system is used to correlate vesicular size with threshold osmotic pressures in order to study the rupture energy of a vesicle.
Funding Provided by: Rose Hills Foundation  

Characterization of Coenzyme A Disulfide Reductase from Pyrococcus Horikoshii:  A Likely Coenzyme A Persulfide Reductase

Albert Liu ('12); Mentor: E. J. Crane

Abstract:  The coenzyme A disulfide reductase (CoADR) from the hyperthermophilic archaeon Pyrococcus horikoshii is a member of the glutathione reductase family of NAD(P)H and FAD-dependent enzymes.  Although significant work has gone into the characterization of this enzyme, its true in-vitro function has not yet been determined. In order to characterize the substrate specificity of the CoADR from P. horikoshii, its rate of reaction with NADH and disulfide, persulfide and polysulfide substrates was tested. In preliminary assays at pH 7.5 and 70C, the polysulfide substrate appeared to have a significant side reaction which did not subside at pH 8.5.  With the persulfide and polysulfide substrates it was difficult to determine steady-state kinetic parameters of the CoADR due to irreproducible results.  In future studies, rates with polysulfide and other small molecular weight thiol persulfide oxidizing substrates will be determined under anaerobic conditions to eliminate side reactions with oxygen.
Funding Provided by: Rose Hills Foundation  

Synthesis of Olefin-stabilized Temporin Analogs via Microwave-assisted SPPS

Ellen McCormack ('12); Ari Filip ('12); Mentor: Daniel O'Leary, Katy Muzikar

Abstract:  Small naturally occurring peptides make attractive candidates for the development of a new class of antibiotics. Temporins are short, highly hydrophobic, alpha-helical peptides with antimicrobial properties. We have designed several temporin-SHf analogs with covalent hydrocarbon olefin staples connecting various amino acid residues. By stabilizing the secondary structure through this linkage, we hope to make the peptides both more resistant to proteases as well as more effective at disrupting bacterial membranes. Because microwave-assisted ring closing metathesis on the temporin analogs has been unsuccessful to date, we have been using a 310-helical peptide as a model system to troubleshoot metathesis conditions in both solid and liquid phases. Our next step will be to apply working metathesis conditions to the resin-bound temporin analogs to identify design flaws and develop a working synthetic strategy.
Funding Provided by: Pomona College SURP

Investigating the membrane protein FeoB from Shewanella oneidensis MR-1

Justin Moser (’11); Mentor: Matthew Sazinsky

Abstract removed upon request.

Development of a Method for Analyzing Biodiesel using High Performance Liquid Chromatography

Kellyann Murphy ('12); Mentor: Charles Taylor

Abstract:  Pomona College students have used waste vegetable oil from the dining halls and the Coop Fountain to make biodiesel. While biodiesel has been shown to reduce greenhouse gas emissions, it can be potentially harmful to engines if it contains impurities. The goal of this project is to develop a simple method of analysis to ensure that biodiesel produced is safe for campus use. Normally, biodiesel is analyzed by gas chromatography (GC) according to the specifications in the ASTM D6584 and EN14105 standards. This method has several drawbacks including a derivatization step and the need for a special column to withstand the high temperatures needed for analysis. This study proposes a method of analysis using high performance liquid chromatography (HPLC) with both a UV detector and a mass spectrometer (MS). The use of the HPLC makes it possible to use a method that both allows for the use of a standard column and requires no derivatization step.
Funding Provided by: Schulz Fund for Environmental Studies  

Synthesis of 2-(5-aminopentyl)-Mannoside for use in Surface Plasmon Resonance using Second Generation Hoveyda-Grubbs

Olsson ('12); Tera Jones ('12); Mentor: Daniel O'Leary, John Unger, Katy Muzikar

Abstract:  Using 2-(5-aminopentyl)-mannoside anchored to acrylamide by conjugate addition in microarray format, we hope to observe the real time interaction between mannose and surface proteins using Surface Plasmon Resonance (SPR). Our synthetic approach involves olefin cross metathesis of homodimerized C-allyl mannoside to resin-anchored  butenyl amine, using 2nd generation Hoveyda-Grubbs catalyst (10 mol%) stabilized by benzoquinone to prevent olefin migration (10 mol%). The use of a basic cysteine wash solubilizes residual catalyst to the aqueous layer during workup, reducing the presence of impurities in NMR spectra. Yields of the benzylated and allylated α-o-methyl-mannoside products approximately doubled with the use of NaH/Benzyl Chloride and freshly distilled allyl trimethylsilane: 89.2% and 80.9%, respectively. Presence of possible alkene activity in NMR spectra of recent cross-metathesis attempts has been promising. Continued research will involve larger scale cross-metathesis, and purification of the highly polar, free-amine containing product.
Funding Provided by: Rose Hills Foundation  

Developing Raman Spectroscopy as a Novel Diagnostic Method for Tuberculosis using Breath VOC Biomarkers

Kelly Park ('12); Lauren Budenholzer ('12); Angelika Niemz*; Hsiang-Wei Lu *; Anna Hickerson*; Andrew Pipino†; Mentor: Charles Taylor, Tyler Moersch
*Keck Graduate Institute of Claremont, CA, †Tanner Research, Monrovia, CA

Abstract:  Tuberculosis is a widespread disease that is treatable but difficult to detect. Current diagnostic methods are often inaccurate and time-inefficient, or require access to research facilities. This project aims to develop a novel method that uses volatile organic compounds (VOCs) in exhaled breath as diagnostic biomarkers. The development of this design involves the following components: optimizing novel optical geometry for evanescent-wave Raman scattering; compiling Raman spectra of VOCs produced in breath, M. bovis-BCG, and E. coli; building and refining a predictive model using chemometric software; demonstrating the effectiveness of the collection device paired with the adapted Raman system; and establishing its competitiveness by running parallel experiments against a gold standard. Preliminary results with benzene indicate that the paired collection-detection system is functional and advantageous  compared to a conventional Raman system. Future experiments will be performed using authentic headspace samples collected over a variety of cultures to prove the method’s viability.
Funding Provided by: Rose Hills Foundation (KP) Pomona College Chemistry Dept. (LB) 

Development of a Fast-Flow FTIR Discharge System to Examine Complex Reactions of Atmospheric Species

Kori VanDerGeest ('12); Mads Andersen*; Stanley Sander*; Mentor: Frederick Grieman
*Jet Propulsion Laboratory,  Pasadena, CA

Abstract:  Models of chemical cycles in the Earth’s atmosphere rely upon an understanding of complex reactions involving volatile organic compounds, nitrogen oxides, hydrogen oxides, and other molecular radicals.  The need for accurate kinetic measurements and knowledge of reaction mechanisms has driven the development of analytical methods with high sensitivity, specificity, and good time resolution for reactive, transient, and product species.  A fast-flow discharge system with a long-path White cell reactor was developed in our laboratory and coupled to a high-resolution Fourier transform spectrometer, which will use IR spectra to identify and quantify atmospheric compounds. The multi-pass system has an optical path length of 57 m and a spectral resolution of 0.0026 cm-1, enabling the detection of IR-active species at concentrations of 1011 – 1012 molecules cm-3 with Doppler-limited absorption spectra.  This instrument will be used to study the transient products of OH and NO2, a reaction that slows stratospheric ozone depletion and pollutant formation in the troposphere.
Funding Provided by: Pomona College Chemistry Dept.

Synthesis of a Parallel Helix Bundle of Peptides by Solution Phase Cross Metathesis with Grubb’s Catalyst

Marvin Vega ('13); Margaret Nguyen ('10); Mentor: Daniel O'Leary, Katy Muzikar

Abstract:  A cross metathesis reaction using Grubb’s Catalyst was done to create a parallel helix bundle of peptide strands in order to strengthen the possible use of any peptides in therapeutics.  Boc-Ser(OAll)-Ala-Ala-Ser(OAll)-Ala-Ala-OMe would be made and the cross metathesis would take place at the allylated L-serines.  The tripeptide Boc-Ser(OAll)-Ala-Ala-OMe was synthesized first to see if the cross metathesis was possible.  The tripeptide reacted with itself using both Grubb’s second generation catalyst with copper (I) iodide and Hoveyda-Grubb’s second generation catalyst with benzoquinone.  Both reactions created the desired product based on NMR analysis.  The reaction with the Hoveyda-Grubb’s catalyst showed a number of possible by-products and impurities with only a little starting material recollected, while the reaction using Grubb’s catalyst showed just another possible by-product with a lot of starting material recollected.  The next steps are to finish the hexapeptide and attempt the second cross metathesis, as well as optimize each reaction.
Funding Provided by: Linares Family Gift for Chemistry Research

The Asymmetric Reduction of Aryl 2H-azirines Using Nonracemically Ligated Copper Hydride

Dylan Zucherman ('13); Mentor: John Unger

Abstract:  Azirine and aziridine systems are defined by their reactivity that is certainly derived from their highly strained bonding nature.  As such, both classes of compounds are extremely powerful synthetic intermediates and have been adopted in several organic syntheses of bioactive natural products and synthetic pharmaceuticals.  In this study, members of the 2H-azirine family, the smallest of the unsaturated nitrogen heterocycles, have been synthesized and characterized.  A versatile route to 3-aryl-2,2-dihydro azirines was employed that involved the clean thermolysis of a vinyl azide derived from inexpensive and readily available styrenes.  2,2-Dialkyl azirines are alternatively accessed through a modified Neber method.  The 2H-azirines have been prepared for an investigation into the asymmetric synthesis of aziridines through 1,2-reduction using nonracemically ligated copper hydride (L*CuH).  Future efforts will focus on developing this general method for use in organic synthesis.
Funding Provided by: Paul K. Richter and Evalyn E. Cook Richter Memorial Fund

Research at Pomona