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Chemistry

Use of Chemical Vapor Deposition in the Fabrication of Metal Oxide Thin Film Gas Microsensors

Joseph Allen Beardslee ('08), Anna Mebust ('08), Charles Taylor

The goal of this summer’s research was to investigate different methods for making selective gas microsensors. Research has shown that metal-oxide thin films deposited on micromachined silicon devices known as microhotplates may be used as chemical sensors since they change resistance upon exposure to various volatile compounds (e.g., acetone, isopropyl alcohol, etc.). The selectivity of the sensor response may be controlled by a variety of means; sensing film composition and microstructure both play large roles in sensor selectivity. In addition, sensing response is temperature dependent, so this may also be used as a variable in changing sensor selectivity. Towards this end, temperature programming during gas exposure can be used to gain additional information about analyte identity. Our research investigated sensors with thin films of three different metal oxides—vanadium oxide, tungsten oxide, and tin oxide. The vanadium oxide films were prepared using vanadium (V) oxy tripropoxide, vanadium (V) oxy triisopropoxide, and vanadium (V) oxy nitrate, while the tungsten oxide films were prepared using tungsten (VI) hexacarbonyl and the tin oxide films were prepared using tin (IV) t-butoxide. We prepared the sensors via chemical vapor deposition (CVD), used scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS) to characterize the microstructure and determine the elemental composition of the films, and tested the sensor responses to varied concentrations of numerous test analytes when held at a constant temperature of 375 °C and 400 °C.
Funding provided by: Pomona College Chemistry Department

Spectroscopic Determination of Lead Concentration in Soil at Puddingstone Reservoir

Emily Bockmon ('08), Elizabeth Harman ('08), Scott Stroup ('08), Charles Taylor

Small airplanes run on leaded fuel, which emit lead halide compounds into the environment. These fuels may contain up to two grams of elemental lead per gallon. Brackett Airport houses many of such airplanes and lies adjacent to Puddingstone reservoir, a popular recreation area for families and children. Due to children’s high susceptibility to lead poisoning, the EPA has mandated a maximum lead contaminant level of 400 ppm in soil where children play. We collected forty-four samples at varying locations around the reservoir. These samples were digested using EPA method 3050b and analyzed with Graphite Furnace Atomic Absorption Spectroscopy. We found lead concentrations ranging from 2 ppm to 54 ppm, all below the EPA’s most stringent lead standard. Locations near the sites sampled on Puddingstone Reservoir appear to be safe areas for children to play.
Funding provided by: Joint Sciences Department (EB); SURP (Schulz - SS, EH)

Discovering Novel Homing Endonucleases in Environmental Archael Samples

Diana Y. Chen ('09), Diana Koulechova ('08), E.J. Crane, Len Seligman

Homing endonucleases (HEs) are proteins encoded by inteins and some introns. These proteins create double stranded breaks in genes that do not contain copies of the respective intein or intron, allowing for the intein or intron to be copied into a new gene. Previous studies have focused on the characterization and sequencing of novel HEs, but few have successfully looked at a broader genetic basis for the existence of these proteins. This project focuses on characterizing novel HEs in Archaea from various geothermal sites in order to understand their impact on microbial diversity. It was hypothesized that novel HEs that have yet to be characterized in Archaeal microbes Pyrococcus, Desulfurococcus, and Methanopyrus, would be found in geothermal environmental samples known to contain the Archaea and analysis of these environmental samples might reveal more novel HEs from species related to these respective Archaea. Possible targets for novel HEs were recorded from the National Center for Biotechnology Information Protein Database and New England Biolabs Intein Database. Novel HEs were confirmed in Pyrococcus furiosus and Pyrococcus abyssi; however their identification in environmental samples has been stalled by difficulties in genomic extraction.
Funding provided by: Merck/AAAS

Investigating Olefin Metathesis in Helical Peptides

Catherine Lynn Farkas ('09), Tafadzwa Nyabanga ('09), Amanda Reider ('09), Sheri Sangji ('08), Leo Garver ('08), Daniel O'Leary

Helices are common in the secondary structure of many proteins and it is likely that modifying the secondary structure has a wide variety of medical applications. Previously, ring-closing metathesis had been used to link two allylated serine resides from position i to i + 3 on a helical octapeptide. The reaction showed high trans selectivity and the peptide produced remained helical. The aim of this study was to transform the double bond into a cyclopropyl group and then observe the enantioselectivity of the reaction and conformation of the resulting peptide. To accomplish this, a number of peptides were synthesized using standard peptide synthesis techniques. The identities and purities of the products were confirmed using 1D NMR spectroscopy. A pentapeptide was synthesized and effectively ring-closed using a 2nd generation Grubbs catalyst. This reaction had a high yield and showed significant trans selectivity. Its conformation remains to be analyzed. The cyclopropanation also remains to be studied and will be carried out according to the Simmons-Smith synthesis, which uses a zinc-copper couple.
Funding provided by: SURP

Investigations In I→I+4 Ring Closings on 3-10 Helical Peptides

Leo Bennett Garver ('08), Daniel O'Leary

One of the major structural devices in peptides and proteins is the helix, a coiled structure resembling a spring. The main type of helix in nature is the alpha helix, but there are several other kinds such as the 3-10 helix. The difference between the alpha and 3-10 helices is how tightly wound they are, and how the residues align with one another. In the alpha helix, amino acids that are four residues apart are aligned looking down the helix (an i→i+4 link), whereas in the 3-10 helix the amino acids three apart are aligned (i→i+3). If we add allyl groups to specific amino acids in the chain, we can connect the allyl groups we have added with a ring-closing metathesis reaction that essentially “staples” the peptide helix into its conformation, a very useful tool for peptide synthesis that could be used in the future for making peptide pharmaceuticals as a spacer or a template. While an i→i+3 link is the easiest to make in a 3-10 helix, I have synthesized peptides with the link as an i→i+4. After the ring-closing, the helix will change conformation to something closer to an alpha helix, which we have verified by circular dichroism and NMR.
Funding provided by: SURP (Craddock-McVicar)

Parametric Investigation of Picoliter Droplet Interfacial Tension Using a Microfluidic Device

Kevin William Kelley ('09), Daniel Chiu*, Gavin Jeffries*
*Chemistry Department, University of Washington, Seattle, WA

The transport and detection of nanoscale objects has become an essential part of sub-cellular biochemical research and with it the use of droplets as controllable confined volumes. To fully understand and utilize the chemical environment of droplet systems, it is necessary to elucidate the physical properties of the droplet interface, namely through studying the interfacial tension. The capillary number (Ca), which depends on interfacial tension, is an important physical factor for designing and calculating fluidic dynamics in microfluidic droplet systems. This project seeks to investigate the Ca by measuring changes in interfacial tension as a function of the following factors: ion concentration, surfactant type, surfactant concentration, and oil type. The interfacial tension of numerous individual droplets was measured by examining the deformation and restoration dynamics of the drops under extensional flow. Droplet generation parameters were independently varied and results were captured using fast imaging techniques. This video data was analyzed using a mathematical model of droplet dynamics, coded with the program Labview, which calculated the interfacial tensions. This project will attempt to further clarify the quantitative relationship among the key factors, and how they govern droplet formation when used in microfluidic devices for bio-analytical applications.
Funding provided by: NSF-REU (NNIN, University of Washington)

Determination of the Three Dimensional Solution Phase Structure of a Peptidic Enantioselective Phosphate Transfer Catalyst from NMR Constraints

Prashant Kotwani ('09), Daniel O'Leary, Wayne Steinmetz, Scott Miller*
*Department of Chemistry, Yale University, New Haven, CT

Peptide based catalysts have been found to catalyze enantioselective phosphorylation of a meso myo- inositol-derived triol. Peptide 3P produces enantiomeric D-myo-inositol-3-phosphate derivatives. The synthesis of Peptide 3P was carried out at Boston College by the Miller group. Detailed NMR characterization of the peptide was done at Pomona College. [Deliminator]The three dimensional structure of this peptide based catalyst in dichloromethane was determined through constrained molecular mechanics and ROESY spectra and torsional constraints from proton-proton coupling constants. All NMR spectra were taken at 25°C on a Bruker 400 MHz spectrometer. The modeling calculations will be carried out in Version 7.3 of SYBYL and the 1994 release of the Merck Molecular Force Field. Detailed modeling of the peptide will be carried out after further purification of the sample.
Funding provided by: SURP

Implementing Backbone Diversity to Model Fast Time Scale Protein Motions

Anthony Linares ('08), Tanja Kortemme*, Gregory D. Friedland*
*Department of Biopharmaceutical Sciences, University of California, San Francisco, CA

Fast time scale protein motions are vital for information pathways that influence catalytic activity, ligand binding and allosteric regulation. Previous computational methods have modeled picosecond to nanosecond side chain dynamics using a static polypeptide backbone. Here we extend our approach to include small scale backbone perturbations using backrub motions. Once backbone diversity has been simulated, ensembles of structures based on scoring potential and structural properties are created. Using the Monte Carlo-based computational method Rosetta, the side chain sampling is verified by predicting experimentally measured side chain order parameters. Results on eight out of ten proteins have shown significant improvements upon previous models. By incorporating backbone dynamics, we hope to gain insight on the properties of proteins near the native state. Future applications of this method will assist in protein design and the prediction of protein functions and allosteric networks.
Funding provided by: Genentech

Characterization and Crystallization of the COADRR From a Psychrotolerant Shewanella Species

Vinita Lukose ('08), E.J. Crane, Matthew Sazinsky

Abstract removed upon request.

Tuning the Optical Properties of a Water-Soluble Cationic PPV Derivative by Sufactant Complexation

Vincent Ma ('08), Jeremy Treger ('08), Malkiat S. Johal

Poly(phenylenevinylene) (PPV) and its derivatives have been known since 1990 to have electroluminescent properties. These conjugated polymers show great promise as building blocks in a variety of useful materials including photovoltaic cells, biosensors, and organic LEDs. In a previous project, we found that the well-known anionic surfactant, sodium dodecyl sulfate (SDS), can be used to improve the emission photoluminescence quantum efficiency, the peak absorption wavelength, and the emission wavelength of an aqueous solution of poly{2,5-bis[3-(N,N,N-triethylammonium bromide)-1-oxapropyl]-1,4- phenylenevinylene}, a PPV derivative also known as P2. This summer, we used the method of electrostatic self-assembly (ESA) to incorporate SDS into multilayer thin film assemblies of P2 and the polyanion poly(sodium 4-styrene-sulfonate) (PSS). Using UV-Visible Spectrophotometry, we found that SDS is effective in significantly increasing the optical density in the visible wavelength region, as well as in preventing photo-oxidation of the films. These findings have the potential to facilitate the integration of P2 into more efficient and longer-lived photovoltaic cells and electroluminescent devices. We hope to use these results to improve upon previous prototype organic LEDs and obtain a working device whose electroluminescent properties can be characterized.
Funding provided by: SURP, Pomona College Chemistry Department

Investigating HIV-1 Protease Inhibitor Designs with Docking and Clustering Methods

Christopher Alan Marsh ('09), Bruce Tidor*, Nathaniel Silver*
*Department of Biological Engineering Massachusetts Institute of Technology, Cambridge, MA

A method is presented for docking and clustering multiple HIV-1 Protease inhibitors in order to find correlations between individual cluster and/or cluster map properties and inhibition efficacy. We hypothesize that certain clustering features can distinguish between active and inactive binding modes, where energy-based scoring may have deficiencies. The model system is HIV-1 Protease, using FDA- approved inhibitors as well as derivatives of the inhibitor amprenavir. Multiple docking methods and restrictions, such as post-docking optimization and hydrogen-bond constraints, were implemented in order to locate a set of parameters that offers the best correlation. Preliminary results suggest that, with hydrogen- bond restrictions set, cluster map features offer some ability to differentiate between tight binders and less active compounds.
Funding provided by: MIT Amgen Scholars UROP Program

Stabilizing Small 310-Helical Peptides Through RCM Between Constituent Amino Acid Side Chains

Custon Tafadzwa Nyabanga ('09), Daniel O'Leary

Following previously reported liquid phase synthesis of simple 310 helical peptides containing allyl residues situated on positions i and i+3, we intend to investigate the conformational stabilization of a tetrapeptide containing ?-aminoisobutiric acid (Aib) and allylated serine residues. These small chains of amino acids have been known to easily conform to 310-helical motifs and we herein intend to investigate conformational stabilization of the tetrapeptide with the structure Boc-Ser(Al)-Aib-Aib-Ser(Al)-OMe, by linking the allylated serines through ring closing metathesis. During the synthesis process of the tetrapeptide we stumbled into an enantiopurity problem with the allylated serine amino acid, and a considerable part of the project was spent on trying to obtain an enantio-pure sample of this compound. Derivatives of the allylated serine amino acid have made it possible to separate the impurity from our desired product through a silica gel column. With successful synthesis and cyclization on this tetrapeptide, we intend to further stabilize the olefin RCM product by forming its dihydrated derivatives without altering the native conformation of the peptide.
Funding provided by: Pomona College Chemistry Department

Structural Analysis of Angiotensin Inhibitor DX600

Richard Benjamin Peprah ('08), Tim Carrell (‘09), Wayne Steinmetz

We use NMR spectroscopy to study the structural characteristics of the peptide DX600, which is an inhibitor of angiotensin-converting enzyme 2. This protein consists of 26 amino acid residues, including four prolines and seven aromatic residues. We determined that DX600 is present as two conformers in aqueous solution at room temperature, and that new species are present in acidic and basic conditions. As our initial step towards determining the structure, we have made assignments for most of the chemical shifts observed in the protein. We plan on using ROE distance constraints and chemical shift differences from the random coil values to determine a three dimensional structure for DX600.
Funding provided by: Pomona College Chemistry Department

Using QCM-D to Monitor the Creation of SSDNA and DSDNA Surfaces and to Examine the DNA-Damaging PROP

Robert James Rawle ('08), Cynthia Selassie, Malkiat Johal

The quartz crystal microbalance with dissipation monitoring (QCM-D) is a nanogram-sensitive gravimetric technique that is ideal for elucidating the properties of thin films. In this study, we use QCM-D to observe the creation of genomic mammalian ssDNA and dsDNA surfaces on a polycation adsorbed to a SiO2 support. We demonstrate that this method can be used to successfully monitor the hybridization reaction between surface-bound ssDNA and complementary strands in solution. We also show that the ssDNA and dsDNA surfaces behave as expected when exposed to a solution of ethidium bromide, a known DNA intercalator, and that the dsDNA surface can be denatured upon exposure to urea. Finally, we use the DNA surfaces to examine the DNA-damaging properties of quercetin, a polyphenolic flavonoid, and our results support previous research which claims that quercetin can nick the DNA backbone in the presence of Cu(II).
Funding provided by: Beckman Foundation (RJR); NIH (#1R15ES014812 - CS)

A Glimpse of the Microbial Diversity at Two Unique Geothermal Sites

Kate Siobhan Reid-Bayliss ('09), E.J. Crane

Previous studies in this lab have utilized culture-independent techniques to determine the microbial diversity of two extreme environments. This study builds upon that previous work, [Deliminator] employing culture-based techniques, while continuing to develop culture-independent methods to help determine the diversity and identity of microorganisms inhabiting the Salton Sea mud volcanoes and surrounding brines, as well as those inhabiting a pool at the Coso Hot Springs. Environmental cultures were grown up and individual colonies isolated and identified by sequencing their 16S rRNA genes. Culture-independent methods encompassed construction of 16S rRNA gene clone libraries from extracted environmental DNA and subsequent sequencing of the clones. Five halophilic microbes from the Salton Sea brines were isolated via culture-dependent techniques: two bacteria, previously identified, and three archaea, whose exact relatedness to similar species has yet to be determined. Additionally three bacteria from the Salton Sea round volcano were identified via construction of 16S rRNA gene clone libraries, two of which may be novel species.
Funding provided by: HHMI (KSRB); Hirsch Foundation (EJC)

Purification and Stereospecific Reations of I to I+3 Hexapeptide Systems

Amanda Clare Reider ('09), Daniel O'Leary

The trans selectivity of metathesis olefin products offers opportunities for stereospecific reactions, such as trans epoxidation of the olefin using metachloroperoxybenzoic acid. Using the L-enantiomers of O- allylated serine (Ser(OAl))and ?-isobutyric acid (Aib), attempts were made to build a pure i to i+3 hexapeptide system (Boc-Ser(OAl)-Aib-Aib-Ser(OAl)-Aib-Aib-OMe), for use in subsequent metathesis and stereospecific epoxidation. Hydrolysis of the O-allylated serine amino acid methyl ester using lithium hydroxide induced racemization, causing impurities observable by HPLC and 1H NMR. Pure peptides were needed before metathesis could continue. Gentler hydrolysis methods also yielded racemization or no reaction. The problem was solved by activation of the O-allylated serine methyl ester with N- hydroxysuccinimde and DCC. Subsequent coupling to Aib-Aib carboxylic acid dimers produced pure tripeptides. Coupling to identical methyl ester tripeptides yielded pure i to i+3 hexapeptides, and metathesis and epoxidation can now be investigated.
Funding provided by: SURP (Richter)

Synthesis of 310 - Helical Peptide Bundles Using Ring Closing Metathesis Reactions

Sheharbano Sangji ('08), Daniel O'Leary, Claudio Toniolo*
*Department of Chemistry, University of Padova, Padova, Italy

Linking amino acids in a peptide with covalent bonds, or “stapling,” has been used to stabilize helical peptides. The Grubbs metathesis catalysts (I and II) can be used to induce Ring Closing Metathesis (RCM) and create cyclic structural elements spanning a peptide helix. In this study, we used RCM reactions to synthesize a 310 – helical peptide bundle 10. Our synthesis utilized two sequences to synthesize intermediate 6. The three step synthesis using a Cross Metathesis (CM) reaction gave a combined yield of 50 %. The two step synthesis using a di-substituted allyl bromide gave a combined yield of 39.5%. Intermediate 6 was hydrogenated (> 91%) and then coupled with tri-peptide 4 (57%). The product underwent RCM (76%) followed by hydrogenation (79 %) to give peptide bundle 10. All intermediates were characterized by Mass Spectrometry and 1H NMR spectroscopy. HPLC analysis of 8 suggested the presence of a stereoisomeric impurity. We suspected that the impurities might arise in the coupling of 7 to the free carboxylic acid of the highly labile tri-peptide 4. To avoid this step, we coupled 7 to di-peptide 2 followed by coupling to free Boc-Ser(OAllyl). Initial analysis of the sample of 10 obtained through this route appears to be free of impurities. CD spectroscopy and X-ray crystallography will then be used to determine the helical nature of 10.
Funding provided by: Pomona College Chemistry Department

Synthesis of Selective Inhibitors of Dihydrofolate Reductase

Shreya Saraf ('09), Cynthia Selassie

The enzyme Dihydrofolate reductase (DHFR) plays a vital role in the thymidylate synthesis pathway. Inhibition of DHFR leads to reduction of tetrahydrofolate levels, and eventually causes the thymineless death of the cell. Homological differences between larger DHFR of vertebrates and that of their bacterial and protozoal counterparts are utilized to design selective and potent inhibitors (called antifolates) that will minimize host toxicity and maximize pathogen toxicity. This project involves the design and synthesis of a series of 2,4-diamino-5-(3’-(4”-X-phenoxymethyl)-anilinomethyl)-pyrimidines as potential protozoal antifolates with enhanced selectivity as well as excellent inhibitory potency. The particular substituent(X) group under study is the carboxamidomethoxy (-OCH2CONH2) analog which is particularly hydrophilic and should improve the bioavailability of the antifolate. The multi-step reaction scheme consists of two parts- the first involves the synthesis of 2,4-diamino-5-cyanopyrimidine, its reduction to 2,4- diaminopyrimidine-5-carboxaldehyde and a further reduction to 2,4-diamino-5-hydroxymethylpyrimidine, followed by its conversion to 5-(bromomethyl)-2,4-pyrimidinediamine dihydrobromide and finally to 1- [(2,4-diamino-5-pyrimidinyl)methyl] pyridinium bromide. The second part comprises of a hydrogenolysis reaction to synthesize 4-carboxamidomethoxy phenol which is coupled to form 3-nitrobenzyl-(4- carboxamido-methoxy) phenyl ether. This is reduced to 3-aminobenzyl-(4-carboxamido-methoxy) phenyl ether and finally coupled to the pyridinium salt to form the product 2,4-diamino-5-(3’-(4”carboxamido- methoxyphenoxymethyl)-anilinomethyl)-pyrimidine. Since the bromide and pyridinium salts in the first part are unstable compounds, they will be synthesized once the reduced ether is ready for coupling.
Funding provided by: SURP (Sontag - CS)

Polyelectrolyte Spin-Assembly: The Effect of Electrostatic Adsorption Time on Film Growth

Kavisha Singh ('10), Malkiat Johal

Polyelectrolyte thin films composed of alternating layers were spin assembled by sequentially dropping an aqueous solution of a polycation and a polyanion on to a spinning substrate. Multilayer assemblies were fabricated from the polyanion poly[1-[4-(3-carboxy-4-hydroxyphenylazo) benzenesulfonamido]-1,2- ethanediyl, sodium salt] (PAZO) and the polycation poly(ethylenimine) (PEI). In this work, we show the effect of adsorption time on the overall growth of the assemblies. Solutions were deposited on to the substrate for a pre determined amount of time and then spun for 1 minute at 3000 rpm. The assemblies were characterized using multi-wavelength ellipsometry and UV-visible absorption spectroscopy. We show that film growth is governed by a competition between steady state electrostatic adsorption and mechanical entanglement under shear flow.
Funding provided by: Pomona College Chemistry Department

Cytotoxicity and CASPASE-9 Activity of Phenolic Compounds in L1210 Cells

Lauren Reade Towne ('09), Cynthia Selassie, Christine Chiu

Chemicals that induce apoptosis, or programmed cell death, could be potentially valuable as anti-cancer drugs. Caspase-9 induction is a reliable indication of apoptosis, since caspase-9 is a protease that initiates the apoptotic cascade. In this project, the cytoxicity and caspase-9 induction of various multi-substituted phenols were tested on L1210, murine leukemia cells. The concentration needed to inhibit cell growth by 50% (IC50) measured cytotoxicity, and capase-9 activity was determined using Bradford assays and a caspase-9 assay kit produced by BioRad. The caspase-9 assay correlates protein concentration and absorbance at 405 nm to determine induction. Absorbance occurs when active caspase-9 cleaves p- nitroaniline from a tetrapeptide. Preliminary results indicate that while many compounds tested induce cell death at very low concentrations in the millimolar range, caspase-9 activity is not always significant when compared with the baseline. Induction is usually between 0 and 100%. One explanation for this trend is that tri-substituted phenols may be too sterically hindered to effectively interact with the caspase enzyme, though further experimentation would be required to draw definitive conclusions.
Funding provided by: NIH (#1R15ES014812 - CS)

Characterization of the Polysulfide Reductase Complex (PSRABC) of Shewanella Oneidensis MR-1

Sneha Vakamudi ('08), E.J. Crane, Nancy Hamlett, Karlo Lopez

Bacteria of the genus Shewanella are of interest to the scientific community due to their ability to utilize various electron acceptors during respiration, employing several and compounds including O2, Mn(III), Fe(III), thiosulfate and elemental sulfur (S0). Of particular significance to this project is the species Shewanella oneidensis MR-1, which reduces sulfur during anaerobic respiration via a polysulfide reductase complex (PsrABC) which this project sought to assay, isolate, and purify, . A major portion of the project was devoted to developing a quantitative assay for sulfur reduction. The assay was based on a previously developed method using the sulfide-dependent formation of methylene blue, which can be detected spectrophotometrically.. After development of the assay, MR-1was grown on a large scale, harvested, and lysed via French press, resulting in a crude extract containing membranes. The ability of this crude extract to reduce elemental sulfur was determined. The results of the experiment revealed that crude extract was able to reduce elemental sulfur using H2 as an electron donor. The implications of these findings establish a qualitative basis for understanding PsrABC. This important step provides the foundations for future studies involving the purification, isolation, and investigation of the complex.
Funding provided by: SURP

Sum-Frequency Spectroscopy of a Polyelectrolyte Multilayer Assembly Containing NLO-Active Chromophor

Amanda Y. Yang ('10), Malkiat Johal, Mike T.L. Casford* Paul B. Davies*
*Department of Chemistry, University of Cambridge, Cambridge, UK

The technique of sum frequency spectroscopy was used to examine the molecular-level ordering of NLO- active moieties in electrostatically bound multilayer assemblies composed of weak polyelectrolytes. Multilayer assemblies of the polyanion poly[1-[4-(3-carboxy-4-hydroxyphenylazo) benzenesulfonamido]- 1,2-ethanediyl, sodium salt] (PAZO) and the polycation poly(ethylenimine) (PEI) were constructed from aqueous solution using the layer-by-layer electrostatic self-assembly method. Films were fabricated on a gold substrate coated with a self-assembled monolayer (SAM) of hydrophilic 11-mercaptoundecanoic acid. The SFG spectra of the SAM exhibit strong CH2 resonances, which indicate the presence of gauche defects in the alkyl chains. Upon the deposition of a PEI/PAZO bilayer, these features disappeared due to extensive interpenetration of the polyelectrolyte film into the SAM. The SFG spectrum of the PEI/PAZO bilayer also exhibited a prominent resonance due to the C-H aromatic stretch (n2), indicating anisotropic ordering of the NLO-active chromophores within the assembly. The deposition of additional layers did not affect the strength of the n2 resonance. We conclude that the ordering of the NLO-active moieties in the multilayers is primarily restricted to the surface of the films.
Funding provided by: Downing Faculty Exchange (MJ); Pomona College Chemistry Department (AYY)

QSAR of Curcumin, Betulinic Acid, and Their Analogs to Indicate Anti-Angiogenic Activity in Huvec

Alice Hae Young Yoo ('08), Cynthia Selassie, Rajeshwar Verma

Tumor growth occurs through angiogenesis, a process in which blood vessels form to provide nutrients and a path of waste removal to the tumor. Anti-angiogenic agents were studied to examine their efficacy in impeding tumor angiogenesis through inhibiting neovascularization. These agents consisted of symmetrical, α,β-unsaturated and saturated ketones of curcumin and its analogs; and the pentacyclic triterpene betulinic acid and its derivatives. Taking data from present literature and inputting it into the QSAR program, I examined the efficacy of these agents in inhibiting neovascularization through generating equations that indicate the concentrations necessary to inhibit fifty percent blood vessel growth. In examining the data, curcumin and its analogs were found to have anti-angiogenic properties. The data indicated that the presence of a 4-hydroxy group on the phenyl ring of the compound impedes its maximum potency in human umbilical vein endothelial cells. This might be explained by steric hindrance, in which the 4-hydroxy group may serve as a deterrent in the binding of these molecules to the VEGF receptors. The data for betulinic acid and its derivatives was inconclusive. These findings serve as preliminary results for a larger study to determine anti-angiogenic properties of phenolic compounds as well as caffeic esters.
Funding provided by: Rose Hills Foundation

Diffusion-Controlled Reactions on Quasicrystals and Crystal Growth Processes

Joseph Tao-Wang Chang ('10), Aaron Kaufman (’10), Reena Patel (’10), Carlos Almanza (’09), Eloisa  Amador*, Andrew Brown*, Connie Fang*, Gilbert Gutierrez*, Francois Patterson*, Anthony Vitug*, Joelle Whyte*, Roberto A. Garza, John Jkozak**
*2007 Summer Scholars Enrichment Program Participant **Department of Chemistry, DePaul University, Chicago, IL

We investigate two specific problems. The first project is the study of the reaction efficiency of diffusion- controlled processes on quasicrystals having chemical receptors and the second is the study of the growth process of crystals. A quasicrystal is a special type of crystal that presents multiple planes of rotational symmetry to an extent that was conventionally believed to break the rules of crystallography, having so- called “forbidden” symmetries. The first one to be identified was an alloy of Al and Mn that displays a diffraction pattern showing both five- and ten-fold symmetries. The problem on both situations translates into the statistical one of examining the geometrical factors affecting the trapping of a random walker on these lattices having N sites and average valency n. The second problem deals with the crystal growth process in biological systems. Extensive calculations of the site-specific average walk length <n> before trapping, a measure of the efficiency of the underlying diffusion-reaction process have been carried on these physical and biological systems.
Funding provided by: SURP (Seaver - JTWC); HHMI (CA); Pomona College Chemistry Department (RP,AK)

Tyrosinase-Catalyzed Oxidation of Flavonoids

Rebeccah Anne McKibben ('08), Cynthia Selassie

Tyrosinase has been shown to oxidize catechols into quinones via a phenolase reaction (slow step) and subsequent catecholase reaction (fast step). Based on the structural similarity between catechols and flavonoids, it was postulated that tyrosinase may oxidize flavonoids to quinones as well. Using UV-Visible spectroscopy, the formation of a quinone was monitored by absorption in the visible range, based on the formation of a Schiff-base adduct between the quinone and MBTH. Analyses of both phenolic and catecholic flavonoids have indicated that this oxidation reaction does occur, and it does so more quickly with catecholic flavonoids based on the slower phenolase step required with phenolic flavonoids. Furthermore, recent findings indicate that bulkier, more rigid flavonoids do not form an adduct with MBTH, a step previously regarded as a fast step. Further experiments have been conducted to reevaluate the kinetic parameters of both catecholic and phenolic flavonoids, and the findings have indicated that flavonoids have lower binding constants and higher kcat values when MBTH is not present in the reaction mixture. This supports the hypothesis that the formation of a Schiff-base adduct between the flavonoid quinone and MBTH may be hindered in some cases.
Funding provided by: Pomona College Chemistry Department

Research at Pomona