Senior Year Experience - Class of 2009 - Research Abstracts [* denotes Honors in Chemistry]
Click on a name for title & abstract: Eric Clark, Nicholas Lovejoy, Matt Millard*, Brendan Mitchell, Hai-Yen Nguyen, Cheyenne Sanchez, Lauren Sischo*, Tiffany Smith, Michael Trembley*, Ryan Wolfe - Click here for Festival of Science !
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Senior Year Research Abstracts – Class of 2009
Matthew J. Millard - Honors Thesis in Chemistry
Advisor: Dr. Samantha Glazier
A Thermodynamic and Kinetic Study of Nogalamycin-DNA Interactions
Nogalamycin is an anthracycline antibiotic and one of less than ten known threading intercalators. Threading intercalators represent a promising although poorly understood class of anti-tumor drugs mechanistically. Thus the association and detergent-induced dissociation kinetics of nogalamycin binding with DNA was studied using stopped-flow fluorescence. A mechanism based on three steps for both the association and dissociation of nogalamycin from CT DNA has been reported. However our data suggests that light sensitivity may explain at least one of the three steps and that a new mechanism must be proposed.
Senior Year Research Abstracts – Class of 2009
Tiffany M. Smith ‘09
Advisor: Dr. French
Aromatic, Boron-Containing Heterocycles as Potential Diels-Alder Dienophiles
Abstract
1,3,2-dioxaboroles are chemically interesting in that they possess a high energy HOMO and low energy LUMO rendering them potential dienophiles in both the normal and inverse electron demand versions of the Diels-Alder reaction. Only a handful of reports related to the synthesis and reactivity of these heterocycles have appeared to date. Several attempts to synthesize 3,4-dimethyl-1-phenyl-1, 3, 2-dioxaborole have provided only low yields of difficult to isolate product owing to its tendencies to decompose. One trial as been successful in isolating trace amounts of 1, 3, 2-dioxaborole by purification of the product via reduced pressure distillation. A major complication has been the formation of acetoin polymers. Efforts to circumvent this problem have included formation and reaction with dienes in situ without isolation of the borole and use of alternative synthetic methods and precursers. The related 3,4-diphenyl-sbustituted borole has been successfully obtained in 50% yield according to the published procedure5. After each boron dienophile is successfully formed, Diels-Alder reaction with various dienes will be attempted.
Senior Year Research Abstracts – Class of 2009
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Lauren Sischo ‘09 - Honors Thesis in Chemistry
Advisor: Dr. Matthew Skeels
Investigating Isoquinoline Alkaloid Content in Hydrastis canadensis (Goldenseal)
Abstract:
The identification and quantification of alkaloids in medicinal plants are of great significance due to their pharmacological properties. Hydrastis canadensis, or Goldenseal, is a medicinal plant native to the eastern parts of North America, characterized by a thick, yellow rhizome. The isoquinoline alkaloid content of the root and rhizome of Goldenseal were investigated under various growing conditions. Conditions consisted of high or low amounts of nitrogen, moisture, and light. The growth of alkaloids of interest included berberine, hydrastine, and hydrastinine. High performance liquid chromatography (HPLC) was used to determine the relative amounts of berberine, hydrastine, and hydrastinine in Goldenseal root and rhizome extracts. An ambient extraction method was used, providing efficient extraction of three isoquinoline alkaloids. Analysis and comparisons of post-treatment samples revealed that under high light conditions, berberine and hydrastine content (mg/g dry plant material) was significantly greater than under low light conditions. The amount of hydrastinine was not significantly affected by different light conditions. A significant positive correlation between the amounts of hydrastine and hydrastinine in both root and rhizome was evident from the investigation. In addition, significant positive correlations between the amounts of berberine and hydrastine in the root, as well as berberine and hydrastinine in the root of H. canadensis were also evident.
Senior Year Research Abstracts – Class of 2009
Cheyenne Sanchez ‘09
Advisor: Dr. Larry French, Chemistry
Synthesis of Novel N-Cyanoguanidine Ligands Targeting the Transient Receptor PotentialVanilloid type-1 Receptor.
Abstract
The vanilliod receptor 1 (VR1) is a nociceptor capable of responding to thermal, chemical, and protic stimuli. Numerous compounds have been demonstrated to act agonistically and antagonistically at this receptor which has led to a new strategy for pain relief through the pharmacological blockade of VR1. Three N-cyanoguanidine analogs of capsaicin were synthesized; 1-(4-chlorophenethyl)-2-cyano-3-(4-hydroxy-3-methoxybenzyl)guanidine, 2-cyano-1-heptyl-3-(4-hydroxy-3-methoxybenzyl)guanidine, and 1-(4-chlorobenzyl)-2-cyano-3-(4-hydroxy-3-methoxybenzyl)guanidine. These analogs of known vanilloid ligands will undergo a screening assay to test these compounds in transgenic C. elegans expressing rat VR1.
Brendan Mitchell ‘09
Advisor: Dr. Neil Law, Chemistry
Formation and Characterization of Copper (ii) Metallacrowns by Use of
2-Methoxybenzohydroxamic Acid and its Derivatives H25Cl
Abstract
Metallacrowns are gaining interest because of the varied functions for which they might be useful. These include, but are not limited to: single molecular magnets, MRI contrasting agents, and liquid crystals. One basic type of metallacrown is constructed through the use of salicylhydroxamic acid as a ligand. My research aimed to address what happens when other metal atoms and ligands with different functional groups are used. The intriguing question was to see if thiols or thioether analogues of salicylhydroxamic acid could form metallacrowns. In order to explore this idea it was believed that starting with the methoxy hydroxamic acid ligand would be illustrative. Complexes of 2-methoxybenzohydroxamic acid (H2mbha) based metallacrowns of copper (II) are under investigation. These interactions should allow the central copper ion to assume a square planar geometry. Faced with these challenges, the chloro and methyl derivatives were synthesized: 5-chloro-2-methoxybenzohydroxamic acid (H25Cl-mbha) and 5-methyl-2-methoxybenzohydroxamic acid (H25Me-mbha), respectively. The derivatives may help with the solubility issues. In addition, 2:1 adducts of these ligands and copper are also being prepared. The use of the H2mbha chloro and methyl derivatives did not aid in the poor solubility problems. The metallacrown complexes would not dissolve in a range of solvents.
The previous problems with solubility using H2mbha and its derivatives led to the creation of a new ligand, dimethylaminopropionate hydroxamic acid (Dmapha). This β-aminohydroxamic acid ligand was able to create a soluble metallacrown complex. The metallacrown showed great solubility in DMF and DMSO. The aim of this project was to synthesize and characterize metallacrown structures.
Senior Year Research Abstracts – Class of 2009
Michael Trembley ‘09
Advisor: Dr. Emily Dixon, Biochemistry
What role do the 14-3-3 proteins, Bmh1p and Bmh2p, play in the transcriptional regulation of genes
in Saccharomyces cerevisiae under a nutrient-limited environment?
Abstract
The TOR pathway regulates gene expression in response to metabolic demands and nutrient availability (Cardenas et al., 1999). Under nutrient deprivation, transcription factors responsible for the up-regulation of nutrient-limited genes localize to the nucleus. Treatment with rapamycin induces a response similar to starvation in yeast, thus providing a model for studying gene expression under nutrient deprivation. As such, it has been shown that 14-3-3 proteins positively regulate rapamycin-sensitive signaling (Bertram et al. 2002). In addition to this regulation, evidence has also shown that 14-3-3 proteins may be involved in mediating DNA accessibility during replication and transcription by binding to accessible loop-like structures in DNA, called cruciform motifs (Callejo et al., 2002; van Heusden et al. 2006; Zannis-Hadjopoulos et al., 2008). Many gene promoters contain conserved sequences that could potentially form multiple cruciform structures, suggesting a functional role in transcriptional regulation (E. Dixon, unpublished data). Since 14-3-3 proteins have been shown to regulate rapamycin-sensitive signaling and have cruciform-binding activity, the purpose of this study was to elucidate if the 14-3-3 proteins, Bmh1p and Bmh2p, do in fact alter the transcription of genes inyeast upon rapamycin treatment. Through reverse-transcription quantitative polymerase chain reaction (RT-QPCR) experiments, we found that transcription of GAP1, a general amino acid permease, is significantly up regulated in 14-3-3 knockout yeast strains, Δbmh1 & Δbmh2, compared to the wild type strain upon treatment with rapamycin. Further analysis using electromobility shift assays revealed that Bmh1p and Bmh2p were binding to rich palindromic sequences upstream of GAP1, which have the potential to form into cruciform motifs. Lastly, we found that there is genome-wide regulation of genes when 14-3-3 knockout strains are treated with rapamycin. Overall, this study provides evidence that not only do 14-3-3 participate in transcriptional regulation, but the possibility that they are regulating in the presence of cruciform DNA since they are binding to palindromic sequences.
Senior Year Research Abstracts – Class of 2009
Eric Clark ‘09
Bioaccumulation of Cadmium, Copper, and Zinc from Water Uptake in Drissena Polymorpha and Dreissena rostriformis bugensis. Advisors: Dr. Carolyn Johns (Environmental Studies) and Dr. Matthew Skeels (Chemistry)
Abstract:
Both the zebra mussel (Dreissena polymorpha) and the quagga mussel (Dreissena bugensis) have been the subject of numerous studies to determine their potential as biological monitoring organisms. The majority of this research has been focused on D. polymorpha which has been experiencing recent population decline while D. Bugensis is currently experiencing population increase throughout north America. Research is needed to compare the bioaccumulation characteristics of the two species. Three water uptake studies were carried out to determine bioaccumulation patterns between zebra and quagga mussels. Zebra mussels were collected from Coles Creek and quagga mussels were collected from Iroquois Point on the St. Lawrence River during summer and fall 2008. The mussels were divided into 4 treatment levels designated as control, low,medium and high levels of copper, cadmium and zinc. These tri-metal, static exposure studies lasted 14 days with the solutions refreshed by replacement every 48 hours. Mussels were not fed during the exposure period. Bioaccumulation of copper, cadmium and zinc for quagga mussels were observed to increase linearly (R2 = 0.9867-0.9907). Bioaccumulation did not follow a linear model in zebra mussels for any of the metals studied. Copper and zinc appeared to follow a saturation curve in zebra mussels, however, further studies are needed to confirm this. The linear bioaccumulation of copper, cadmium and zinc by quagga mussels in this study suggest a future for Dreissena bugensis as a biological monitoring organism.
Senior Year Research Abstracts – Class of 2009
Nicholas Lovejoy ‘09
Advisor: Dr. Larry French
Identification of Route Specific Impurities Present in 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) Prepared via PIHKAL Synthesis
Abstract
The synthesis of hallucinogenic phenethylamines by clandestine chemistry within the United States and across the world continues to be a major source of these potential drugs of abuse. The synthesis of 4-Bromo-2,5-Dimethoxyphenethylamine (2C-B) is outlined in the book PIHKAL by Alexander Shulgin. This book, and the synthesis outlined therein, has been discovered in clandestine labs across the country. Because of the rising use of phenethylamines, like 2C-B, it is becoming increasingly necessary to create a definitive impurity profile for the drug produced via different synthetic routes. The product, 1, was synthesized via the route described in PIHKAL, first by Knoevenagel condensation of 2,5-dimethoxybenzaldehye with nitromethane, then reduction of the nitrostyrene to the unbrominated phenethylamine, 2,5-dimethoxyphenethylamine (2C-H, 2), was carried out with both LiAlH4 and NaGH4 with Pd/C. So far, attempts to obtain a final brominated products have been unsuccessful. The proposed impurities which may contaminate the final product are electrophilic aromatic substitution products formed during the Knoevenagel condensation when a carbocation is formed, EAS products formed due to partial reduction, and the n-acetyl derivative of 1 formed during the bromination process which takes place in acetic acid. Analysis of the starting materials using GC-MS and 1H NMR proved both the 2,5-dimethobenzaldehye and the nitromethane to be relatively pure. 1H NMR analysis of the nitrostyrene intermediate and 2C-H (2) were found to have the expected molecular structure and were of acceptable purity. Further analysis of the intermediates and analysis of the final product will be carried out when possible.
Senior Year Research Abstracts – Class of 2009
Hai-Yen Nguyen ‘09
Advisor: Dr. Neil Law
Nondestructive Analytical Techniques for the Identification of Pigments and Binders in 17th Century Dutch Oil Paintings for Authentication Purposes
The purpose of this paper is to examine the noninvasive chemical techniques available for the analysis of the materials in 17th century Dutch oil paintings to detect possible anachronisms and consequently forgeries. The materials that the paper will focus on are pigments, specifically for the colors blue and white, and linseed oil as a binder. The analytical methods focused on in this paper are X-ray radiography, neutron activation autoradiography, X-ray fluorescence spectroscopy, Raman and IR spectroscopy, ultraviolet fluorescence, fiber optic reflectance spectroscopy, and particle induced X-ray/gamma ray emission. Using these methods, the paper answers the question of how it would be possible to detect Johannes Vermeer forgeries made by Hans Van Meegeren.
Senior Year Research Abstracts – Class of 2009
Ryan Wolfe ‘09
Advisor: Dr. Lorraine Oldendzenski
Synechococcus from Fayetteville Green Lake: Analysis of ntcA and 165 rDNA Sequences by Depth
Fayetteville Green lake is a meromictic, or permanently stratified lake. This stratification is defined by differences in oxygen and other electron acceptors used in respiration and leads to stratification of the bacterial populations found at the lake’s various depths. Within the water column, the primary genus of cyanobacterium is Synechococcus. The ntcA gene codes for a transcription activator that controls the assimilation of alternative nitrogen sources in ammonium stressed conditions and has been shown to be a good genetic target for differentiating populations of marine Synechococcus. My study characterizes the microdiversity of Synechococcus populations at different depths by using the 16s rRNA gene in conjunction with ntcA. Phylogenetic trees incorporating both genetic targets will be compared to characterize Synechococcus substrains. To accomplish this, Synechococcus cultures from the various depths were grown on SN media and sequenced for both 16s rRNA and ntcA. By culturing and analyzing the ntcA diversity of the cyanobacteria, we can characterize the microdiversity of Synechococcus strains at varying water deptsh in the meromictic environment and track changes in this diversity with regard to available nitrogen sources such as ammonium or nitrate ions.