2000 Research Abstracts
JUNE 30, 2000
Green, Charalene. 2000. Synthesis of napthalimides. Baylor University. Dr. Robert Kane (Biochemistry-Department of Drug Discovery).
Our interest in napthalimide compounds is sparked by the fact that they have cancer-fighting abilities and can also cross-link proteins. The napthalimides work as DNA intercalators, which means that they interfere with DNA replication. The napthalimides therefore cause fatal mutations in the cancer cells, stopping the growth of new cells and the spread of the cancer. Dr. Kane's research group is working to create napthalimide compounds that are the best intercalators. During their research it was discovered that nathalimides also cross-linked proteins when exposed to certain wavelengths of light. This information may lead to potentially useful techniques to repair worn cartilage and other tissues. My project was to create a napthalimide molecule with an ethane thiolate substituent (CH3CH2S). During this two-step synthesis, I used many techniques such as: high-pressure liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and spectroscopy. HPLC is used to test the compound's purity. NMR is used to confirm the arrangement of the atoms in the molecule. Spectroscopy is used to find the concentration of the compound that absorbs the most light, which is useful when testing the protein cross-linking ability of the compound. When the molecule was created, I tested its cytotoxicity (cell toxicity level) and protein cross-linking ability using these techniques. This compound and the test results will be compared to other drugs to produce the most efficient and least harmful chemotherapy drugs.
One of the most exciting areas of biochemistry research is the synthesis of potential cancer fighting agents. One such compound is combretastatin A-4 (CA-4), a prodrug developed by the Pettit group at Arizona State University to inhibit tubulin polymerization. During my stay at Baylor University, I have been carrying out research in the Pinney group, which is focused on the development of new molecular templates which mimic CA-4 in an effort to create effective prodrugs to treat cancer. My research focused on creating a novel benzo[b]thiophene molecule utilizing a halogen-metal exchange reaction as a key synthetic step. Throughout this synthesis effort, thin-layer chromatography, gas chromatography-mass spectrometry, and nuclear magnetic resonance were used to confirm the purity and structure of each compound created. As of the publication of this abstract, I have been unable to confirm the synthesis of my final target molecule, however, evidence for synthetic intermediates has been obtained. Once the target molecule can be confirmed and purified, it will be sent to the Pettit group for further biological testing.
One current area of interest in the field of cancer-fighting drugs involves the development of anti-angiogenesis and vascular targeting agents. The goal of anti-angiogenesis is to inhibit the further growth of blood vessels that supply the tumor with oxygen and nutrients. The goal of vascular targeting is to destroy the existing blood vessels that support the tumor. Without these blood vessels, the cancer cells will die. One of these new drugs that is undergoing current clinical trials is called Combretastatin A-4 (CA-4). CA-4 has been shown to have both vascular targeting and anti-angiogenesis properties; that is, it prevents the new formation of blood vessels that could support the tumor and it also targets the existing blood vessels of the tumor. CA-4 has been shown to selectively target only cancer cells while leaving healthy cells alone. The primary goal of this experiment was to synthetically modify the ethylene bridge of CA-4 and to prepare new, more highly functionalized analogs which may display enhanced cytotoxicity profiles against cancer cells. The new target molecule that we designed may be synthetically prepared by joining two key synthetic intermediates through a McMurry coupling reaction. When finally completed, the molecule will be evaluated biologically.
Chavez, Joy. 2000. Flow rate of vacuum pumps. Baylor University. Dr. Kenneth Park (Department of Physics).
Surface physics studies in detail the surface of different substances. By analyzing
the surfaces, mechanics can develop better lubricants, chemists can understand
bonding better, and physicists can satisfy their curiosity about this area of
the world. Because surface scientists work at the atomic level, the samples
they analyze must be free from the slightest contamination. Therefore, we use
ultra high vacuum (UHV) chambers in the Laboratory for Surface Analysis and
Modification. Different types of vacuum pumps create UHV. I studied and tested
how quickly the turbomolecular pump "sucked" different gases out of
the chamber. I started timing when I started the pump and checked the pressure
every few seconds. I charted this progress for two hours and then compared the
flow rate of the different gases. This comparison showed me the differences
between natural air, Helium, and Argon. Helium was the slowest because its small
atom has a small momentum and is harder to pull out. Argon on the other hand
was the fastest since it was so much bigger. This research helps consumers determine
the efficiency of the pump they want to buy. This efficiency is a major part
of how much the pump will cost and is a main feature of the pump.
Using the power of capillary gas chromatography (GC), we have developed an experiment to simultaneously analyze the results of multiple reactions. Our experiment consists of two parts. Part A involved reacting an alcohol mixture (MeOH, EtOH, i-PrOH, t-BuOH) with distilled diketene and resulted in four acetoacetate esters. These keto esters were then reacted with sodium borohydride to be converted into alcohols. The alcohols were swept through the GC and the results showed a racemic mixture of each alcohol. Part-B used yeast to effect a reduction of the keto esters to non-racemic alcohols. After the alcohols were swept through the GC, the chromatogram showed an optical purity of 86% for methyl, 79% for ethyl, 65% for iso-propyl, and 71% for tert-butyl. The research completed was highly successful. The chromatograms we gained from the experiment were beyond our expectations. This experiment has not only aided me in learning organic chemistry, but might be used in the future in an advanced organic chemistry lab.
Hejl, Laura and Chad Rose. 2000. Relationships Between Songbirds, Vegetation, and Disturbance in State Parks. Baylor University. Professor Heidi Marcum (Department of Environmental Science).
Complex interactions exist between animals and their habitats. Impacts made
by increasing human recreational activities and disturbance affect these relationships.
The goal of this project was to determine how human disturbances and vegetation
influenced the richness, density, and abundance of avian species in Bastrop
State Park in 1998 and 1999. To determine whether bird presence in an area depended
on the vegetation and/or degree of human disturbance, we analyzed data from
the park. Principal component analyses were conducted on the disturbances and
vegetation variables to calculate the factors that caused the most variance
in the data. We then conducted regression analyses to decide which habitat and
disturbance variables had the greatest effect on various bird species. Results
of this project show that the number of bird species (39) was the same for both
years at Bastrop. However, the avian abundance and richness dropped from 1998
to 1999. The regression and principal component analyses showed that for vegetation,
the most important characteristics over the two years for bird species were
small coniferous trees, tree canopy cover, and deciduous trees. Hikers were
the major source of disturbance at Bastrop State Park. The results of this project
help provide information about avian habitat and responses to various levels
of recreation and disturbance. These data help humans know how to properly manage
their environment in order to protect avian species.
To this date, gasoline has been the most economical and efficient fuel source; however, with diminishing oil reserves and rising oil prices, the use of alternative fuels becomes more and more feasible. The most promising of these is ethanol, particularly bioethanol, ethanol produced from biomass. In this process, biomass is pretreated in order to break down complex sugars into much simpler sugars so that bacteria can metabolize and, thereby, produce ethanol. By pretreating the organic matter, a large portion of the previously undigestable sugars become digestable which in turn yields a larger ethanol to biomass ratio. Unfortunately, one result of pretreatment is the formation of toxic compounds that inhibit the fermentation process of yeast. My work examined the relative toxicities of various chemicals used for pretreatment. These included: sulfuric acid, carbonic acid, and water; however, due to the extensive study of sulfuric acid pretreatment, we confined our work to the study of carbonic acid and water. The first experiment was to quantify the amount of acetate present after aspen wood underwent hydrolysis in a sand bath at 190( C for 18-25 minutes using both carbonic acid and water. The second experiment was to study the break down of xylan into small oligomers to determine how complete the hydrolysis was under various temperatures and time. Finally, we examined the hydrolysis of aspen wood using both water and carbonic acid to determine the pH of the hydrolyzate, which may be an indicator of toxicity. The results of these experiments will help decrease the toxicity of the hydrolyzate and increase the efficiency of fermentation.