The ability to predict the structure of the surface loops of proteins is important because this is currently the biggest obstacle to determining the three-dimensional structure of the entire protein. The antibody H3 loop was chosen for study because of its potential applications such as cancer recognition drugs in addition to the general protein structure applications. Molecular dynamics simulations were performed on various antibody fragments with known structures. The H3 loop area of interest, and the protein region within 10 A of the loop was included in the calculations. Simulations were first run at 1000K to randomize the structure of the loop, whereupon these randomized structures were run at 300K to confirm the structure would not change in the absence of a force field. The initial structure was also run at 300K as a control. The randomized structure will be put through molecular dynamics simulations using force fields in an attempt to regain the original loop structure. In order to decrease the preparation time for the simulations, a program was developed to find the H3 loop in the PDB file and write a new file including only the loop and the desired region around it. This project was funded by grant #CHE-0139256 from the National Science Foundation.

Novel Oleandomycin Derivatives.
Dominique Fontanilla, Carleton College; Peng Wang, and Kathy Parker, Department of Chemistry, Stony Brook University.

The macrolide antibiotic, oleandomycin, is a source of intrigue in both medicine and organic synthesis. As an antibiotic, oleandomycin proves to be vastly effective against Gram-positive bacteria and mycoplasma while also maintaining low toxicity levels. Given its structural, stereochemical, and heterofunctional complexities, oleandomycin also provides a realm of organic synthesis challenges. Nevertheless, a derivative of compound 2 was previously found to show antibiotic activity. Consequently, the synthesis of aglycone 3 will aid ongoing studies to discover more derivatives with potential antibiotic activity. Thus, this investigation concerns the 5-step removal of both D-desosamine and L-oleandrose from enone 2 in an attempt to produce aglycone 3. The first step of this process reduces the carbon-8 epoxide of oleandomycin to furnish enone 2. Then the D-desosamine appendage is acetylated followed by a Cope elimination, which removes the dimethyl amine substituent. After removing the acetate with potassium carbonate, rhodium (III) chloride initiates double bond migration at carbon-8 and cleaves both sugars in a controlled fashion. Supporting evidence was elucidated by NMR spectroscopy, thin layer chromatography, and infrared spectroscopy.

Funding for this research, CHE-0139256, was granted by NSF.

Investigation of the Dependence of Integrin-mediated Adhesion to Fertilin ß on Divalent Metal Cations.
Ju Hoan Joh, Haishan Li, Gibby Chen and Nicole S. Sampson, Department of Chemistry, Stony Brook University.

Fertilin ß is a widely studied ADAM protein (A Disintegrin and Metalloprotease) that is important for sperm-egg binding and fusion at the egg plasma membrane. Fertilin ß is located in the extracellular membrane surface of the sperm. The small peptide sequences (ECD) of the disintegrin domain of fertilin ß have been found to inhibit sperm-egg binding. To test the efficacy of polyvalent peptide mimics of fertilin ß being made in our laboratory, a cell-culture based adhesion assay was developed. An in vitro fertilization assay has limited throughput due to the limited number of eggs and sperm isolable. Fertilin ß was used as ligands for the a6ß1 integrin expressed on the surface of F9 (embryonal carcinoma) cells to mimic the sperm-egg fertilin ß-a6ß1 integrin interaction during fertilization. The production of a large quantity of recombinant GST-fertilin ß protein, required for cell-culture based adhesion, was achieved by over expression in E.Coli. The protein was purified by affinity (glutathione sepharose) chromatography. Using F9 cells, the affinities between the cells and adhesion proteins: GST (negative control), GST-fertilin ß and polylysine (positive control), were determined with different concentrations of protein and different types and concentrations of divalent cations. By studying the ADAM protein, fertilin ß, a better understanding of fertilization and infertility will be achieved, allowing the design of new contraceptives. This project was supported by the Research Experience for Undergraduate Program sponsored by the National Science Foundation (CHE-0139256), and by the National Institutes of Health.

Two Routes for Synthesizing Triynes.
Gary David Kasper, Rutgers University; Peihua Liu, and Nancy S. Goroff, Department of Chemistry, Stony Brook University.

The goal of this project is to compare two different routes to synthesize triynes from diynyl ketones. We converted different acetylenes into their corresponding alcohols that were then oxidized to their corresponding ketones. Most of the difficulty in preparing the ketone was found during the purification of the alcohol. The resulting ketone can be further reacted to produce either a monobromomethylene product via the Takai reaction, or a dibromomethylene product through a Wittig reaction. Both bromomethylene products were reacted with strong base to form a carbenoid species, which undergoes the Fritsch-Buttenberg-Wiechell (FBW) rearrangement forming a triyne. With these experiments we aim to find the bromomethylene product which produces the highest yields and purest triyne product. This work was supported by the REU program funded by NSF award number CHE-0139256.

Synthesis of a Cooperative Glucose Sensor.
Jessica Leber, Columbia University; and Dale G. Drueckhammer; Department of Chemistry, Stony Brook University.

Arylboronic acids exhibit decreased fluorescence intensity upon bonding with sugars. The goal of this project is to synthesize a fluorescence based boronic acid receptor specific to the D-pyranose form of glucose. The receptor was designed to exhibit cooperativity, such that, though the binding of the first glucose to the receptor is not favored, the complex formed is in an ideal conformation such that the complex formation of 3 is favored. The receptor was designed previously using the molecular modeling program CAVEAT.

The synthesis of 1 was undertaken starting with 2-amino 5-iodobenzoic acid. The amino group was converted to a bromide with the Sandmeyer reaction. The carboxylic acid was successfully reduced to the alcohol, activated as a leaving group with methanesulfonyl chloride, and displaced by an azide. Lithium-halogen exchange at the iodide position with immediate reaction with triisopropyl borate and reaction with pinacol formed a protected arylboronic acid. Future work will include coupling the above synthesized molecule with p-ethynyl phenyl boronic acid, reduction of the azide to an amine, coupling with phthaloyl chloride, followed by deprotection of the boronic acids. Once synthesized, binding of the receptor to glucose to form the complex 3 will be confirmed by NMR. Fluorescence studies will be performed to determine the binding constant for glucose and the magnitude of the fluorescence signal caused by the complex formation to assess the viability of 1 as a biological glucose sensor. NSF Grant CHE-013925 and NY State Department of Health Grant C017908 supported this research.

An approach to the preparation of a polyacetylene.
Kyle Levy, Spelman College; and the Fowler/ Lauher Research Group, Department of Chemistry, Stony Brook University.

The goal of this research project is the topochemical polymerization of an acetylene. An acetylene is the simplest alkyne C2H2; a polyacetylene is simply an acetylene monomer that is polymerized by a one of many possible catalyst and propogated until the desired chain length is formed. These polymers are important because of their metallic and conductive properties. There was a four- step synthesis designed to generate my final goal. This study was supported by the NSF-REU program of State University of New York at Stony Brook award number CHE-0139256.

Complexation of DNA with Single Walled Carbon Nanotubes.
Sara Dawn Patt, Mills College; Sarbajit Banerjee, and Stanislaus S. Wong, Department of Chemistry, Stony Brook University, and Brookhaven National Laboratory.

This study tested the possibility of complexation of single walled carbon nanotubes with plasmid DNA. Perfection of this technique could lead to the possibility of self-assembling structures, using this DNA scaffold. A multi-step reaction was required to functionalize the single walled carbon nanotubes (SWNTs). SWNTs were air-oxidized to purify them of metal catalyst impurities. They were reacted with an amino acid derivative, and an aldehyde derivative, in N,N-dimethylformamide (DMF), as previously described in published procedures. After workup, the product was then treated with a methyl halide and reacted with the plasmid DNA. The final product was analyzed by atomic force microscopy (AFM) and transmission electron microscopy (TEM). As of now, results from AFM have been inconclusive. TEM measurements show promising results. The length of the suspected DNA/SWNT complex is 1.4 µm. This is slightly shorter than expected, but may be due to an intramolecular attraction with the nanotubes. The width of the complex ranges from 180 nm to 320 nm. Again, these slightly smaller than expected diameters may be due to a similar interaction, as described above. These TEM measurements, which are near expected measurements, indicate the possibility that the DNA/SWNT complex did form. Further investigation needs to be carried out in order to ensure that a DNA/SWNT complex is being imaged, rather than an intermediate product. Once a final conclusion is reached, further study may be done into the self-assembling properties of this complex, using the DNA scaffold. This study was supported by a research experience for undergraduates grant from the National Science Foundation (CHE-0139256), and by startup grants from SUNY Stony Brook and Brookhaven National Laboratory.

Solid state NMR and X-ray powder diffraction studies of Vanadyl Phosphate Dihydrate VOPO4·2H2O as a possible cathode material for rechargeable lithium batteries.
Jorge Alex Pavon, Rutgers University; Nicolas Dupré, Younkee Paik and Clare P. Grey, Department of Chemistry, Stony Brook University.

Lithium rechargeable batteries have generated considerable recent interest because they are excellent power sources for portable devices such as cell phones and laptops. Vanadyl phosphate dihydrate VOPO4·2H2O, has the potential to become a cathode material for these batteries. A desirable cathode material should be inexpensive, have good reversibility for lithium insertion/extraction, and high voltage. VOPO4·2H2O has those characteristics. The two water molecules in VOPO4·2H2O create an interlayer space of about 7.41 Å making lithium diffusion a facile process. In the anhydrous form VOPO4, the interlayer space is 4.17 Å, which leads to kinetic problems for lithium insertion. VOPO4·2H2O undergoes a decrease in the amount of intercalated/deintercalated lithium after being cycled multiple times, due to the interlayer oxidation of water molecules, resulting in the collapse of the layers. In order to find out the mechanism of this oxidation our strategy was to synthesize the deuterated material under different conditions and study samples equilibrated at different stages of the electrochemical cycling via X-ray powder diffraction and solid state NMR. We discovered that cells made with deuterated samples sustained a longer lifetime than the hydrated ones, probably because of a shorter and stronger O-D bond. This hypothesis is supported by variable X-ray diffraction temperature experiments. Moreover, no water oxidation is seen for an electrochemical cycling between 2.8 and 4.3 Volts, and only one water molecule is found to be oxidized when the upper limit is raised up to 4.5 volts for an oxidation start. For the 2D experiments no signal was detected for any of the hydrated samples. The only signal obtained was for VOPO4·D2O, which is synthesized by partial dehydration of VOPO4·2D2O under vacuum for several hours. We speculate that the first water molecule is very mobile, while the other molecule is static and only undergoes rocking in place. We are continuing to study VOPO4·D2O hoping to obtain information from the NMR experiments (if a signal is detected.) I would like to thank everyone from Professor Clare Grey's group for their help and the organizations that funded this project NSF 54558-1023478, DMR award #007061 and the NSF-REU grant #CHE-0139256.

Synthesis and Testing of a Single-Electron Molecular Computer Component.
Natalie St. Fleur, Manhattanville College; Qun Zhao and Andreas Mayr, Department of Chemistry, Stony Brook University.

The research conducted aims to test molecules that may be used as transistor components in nano-electrical computers that have a design based on the principles of single-electronics. For single-electronics applications, molecules must have the ability to store and conduct electrons, and act as a bridge between electrodes which may be separated up to 10nm. In one of the proposed molecular single-electron transistors, pyromellitimide is used as an electron acceptor. In order to test the ability of the pyromellitimide unit to accept an electron from a remote site, molecule 1 was designed. Molecule 1 contains a photo-physically active tungsten center. This tungsten component exhibits luminescence which may be quenched by a nearby electron-acceptor.

Molecule 1 was synthesized by a sequence of palladium-catalyzed alkynyl-iodoarene coupling reactions. The final product was purified by chromatography and characterized by NMR and IR spectroscopy. To test if the oligo(phenylene-ethynylene)-pyromellitimide unit of molecule 1 conducts and accepts an electron readily, molecule 1 and the separate tungsten complex were placed under UV light to test for luminescence. It was found that molecule 1 does not luminesce while the isolated tungsten complex does. Evidently, the luminescence of the tungsten center in 1 is readily quenched by the pyromellitimide unit through electron transfer across the oligo (phenylene-ethynylene) bridge. These results substantiate that the pyromellitimide unit is promising as an electron acceptor in single-electronics applications.

Rhodium-Catalyzed Formation of Unsymmetrical 5-7-5 Ring Systems.
Michael P. Zacharias, John Carroll University; Victor Vassar, and Iwao Ojima, Department of Chemistry, Stony Brook University.

In recent years metal-catalyzed carbocyclizations have played an important role in organic syntheses. Through the use of a metal catalyst (i.e. Rh) acyclic molecules can be converted into polycyclic ring systems. Polycyclic ring systems are found in many interesting naturally occurring molecules, which exhibit the potential to be of interest for medicinal purposes. One particular ring system, undergoing study, are unsymmetrical 5-7-5 ring systems. The tricyclic molecules are proposed to be synthesized from different unsymmetrical enediynes (1-3). Previously in our laboratories enediynes have been shown to afford the 5-7-5 membered ring system through a novel carbonylative tricyclization (CO-CaT reaction). A key focus of this study is to make substrates with various combinations of esters and amines. The amines will be protected with either a t-butoxy carbonyl or benzyl group. The enediynes, once synthesized, are subjected to the CO-CaT reaction to afford the unsymmetrical 5-7-5 membered ring structures (4-6) via cascade tricyclization. Preliminary results of the catalytic reaction with substrate 2 indicate that cyclization had taken place forming the unsymmetrical tricyclic 5-7-5 compound 5. Currently studies are being conducted to test the cyclizations of substrates 1 and 3. In the future the amine protecting groups will be removed which will allow the amine group to act as a handle for functionalization. This study was supported by the NSF Grant # CHE-0139256.

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