Previously, members of the Parker group developed a "reverse polarity" method for the synthesis of aryl C-glycals. This exercise focused on the synthesis of a protected angolosamine glycal on which the "reverse polarity" approach could be worked on to synthesize kidamycin, an anti-tumor drug.
Two different synthetic routes were attempted starting with commercially available 3,4,6-tri-O-acetyl D-glucal, both aimed at the achieving a stereo-specific urethane at the C-3 position of the glycal. As reported in previous literature, the key urethane intermediate was obtained in poor yield. To optimize this step, various conditions were investigated to obtain the desired product. Thin layer chromatography was used to monitor the progress of all the reactions, purification of intermediates by flash chromatography, and characterization of products was done by 1H-NMR and infrared spectroscopy.
An approach to synthesizing the urethane that was done by a lab member used an isocyante in a rearrangement type mechanism. The presence of several by-products led to the development of a new synthetic route involving trichloroacetonitrile.

Diiodobutadiyne (1) is a diacetylene made of only carbon and iodine that can form polydiiododiacetylene (2) by ordered solid-state polymerization. This unique polymer is predicted to have optical and electrical properties for material science applications. The goal of this project was to find new and efficient ways of making the polymer in thin films. In our research, the polymer was made by using a bisnitirile oxalamide (3) as a cocrystallizing "host" molecule that directs the diiodobutadiyne monomers through halogen bonding to crystallize in the proper arrangement for polymerization. We prepared methanol solutions with a range of cosolvents, including hexane, toluene, and 2-butanone. After depositing these solutions on silicon wafer substrates, we have compared the morphology of the thin films resulting from the different solutions, using both optical and scanning electron microscopy. This research has been funded by the National Science Foundation.

ANALYSIS OF JETS USING TWO AND THREE PARTICLE CORRELATIONS
Judith Lattimer, Brendeis University; N. N. Ajitanand, Roy Lacey, Chemistry Department,
Stony Brook University

At RHIC, gold nuclei are collided at extremely high energies, creating a hot, dense overlap zone called the quark-gluon plasma, or QGP. In the QGP it is theorized that the energy density is high enough that the individual quarks and gluons of which the protons and neutrons are comprised can become unconfined and move freely. The almond shaped overlap zone gives rise to an anisotropic pressure gradient which is governed by a harmonic distribution. The second harmonic coefficient, v2, is used to measure the anisotropic flow of the collisions. In addition to the flow, there are also a few particles that collide head-on in each collision. These are called jets because the particles bounce off one another and leave a trail of particles following in either direction. Because these jets travel through the plasma, it is possible to learn more about the nature of the plasma by studying the jets. My project this summer involved using models to develop tools for studying jets. I used a program written by Ajit which mathematically modeled the results of a Au-Au collision at RHIC. This was a 2-source model, which means that it created particles of two varieties - those that would result from flow and those that would result from jets. To analyze this information, I used two particle and three particle correlations. Particle correlations are done by selecting one particle with a pt between 2.5 and 4 GeV and another particle with a pt between 1 and 2.5 GeV from the same event, and finding the difference in their phi angles, delta phi. For two particle correlations, pair distributions from the same event are summed and normalized. Then delta phi distributions from mixed events are summed and normalized. Then the same event distributions are divided by the mixed event distributions. The division by mixed events is done to remove any patterns which are the result of the detector acceptance and leave only the physics correlations. Three particle correlations are done by correlating a high-pt particle with 2 low-pt particles and plotting the delta phi's on a
3-dimensional surface. Under certain conditions, the flow particles can be effectively zeroed out, leaving only the jet patterns. I used particle correlations to find those conditions and test them. This is a useful technique for studying actual data because it shows how to separate out the harmonic part of the data and leave only jets to be studied. This work was supported by a grant from the National Science Foundation.

FabI: THE "KEY" TO COMBATING STAPHYLOCOCCUS AUREUS
Karen McGuigan; University of Scranton; Carl Machutta, Chris Stratton, Patty Cheung and Peter Tonge; Chemistry Department; Stony Brook University

Staphylococcus aureus is one of the principle causes of hospital-acquired infections which claim about 20,000 lives each year. This bacterium lives on the surface of the skin and only becomes harmful once it penetrates into the bloodstream. About 30% of healthy people carry Staphylococcus aureus, but those taking high amounts of antibiotics or with weakened immune systems are the most susceptible to infection. (Peacock, S.J., et. al.) Treatment is available with methicillin, vancomycin, rifampin, and other drugs, but antibiotics are futile against drug-resistant strains of the bacteria. In order to inhibit these strains, research has been directed to novel targets in the fatty acid synthesis of Staphylococcus aureus that require the NADH-dependent reduction of enoyl-ACP to acyl-ACP. FabI is the enzyme that catalyzes this reaction. The purpose of this project is to over-express and purify FabI from Staphylococcus aureus. Having isolated the protein, its kinetic catalytic properties will be determined. FabI can also be tested against various inhibitors to assess prospective treatment options for infection.
FabI was expressed in bacteria from several cell lines that were transformed and grown under various conditions. After inducing the protein, its expression was verified with SDS-PAGE. In order to purify the protein, the cells were lysed and cell-free lysate was passed through a His-tag or Ni-NTA affinity column. After washing with imidazole to wash nonspecific proteins off of the column, the fractions passed through G25 gel-filtration chromatography to remove the imidazole. The use of a centricon to concentrate protein in a centrifuge increased the concentration of the final protein. This was then scanned to reveal an absorbance maximum at 280 nm. An assay with substrate revealed that the protein was active. Kinetic studies were then run using C12CoA substrate. The yield and purity of this protein will be shown, as well as the Km and kcat of FabI from Staphylococcus aureus. This research was made possible by funding from the National Science Foundation in the Research Experiences for Undergraduates program.

Peacock, S.J. et. al. (2001). What determines nasal carriage of Staphylococcus aureus? Trends Microbiol. 9, 605-610.

Hydrogenase enzymes catalyze the interconversion of H2 to or from 2H+ and 2e-. The pair of electrons can be funneled to or siphoned off various substrates for redox chemistry. While such a simple reaction can easily be overlooked, a breakthrough in hydrogenase chemistry could revolutionize fuel cell technology and lead to a cheap, efficient, and environmentally-friendly energy source. In this study, a simple ligand-metal center model was used in attempts to mimic the structure and reactivity of the active sites of FeFe and Fe-S-cluster-free hydrogenases. Two novel organic compounds, dilithium 4-methylbenzyl-bis(2-thiolatonapthylmethyl)amine [Li2ChxNS2] and dilithium cyclohexyl-bis(2-thiolatobenzyl)amine [Li2NaphNS2], were synthesized and characterized. The crystal structure of Li2ChxNS2 was determined, and the reaction of Li2ChxNS2 with iron(II) tetracarbonyldibromide was monitored by Fourier-transform infrared spectroscopy. The spectral data collected from the reaction mixture after 27 hours showed peaks at 1920, 1974, and 2036 cm-1 with intensities in a 1:5:5 ratio, respectively. This signature is somewhat similar to the IR spectrum of the removable cofactor of H2-forming methylenetetramethanopterin dehydrogenase (Hmd), an Fe-S-cluster-free hydrogenase, which has peaks at 1972 and 2031 cm-1 with intensities in a 1:1 ratio that have been attributed to two CO molecules arranged in a cis fashion around an iron center. From this observation, it is reasonable to suppose that the structure of the synthesized iron complex is similar to that of the Hmd cofactor. Attempts are underway to obtain the crystal structure of the complex. This work was funded by an NSF-REU grant.

A SIMPLE ACID-BASE PAIR AS A REPLACEMENT FOR NATURAL DNA BASE PAIR
Onyi Wong, University of Massachusetts at Amherst; Yongliang Yang and Dale Drueckhammer, Department of Chemistry, Stony Brook University

Some modified nucleosides have anticancer and antiviral properties, an X-DNA duplex containing a novel synthetic acid-base pair was made to study the effect of this base pair on duplex stability. The DNA base pairs dA-dT and dG-dC is one of the most amazing designs of nature. The helical structure of DNA is a molecular assembly that consist a stacked set of four aromatic bases, held in place by a phosphodiester repeating scaffold. Many simple modifications such as replacing the methyl group of thymine with fluorine, or the oxygen of guanine with sulfur can result important biological activities. To accomplish this, computer modeling program Spartan was employed to design the analog of acid-base pair with the ability to stack well with other natural bases that stabilize the structure of DNA. We proposed a design of a X-DNA base pair with a general acid/base hydrogen bonding couple. Pyrrolo [3,2-b:4,5-b'] dipyridine (PDP), a base, and p-benzoic acid (p-BZ), and acid, that could potentially used to stabilize DNA with the potential anticancer and antiviral applications.

DEVELOPMENT OF BENZIMIDAZOLE BASED FTSZ INHIBITORS
Adam Wood, Hartwick College; Seung-Yub Lee, Kan Ma, Institute of Chemical Biology & Drug Discovery at Stony Brook University; Qing Huang, Department of Chemistry, Stony Brook University; and Iwao Ojima, Institute of Chemical Biology & Drug Discovery at Stony Brook University and Department of Chemistry, Stony Brook University

Due to the emergence of multidrug-resistance tuberculosis (MDR-TB) and TB's role as a major opportunistic pathogen in patients with HIV/AIDS, the need for new chemotherapeutics that will be effective against both sensitive and MDR-TB has become prominent. The current area of investigation for the development of new novel drugs against TB is bacterial cell division. FtsZ, a homologue of the mammalian cytoskeletal protein tubulin, polymerizes into filaments that produce the Z-ring on the inner membrane at mid cell which with the aid of other cell division proteins contracts resulting in septation. Therefore, FtsZ has become the biological target for the development of new antimicrobial drugs because of its central role in bacterial cell division. The exploration of compounds that were known to affect the assembly of the FtsZ homolog tubulin into microtubules was used as the starting point for discovering inhibitors of FtsZ polymerization or depolymerization. From the class of 2-alkoxycarbonylaminopyridine analogues, SRI-3072 was determined to be the most active in inhibiting the in vitro polymerization and GTP hydrolysis of TB; therefore, serving as the initial target of examination for antitubercular activity. Although the 2-alkoxycarbonylaminopyridines have been proven to be effective antitubercular drugs against the current strands of MDR-TB, the synthesis of benzimidazole compounds is the target for a more powerful antitubercular drug. The idea to investigate benzimidazole compounds comes from the fact that albendazole, thiabendazole, and 2-methylbenzimidazole are known inhibitors of tubulin polymerization via competitive binding at the same site as colchicine. Importantly, studies demonstrate that thiabendazole and 2-methylbenzimidazole caused cell elongation in
E. coli and cyanobacteria, a phenotypic response identical to that elicited by disruption of the FtsZ gene in these organisms. Accordingly, a series of new benzimidazoles were designed and ethyl [7-acetylamino-2-(1H-imidazol-4-yl)-1H-benzoimidazol-5-yl]carbamate was synthesized by solution method. This forms the basis for a library synthesis using combinatorial chemistry. In progress, the synthetic routes, thus designed, are being applied to solid-phase synthesis to produce a library of benzimidazole derivatives. To determine the inhibitory effect of the benzimidazole compounds on FtsZ, a polymerization and GTPase assay will be performed on the library. The polymerization assay will follow the progress of FtsZ polymerization by using light scattering on a fluorimeter. For the GTPase assay, the phosphate released from GTP hydrolysis will be coupled to the nucleoside phosphorylase reaction using 7-methylguanosine as a fluorescent substrate for the nucleoside phosphorylase reaction. The hydrolysis of 7-methylguanosine produces 7-methylguanine, which has a lower quantum yield; therefore, by monitoring the loss of fluorescence of 7-methylguanosine the rate of hydrolysis can be determined. This work was funded by the National Science Foundation Research Experience for Undergraduates (NSF-REU) 2005 Summer Research Grant, New York State Office of Science, Technology and Academic Research (NYSTAR), and the National Institute of Allergy and Infectious Diseases.

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