Levamisole, a powerful antihelmintic for lung and intestinal worms in both humans and animals is thought to possess immunostimulatory effects specifically beneficial to patients with colorectal cancer. It has been hypothesized that levamisole can be derivatized to increase its affinity for the binding pocket of thymidylate synthase and thus be a more active treatment against the DNA repair mechanism of harmful cancer cells. A synthetic route toward the synthesis of para-nitrolevamisole has been explored and further efforts to reduce the nitro group via two very different mechanisms to form the amino-derivative of levamisole have been conducted, and the results from the syntheses will be reported.
The Department of Chemistry and Biochemistry believes that teaching students to be effective chemists requires exposure to real research. As sophomores, our students are introduced to faculty research and given the opportunity to pursue any project they wish. Students work directly with faculty on research projects and are trusted to carry out high-level work. Students have ample opportunities to present their research at regional and national conferences, and some have even had their work published. Explore the projects listed below for a sampling of department research projects.
Polymers used for food and beverage packaging often must have very good gas-barrier properties. Since the permeability of O2 gas through common feedstock materials such as poly(ethylene terephthalate), PET, is affected by typical stretch-blow molding processes for bottle fabrication, we are developing an optical method for determining oxygen transport through intact drink bottles. The sensor material, tris(4,7-diphenyl-1,10-phenanthroline) ruthenium(II) encapsulated in silicone rubber, is applied as a thick film to the inner surface of a transparent bottle and excited using a pulsed laser operating at blue or UV wavelengths. Red fluorescence from the sensor salt is resolved on the microsecond time scale and the fitted decay rate is a function of quenching by oxygen present. Our present limit of detection for O2 is below 1000 ppmv. Fluorescence-based sensors may be applied to rapid testing of permeability through actual containers and will enable measurements of oxygen dissolved within novel micro-layered polymers being developed for advanced packaging applications.
Improved techniques in analytical chemistry have enabled the detection of trace levels of chemicals in the environment, especially synthetic compounds. When released into the environment, synthetic compounds such as pharmaceuticals and pesticides have the ability to make their way into rivers, drinking water, and even the human body. Many of these substances can bioaccumulate within an organism, sometimes having a toxic result. Once in the environment, many chemicals degrade or biotransform, but some such as DDT are persistent. The significance of trace levels of a chemical must be evaluated in order to assess its risk to humans and other organisms. Benzotriazole (BT) is an organic compound with a variety of applications in industrial and household settings. This study seeks to explore one possible source of trace levels of BT, the automatic dishwasher. BT is commonly added to dishwasher detergent as an aid in silver protection. The question investigated here is how much BT a person may ingest if the chemical remains on a dish instead of being carried away by the rinse water. Three dishwasher detergents were analyzed using High-Performance Liquid Chromatography (HPLC) to determine the amount of possible BT remaining on a dish after cleaning.
Long-wavelength, Photo-controllable Sources of Nitric Oxide Based on the Diazeniumdiolate Functional Group
Nitric Oxide, known to cause cell apoptosis, would be a useful agent to combat tumor cells in the body. Diazeniumdiolates, when dissolved in a solution at physiological condition, will release Nitric Oxide, NO. A photo-controllable group that absorbs in the visible red region is a good candidate for a protecting group to the molecule, due to red light being able to penetrate the skin much deeper than UV, with no damage to the tissues. A method of therapeutic application involves the attachment of the diazeniumdiolate complex with photo-controllable group to a dendrimer macromolecule. The dendrimer would automatically accumulate by the tumor cells due to the Enhanced Permeation and Retention, or EPR, phenomena, which is accumulation of macromolocules in tumor tissue due to little lymphatic drainage. Possible photo-controllable groups include benzophenoxazine analogues of the fluorescent dye, Nile Red. Synthesis and purification techniques are currently in progress on several of these analogues.
Metal ions purportedly bind to and stabilize unique DNA structures such as loops, bulges, hairpins, and base pair mismatches. Spectroscopic techniques are useful for the study of metal ion binding. In our work, the biologically relevant metal ion magnesium (II) is substituted by luminescent lanthanide ions. Direct-excitation europium (III) ion luminescence spectroscopy is used to study europium (III) ion binding to various DNA hairpin loops. New 7Fo to 5Do excitation peaks are observed for sequences containing thymines including 5’-GCG CTT TGC GC-3’. Excitation peak position and intensity is dependent on the closing base pair but not the stem sequence. Other more highly structured loops including GNRA tetraloops do not strongly bind europium (III). Time resolved luminescence spectroscopy experiments show that the europium (III) ion looses at least one water ligand upon binding to the thymidine containing hairpin loops. Thermal melting experiments confirm that the hairpin loops form in the presence of an equivalent (20 micromolar) of europium (III) with very little change in melting temperature.
For a number of years, students taking organic chemistry here at Ohio Northern University have routinely completed a standard laboratory experiment wherein trans-cinnamic acid is treated with highly corrosive liquid bromine. This chemical reaction results in the synthesis of a solid dibrominated addition product, which is isolated, purified, and characterized by the students. While chemists must learn to work safely with dangerous chemicals, it is prudent to improve the safety of procedures used by chemistry students whenever possible. Thus, an alternate reaction was developed that includes substituting liquid bromine with commercially available N-bromosuccinimide (NBS), which is a nonvolatile, relatively safe, solid reagent. Furthermore, the experiment helps students better understand (and remember) the reaction mechanism of haloether formation--a slightly more complicated reaction outcome than dibromonation due to the use of nucleophilic solvents in the reaction.
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