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The Joseph A. Dixon Travel Award 2003 Spring ACS Meeting, New Orleans, LA
Progress in the Synthesis of 1,5-Methylenesemibullvalene Two steps remain in the projected nine step synthesis of 1,5-Methylenesemibullvalene (1); the bromination of [3.3.1]propellane-3,6-diene-2,8-diol (2) and the reductive coupling of the corresponding [3.3.1]propellane-3,6-diene-2,8-dibromide (3). Bromination of [3.3.1]propellane-3,6-diene-2,8-diol (2) has been completed with phosphorus tribromide and mixture of six isomers was obtained Scheme 1. Zn/Cu couple and a McMurry couple are being investigated as possible coupling agents for the final cyclization step. Zn/Cu couple has been completed on [3.3.1]propellane-3,6-diene-2,8-dibromide (3) Scheme 2, and McMurry couple has been completed on [3.3.1]propellane-3,6-diene-2,8-diol (2) with mixed results Scheme 3. With further investigation of the final step, the synthesis of 1,5-Methylenesemibullvalene (1) can be completed and the molecule could be the first neutral homoaromatic compound.
The applicability of nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy for the determination of hydrogen bonding in perfluoropolyether lubricants was studied. The relative strength of the hydrogen bonds found in Fomblin Z-DOL 2000 and Z-Tetraol, lubricants commonly used in hard disk drives, was readily determined from chemical shift values while IR was used to ascertain the relative amount of hydrogen bond disruption after dilution. It was also possible to show that Z-DOL only forms intermolecular hydrogen bonds which are easily disrupted by fluorinated solvents. Z-Tetraol, however, was shown to form both inter- and intramolecular hydrogen bonds. These intramolecular hydrogen bonds were observed to remain intact even at low concentrations. An additional mechanism of solvation by hexafluorobenzene was also discovered which involves an interaction between the p-system of the aromatic ring and the backbone fluorines of the polymer. Non-Natural
Cell Surface Receptors As Tools For Drug Delivery The efficient delivery of small molecules and proteins into living cells is critical for the effectiveness of therapeutics and cellular probes. We are investigating a novel protein delivery approach based on cholesterylamine derivatives that function as non-natural cell surface receptors and deliver protein ligands into mammalian cells. One such non-natural cell surface receptor termed streptaphage comprises cholesterylamine linked to the carboxylate of biotin via an 11-atom tether. Treatment of Jurkat lymphocytes with this compound results in persistent localization of the cholesterylamine moiety with cellular plasma membranes. Subsequent addition of streptavidin proteins to treated cells results in binding to this small molecule receptor at the cell surface and uptake of the streptavidin protein by triggering the cellular uptake process of endocytosis. This delivery strategy appears to require divalent or multivalent crosslinking of the receptor at the cell surface, and we are currently investigating the biological activities of dimeric cholesterylamine derivatives that may provide novel probes of endocytic pathways and shed light on mechanisms of this protein delivery approach. Cancer cells appear to be particularly susceptible to this delivery strategy, and studies are underway to link toxins to streptavidin and use these conjugates with non-natural cell surface receptors as potential agents for the regulated ablation of cancer cells. Environmental Chemistry: Determination of the Physical Properties
Spanning from the Arctic to the Antarctic as global contaminants, perfluorinated compounds have been recognized as an environmental concern due to their persistence and potential toxicity. Through NMR, the molecular geometry and physical properties of a compound may be investigated; to fully understand the transport in the environment, a fundamental understanding of perfluorinated molecules is necessary. We have measured 19F chemical shift values, spin-lattice relaxation times, and spin-spin relaxation times to investigate the physical properties of a series of perfluorinated acids of increasing chain length; in addition, variable temperature experiments have been employed to examine geometry and rigidity. 19F 2D J-resolved NMR has been used to gather 19F-19F spin-spin coupling constants. These values were compared to those of an equivalent series of carboxylic acids. Empirical data have shown that carboxylic acids and perfluorinated acids do not behave similarly, indicating that generalizations made from carboxylic acids are not necessarily accurate. |
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