ORGN 540 |
| Nitrogen-onium salts based on heteroaromatic compounds contain a fragmentable nitrogen-oxygen bond that yield a heteroaromatic radical cation and an alkoxy radical upon photoinduced homolytic cleavage. Those reactive intermediates can potentially cleave DNA and other biomolecules. The oxidation reactions initiated by the heteroaromatic radical cation are potentially irreversible because the product is a neutral heteroaromatic compound. To effectively target biomolecules, ground state association with DNA of all onium-salts was determined with absorption and emission spectroscopy. DNA binding of the initially used simple onium-salts (based on quinoline, isoquinoline and phenanthridine) is weak. We are currently attempting to attach an efficient DNA intercalator based on naphthalimides and naphthaldiimides. The synthesis involves the condensation of naphthalic anhydride with a series of amines. Oxidation of the hetercycles and subsequent alkylation yields the onium-salts as either their tetrafluoroborates or tosylates. The orientation of the fragmentable nitrogen-oxygen bond decides which fragment will have a higher mobility. One orientation will have the radical cation bound to DNA, while in the other the alkoxy radical is linked to the DNA binder. To explore the potential of the onium-salts towards photodynamic therapy we determined the cytotoxicity as well as their phototoxicity. The cytotoxicity of the first generation onium-salts is being tested using Saccharomyces cerevisiae. The cells are then exposed to tolerated levels of the drug and irradiated. So far, only the quinoline-based onium-salts exhibit an increased toxicity upon irradiation. We expect that increased binding will have a strong effect on retention of the drug in the exposed cells and thus on the phototoxicity of the drug.
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Materials, Devices and Switches, Metal-Mediated Reactions, Asymmetric Reactions, Total Synthesis, Biologically-Related Molecules and Processes
7:00 PM-9:00 PM, Wednesday, April 9, 2008 Morial Convention Center -- La Louisiane, Blrm. C, Poster
Division of Organic Chemistry |
