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Development of a Photochromic Nitroxyl Delivery System

This project explores a stable nitroxyl donor for therapeutic benefits, utilizing photochromism for reversible color change. UV/Vis studies and NMR monitoring were conducted to optimize reaction and HNO release. Future plans aim to enhance the closed conformation. References support the research on nitroxyl. Acknowledgments to Dr. Kevin Schultz, Goucher Chemistry Department, and contributors for their support.

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Development of a Photochromic Nitroxyl Delivery System

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  1. Development of a Photochromic Nitroxyl Delivery System David Spivey Mentor: Dr. Kevin P. Schultz Goucher College

  2. Nitroxyl (HNO) • HNO has been found to have pharmacological effects: • Positive cardiac inotropy • Vasodilation • Inhibits breast cancer tumor growth • Potential therapeutic agent for heart disease • Downside: highly unstable in physiological conditions

  3. Current HNO Donors • A stable and controllable nitroxyl donor is needed to further study its therapeutic benefits and potential usefulness as a drug

  4. Chromism • A process that induces a reversible color change in compounds • Types of chromism: • Photochromism - color change caused by light • Thermochromism - color change caused by heat • Electrochromism - color change caused by an electrical current • Solvatochromism - color change caused by solvent polarity • Tribochromism - color change caused by mechanical friction

  5. Photochromism • The reversible transformation of a chemical species between two forms by the absorption of electromagnetic radiation, where the two forms have different absorption spectra. • Electrocyclic ring closing reaction

  6. Diene Synthesis

  7. Nitroxyl Binding and Release

  8. UV/Vis Studies of Photochromic Transformation • First compound used produced results indicative of degradation

  9. UV/Vis of New Compound

  10. Photostationary State • The equilibrium chemical composition under a specific kind of electromagnetic radiation

  11. Parallel vs. Antiparallel UV light

  12. Monitoring Closing by NMR Open form After 10 min of irradiation

  13. Isolation of Closed Isomer

  14. Nitroxyl Release • Tried heating open ring form in xylene/water at 140° C

  15. Future Plans • Optimize retro-Diels Alder reaction and HNO release • Optimize side groups to obtain a higher percent in the closed conformation

  16. References • Fukuto, J.M.; Dutton, A.S.; Houk, K.N. “The chemistry and biology of nitroxyl (HNO): a chemically unique species with novel and important biological activity,” Chembiochem,2005, 6, 612–619. • Lopez, B. E.; Shinyashiki, M.; Han, T. H.; Fukuto, J. M. “Antioxidant actions of nitroxyl (HNO),” Free Radical Biol. Med.2007, 42, 482–91. • Atkinson, R. N.; Storey, B. M.; King, S. B. “Reactions of Acyl Nitroso Compounds with Amines : Production of Nitroxyl (HNO) with the Preparation of Amides” Tetrahedron Lett.1996, 37, 9287–9290. • Irie, M., “Diarylethenes for Memories and Switches,” Chem. Rev.2000, 100, 1685–1716. • Lemieux, V.; Gauthier, S.; Branda, N. R. “Selective and sequential photorelease using molecular switches,” Ang. Chem. Int. Ed.2006, 45, 6820–6824. • Erno, Z.; Asadirad, A. M.; Lemieux, V.; Branda, N. R. “Using light and a molecular switch to “lock” and “unlock” the Diels-Alder reaction,” Org. Biomol. Chem.2012, 10, 2787–2792.

  17. Acknowledgements • Kevin Schultz, Ph.D • Goucher Chemistry Department • Claasen Summer Research Fund • KirkbrideLoya • Jaclyn Kellon • Kat Flanagan • Marie McConville

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