Development of a Photochromic Nitroxyl Delivery System
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DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM
David SpiveyMentor: Dr. Kevin P. SchultzGoucher College
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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
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Current HNO Donors
A stable and controllable nitroxyl donor is needed to further study its therapeutic benefits and potential usefulness as a drug
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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
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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
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Diene Synthesis
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Nitroxyl Binding and Release
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UV/Vis Studies of Photochromic Transformation
First compound used produced results indicative of degradation
200217234251268285302319336353370387404421438455472489506523540557574591-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
3 sec A6 sec A11 sec A16 sec A26 sec A36 sec A56 sec A
Wavelength (nm)
Abso
rban
ce
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UV/Vis of New Compound
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Photostationary State The equilibrium chemical composition
under a specific kind of electromagnetic radiation
0 10 20 30 40 50 60 700
0.050.1
0.150.2
0.250.3
0.350.4
440 nm Peak
Time (s)
Abso
rban
ce
0 10 20 30 40 50 60 703.63.8
44.24.44.64.8
5
237 nm Peak
Time (s)
Abso
rban
ce
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Parallel vs. Antiparallel
UV light
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Monitoring Closing by NMROpen form
After 10 min of irradiation
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Isolation of Closed Isomer
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Nitroxyl Release Tried heating open ring form in
xylene/water at 140° C
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Future Plans Optimize retro-Diels Alder reaction and
HNO release
Optimize side groups to obtain a higher percent in the closed conformation
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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.
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Acknowledgements Kevin Schultz, Ph.D Goucher Chemistry Department Claasen Summer Research Fund Kirkbride Loya Jaclyn Kellon Kat Flanagan Marie McConville