Development of a Photochromic Nitroxyl Delivery System
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Transcript Development of a Photochromic Nitroxyl Delivery System
DEVELOPMENT OF A
PHOTOCHROMIC NITROXYL
DELIVERY SYSTEM
David Spivey
Mentor: Dr. Kevin P. Schultz
Goucher College
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
Current HNO Donors
A stable and controllable nitroxyl donor is needed to further study its
therapeutic benefits and potential usefulness as a drug
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
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
Diene Synthesis
Nitroxyl Binding and Release
UV/Vis Studies of Photochromic
Transformation
First compound used produced results indicative of
degradation
1.4
1.2
1
3 sec A
Absorbance
0.8
6 sec A
11 sec A
0.6
16 sec A
26 sec A
0.4
36 sec A
56 sec A
0.2
0
200
-0.2
250
300
350
400
Wavelength (nm)
450
500
550
600
UV/Vis of New Compound
Photostationary State
The equilibrium chemical composition under a
specific kind of electromagnetic radiation
440 nm Peak
237 nm Peak
0.4
5
0.35
4.9
4.8
4.7
0.25
Absorbance
Absorbance
0.3
0.2
0.15
4.6
4.5
4.4
4.3
0.1
4.2
0.05
4.1
0
4
0
10
20
30
40
Time (s)
50
60
70
0
10
20
30
40
Time (s)
50
60
70
Parallel vs. Antiparallel
UV light
Monitoring Closing by NMR
Open form
After 10 min
of irradiation
Isolation of Closed Isomer
Nitroxyl Release
Tried heating open ring form in xylene/water at
140° C
Future Plans
Optimize retro-Diels Alder reaction and HNO
release
Optimize side groups to obtain a higher percent in
the closed conformation
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.
Acknowledgements
Kevin Schultz, Ph.D
Goucher Chemistry Department
Claasen Summer Research Fund
Kirkbride Loya
Jaclyn Kellon
Kat Flanagan
Marie McConville