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