development of a photochromic nitroxyl delivery system david spivey mentor: dr. kevin p. schultz...
TRANSCRIPT
![Page 1: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/1.jpg)
DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM
David Spivey
Mentor: Dr. Kevin P. Schultz
Goucher College
![Page 2: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/2.jpg)
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
![Page 3: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/3.jpg)
Current HNO Donors
A stable and controllable nitroxyl donor is needed to further study its therapeutic benefits and potential usefulness as a drug
![Page 4: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/4.jpg)
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
![Page 5: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/5.jpg)
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
![Page 6: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/6.jpg)
Diene Synthesis
![Page 7: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/7.jpg)
Nitroxyl Binding and Release
![Page 8: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/8.jpg)
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)
Absorb
ance
![Page 9: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/9.jpg)
UV/Vis of New Compound
![Page 10: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/10.jpg)
Photostationary State
The equilibrium chemical composition under a specific kind of electromagnetic radiation
0 10 20 30 40 50 60 700
0.05
0.1
0.15
0.2
0.25
0.3
0.35
0.4
440 nm Peak
Time (s)
Absorb
ance
0 10 20 30 40 50 60 703.6
3.8
4
4.2
4.4
4.6
4.8
5
237 nm Peak
Time (s)
Absorb
ance
![Page 11: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/11.jpg)
Parallel vs. Antiparallel
UV light
![Page 12: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/12.jpg)
Monitoring Closing by NMR
Open form
After 10 min of irradiation
![Page 13: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/13.jpg)
Isolation of Closed Isomer
![Page 14: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/14.jpg)
Nitroxyl Release
Tried heating open ring form in xylene/water at 140° C
![Page 15: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/15.jpg)
Future Plans
Optimize retro-Diels Alder reaction and HNO release
Optimize side groups to obtain a higher percent in the closed conformation
![Page 16: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/16.jpg)
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.
![Page 17: DEVELOPMENT OF A PHOTOCHROMIC NITROXYL DELIVERY SYSTEM David Spivey Mentor: Dr. Kevin P. Schultz Goucher College](https://reader033.vdocuments.net/reader033/viewer/2022042717/56649d205503460f949f4056/html5/thumbnails/17.jpg)
Acknowledgements
Kevin Schultz, Ph.D Goucher Chemistry Department Claasen Summer Research Fund Kirkbride Loya Jaclyn Kellon Kat Flanagan Marie McConville