Development of a Photochromic Nitroxyl Delivery System

Student: David Spivey (Dept. of Chemistry)

Faculty Adviser: Kevin Schultz (Dept. of Chemistry )

Abstract

Dithienylethene photochromic molecules have the distinctive property of being able to interconvert between two thermally stable forms when irradiated with the appropriate wavelength of light.  These two isomers have unique bonding patterns resulting in changes in the physical and electronic properties of the two forms.  We would like to take advantage of these unique properties to control the release of the drug nitroxyl, which has been shown to have benefits in treating heart failure and cancer.  Nitroxyl (HNO) can be attached to the photochromic molecule by coupling a Diels-Alder reaction with UV radiation, thus making it stable at physiological temperature.  Upon irradiation with a near-IR wavelength of light, the bonding arrangement will unlock and release nitroxyl via a retro Diels-Alder reaction.  We have synthesized a cyclohexadiene bridged dithienyl photochromic system that binds to a nitroxyl donor molecule via a Diels-Alder reaction.  Upon irradiation with 312nm light the Diels-Alder adduct reaches its photostationary state at 32% of the closed isomer.  We are currently optimizing the nitroxyl release conditions.  In addition, we are derivatizing the bridging diene to make the nitroxyl release more physiologically appropriate. 

Click here for the research poster presented at the Fifth Annual Landmark Conference Summer Research Symposium