Cyclopropenone-based Platform for Light-directed Drug Delivery, Photo-medicine, and Bio-imaging

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In this project supported by the Chemical Structure, Dynamics, and Mechanisms-B Program of the Chemistry Division, Professor Vladimir Popik of the Department of Chemistry at the University of Georgia (UGA) develops new photochemical reactions which have potential applications for drug delivery and activation. The fundamental chemistry is based on organic molecules which undergo light-induced dissociation, and where carbon monoxide is one of the products. Since the opacity of tissues limits the amount of light that can be delivered to target areas in therapy, Professor Popik explores methods to boost the efficiency of the photo-induced released of molecules with the body through a quantum chain reaction. This is a process in which one packet (photon) of light causes multiple molecules to be released. This strategy may allow for the selective treatment of localized malignancies, while avoiding common side effects of common chemotherapies. The project provides students with interdisciplinary training at the interface of synthetic and physical organic chemistry, as well as photochemistry and biochemistry. High school students conducting summer internship in Professor Popik's laboratory via the UGA Young Dawgs Program are exposed to modern scientific research.The quantum efficiency of the photodecarbonylation reaction of cyclopropenones in the crystalline state is several times higher than in solution, and could exceed 400%. Professor Popik explores the mechanism of the quantum yield amplification phenomenon and parameters that control the energy propagation process in cyclopropenone crystals. Harnessing the quantum chain reaction allows for the production of several molecules of the product per one photon absorbed. Such photoreactions are especially important in the expected applications, where light delivery is hampered by the opacity or scattering properties of the medium. Nanocrystalline suspensions of specially designed cyclopropenone derivatives permit practical use of the quantum yield amplification. The covalent surface derivatization of the crystals and control of the size of the crystals allows for the preparation of stable suspensions or colloidal solutions and provides control over the transport and bio-distribution properties of nanocrystals. Light-directed delivery of bioactive substrates using cyclopropenone nanocrystalline suspensions offers very high light sensitivity, ability to control bio-distribution, and is accompanied by the release of carbon monoxide, which is an important bio-active agent in itself as well as a valuable adjuvant for anti-cancer antibiotics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.