Using Light to Probe and Manipulate Biology: Photophysical Challenges and Molecular Solutions

David S. Lawrence, Ph.D.
Fred Eshelman Distinguished Professor Chair, Division of Chemical Biology & Medicinal Chemistry Professor of Chemistry, Chemical Biology & Medicinal Chemistry, and Pharmacology Univeristy of North Carolina at Chapel Hill
Thursday, October 3, 2013 - 4:30pm

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Light-induced bond cleavage/formation plays an increasingly important role in biological research and biomedical applications.1-4 Light has been used to control the conversion of appropriately designed photo-responsive inactive drugs/biological reagents to their corresponding active forms, their delivery to specific tissues, cells, and organelles, and the means to do so with a high degree of temporal resolution. However, the photo-responsive species described to date are typically triggered by UV/short visible wavelengths. Short wavelengths suffer a number of disadvantages, including inflicting biological damage, a limited penetrating path length in tissue, 5 and the inability to orthogonally control multiple species at distinct wavelengths. Indeed, a recent review noted that two key challenges remain to be surmounted to move this field forward: “extending the wavelength coverage for activation…..with visible and infrared light and improving the absorption properties for wavelength-selective, orthogonal activation, and melding these features”.1 A surprisingly simple solution to these challenges along with applications to drug delivery, cell remodeling, and material fabrication will be discussed.

1.         Klán, P., Šolomek, T., Bochet, C. G., Blanc, A., Givens, R., Rubina, M., Popik, V., Kostikov, A., & Wirz, J. Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chem. Rev. 113,119 – 91 (2013).2.          Lee, H. M., Larson, D. R., & Lawrence, D. S. Illuminating the chemistry of life: design, synthesis, and applications of "caged" and related photoresponsive compounds. ACS Chem. Biol. 4, 409-427 (2009).3.          Brieke, C., Rohrbach, F., Gottschalk, A., & Mayer, G. Light-controlled tools. Angew Chem Int Ed Engl. 51, 8446-8476 (2012).4.          Klán, P., et al., Photoremovable Protecting Groups in Chemistry and Biology: Reaction Mechanisms and Efficacy. Chem. Rev. 113, 119-191 (2013).5.          Heckel, A.Tromberg, B. J. et al. Non-Invasive In Vivo Characterization of Breast Tumors Using Photon Migration Spectroscopy. Neoplasia 2, 26 – 40 (2000).


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