Molecular Electronic Tuning of Photosensitizers to Enhance Photodynamic Therapy: Synthetic Dicyanobacteriochlorins as a Case Study |
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| Authors: | Eunkyung Yang James R Diers Ying‐Ying Huang Michael R Hamblin Jonathan S Lindsey David F Bocian Dewey Holten |
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| Institution: | 1. Department of Chemistry, Washington University, , St. Louis, MO;2. Department of Chemistry, University of California, , Riverside, CA;3. Wellman Center for Photomedicine, Massachusetts General Hospital, , Boston, MA;4. Department of Dermatology, Harvard Medical School, , Boston, MA;5. Aesthetic and Plastic Center of Guangxi Medical University, , Nanning, China;6. Harvard‐MIT Division of Health Sciences and Technology, , Cambridge, MA;7. Department of Chemistry, North Carolina State University, , Raleigh, NC |
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| Abstract: | Photophysical, photostability, electrochemical and molecular‐orbital characteristics are analyzed for a set of stable dicyanobacteriochlorins that are promising photosensitizers for photodynamic therapy (PDT). The bacteriochlorins are the parent compound (BC), dicyano derivative (NC)2BC and corresponding zinc (NC)2BC‐Zn and palladium chelate (NC)2BC‐Pd. The order of PDT activity against HeLa human cancer cells in vitro is (NC)2BC‐Pd > (NC)2BC > (NC)2BC‐Zn ≈ BC. The near‐infrared absorption feature of each dicyanobacteriochlorin is bathochromically shifted 35–50 nm (748–763 nm) from that for BC (713 nm). Intersystem crossing to the PDT‐active triplet excited state is essentially quantitative for (NC)2BC‐Pd. Phosphorescence from (NC)2BC‐Pd occurs at 1122 nm (1.1 eV). This value and the measured ground‐state redox potentials fix the triplet excited‐state redox properties, which underpin PDT activity via Type‐1 (electron transfer) pathways. A perhaps counterintuitive (but readily explicable) result is that of the three dicyanobacteriochlorins, the photosensitizer with the shortest triplet lifetime (7 μs), (NC)2BC‐Pd has the highest activity. Photostabilities of the dicyanobacteriochlorins and other bacteriochlorins studied recently are investigated and discussed in terms of four phenomena: aggregation, reduction, oxidation and chemical reaction. Collectively, the results and analysis provide fundamental insights concerning the molecular design of PDT agents. |
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