Molecular electronic tuning of photosensitizers to enhance photodynamic therapy: synthetic dicyanobacteriochlorins as a case study.

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.

• Authors: Eunkyung Yang, James R Diers, Ying-Ying Huang, Michael R Hamblin, Jonathan S Lindsey, David F Bocian, Dewey Holten
• Journal: Photochemistry and photobiology (Photochem Photobiol) 2013 May-Jun Vol. 89 Issue 3 Pg. 605-18 ISSN: 1751-1097 [Electronic] United States
• PMID: 23163632 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: © 2013 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2013 The American Society of Photobiology.

Chemical References

• Bacteriochlorophylls
• Coordination Complexes
• Photosensitizing Agents
• Porphyrins
• bacteriochlorin
• palladium-bacteriopheophorbide
• Palladium
• padeliporfin
• Zinc

Topics

• Bacteriochlorophylls (chemistry)
• Coordination Complexes (chemical synthesis, chemistry)
• Drug Stability
• Electrons
• HeLa Cells
• Humans
• Kinetics
• Luminescent Measurements
• Oxidation-Reduction
• Palladium (chemistry)
• Photochemotherapy
• Photosensitizing Agents (chemical synthesis, chemistry)
• Porphyrins (chemical synthesis, chemistry)
• Quantum Theory
• Spectroscopy, Near-Infrared
• Thermodynamics
• Zinc (chemistry)