title: 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.affiliation: Department of Chemistry, Washington University, St. Louis, MO, USA.
authors.forename: Eunkyung
authors.initials: E
authors.lastname: Yang
authors.forename: James R
authors.initials: JR
authors.lastname: Diers
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Huang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Lindsey
authors.forename: David F
authors.initials: DF
authors.lastname: Bocian
authors.forename: Dewey
authors.initials: D
authors.lastname: Holten
mesh_terms: D001429:Bacteriochlorophylls / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D004583:Electrons; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008163:Luminescent Measurements; D010084:Oxidation-Reduction; D010165:Palladium / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D019265:Spectroscopy, Near-Infrared; D013816:Thermodynamics; D015032:Zinc / Q000737:chemistry
chemical_list: D001429:Bacteriochlorophylls; D056831:Coordination Complexes; D017319:Photosensitizing Agents; D011166:Porphyrins; C452433:bacteriochlorin; C456120:palladium-bacteriopheophorbide; D010165:Palladium; C503696:padeliporfin; D015032:Zinc