title: Syntheses, photophysical properties, and photocytotoxicities of tetrakis(fluorophenyl)porphyrin derivatives bearing 2-hydroxyethylthio groups.
abstract: Porphyrin derivatives for photodynamic therapy are frequently modified with hydrophilic groups to improve their water solubility; however, such hydrophilic groups not only improve the solubility but also affect the photodynamic behavior of the compound. The suitable number and pattern of the hydrophilic substituents depend on the nature of the hydrophilic groups. In this article, we explore the optimum architecture for 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (TFPP) derivatives bearing 2-hydroxyethylthio substituents. All five derivatives, namely mono-, cis-bis-, trans-bis-, tris- and tetrakis-substituted TFPP, were successfully synthesized by the nucleophilic aromatic substitution of TFPP with 2-hydroxyethanethiol, separated, and subsequently identified using ESI-TOF mass spectrometry and (1)H and (19)F NMR spectroscopies. The hydrophilicity of the compounds increased with an increase in the number of 2-hydroxyethylthio groups. The singlet oxygen and hydroxyl radical generation efficiencies were estimated using chemical probes following photoirradiation (λ>500nm). trans-Bissubstituted TFPP exhibited the highest efficiency for both singlet oxygen and hydroxyl radical generation. The photocytotoxicities of the photosensitizers were evaluated in HeLa cells following photoirradiation (λ>500nm, 16Jcm(-2)), and increased with an increase in number of 2-hydroxyethylthio groups. In the case of 2-hydroxyethylthio-substituted TFPPs, the fully substituted TFPP was the most efficient architecture plausibly because of the result of the hydrophilicity of the compound rather than a greater efficiency in the generation of reactive oxygen species.
authors.affiliation: Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 4-4-37 Takeda, Kofu 400-8510, Japan. Electronic address: mobata@yamanashi.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Obata
authors.affiliation: Department of Chemical and Biological Engineering, National Institute of Technology, Ube College, 2-14-1 Tokiwadai, Ube 755-8555, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Hirohara
mesh_terms: D060326:Chemistry Techniques, Synthetic; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012995:Solubility
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D017382:Reactive Oxygen Species
keywords: Photocytotoxicity; Photodynamic therapy (PDT); Reactive oxygen species (ROS)