Premium
Water‐Soluble Zinc Porphyrin Capable of Light‐Induced Photocleavage of DNA: Cell Localization Studies in Drosophila Melanogaster and Light Activated Treatment of Lung Cancer Cells
Author(s) -
Yoho Joshua,
Wogensthal Kevin,
Bennett Thomas L.,
Palmer Jessica,
Comfort Kristen K.,
KangoSingh Madhuri,
Swavey Shawn,
Stuart Christopher H.,
Gmeiner William H.
Publication year - 2017
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201601077
Subject(s) - chemistry , porphyrin , photochemistry , zinc , dna , photodynamic therapy , irradiation , dna damage , a549 cell , biophysics , cell , biochemistry , organic chemistry , physics , biology , nuclear physics
A new water‐soluble zinc(II) porphyrin has been synthesized and characterized by high resolution mass spectroscopy, elemental analysis, and electronic absorption spectroscopy. The zinc(II) porphyrin (ZnPor) is designed with three N‐methylated pyridyl groups at the meso ‐positions to make the compound water soluble. In addition, a meso ‐pentafluorophenyl substituent has been incorporated to enhance the excited state lifetime of the porphyrin. The addition of zinc(II) into the porphyrin core lends itself to longer excited lifetimes as well as the ability to coordinate to DNA bases exposed in the major groove. The ZnPor and its free‐base analog (FBPor) demonstrate high binding affinity to calf thymus DNA (ctDNA) with binding constants greater than 1 m –1 . Both porphyrins show the ability to photonick DNA when irradiated within the photodynamic therapy window (600–850 nm); however, ZnPor shows enhanced photoreactions and the ability to cause double strand breaks. Under hypoxic conditions only ZnPor is capable of causing single strand breaks when irradiated with visible light. Both ZnPor and FBPor are nontoxic to the lung cancer cell line A549 in the dark at concentrations as high as 100 µ m but show cytotoxicity to A549 cells at concentrations as low as 75 n m when irradiated with visible light. Studies of the ZnPor in Drosophila melanogaster indicate statistically insignificant toxicity when compared to control at concentrations well above the light‐induced toxicity levels. Evidence for localization of ZnPor in the nuclei of the Drosophila salivary gland cells suggests a mechanism for cellular transport, which may prove beneficial in PDT treatment.