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

Abstract

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 100000 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 µm but show cytotoxicity to A549 cells at concentrations as low as 75 nm 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.