Photogeneration of Reactive Oxygen Species from Water-Soluble Phthalocyanine Derivatives Bound to a G-Quadruplex DNA

Abstract

Abstract Water-soluble phthalocyanine (Pc) derivatives have been studied extensively as not only effective photosensitizers for photodynamic therapy (PDT), but also G-quadruplex ligands which have the potential to be anticancer drugs. We investigated the photogeneration of reactive oxygen species (ROS) from cationic Pc derivatives, 2,3,6,7,10,11,14,15-octakis-[N-methyl-(4-methylpyridinium-3-yloxy)phthalocyaninato] chloro gallium(III) iodide (GaPc) and zinc(II) iodide (ZnPc), in the presence of an all parallel-stranded tetrameric G-quadruplex DNA, i.e., [d(TTAGGGT)4]. We found that the photo ROS generation from GaPc is suppressed in the presence of the DNA, whereas that from ZnPc is enhanced on the addition of the DNA. The suppression of the photo ROS generation for GaPc by the DNA was found to be due to electron transfer from the ground state of the guanine base of the DNA to the photo-excited state of GaPc. This finding provides a clue as to why phototoxicity of GaPc is lower than that of ZnPc in human Hep2 cells (Fujishiro et al. J. Inorg. Biochem.2019, 192, 7). On the other hand, the enhancement of the photo ROS generation from ZnPc by the DNA is possibly due to the dissociation of its non-fluorescent aggregate through its interaction with the DNA. Thus the interaction of photosensitizers with DNA and RNA is crucial for their PDT efficacy.