Linker dependence of ¹O₂ generation by G4-binding tetra-imidazolium porphyrins

Three water-soluble porphyrins with tetracationic imidazolium groups were synthesized and assessed for complexation with human telomeric guanine-quadruplex (G4) DNA. Based on UV-vis titration studies, these porphyrins showed 10-fold higher complexation stability toward G4 DNA over non-G4 DNA. This was consistent with FRET experimental data, which showed that G4 stabilization by these porphyrins was significantly enhanced in comparison with that of non-G4 DNA. The porphyrins had slightly longer absorption wavelengths than a previously reported cationic porphyrin with the same functional groups but shorter linkers, indicating that they may be more suitable as photosensitizers (PSs) for photodynamic therapy (PDT). Significant photoinduced singlet oxygen (¹O₂) generation of these porphyrins was observed by the ESR spin-trapping method under irradiation with deep red LED light (max at 660 nm). In the presence of telo24 G4 DNA, this photoinduced ¹O₂ generation was enhanced. Cellular internalization of these porphyrins was observed by flow cytometry, resulting in sufficient photocytotoxicity of these porphyrins toward both cancer cells (HeLa) and normal cells (NHDF). Photocytotoxicity to a cancer cell line was higher than that to normal cells. Although this mechanism was not clearly explained, the results show superior properties of these porphyrin molecules reported here as PDT-PSs.