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

Abstract

Three water-soluble porphyrins with tetra-cationic imidazolium groups were synthesized and assessed for complexation with human telomeric guanine-quadruplex (G4) DNA. By UV titration studies, these porphyrins showed 10-fold higher complexation stability to G4 DNA over non-G4 DNA. This was consistent with FRET experimental data showing G4 stabilization by these porphyrins was significantly enhanced in comparison to non-G4 DNA. The porphyrins had slightly longer wavelength of absorption in comparison to a previously reported cationic porphyrin with the same cationic 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 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 to both cancer cells (HeLa) and normal cells (NHDF). Photocytotoxicity to a cancer cell line was higher than to the normal cells. Although this mechanism was not clearly explained, the results show superior properties of these porphyrin molecules reported here as PDT-PSs.