A Photochemical Study of Photo-induced Electron Transfer from DNAs to a Cationic Phthalocyanine Derivative

Abstract Water-soluble phthalocyanines (Pcs) have emerged as promising photosensitizers for photodynamic therapy (PDT). Elucidation of their photochemical and photophysical properties, such as the photogeneration of reactive oxygen species (ROSs) and photocytotoxicity, is essential for the molecular design of PDT photosensitizing agents. Water-soluble cationic gallium(III)-Pc complex (GaPc) is capable of photogenerating ROSs in vitro and is well taken up by cells but does not exhibit photocytotoxicity in vivo. GaPc binds selectively, through a π-π stacking interaction, to the 5’-terminal G-quartet of a G-quadruplex DNA. The photo-excited state of GaPc of the complex is effectively quenched through electron transfer (ET) from the ground state of DNA guanine (G) bases to the photo-excited state of GaPc (ET(G−GaPc)). Hence the loss of the photocytotoxicity of GaPc in vivo is most likely to be due to the effective quenching of its photo-excited state through ET(G−GaPc). In this study, we investigated the photochemical properties of GaPc in the presence of duplex DNAs formed from a series of sequences to elucidate the nature of ET(G−GaPc). We found that ET(G−GaPc) is allowed in electrostatic complexes between GaPc and G-containing duplex DNAs and that the rate of ET(G−GaPc) (kET(G−GaPc)) can be reasonably interpreted in terms of the distance between Pc moiety of GaPc and DNA G base in the complex. These results indicated that photocytotoxicity of GaPc is crucially affected by ET(G−GaPc). Thus elucidation of interaction of a photosensitizer with biomolecules, i.e., an initial process in PDT, would be helpful to understand its subsequent photochemical processes.