Selective photodegradation of G-quadruplex DNA by a cationic zinc phthalocyanine: role of binding geometry

The selective photodegradation of G-quadruplex DNA (GQ) was investigated using the cationic zinc phthalocyanine ZnPc as a photosensitizer. UV-Vis absorption titration suggests that electrostatic interactions contribute to ZnPc association with both duplex and G-quadruplex DNA, whereas ¹H NMR analysis indicates that one major ZnPc-GQ association mode involves π-π end-stacking at the 5'-terminal G-quartet. The efficiency of singlet oxygen generation by ZnPc is similar in the presence of duplex and G-quadruplex DNA, and fluorescence-based assays indicate comparable hydroxyl radical-type reactivity in both systems. Nevertheless, red-light irradiation selectively induced photodegradation of G-quadruplex DNA, whereas duplex DNA remained largely unaffected under the present conditions. This selectivity appears to arise from distinct ZnPc-DNA association modes that influence local oxidative reactivity. In ZnPc-GQ systems, the data are consistent with the possible coexistence of association states with different photochemical properties: strongly π-stacked states may suppress effective oxidative damage through excited-state quenching, whereas non-stacked or weakly associated ZnPc species may retain oxidative activity toward accessible guanine-rich regions. In contrast, ZnPc association with duplex DNA is spatially separated from the base-paired core, limiting global structural disruption. Consistent with this interpretation, free or weakly associated GQ species appear more susceptible to oxidative damage than strongly associated ZnPc-bound states. These findings highlight the importance of binding geometry and local oxidative reactivity in determining DNA photodamage and provide a basis for designing photosensitizers with structural selectivity through G-quadruplex recognition.