Complexed Photosensitizer of Hypericin with G-Quadruplex: Structure-Dependent Behavior

Area of Science:

• Photochemistry
• Biochemistry
• Molecular Biology

Background:

• Hypericin (Hyp) is a visible-light-absorbing compound with potential in photodiagnosis and photodynamic therapy (PDT).
• Hyp's aggregation in aqueous environments leads to excited-state quenching, reducing its photoactivity.
• DNA G-quadruplexes are unique nucleic acid structures with diverse biological roles.

Purpose of the Study:

• To investigate the excited-state properties of Hypericin when bound to DNA G-quadruplexes.
• To determine if G-quadruplex binding can prevent Hypericin aggregation and photoactivity quenching.
• To explore the potential of Hypericin/G-quadruplex complexes as photosensitizers for PDT.

Main Methods:

• Steady-state and time-resolved spectroscopy were employed to study Hypericin/G-quadruplex interactions.
• Selective binding of Hypericin to different types of G-quadruplexes was assessed.
• The efficiency of singlet oxygen (¹O₂) production and photostability of the complexes were evaluated.

Main Results:

• G-quadruplex binders successfully dispersed Hypericin, preventing aggregation-induced quenching and restoring photoactivity.
• Hypericin exhibited selective binding, preferentially interacting with parallel G-quadruplexes over antiparallel or hybrid forms.
• The binding affinity correlated with improved triplet Hypericin lifetime and enhanced ¹O₂ generation efficiency, with the Hyp/c-kit2 complex showing the highest ¹O₂ quantum yield (0.67).

Conclusions:

• DNA G-quadruplex binding is an effective strategy to overcome Hypericin aggregation and quenching issues.
• The Hyp/G-quadruplex complex, particularly with parallel structures like c-kit2, demonstrates superior photophysical properties.
• These findings suggest the potential development of biocompatible Hypericin/G-quadruplex complexes as effective photosensitizers for therapeutic applications like PDT.