Photosensitization with anticancer agents. 16. The photo-oxidation of hypocrellin A. A mechanism study using 18O...

Hypocrellin A was selected as a representative structure to investigate the mechanism of photo-oxidation of perylenequinonoid pigments (PQPs). It was found that singlet oxygen plays a key role in the photo-oxidation of PQPs. The following processes were determined to be involved in the photo-oxidation of PQPs using 18O atom labelling. After the PQP is photoexcited, it tautomerizes and dissociates to produce the anion, which reacts with singlet oxygen generated during irradiation, resulting in the formation of an endoperoxide. The endoperoxide then rearranges to form a dioxetane which undergoes cycloreversion to produce the final product, a di-alpha-naphthoquinone. The factors affecting the photo-oxidation of hypocrellin A were also investigated, including the pH of the solution, nature of the solvent, irradiation wavelength and hydration phenomena. Of these factors, the extremely strong effect of pH on the photo-oxidation of hypocrellin A may be used as a basis for the selective localization of hypocrellin A in tumor tissue. On the basis of the proposed mechanism for the photo-oxidation of PQPs, it may be possible to design and synthesize an optimal tumor-selective PQP photosensitizer for the photodynamic therapy of human tumors.