Photosensitization with anticancer agents. 15. Perylenequinonoid pigments as potential photodynamic therapeutic agents: formation of semiquinone radicals and reactive oxygen species on illumination.

Visible light illumination of solutions of perylenequinonoid pigments generates the corresponding semiquinone radicals, singlet oxygen, superoxide anion radical, hydroxyl radical and hydrogen peroxide. In anaerobic solution, the semiquinone radicals are predominantly photoproduced via the self-electron transfer between the excited and ground state species. In aerobic solution, singlet oxygen is the principal product in the photosensitization of perylenequinonoid pigments. The 3,10-dihydroxy-4,9-perylenequinonoid chromophore was shown to be the necessary structural requirement for the generation of singlet oxygen, and the side-chains of the quinones had little effect on the production of singlet oxygen. This conclusion is useful in the development of more efficient photodynamic therapeutic agents than natural perylenequinonoid pigments themselves. Such agents should ideally contain the 3,10-dihydroxy-4,9-perylenequinonoid chromophore to produce singlet oxygen together with appropriate elaborated side-chains to permit the selective localization of the sensitizer in tumor tissue. In addition to singlet oxygen, superoxide anion radical is generated by the perylenequinones on illumination in aerobic solution, but to a lesser extent than singlet oxygen, via the reduction of oxygen by the corresponding semiquinone radicals. This latter process is significantly enhanced by the presence of electron donors.