Photosensitization with anticancer agents 14. Perylenequinonoid pigments as new potential photodynamic therapeutic agents: formation of tautomeric semiquinone radicals

Abstract

Abstract When perylenequinonoid pigments were irradiated with visible light, semiquinone radicals, singlet oxygen, superoxide anion radical, hydroxyl radical and hydrogen peroxide were detected. The formation of the semiquinone radicals and activated oxygen species and the transformations and competitions between them depend on the quinone and oxygen concentrations, time and intensity of irradiation and the nature of the substrate. In anaerobic solution, the semiquinone radicals, which exhibit well-defined electron paramagnetic resonance (EPR) spectra at room temperature, are predominantly photoproduced via the self-electron transfer between the excited and ground species. The EPR spectra of the semiquinone radicals were assigned by reference to simulated spectra. The presence of electron donors significantly promotes the production of the semiquinone radicals. The EPR hyperfine splittings of the semiquinone radicals mainly originate from the coupling interactions of the aromatic, phenolic hydroxyl and methoxyl protons with the unpaired spin. An exception is hypocrellin B in which the two methylene protons of the side-ring are also involved in the hyperfine splitting to a minor extent because the double bond of the side-ring conjugates with the perylenequinonoid chromophore. In addition, compared with cercosporin, the EPR spectra of the hypocrellin semiquinone radicals are further complicated by tautomerizations at ambient temperature. Therefore EPR spectroscopy can also be utilized to study the tautomerization together with nuclear magnetic resonance (NMR), absorption spectroscopy and some specific chemical trapping reactions. In aerobic solution, singlet oxygen is the principal product in the photosensitization of perylenequinonoid pigments. In addition to singlet oxygen, superoxide anion radical is also generated, to a lesser extent, by the quinones on illumination in aerobic solution via the reduction of oxygen by the semiquinone radicals, and this process is significantly enhanced by the presence of electron donors.