EPR studies of the photodynamic properties of a novel potential photodynamic therapeutic agent: photogeneration of semiquinoneradical anion and active oxygen species (O2˙−, OH˙, H2O2 and 1O2)

Abstract

Cyclohexylamino-substituted hypocrellin B (CHAHB) has been synthesized with the aim of improving the red absorption and specific affinity for malignant tumors over those of the parent compound. Irradiation of a deoxygenated DMSO solution of CHAHB generates a strong electron paramagnetic resonance (EPR) signal, which is assigned to the semiquinone radical anion of CHAHB with the aid of a series of experimental results. In the presence of oxygen, superoxide radical anions (O₂˙⁻) are generated via electron transfer from CHAHB˙⁻, the precursor, to ground-state molecular oxygen. Hydroxyl radicals were detected by spin-trapping EPR when an oxygen-saturated aqueous solution containing CHAHB and DMPO was irradiated. Singlet oxygen (¹O₂) is produced via energy transfer from triplet CHAHB to ground-state oxygen molecules, with a sharply decreased quantum yield, i.e. 0.11. Furthermore, cell survival studies reveal CHAHB exhibits much higher photodynamic activities than its parent hypocrellins. The strongly enhanced photodynamic activities and sharply decreased quantum yield of ¹O₂ generation suggest that the type I (free radical) mechanism may play a significant role in CHAHB-PDT, rather than the type II (singlet oxygen) mechanism found in photofrin-PDT.