EPR and Spectrophotometric Studies of Free Radicals (O2°−, °OH, BPD‐MA°−) and Singlet Oxygen (1O2) Generated by Irradiation of Benzoporphyrin Derivative Monoacid Ring A

Abstract

Abstract— Benzoporphyrin derivative monoacid ring A (BPD‐MA), a chlorin‐type molecule, is a new photosensitizer currently in phase II clinical trials for the treatment by pho‐todynamic therapy of cancerous lesions, psoriasis and pathologic neovascularization. The photochemistry (type I and/or II) of BPD‐MA has been studied in homogeneous solution and in aqueous dispersions of unilamellar liposomes of dipalmitoylphosphatidylcholine (DPPC) using electron paramagnetic resonance and spectrophotometric methods. When oxygen‐saturated solutions of BPD‐MA were illuminated with 690 nm light, singlet oxygen (1O2), superoxide anion radical (O2−), hydroxyl radical (OH) and hydrogen peroxide (H2O2) were formed. The BPD‐MA generates 1O2 with a quantum yield of ca 0.81 in ethanolic solution. The quantum yield does not change upon incorporation of BPD‐MA into liposomes of DPPC. The superoxide anion radical was generated by the BPD‐MA anion radical (BPD‐MA−) via electron transfer to oxygen, and this process was significantly enhanced by the presence of electron donors. The rate of production of 02 was also dependent on the concentration of BPD‐MA used (3‐100 μM). The quantum yield of O2−was found to be 0.011 and 0.025 in aqueous solution and DPPC liposomes, respectively. Moreover, O2_upon dis‐proportionation can generate H2O2 and ultimately the highly reactive OH via the Fenton reaction. In anaerobic homogeneous solution, BPD‐MA−was predominantly photoproduced via the self‐electron transfer between the excited‐ and ground‐state species. The presence of an electron donor significantly promotes the reduced form of BPD‐MA. These findings suggest that the photodynamic action of BPD‐MA may proceed via both type I and type II mechanisms.