EPR and spectrophotometric studies of free radicals (O-2 center dot(-), center dot OH, BPD-MA center dot(-)) and singlet oxygen (O-1(2)) generated by irradiation of benzoporphyrin derivative monoacid ring A

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 photodynamic 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 (O-1(2)), superoxide anion radical (O-2 .(-)), hydroxyl radical (. OH) and hydrogen peroxide (H2O2) were formed, The BPD-MA generates O-1(2) 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 O-2 .(-) was also dependent on the concentration of BPD-MA used (3-100 mu M). The quantum yield of O-2 .(-) was found to be 0.011 and 0.025 in aqueous solution and DPPC liposomes, respectively, Moreover, O-2 .(-) upon disproportionation 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.