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 mol ecule, is a new photosensitizer currently in phase II clinical trials for the treatment by photodynamic therapy of cancerous lesions, psoria sis and pathologic neovascularization. The photochemistry (type I and/ or II) of BPD-MA has been studied in homogeneous solution and in aqueo us dispersions of unilamellar liposomes of dipalmitoylphosphatidylchol ine (DPPC) using electron paramagnetic resonance and spectrophotometri c 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 f ormed, 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 incorporati on of BPD-MA into liposomes of DPPC, The superoxide anion radical was generated by the BPD-MA anion radical (BPD-MA .(-)) via electron trans fer to oxygen, and this process was significantly enhanced by the pres ence of electron donors, The rate of production of O-2 .(-) was also d ependent 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 disproporti onation can generate H2O2 and ultimately the highly reactive . OH via the Fenton reaction, In anaerobic homogeneous solution, BPD-MA .(-) wa s predominantly photoproduced via the self-electron transfer between t he excited- and ground-state species, The presence of an electron dono r significantly promotes the reduced form of BPD-MA, These findings su ggest that the photodynamic action of BPD-MA may proceed via both type I and type II mechanisms.