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
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
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DOI：
10.1111/j.1751-1097.1997.tb01929.x
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发表时间：
1997-05-01
影响因子：
3.3
通讯作者：
vandenBergh, H
中科院分区：
文献类型：
--
作者：
Hadjur, C;Wagnieres, G;vandenBergh, H
苯并卟啉衍生物单酸环A（BPD-MA）是一种二氢卟酚型分子，是一种新型光敏剂，目前正在进行II期临床试验，用于通过光动力疗法治疗癌性病变、牛皮癣和病理性新生血管。使用电子顺磁共振和分光光度法研究了 BPD-MA 在均匀溶液和二棕榈酰磷脂酰胆碱 (DPPC) 单层脂质体水分散体中的光化学（I 型和/或 II 型）。当用 690 nm 光照射 BPD-MA 的氧饱和溶液时，单线态氧 (O-1(2))、超氧阴离子自由基 (O-2 .(-))、羟基自由基 (.形成OH)和过氧化氢(H2O2)，BPD-MA在乙醇溶液中生成量子产率约0.81的O-1(2)。将 BPD-MA 掺入 DPPC 脂质体后，量子产率不会改变。超氧阴离子自由基是由 BPD-MA 阴离子自由基 (BPD-MA .(-)) 通过电子转移到氧而产生的，并且该过程因电子供体的存在而显着增强。O-2 .(-) 的产生速率也取决于所用 BPD-MA 的浓度 (3-100 μM)。发现O-2.(-)在水溶液和DPPC脂质体中的量子产率分别为0.011和0.025。此外，O-2.(-)歧化后可生成H2O2并最终产生高反应性。通过芬顿反应产生 OH，在厌氧均相溶液中，BPD-MA .(-) 主要通过激发态和基态物质之间的自电子转移产生光产生，电子供体的存在显着促进 BPD-MA 的还原形式，这些发现表明 BPD-MA 的光动力作用可能通过 I 型和 II 型机制进行。
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.