PHOTOSENSITIZATION WITH ANTICANCER AGENTS .16. THE PHOTOOXIDATION OF HYPOCRELLIN-A - A MECHANISM STUDY USING O-18 LABELING
PHOTOSENSITIZATION WITH ANTICANCER AGENTS .16. THE PHOTOOXIDATION OF HYPOCRELLIN-A - A MECHANISM STUDY USING O-18 LABELING
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DOI：
10.1016/1011-1344(93)80056-f
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发表时间：
1993-05-01
影响因子：
5.4
通讯作者：
LOWN, JW
中科院分区：
文献类型：
--
作者：
DIWU, ZJ;LOWN, JW
以竹红菌素A为代表结构，研究了萜酮类色素(PQPs)的光氧化机理。研究发现，单线态氧在PQP的光氧化过程中起着关键作用。用O-18原子标记确定了以下过程参与了对苯二酚的光氧化。在PQP被光激发后，它互变异构化并解离产生阴离子，阴离子与辐射过程中产生的单线态氧反应，产生内源过氧化物质。然后，内过氧物重新排列形成二氧杂环己烷，该二氧杂环己烷经过环化反应生成最终产品，即双α-萘醌。考察了溶液pH值、溶剂性质、光照波长和水合现象等因素对竹红菌甲素光氧化的影响。在这些因素中，pH对竹红菌素A光氧化的极强影响可以作为竹红菌素A在肿瘤组织中选择性定位的基础。根据PQP的光氧化机理，有可能设计和合成一种最佳的肿瘤选择性PQP光敏剂，用于人体肿瘤的光动力治疗。
Hypocrellin A was selected as a representative structure to investigate the mechanism of photo-oxidation of perylenequinonoid pigments (PQPs). It was found that singlet oxygen plays a key role in the photo-oxidation of PQPs. The following processes were determined to be involved in the photo-oxidation of PQPs using O-18 atom labelling. After the PQP is photoexcited, it tautomerizes and dissociates to produce the anion, which reacts with singlet oxygen generated during irradiation, resulting in the formation of an endoperoxide. The endoperoxide then rearranges to form a dioxetane which undergoes cycloreversion to produce the final product, a di-alpha-naphthoquinone. The factors affecting the photo-oxidation of hypocrellin A were also investigated, including the pH of the solution, nature of the solvent, irradiation wavelength and hydration phenomena. Of these factors, the extremely strong effect of pH on the photo-oxidation of hypocrellin A may be used as a basis for the selective localization of hypocrellin A in tumor tissue. On the basis of the proposed mechanism for the photo-oxidation of PQPs, it may be possible to design and synthesize an optimal tumor-selective PQP photosensitizer for the photodynamic therapy of human tumors.