MECHANISMS OF SINGLET OXYGEN-DEPENDENT PHOTOSENSITIVITY

单线态氧依赖性光敏性机制

• 批准号: 3755447
• 负责人: C F CHIGNELL
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3755447
• 关键词: anthracenes; benzanthracenes; benzimidazoles; dyes; emission spectrometry; flash photolysis; free radicals; laser spectrometry; lighting; neoplasm /cancer photoradiation therapy; nonvisual photosensitivity; phenothiazines; phosphorescence; photochemistry; photosensitizing agents; physical chemical interaction; psoralens; psoriasis; singlet oxygen; tetracyclines

Photosensitization can result when light interacts with endogenous or exogenous chemical agents in the skin and eyes. This process can produce undesirable clinical consequences, as in phototoxicity and photoallergy; or it can have beneficial effects, as in tumor photodynamic therapy (PDT) and coal-tar or psoralen (PUVA) therapy against psoriasis. Photosensitization results from the light-induced production of free radicals and/or singlet oxygen (1O2), the lowest electronic excited state of molecular oxygen. Because the latter species may be important in both phototoxic reactions and PDT, we have developed state-of-the-art instrumentation capable of detecting the characteristic phosphorescence of 1O2 at 1268 nm. This instrumentation has permitted us to delineate the photophysics of 1O2 production from a number of photosensitizers including phenothiazines, tetracycline, benzoxazoles synthetic dyes, anthralin and 1,8-dihydroxy-anthraquinone. Singlet oxygen has been implicated in the phototoxicity of benzanthrone (7H-benz[de]anthracene-7- one), a dye intermediate prepared from 1,8-dihydroxyanthraquinone. Potential photodynamic agent 1,5-diamino-4,8-dimethoxy-anthraquinone and related compounds were shown to be efficient 1O2 generators which may explain their cytotoxicity to human leukemic cells in culture. The influence of cationic surfactants on the photoprocesses of the sensitizers eosin and rose bengal have been studied in both aqueous and organic solvents. A nano-second laser flash photolysis spectrometer has been built and successfully tested. This equipment now permits us to carry out time-resolved transient absorption and emission spectroscopy on excited state intermediates (precursors to 1O2) of photosensitizers. The spectrometer is being modified to measure singlet oxygen lifetimes in organic solvents and biological systems.

当光与内源或其他物质相互作用时会产生光敏作用 皮肤和眼睛中的外源性化学物质。这一过程可以产生 不良的临床后果，如光毒性和光过敏； 或者它也可以有有益的效果，比如在肿瘤光动力疗法(Pdt)中。 以及煤焦油或补骨脂素(PUVA)治疗银屑病。 光敏化是由光诱导产生的游离 自由基和/或单线态氧(1O2)，最低电子激发态 分子氧的能量。因为后一种可能在两种情况下都很重要 光毒性反应和光动力疗法，我们已经开发出最先进的 一种能够检测特征磷光的仪器 在1268 nm处的1O2。这一仪器使我们能够描绘出 几种光敏剂产生氧气的光物理 包括吩噻嗪、四环素、苯并恶唑类合成染料、 和1，8-二羟基-蒽醌。单线态氧已经被 与苯并三酮的光毒性有关(7H-苯并菲-7- 1)，由1，8-二羟基蒽醌制备的染料中间体。 潜在的光动力试剂1，5-二氨基-4，8-二甲氧基-蒽醌和 相关化合物被证明是有效的氧气产生器，可以 解释它们在培养中对人类白血病细胞的细胞毒性。这个 阳离子表面活性剂对染料光过程的影响 敏化剂曙红和玫瑰孟加拉已经在水和水中进行了研究 有机溶剂。一台纳秒激光闪光光解光谱仪 已经建成并成功进行了测试。这台设备现在允许我们 进行时间分辨的瞬时吸收和发射光谱 关于光敏剂的激发态中间体(到1O2的前体)。 分光计正在改装，以测量单线态氧寿命。 在有机溶剂和生物系统中。