Membrane Damage Efficiency of Phenothiazinium Photosensitizers
Membrane Damage Efficiency of Phenothiazinium Photosensitizers
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DOI：
10.1111/php.12264
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发表时间：
2014-07-01
影响因子：
3.3
通讯作者：
Baptista, Mauricio S.
中科院分区：
文献类型：
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作者：
Bacellar, Isabel O. L.;Pavani, Christiane;Baptista, Mauricio S.
卟啉和酞菁类光敏剂的构效关系已被广泛报道，但吩噻嗪鎓衍生物的构效关系还没有报道。在这里，四吩噻嗪盐（亚甲蓝，甲苯胺蓝O，1，9-二甲基亚甲蓝和五环衍生物DO 15）被用来研究如何破坏膜的能力是受膜/溶液分配，物理性质和聚集的光敏剂的倾向。后两个方面都在各向同性溶液和膜中进行了研究。膜损伤进行了评估，通过泄漏的荧光探针包埋在脂质体和硫代巴比妥酸反应性物种（TBARS）的产生，而在脂质双层的结构变化进行了检测，通过小角度X-射线散射。我们观察到，所有的化合物在乙醇中具有相似的单线态氧量子产率，但只有具有较高的膜/溶液分配（1，9-二甲基亚甲基蓝和DO 15，后者具有较高的值）的光敏剂可以透化脂质双层。此外，在这两种光敏剂中，只有DO 15改变了膜结构，这一结果归因于其使更高阶聚集体不稳定、在膜内产生更高量的单线态氧以及在其二聚体内的有效电子转移反应。我们的结论是，基于膜的协议可以提供一个更好的洞察光敏剂的光动力学效率。
Structure-activity relationships have been widely reported for porphyrin and phthalocyanine photosensitizers, but not for phenothiazinium derivatives. Here, four phenothiazinium salts (methylene blue, toluidine blue O, 1,9-dimethyl methylene blue and the pentacyclic derivative DO15) were used to investigate how the ability to damage membranes is affected by membrane/solution partition, photophysical properties and tendency to aggregation of the photosensitizer. These two latter aspects were studied both in isotropic solutions and in membranes. Membrane damage was assessed by leakage of a fluorescent probe entrapped in liposomes and by generation of thiobarbituric acid-reactive species (TBARS), while structural changes at the lipid bilayer were detected by small-angle X-ray scattering. We observed that all compounds had similar singlet-oxygen quantum yields in ethanol, but only the photosensitizers that had higher membrane/solution partition (1,9-dimethyl methylene blue and DO15, the latter having the higher value) could permeabilize the lipid bilayer. Moreover, of these two photosensitizers, only DO15 altered membrane structure, a result that was attributed to its destabilization of higher order aggregates, generation of higher amounts of singlet oxygen within the membranes and effective electron-transfer reaction within its dimers. We concluded that membrane-based protocols can provide a better insight on the photodynamic efficiency of the photosensitizer.