Heavy-Atom-Substituted Nucleobases in Photodynamic Applications: Substitution of Sulfur with Selenium in 6-Thioguanine Induces a Remarkable Increase in the Rate of Triplet Decay in 6-Selenoguanine
Heavy-Atom-Substituted Nucleobases in Photodynamic Applications: Substitution of Sulfur with Selenium in 6-Thioguanine Induces a Remarkable Increase in the Rate of Triplet Decay in 6-Selenoguanine
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DOI：
10.1021/jacs.8b07665
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发表时间：
2018-09-12
影响因子：
15
通讯作者：
Crespo-Hernandez, Carlos E.
中科院分区：
文献类型：
--
作者：
Farrell, Kieran M.;Brister, Matthew M.;Crespo-Hernandez, Carlos E.
DNA/RNA碱基上的氧原子的硫取代促进了超快的系间交叉和接近单位的三联体产率，这些都被用于光动力治疗和结构生物学应用。用硒或碲取代硫应该会显著红移碱基的吸收光谱，而不会牺牲高的三重线产率。因此，相对于硫取代的类似物，硒/碲取代的核苷酸碱基被认为有助于治疗更深层次的组织癌，但它们的光动力学尚未被探索。在这一贡献中，阐明了6-硒鸟嘌呤的光化学松弛机制，并与6-硫代鸟嘌呤前药进行了比较。硒的替代导致了进出三重态流形的系间交叉寿命的显著提高，导致了有效填充的但短暂的三重态。令人惊讶的是，与6-硫代鸟嘌呤相比，6-硒鸟嘌呤的三重态衰减率增加了835倍。这似乎是有机光化学中经典重原子效应的极端表现，这挑战了传统智慧。
Sulfur substitution of carbonyl oxygen atoms of DNA/RNA nucleobases promotes ultrafast intersystem crossing and near-unity triplet yields that are being used for photodynamic therapy and structural biology applications. Replacement of sulfur with selenium or tellurium should significantly red-shift the absorption spectra of the nucleobases without sacrificing the high triplet yields. Consequently, selenium/tellurium-substituted nucleobases are thought to facilitate treatment of deeper tissue carcinomas relative to the sulfur-substituted analogues, but their photodynamics are yet unexplored. In this contribution, the photochemical relaxation mechanism of 6-selenoguanine is elucidated and compared to that of the 6-thioguanine prodrug. Selenium substitution leads to a remarkable enhancement of the intersystem crossing lifetime both to and from the triplet manifold, resulting in an efficiently populated, yet short-lived triplet state. Surprisingly, the rate of triplet decay in 6-selenoguanine increases by 835-fold compared to that in 6-thioguanine. This appears to be an extreme manifestation of the classical heavy-atom effect in organic photochemistry, which challenges conventional wisdom.