Femtosecond intersystem crossing to the reactive triplet state of the 2,6-dithiopurine skin cancer photosensitizer
Femtosecond intersystem crossing to the reactive triplet state of the 2,6-dithiopurine skin cancer photosensitizer
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飞秒系间穿越至 2,6-二硫嘌呤皮肤癌光敏剂的反应性三重态
DOI：
10.1039/d1cp04415j
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发表时间：
2021
影响因子：
3.3
通讯作者：
Crespo-Hernández, Carlos E.
中科院分区：
文献类型：
--
作者：
Ortiz-Rodríguez, Luis A.;Hoehn, Sean J.;Acquah, Chris;Abbass, Nadia;Waidmann, Lidia;Crespo-Hernández, Carlos E.
选择性硫取代核碱基是一类用于光动力治疗的全有机、无重原子光敏剂，具有优异的光物理性质，如在电磁波谱的紫外-a区强吸收、近单位三重态产率和单线态产氧率高。最近对双硫代核碱基，2,4-二硫代胸腺嘧啶，2,4-二硫代尿嘧啶和2,6-二硫代嘌呤的研究表明，这些双硫代核碱基的光动力功效优于4-硫代胸腺嘧啶，这是迄今为止研究最广泛的单取代硫代碱基。在三种二硫代核碱基中，2,6-二硫代嘌呤被证明是最有效的，当与5 J cm−2的低UVA剂量联合使用时，显示出高达63%的细胞增殖抑制。在这项研究中，我们阐明了导致2,6-二硫嘌呤反应三重态居群的电子弛豫途径。2,6-二硫嘌呤在不到150秒的时间内填充三重态歧管，在280±50秒的寿命内达到nπ*三重态的最小值。随后，在nπ*三重态最小值内的居群在3±1 ps的寿命内转变为长寿命的ππ*三重态。相对较慢的内部转换寿命与从nπ*到ππ*三重态最小值的主要构象弛豫有关。测得统一三重态产率为1.0±0.1。
Site-selected sulfur-substituted nucleobases are a class of all organic, heavy-atom-free photosensitizers for photodynamic therapy applications that exhibit excellent photophysical properties such as strong absorption in the ultraviolet-A region of the electromagnetic spectrum, near-unity triplet yields, and a high yield of singlet oxygen generation. Recent investigations on doubly thionated nucleobases, 2,4-dithiothymine, 2,4-dithiouracil, and 2,6-dithiopurine, demonstrated that these set of dithionated nucleobases outperform the photodynamic efficacy exhibit by 4-thiothymidine–the most widely studied singly substituted thiobase to date. Out of the three dithionated nucleobases, 2,6-dithiopurine was shown to be the most effective, exhibiting inhibition of cell proliferation of up to 63% when combined with a low UVA dose of 5 J cm−2. In this study, we elucidated the electronic relaxation pathways leading to the population of the reactive triplet state of 2,6-dithiopurine. 2,6-Dithiopurine populates the triplet manifold in less than 150 fs, reaching the nπ* triplet state minimum within a lifetime of 280 ± 50 fs. Subsequently, the population in the nπ* triplet state minimum internally converts to the long-lived ππ* triplet state within a lifetime of 3 ± 1 ps. The relatively slow internal conversion lifetime is associated with major conformational relaxation in going from the nπ* to ππ* triplet state minimum. A unity triplet yield of 1.0 ± 0.1 is measured.