Institute of Theoretical Chemistry, Faculty of Chemistry , University of Vienna , Währinger Straße 17 , 1090 Vienna , Austria.
J Chem Theory Comput. 2019 Jun 11;15(6):3730-3742. doi: 10.1021/acs.jctc.9b00208. Epub 2019 May 10.
Excited-state MS-CASPT2 and ADC(2) quantum chemical calculations and nonadiabatic dynamics simulations show that 2-selenouracil is able to both efficiently populate and depopulate reactive triplet states in an ultrashort time scale. Thus, the heavier homologue of 2-thiouracil unites the ultrafast, high-yield intersystem crossing of 2-thiouracil with the short excited-state lifetime and photostability of the parent nucleobase uracil-two properties that have been traditionally thought to be diametrically opposed. Remarkably, while the S → S → T → T deactivation dynamics of 2-selenouracil is analogous to that of 2-thiouracil, the calculations show that the triplet lifetime of 2-selenouracil should decrease by up to 3 orders of magnitude in comparison to that 2-thiouracil, possibly down to the few-picosecond time scale. The main reasons for this decrease are the lack of a second T minimum, the enhanced spin-orbit coupling, and the reduction of the energy barrier to access the T/ S crossing-in particular in aqueous solution-compared to 2-thiouracil. Such unusual photophysical properties, together with its significant red-shifted absorption spectrum, could make 2-selenouracil a useful specialized photosensitizer for photodynamical therapy.
激发态 MS-CASPT2 和 ADC(2) 量子化学计算和非绝热动力学模拟表明，2-硒尿嘧啶能够在超短时间尺度内有效地填充和排空反应三重态。因此，2-硫代尿嘧啶的较重同系物结合了 2-硫代尿嘧啶的超快、高产系间窜越，以及母体核碱基尿嘧啶的短激发态寿命和光稳定性——这两个性质传统上被认为是截然相反的。值得注意的是，虽然 2-硒尿嘧啶的 S → S → T → T 失活动力学类似于 2-硫代尿嘧啶，但计算表明，2-硒尿嘧啶的三重态寿命应该比 2-硫代尿嘧啶下降多达 3 个数量级，可能降至几皮秒的时间尺度。这种下降的主要原因是缺乏第二个 T 最小值、增强的自旋轨道耦合以及与 2-硫代尿嘧啶相比，进入 T/S 交叉的能垒降低，特别是在水溶液中。这种不寻常的光物理性质，加上其显著的红移吸收光谱，可能使 2-硒尿嘧啶成为光动力治疗的有用专用光敏剂。
