Pollum M, Jockusch S, Crespo-Hernández C E
Department of Chemistry and Center for Chemical Dynamics, Case Western Reserve University, Cleveland, OH 44106, USA.
Phys Chem Chem Phys. 2015 Nov 7;17(41):27851-61. doi: 10.1039/c5cp04822b.
The ability of 4-thiouracil to strongly absorb UVA radiation and to populate a reactive triplet state in high yield has enabled its use as a versatile photocrosslinker for nearly 50 years. In this contribution, we present a detailed spectroscopic and photochemical investigation of the 2-thiouracil, 4-thiouracil, and 2,4-dithiouracil series in an effort to further advance this chemistry and to scrutinize the photoreactivity of 2,4-dithiouracil. Our results reveal that excitation of 2,4-dithiouracil leads to intersystem crossing to the triplet manifold in 220 ± 40 fs, which enables the population of the reactive triplet state with near unity yield (ΦT = 0.90 ± 0.15) and ultimately leads to a ca. 50% singlet oxygen generation (ΦΔ = 0.49 ± 0.02)-one of the highest singlet oxygen yields reported to date for a photoexcited thiobase. In addition, the long-lived triplet state of 2,4-dithiouracil reacts efficiently with the nucleic acid base adenine 5'-monophosphate through a direct, oxygen-independent photocycloaddition mechanism and at a rate that is at least 3-fold faster than that of 4-thiouracil under equal conditions. The new physico-chemical insights reported for these RNA-thiobase derivatives are compared to those of the DNA and RNA bases and the DNA-thiobase derivatives. Furthermore, the strong near-visible absorption and increased photoreactivity measured for 2,4-dithiouracil lays a solid foundation for developing RNA-targeted photocrosslinking and phototherapeutic agents that are more effective than those currently available.
4-硫尿嘧啶能够强烈吸收紫外光A辐射并高产率地形成反应性三线态，这使得它作为一种通用的光交联剂已被使用了近50年。在本论文中，我们对2-硫尿嘧啶、4-硫尿嘧啶和2,4-二硫尿嘧啶系列进行了详细的光谱和光化学研究，以进一步推动该化学领域的发展，并仔细研究2,4-二硫尿嘧啶的光反应活性。我们的结果表明，2,4-二硫尿嘧啶的激发在220±40飞秒内导致系间窜越至三线态，这使得反应性三线态的产率接近100%（ΦT = 0.90±0.15），并最终导致约50%的单线态氧生成（ΦΔ = 0.49±0.02）——这是迄今为止报道的光激发硫代碱基中最高的单线态氧产率之一。此外，2,4-二硫尿嘧啶的长寿命三线态通过直接的、不依赖氧气的光环加成机制与核酸碱基5'-单磷酸腺苷高效反应，其反应速率在相同条件下比4-硫尿嘧啶至少快3倍。将这些RNA硫代碱基衍生物的新物理化学见解与DNA和RNA碱基以及DNA硫代碱基衍生物的见解进行了比较。此外，2,4-二硫尿嘧啶所测量到的强烈近可见吸收和增强的光反应活性为开发比现有药物更有效的RNA靶向光交联和光治疗剂奠定了坚实基础。
