Gas-Phase Experimental and Computational Studies of 5-Halouracils: Intrinsic Properties and Biological Implications
Gas-Phase Experimental and Computational Studies of 5-Halouracils: Intrinsic Properties and Biological Implications
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DOI：
10.1021/acs.joc.1c00183
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发表时间：
2021-04-23
影响因子：
3.6
通讯作者：
Lee, Jeehiun K.
中科院分区：
文献类型：
--
作者：
Krajewski, Allison E.;Lee, Jeehiun K.
用理论和实验方法研究了5-氟脲嘧啶、5-氯脲嘧啶、5-溴脲嘧啶和5-碘脲嘧啶的气相酸度和质子亲和（PA）。这项工作代表了对这些核碱基的热化学性质的全面研究。除5-氟尿嘧啶的酸度外，这些氟脲嘧啶的固有酸度和PA尚未测定过；这些新的实验数据为计算值提供了一个基准。此外，我们在胸腺嘧啶DNA糖基化酶（TDG）的背景下研究了这些5-卤脲嘧啶，这是一种通过从DNA中切割这些底物来保护基因组的酶。我们的气相结果与TDG切除率进行了比较和对比，以深入了解TDG的机制。
The gas-phase acidity and proton affinity (PA) of 5-halouracils (5-fluorouracil, 5-chlorouracil, 5-bromouracil, and 5-iodouracil) have been examined using both theoretical and experimental methods. This work represents a comprehensive study of the thermochemical properties of these nucleobases. Other than 5-fluorouracil acidity, the intrinsic acidity and PA of these halouracils have not been heretofore measured; these new experimental data provide a benchmark for the computational values. Furthermore, we examine these 5-halouracils in the context of the enzyme thymine DNA glycosylase (TDG), which is an enzyme that protects the genome by cleaving these substrates from DNA. Our gas-phase results are compared and contrasted to TDG excision rates to afford insights into the TDG mechanism.