Atomistic Simulation Centre, Queen's University Belfast, UK.
J Am Chem Soc. 2012 Jun 6;134(22):9122-5. doi: 10.1021/ja303776r. Epub 2012 May 25.
When biological matter is subjected to ionizing radiation, a wealth of secondary low-energy (<20 eV) electrons are produced. These electrons propagate inelastically, losing energy to the medium until they reach energies low enough to localize in regions of high electron affinity. We have recently shown that in fully solvated DNA fragments, nucleobases are particularly attractive for such excess electrons. The next question is what is their longer-term effect on DNA. It has been advocated that they can lead to strand breaks by cleavage of the phosphodiester C(3')-O(3') bond. Here we present a first-principles study of free energy barriers for the cleavage of this bond in fully solvated nucleotides. We have found that except for dAMP, the barriers are on the order of 6 kcal/mol, suggesting that bond cleavage is a regular feature at 300 K. Such low barriers are possible only as a result of solvent and thermal fluctuations. These findings support the notion that low-energy electrons can indeed lead to strand breaks in DNA.
当生物物质受到电离辐射时，会产生大量的次级低能（<20 eV）电子。这些电子非弹性传播，在能量降低到足以在高电子亲和力区域定位之前，不断向介质中损失能量。我们最近表明，在完全溶剂化的 DNA 片段中，碱基对这些过剩电子具有特别的吸引力。下一个问题是它们对 DNA 的长期影响是什么。有人主张，它们可以通过磷酸二酯 C(3')-O(3')键的断裂导致链断裂。在这里，我们对完全溶剂化核苷酸中这种键的断裂的自由能势垒进行了第一性原理研究。我们发现，除了 dAMP，势垒的大小约为 6 千卡/摩尔，这表明在 300 K 时键断裂是一个常见特征。只有在溶剂和热波动的情况下，这种低势垒才是可能的。这些发现支持了这样一种观点，即低能电子确实可以导致 DNA 链断裂。
