Li Xifeng, Sanche Léon, Sevilla Michael D
Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, Université de Sherbrooke, Quebec, J1H 5N4, Canada.
Radiat Res. 2006 Jun;165(6):721-9. doi: 10.1667/RR3568.1.
Low-energy electrons are known to induce strand breaks and base damage in DNA and RNA through fragmentation of molecular bonding. Recently the glycosidic bond cleavage of nucleosides by low-energy electrons has been reported. These experimental results call for a theoretical investigation of the strength of the C(1)'-N link in nucleosides (dA, dC and dT) between the base and deoxyribose before and after electron attachment. Through density functional theory (DFT) calculations, we compare the C(1)'-N bond strength, i.e., the bond dissociation energy of the neutral and its anionic radical, and find that an excess electron effectively weakens the C(1)'- N bond strength in nucleosides by 61-75 kcal/mol in the gas phase and 76-83 kcal/mol in the solvated environment. As a result, electron-induced fragmentation of the C(1)'-N bond in the gas phase is exergonic for dA (DeltaG=-14 kcal/mol) and for dT (DeltaG=-6 kcal/mol) and is endergonic (DeltaG=+1 kcal/ mol) only for dC. In the gas phase all the anionic nucleosides are found to be in valence states. Solvation is found to increase the exergonic nature by an additional 20 kcal, making the fragmentation both exothermic and exergonic for all nucleoside anion radicals. Thus C(1)'-N bond breaking in nucleoside anion radicals is found to be thermodynamically favorable both in the gas phase and under solvation. The activation barrier for the C(1)'-N bond breaking process was found to be about 20 kcal/mol in every case examined, suggesting that a 1 eV electron would induce spontaneous cleavage of the bond and that stabilized anion radicals on the DNA strand would undergo base release at only a modest rate at room temperature. These results suggest that base release from nucleosides and DNA is an expected consequence of low-energy electron-induced damage but that the high barrier would inhibit this process in the stable anion radicals.
已知低能电子可通过分子键断裂在DNA和RNA中诱导链断裂和碱基损伤。最近有报道称低能电子可导致核苷的糖苷键断裂。这些实验结果需要对电子附着前后核苷（dA、dC和dT）中碱基与脱氧核糖之间C(1)'-N键的强度进行理论研究。通过密度泛函理论（DFT）计算，我们比较了C(1)'-N键强度，即中性分子及其阴离子自由基的键解离能，发现一个多余电子在气相中可有效削弱核苷中C(1)'-N键强度61 - 75千卡/摩尔，在溶剂化环境中可削弱76 - 83千卡/摩尔。结果，气相中电子诱导的dA（ΔG = -14千卡/摩尔）和dT（ΔG = -6千卡/摩尔）的C(1)'-N键断裂是放能的，而dC的则是吸能的（ΔG = +1千卡/摩尔）。在气相中，所有阴离子核苷都处于价态。发现溶剂化会使放能性质额外增加20千卡，使得所有核苷阴离子自由基的断裂既是放热的也是放能的。因此，发现核苷阴离子自由基中的C(1)'-N键断裂在气相和溶剂化条件下在热力学上都是有利的。在所研究的每种情况下，发现C(1)'-N键断裂过程的活化能垒约为20千卡/摩尔，这表明1电子伏特的电子会诱导该键自发断裂，并且DNA链上稳定的阴离子自由基在室温下仅以适度的速率发生碱基释放。这些结果表明，核苷和DNA的碱基释放是低能电子诱导损伤的预期结果，但高能量垒会在稳定的阴离子自由基中抑制这一过程。
