Department of Chemistry and Henry Eyring Center for Theoretical Chemistry, University of Utah, Salt Lake City, Utah, USA.
J Phys Chem A. 2013 Feb 14;117(6):1240-53. doi: 10.1021/jp305561u. Epub 2012 Aug 28.
A wide range of experimental data from earlier studies by other workers are combined with recent data from the Burrows group to interpret that group's thymine dimer (T = T) repair rate data for 8-oxo-7,8-dihydroguanine (OG)-containing DNA duplexes. The focus of this effort is to explain (i) how and why the repair rates vary as the sequence location and distance of the OG relative to the T═T is changed and (ii) why the spatial extent over which repair is observed is limited to OG-T═T distances of ~6 Å. It is proposed that, if the OG and T═T are within ~5-6 Å, a Coulomb potential moves the energy of the OG(+)···T═T(-) ion-pair state below the photoexcited OG*···T═T state, even in the absence of full solvent relaxation, thus enhancing forward electron transfer from OG* to T═T by allowing it to occur as a radiationless internal conversion process rather than by overcoming a solvation-related barrier. The rate of this forward electron transfer is estimated to be ~10% of the decay rate of the photoexcited OG*. For OG-to-T═T distances beyond 5-6 Å, electron transfer is still exothermic, but it must occur through solvent reorganization, overcoming an energy barrier, which presumably renders this rate too slow to be detected in the experiments under study here. Once an electron has been injected into the T═T, as many other workers have shown, the reaction proceeds through two low-energy barriers first connecting T═T(-) to an intermediate in which the C(5)-C(5') bond of the cyclobutane unit is cleaved, and onward to where the cyclobutane unit is fully broken and two intact thymine sites are established. Our ab initio data show that the energy landscape for these bond cleavages is altered very little by the presence of the proximal OG(+) cation, which therefore allows us to use data from the earlier studies to conclude that it takes ~100 ps for complete bond cleavage to occur. The experimentally determined overall T═T repair quantum yield of 1% then allows us to estimate the rate at which an electron is transferred from the T═T(-) anion back to the OG(+) cation as 10 times the rate of bond cleavage. The experimental variations in T═T repair rates among several sequences are shown to be reasonably consistent with an exponential OG-to-T═T distance dependence, e(-βR), with a decay parameter of β = 0.6 Å(-1). Finally, suggestions are offered for experimental studies that would test the predictions offered here and shed further light on the OG-induced T═T repair mechanism.
将其他研究人员在早期进行的大量实验数据与 Burrows 小组的最新数据相结合,以解释该小组的胸腺嘧啶二聚体 (T = T) 修复率数据,这些数据与含有 8-氧代-7,8-二氢鸟嘌呤 (OG) 的 DNA 双链体有关。这项研究的重点是解释 (i) 修复率如何以及为何随着 OG 相对于 T = T 的序列位置和距离的变化而变化,以及 (ii) 为什么观察到的修复范围仅限于 OG-T = T 距离约为 6 Å。据推测,如果 OG 和 T = T 在 ~5-6 Å 范围内,库仑势将 OG(+)···T = T(-) 离子对态的能量降低到光激发的 OG*···T = T 态以下,即使在没有完全溶剂弛豫的情况下,也会通过允许它作为无辐射内部转换过程而不是通过克服与溶剂相关的势垒来增强从 OG* 到 T = T 的正向电子转移。正向电子转移的速率估计为光激发的 OG* 衰减速率的 ~10%。对于 OG 到 T = T 的距离超过 5-6 Å,电子转移仍然是放热的,但它必须通过溶剂重组来发生,克服一个能量势垒,这大概使得在我们在这里研究的实验中无法检测到这种速率。一旦电子被注入到 T = T 中,正如许多其他研究人员所表明的那样,反应通过两个低能势垒进行,首先将 T = T(-)连接到环丁烷单元的 C(5)-C(5') 键断裂的中间态,然后继续连接到环丁烷单元完全断裂并且两个完整的胸腺嘧啶位点建立的状态。我们的从头算数据表明,这些键断裂的能量景观几乎不受邻近的 OG(+)阳离子的存在影响,这使得我们能够使用早期研究的数据得出结论,即完全键断裂需要 ~100 ps 才能发生。实验确定的整体 T = T 修复量子产率为 1%,然后允许我们估计电子从 T = T(-)阴离子转移回 OG(+)阳离子的速率是键断裂速率的 10 倍。实验中观察到的几个序列之间的 T = T 修复速率的变化与指数型 OG 到 T = T 的距离依赖性,e(-βR),衰减参数 β = 0.6 Å(-1),具有合理的一致性。最后,提出了一些实验研究建议,这些建议将检验这里提出的预测,并进一步阐明 OG 诱导的 T = T 修复机制。