Gas-phase thermochemical properties of the damaged base O(6)-methylguanine versus adenine and guanine.
Gas-phase thermochemical properties of the damaged base O(6)-methylguanine versus adenine and guanine.
复制标题
受损碱基 O(6)-甲基鸟嘌呤与腺嘌呤和鸟嘌呤的气相热化学性质。
DOI：
--
复制
发表时间：
2009
影响因子：
3.6
通讯作者：
Jeehiun K. Lee
中科院分区：
文献类型：
--
作者：
Anna E. Zhachkina;Min Liu;Xuejun Sun;F. Amegayibor;Jeehiun K. Lee
用理论方法(B3LYP/6-31+G*)和实验方法(Backering，Cooks动力学)研究了腺嘌呤、鸟嘌呤和O(6)-甲基鸟嘌呤(OMG)的气相酸性(DeltaH(酸)和DeltaG(酸))和质子亲和力(PA和气相碱性(GB))。以前我们用夹带法测定腺嘌呤的酸度，这里我们用Cooks动力学方法测定腺嘌呤的酸度(DeltaH(酸)=335+/-3kcal摩尔(-1)；DeltaG(酸)=329+/-3kcal摩尔(-1))。我们还用支架法和Cooks法测量了腺嘌呤的PA/GB(PA=224和225千卡摩尔(-1)；GB=216和217千卡摩尔(-1))。根据计算，鸟嘌呤在气相中有几个稳定的互变异构体，而在溶液中，正则互变异构体占主导地位。由于鸟嘌呤的非挥发性，实验测量它的性质是困难的；使用电喷雾和Cooks动力学方法，我们能够测量到335+/-3kcal摩尔(-1)的DeltaH(酸)(DeltaG(酸)=328+/-3kcal摩尔(-1))。质子亲和力为227+/-3千卡摩尔(-1)(GB=219+/-3千卡摩尔(-1))。这些值与计算的比较表明，在我们的条件下，在气相中可能有酮和烯醇互变异构体的混合物，尽管也可能只有正则形式，因为在Cooks方法中，我们通过电喷雾水溶液形成质子结合的二聚体，这应该有利于正则形式的鸟嘌呤。我们还检测了O(6)-甲基鸟嘌呤(OMG)，这是一种由鸟嘌呤烷基化而产生的高度突变的受损碱基。我们的计算表明，OMG可能在气相中以“N9”(正则)和“N7”(N7上的质子而不是N9上的质子)互变异构体的形式存在，因为两者的能量都在3kcal mol(-1)以内。我们对OMG的酸性和质子亲和力进行了分类，这是以前未知的。酸性较强的OMG中心的DeltaH(酸)值为338+/-3kcal摩尔(-1)(DeltaG(酸)=331+/-3kcal摩尔(-1))。我们还包括了弱酸性中心(DeltaH(酸)=362+/-3kcal mol(-1)，DeltaG(酸)=355+/-3kcal(-1))和PA(229+/-4kcal(-1)(GB=222+/-4kcal(-1)。我们也通过Cooks动力学方法的测量证实了这些结果。我们的最终目标是了解核苷酸碱基的内在反应性；气相的酸性和碱性属性对化学原因感兴趣，也可能出于生物目的，因为生物介质可以是相当非极性的。我们发现OMG在N9位的酸性比腺嘌呤和鸟嘌呤弱得多，在O6位的碱性比鸟嘌呤弱得多；我们讨论了这些差异的生物学意义。
The gas phase acidity (DeltaH(acid) and DeltaG(acid)) and proton affinity (PA, and gas phase basicity (GB)) of adenine, guanine, and O(6)-methylguanine (OMG) have been examined using both theoretical (B3LYP/6-31+G*) and experimental (bracketing, Cooks kinetic) methods. We previously measured the acidity of adenine using bracketing methods; herein we measure the acidity of adenine by the Cooks kinetic method (DeltaH(acid) = 335 +/- 3 kcal mol(-1); DeltaG(acid) = 329 +/- 3 kcal mol(-1)). We also measured the PA/GB of adenine using both bracketing and Cooks methods (PA = 224 and 225 kcal mol(-1); GB = 216 and 217 kcal mol(-1)). Guanine is calculated to have several stable tautomers in the gas phase, in contrast to in solution, where the canonical tautomer predominates. Experimental measurements of gas phase guanine properties are difficult due to its nonvolatility; using electrospray and the Cooks kinetic method, we are able to measure a DeltaH(acid) of 335 +/- 3 kcal mol(-1) (DeltaG(acid) = 328 +/- 3 kcal mol(-1)). The proton affinity is 227 +/- 3 kcal mol(-1) (GB = 219 +/- 3 kcal mol(-1)). Comparison of these values to calculations indicates that we may have a mixture of the keto and enol tautomers under our conditions in the gas phase, although it is also possible that we only have the canonical form since in the Cooks method, we form the proton-bound dimers via electrospray of an aqueous solution, which should favor guanine in the canonical form. We also examined O(6)-methylguanine (OMG), a highly mutagenic damaged base that arises from the alkylation of guanine. Our calculations indicate that OMG may exist as both the "N9" (canonical) and "N7" (proton on N7 rather than N9) tautomers in the gas phase, as both are calculated to be within 3 kcal mol(-1) in energy. We have bracketed the acidity and proton affinity of OMG, which were previously unknown. The more acidic site of OMG has a DeltaH(acid) value of 338 +/- 3 kcal mol(-1) (DeltaG(acid) = 331 +/- 3 kcal mol(-1)). We have also bracketed the less acidic site (DeltaH(acid) = 362 +/- 3 kcal mol(-1), DeltaG(acid) = 355 +/- 3 kcal mol(-1)) and the PA (229 +/- 4 kcal mol(-1) (GB = 222 +/- 4 kcal mol(-1))). We confirmed these results through Cooks kinetic method measurements as well. Our ultimate goal is to understand the intrinsic reactivity of nucleobases; gas phase acidic and basic properties are of interest for chemical reasons and also possibly for biological purposes, since biological media can be quite nonpolar. We find that OMG is considerably less acidic at N9 than adenine and guanine and less basic at O6 than guanine; the biological implications of these differences are discussed.