Pramod G, Prasanthkumar K P, Mohan Hari, Manoj V M, Manoj P, Suresh C H, Aravindakumar C T
School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, India.
J Phys Chem A. 2006 Oct 12;110(40):11517-26. doi: 10.1021/jp063958a.
Pulse radiolysis and density functional theory (DFT) calculations at B3LYP/6-31+G(d,p) level have been carried out to probe the reaction of the water-derived hydroxyl radicals (OH) with 5-azacytosine (5Ac) and 5-azacytidine (5Acyd) at near neutral and basic pH. A low percentage of nitrogen-centered oxidizing radicals, and a high percentage of non-oxidizing carbon-centered radicals were identified based on the reaction of transient intermediates with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate), ABTS2-. Theoretical calculations suggests that the N3 atom in 5Ac is the most reactive center as it is the main contributor of HOMO, whereas C5 atom is the prime donor for the HOMO of cytosine (Cyt) where the major addition site is C5. The order of stability of the adduct species were found to be C6-OH_5Ac>C4-OH_5Ac*>N3-OH_5Ac*>N5-OH_5Ac* both in the gaseous and solution phase (using the PCM model) respectively due to the additions of OH at C6, C4, N3, and N5 atoms. These additions occur in direct manner, without the intervention of any precursor complex formation. The possibility of a 1,2-hydrogen shift from the C6 to N5 in the nitrogen-centered C6-OH_5Ac radical is considered in order to account for the experimental observation of the high yield of non-oxidizing radicals, and found that such a conversion requires activation energy of about 32 kcal/mol, and hence this possibility is ruled out. The hydrogen abstraction reactions were assumed to occur from precursor complexes (hydrogen bonded complexes represented as S1, S2, S3, and S4) resulted from the electrostatic interactions of the lone pairs on the N3, N5, and O8 atoms with the incoming OH radical. It was found that the conversion of these precursor complexes to their respective transition states has ample barrier heights, and it persists even when the effect of solvent is considered. It was also found that the formation of precursor complexes itself is highly endergonic in solution phase. Hence, the abstraction reactions will not occur in the present case. Finally, the time dependent density functional theory (TDDFT) calculations predicted an absorption maximum of 292 nm for the N3-OH_5Ac adduct, which is close to the experimentally observed spectral maxima at 290 nm. Hence, it is assumed that the addition to the most reactive center N3, which results the N3-OH_5Ac* radical, occurs via a kinetically driven process.
采用脉冲辐解和密度泛函理论（DFT）在B3LYP/6-31+G(d,p)水平上进行计算，以探究在近中性和碱性pH条件下，源自水的羟基自由基（OH）与5-氮杂胞嘧啶（5Ac）和5-氮杂胞苷（5Acyd）的反应。基于瞬态中间体与2,2'-偶氮双（3-乙基苯并噻唑啉-6-磺酸盐）（ABTS2-）的反应，鉴定出低比例的以氮为中心的氧化自由基和高比例的非氧化以碳为中心的自由基。理论计算表明，5Ac中的N3原子是最具反应活性的中心，因为它是最高占据分子轨道（HOMO）的主要贡献者，而C5原子是胞嘧啶（Cyt）HOMO的主要供体，主要加成位点是C5。发现加合物物种在气相和溶液相（使用极化连续介质模型（PCM））中的稳定性顺序分别为C6-OH_5Ac>C4-OH_5Ac*>N3-OH_5Ac*>N5-OH_5Ac*，这是由于OH分别加成到C6、C4、N3和N5原子上。这些加成以直接方式发生，没有任何前体复合物形成的干预。考虑了以氮为中心的C6-OH_5Ac自由基中从C6到N5的1,2-氢转移的可能性，以解释非氧化自由基高产率的实验观察结果，发现这种转化需要约32 kcal/mol的活化能，因此排除了这种可能性。假设氢原子夺取反应发生在前体复合物（表示为S1、S2、S3和S4的氢键复合物）中，这些复合物是由N3、N5和O8原子上的孤对电子与进入的OH自由基的静电相互作用产生的。发现这些前体复合物向各自过渡态的转化具有足够的势垒高度，即使考虑溶剂的影响也依然存在。还发现前体复合物本身的形成在溶液相中是高度吸热的。因此，在当前情况下不会发生夺取反应。最后，含时密度泛函理论（TDDFT）计算预测N3-OH_5Ac加合物的最大吸收峰为292 nm，这与实验观察到的290 nm光谱最大值接近。因此，假设加成到最具反应活性的中心N3上，从而产生N3-OH_5Ac*自由基，是通过动力学驱动过程发生的。
