Model studies of DNA C5′ radicals. Selective generation and reactivity of 2′-deoxyadenosin-5′-yl radical
Model studies of DNA C5′ radicals. Selective generation and reactivity of 2′-deoxyadenosin-5′-yl radical
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DOI：
10.1021/ja029374d
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发表时间：
2003-04-02
影响因子：
15
通讯作者：
Mulazzani, QG
中科院分区：
文献类型：
--
作者：
Chatgilialoglu, C;Guerra, M;Mulazzani, QG
水合电子 (e(aq)(-)) 与 8-溴-2'-脱氧腺苷的反应已通过放射分解方法与产物研究相结合进行了研究，并通过 DFTB3LYP 计算进行了计算。脉冲放射分解表明该反应在大约0.3μs内完成，并且此时没有检测到显着的吸收。 20us 内产生的瞬态光谱在 300-500 nm 范围内具有吸光度（是在 360 nm 处与 9600 M-1 cm(-1) 一致的元素），并将其分配给芳香族氨基自由基 3。计算出的垂直跃迁 (TD-UB3LYP/6-311+G*) 与实验观察结果非常一致。自由基3通过以下反应顺序获得：C-Br键的单电子还原裂解产生C8自由基，从C8到C5'位置的快速自由基易位，以及C5'自由基在腺嘌呤部分的C8,N7双键处的分子内攻击。环化的速率常数为1.6 x 10(5) s(-1)。根据理论研究结果，环化步骤是高度立体特异性的。通过脉冲辐射分解法测定了C5'和氨基3自由基与不同氧化剂的反应速率常数。环境温度下，2'-脱氧腺苷-5'-基自由基与分子氧、Fe(CN)(6)(3-) 和 MV2+ 在水中反应的速率常数分别为 1.9 x 10(9)、4.2 x 10(9) 和 2.2 x 10(8) M-1 s(-1)。氨基自由基3与Fe(CN)(6)(3-)的反应值为8.3 x 10(8) M-1 s(-1)，而与分子氧的反应是可逆的。定制的实验可以更详细地定义反应机理。还开发了一种合成上有用的自由基级联方法，通过在 K4Fe(CN)(6) 存在下与水合电子反应，可以一锅法将 8-溴-2'-脱氧腺苷以非对映异构体比例 (5'R):(5'S) = 6:1 转化为 5',8-环-2'-脱氧腺苷，且收率高。
The reaction of hydrated electrons (e(aq)(-)) with 8-bromo-2'-deoxyadenosine has been investigated by radiolytic methods coupled with product studies and addressed computationally by means of DFTB3LYP calculations. Pulse radiolysis revealed that this reaction was complete in similar to0.3 mus, and, at this time, no significant absorption was detected. The spectrum of a transient developed in 20,us has an absorbance in the range 300-500 nm (is an element of(max) congruent to 9600 M-1 cm(-1) at 360 nm), and it was assigned to aromatic aminyl radical 3. Computed vertical transitions (TD-UB3LYP/6-311+G*) are in good agreement with the experimental observations. Radical 3 is obtained by the following reaction sequence: one-electron reductive cleavage of the C-Br bond that gives the C8 radical, a fast radical translocation from the C8 to C5' position, and an intramolecular attack of the C5' radical at the C8,N7 double bond of the adenine moiety. The rate constant for the cyclization is 1.6 x 10(5) s(-1). On the basis of the theoretical findings, the cyclization step is highly stereospecific. The rate constants for the reactions of C5' and aminyl 3 radicals with different oxidants were determined by pulse radiolysis methods. The respective rate constants for the reaction of 2'-deoxyadenosin-5'-yl radical with dioxygen, Fe(CN)(6)(3-), and MV2+ in water at ambient temperature are 1.9 x 10(9), 4.2 x 10(9), and 2.2 x 10(8) M-1 s(-1). The value for the reaction of aminyl radical 3 with Fe(CN)(6)(3-) is 8.3 x 10(8) M-1 s(-1), whereas the reaction with dioxygen is reversible. Tailored experiments allowed the reaction mechanism to be defined in some detail. A synthetically useful radical cascade process has also been developed that allows in a one-pot procedure the conversion of 8-bromo-2'-deoxyadenosine to 5',8-cyclo-2'-deoxyadenosine in a diastereoisomeric ratio (5'R):(5'S) = 6:1 and in high yield, by reaction with hydrated electrons in the presence of K4Fe(CN)(6).