Efficient inhibition of photo[2 + 2]cycloaddition of thymidilyl(3'- 5')thymidine and promotion of photosplitting of the cis-syn-cyclobutane thymine dimer by dimeric zinc(II)-cyclen complexes containing m- and p-xylyl spacers
Efficient inhibition of photo[2 + 2]cycloaddition of thymidilyl(3'- 5')thymidine and promotion of photosplitting of the cis-syn-cyclobutane thymine dimer by dimeric zinc(II)-cyclen complexes containing m- and p-xylyl spacers
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DOI：
10.1021/ja981788c
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发表时间：
1998-09
影响因子：
15
通讯作者：
S. Aoki;Chizuyo Sugimura;E. Kimura
中科院分区：
文献类型：
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作者：
S. Aoki;Chizuyo Sugimura;E. Kimura
Cyclen 的单体和二聚锌 (II) 配合物（cyclen = 1,4,7,10-四氮杂环十二烷）在中性 pH 条件下，在水溶液中抑制胸苷基 (3‘−5’) 胸苷 (d(TpT)) 的光[2 + 2]环加成，这是一种新机制。通过高压汞灯在 3−5 °C 下比较 d(TpT) 光二聚化的初始速率和产物产量（在 pH 7.6 的 Tris 缓冲液中，I = 0.10 (NaNO3)）表明二聚锌 (II) 配合物，p- 和 m-二甲苯基-bis(Zn2+−cyclen)（Zn2L2 和 Zn2L3）是有效的抑制剂（70−85%）与对照反应相比，[d(TpT)] = [bis(Zn2+−cyclen)] = 0.2 mM（照射 20 分钟后）的抑制。这种抑制是由于两个去质子化胸苷 (dT-) 部分与两个 Zn2+−cyclen 部分之间极强的 1:1 络合（表观络合常数，log Kapp (Kapp = [Zn2L2 (或 Zn2L3)−d(T-pT-)]/[Zn2L2free (或 Zn2L3free)][d(TpT)free] (M-1))，通过等温热量测定，pH 7.6（50 mM HEPES，I = 0.1 (NaNO3)）和 25 °C 时为 6.4 ± 0.1
Monomeric and dimeric zinc(II) complexes of cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) inhibited the photo[2 + 2]cycloaddition of thymidilyl(3‘−5‘)thymidine (d(TpT)) at neutral pH in aqueous solution for a novel mechanism. Comparison of the initial rates and the product yields of the photodimerization of d(TpT) (in Tris buffer at pH 7.6 with I = 0.10 (NaNO3)) at 3−5 °C by high-pressure mercury lamp indicates that the dimeric zinc(II) complexes, p- and m-xylyl-bis(Zn2+−cyclen) (Zn2L2 and Zn2L3), are effective inhibitors (70−85% inhibition compared with the control reaction at [d(TpT)] = [bis(Zn2+−cyclen)] = 0.2 mM after 20 min irradiation). This inhibition is due to the extremely strong 1:1 complexation of two deprotonated thymidine (dT-) moieties with two Zn2+−cyclen moieties (apparent complexation constants, log Kapp (Kapp = [Zn2L2 (or Zn2L3)−d(T-pT-)]/[Zn2L2free (or Zn2L3free)][d(TpT)free] (M-1)), of 6.4 ± 0.1 at pH 7.6 (50 mM HEPES, I = 0.1 (NaNO3)) and 25 °C, as determined by the isothermal calo...