Preferential DNA cleavage under anaerobic conditions by a DNA-binding ruthenium dimer.
Preferential DNA cleavage under anaerobic conditions by a DNA-binding ruthenium dimer.
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DNA 结合钌二聚体在厌氧条件下优先切割 DNA。
DOI：
10.1021/ic0619714
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发表时间：
2007
影响因子：
4.6
通讯作者：
MacDonnell,FrederickM
中科院分区：
文献类型：
--
作者：
Janaratne,ThamaraK;Yadav,Abhishek;Ongeri,Fiona;MacDonnell,FrederickM
在缺乏双氧的情况下，阳离子络合物[(phen)2Ru(tatpp)Ru(phen)2]4+(P4+)被谷胱甘肽（GSH）原位还原，形成诱导DNA切割的物种。暴露在空气中，即使存在大量过量的还原剂（例如，40当量GSH perP4+），也会强烈减弱裂解活性，这表明该复合物可能在低氧微环境（缺氧）下靶向细胞，通过DNA裂解进行破坏。活性物质被鉴定为双重还原、双重质子化的络合物h2p4 +，一个碳基自由基参与了裂解作用。我们假设二氧浓度调节碳自由基形成的程度，从而调节DNA裂解活性。
In the absence of dioxygen, the cationic complex [(phen)2Ru(tatpp)Ru(phen)2]4+(P4+) undergoes in situ reduction by glutathione (GSH) to form a species that induces DNA cleavage. Exposure to air strongly attenuates the cleavage activity, even in the presence of a large excess of reducing agent (e.g., 40 equiv of GSH perP4+), suggesting that the complex may be useful in targeting cells with a low-oxygen microenvironment (hypoxia) for destruction via DNA cleavage. The active species is identified as the doubly reduced, doubly protonated complexH2P4+, and a carbon-based radical species is implicated in the cleavage action. We postulate that the dioxygen concentration regulates the degree to which the carbon radical forms and thus regulates the DNA cleavage activity.