A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation
A pro-chelator triggered by hydrogen peroxide inhibits iron-promoted hydroxyl radical formation
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DOI：
10.1021/ja064806w
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发表时间：
2006-09-27
影响因子：
15
通讯作者：
Franz, Katherine J.
中科院分区：
文献类型：
--
作者：
Charkoudian, Louise K.;Pham, David M.;Franz, Katherine J.
新型前螯合剂异烟酸的合成及结构表征（4，4，5，5-四甲基-[1，3，2]二氧杂硼杂环戊烷-2-基）-亚苄基]-酰肼（BSIH），BSIH仅与铁弱地相互作用，除非存在过氧化氢（H2 O2）以除去硼酸酯保护基，以显示作为关键金属的酚。三齿水杨醛异烟酰腙（SIH）的结合基团。BSIH通过螯合Fe 3+和防止铁促进的羟基自由基形成来防止由H2 O2和氧化还原活性铁产生的羟基自由基引起的脱氧核糖降解。铁螯合的速率决定步骤是BSIH向SIH的转化，然后是快速的Fe 3+络合。BSIH的亲螯合方法代表了一种有前途的策略，用于螯合有害金属离子的特定池，而不干扰健康的金属离子分布。
The synthesis and structural characterization of a new pro-chelating agent, isonicotinic acid [2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzylidene]-hydrazide (BSIH), are presented.BSIHonly weakly interacts with iron unless hydrogen peroxide (H2O2) is present to remove the boronic ester protecting group to reveal a phenol that is a key metal-binding group of tridentate salicylaldehyde isonicotinoyl hydrazone (SIH).BSIHprevents deoxyribose degradation caused by hydroxyl radicals that are generated from H2O2and redox-active iron by sequestering Fe3+and preventing iron-promoted hydroxyl radical formation. The rate-determining step for iron sequestration is conversion ofBSIHtoSIH, followed by rapid Fe3+complexation. The pro-chelate approach ofBSIHrepresents a promising strategy for chelating a specific pool of detrimental metal ions without disturbing healthy metal ion distribution.