Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity
Crystal and molecular structure of 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and its iron(III) complex: an iron chelator with anti-tumour activity
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DOI：
10.1007/s007750050312
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发表时间：
1999-06-01
影响因子：
3
通讯作者：
Bernhardt, PV
中科院分区：
文献类型：
--
作者：
Richardson, DR;Bernhardt, PV
先前的研究已经证明，2-羟基-1-萘甲醛异烟酰腙（NIH）和其他几种芳酰腙螯合剂具有抗肿瘤活性，因为它们能够结合细胞内铁。在这项研究中，我们研究了NIH及其Fe-III复合物的结构和性质，以进一步了解其抗肿瘤活性。两个三齿NIH配体在与Fe-III配位后以双配位的方式去质子化，形成扭曲的八面体高自旋络合物。[Fe（NIH-H）（2）]（+）的溶液电化学表明，在很宽的电位范围内，三价氧化态占主导地位，并且Fe-II类似物不是该络合物的稳定形式。[Fe（NIH-H）（2）]（+）不能在Fe-II和Fe-III状态之间循环的事实表明，有毒自由基物质的产生，例如OH。或O2（.-），不是配体细胞毒性作用的一部分这一建议得到了细胞培养实验的支持，实验证明，向NIH中加入Fe-III会阻止其抗增殖作用。在理解其抗肿瘤活性的背景下讨论了这种螯合剂及其Fe-III络合物的化学。
Previous studies have demonstrated that 2-hydroxy-1-naphthaldehyde isonicotinoyl hydrazone (NIH) and several other aroylhydrazone chelators possess anti-neoplastic activity due to their ability to bind intracellular iron. In this study we have examined the structure and properties of NIH and its Fe-III complex in order to obtain further insight into its anti-tumour activity. Two tridentate NIH ligands deprotonate upon coordination to Fe-III in a meridional fashion to form a distorted octahedral, high-spin complex. Solution electrochemistry of [Fe(NIH-H)(2)](+) shows that the trivalent oxidation state is dominant over a wide potential range and that the Fe-II analogue is not a stable form of this complex. The fact that [Fe(NIH-H)(2)](+) cannot-cycle between the Fe-II and Fe-III states suggests that the production of toxic free- radical species, e.g. OH. or O2(.-),is not part of this ligand's cytotoxic action. This suggestion is supported by cell culture experiments demonstrating that the addition of Fe-III to NIH prevents its anti-proliferative effect. The chemistry of this chelator and its Fe-III complex are discussed in the context of understanding its anti-tumour activity.