The solution structure of the copper clioquinol complex
The solution structure of the copper clioquinol complex
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DOI：
10.1016/j.jinorgbio.2014.01.003
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发表时间：
2014-04-01
影响因子：
3.9
通讯作者：
George, Graham N.
中科院分区：
文献类型：
--
作者：
Pushie, M. Jake;Nienaber, Kurt H.;George, Graham N.
氯碘羟喹（5-氯-7-碘-8-羟基喹啉）最近在治疗阿尔茨海默病和癌症治疗中显示出有希望的结果，这两者也被认为是由于氯碘羟喹作为亲脂性铜螯合剂的能力。以前，氯碘羟喹被用作抗真菌和抗原虫药物，导致20世纪60年代日本亚急性脊髓视神经病变（SMON）流行，可能是氯碘羟喹诱导的铜缺乏引起的脊髓神经病。以前的X射线吸收光谱的氯碘羟喹的铜螯合物的解决方案建议不寻常的配位化学。在这里，我们使用电子顺磁，紫外可见和X-射线吸收光谱的组合，以提供澄清氯碘羟喹和铜之间的螯合化学。我们发现，化学计量和过量氯碘羟喹形成的铜络合物的溶液结构是常规的8-羟基喹啉螯合物。因此，氯碘羟喹在阿尔茨海默病的新治疗和癌症治疗中的前景不太可能是由于任何新的螯合化学，而是由于其他因素，包括游离配体和螯合物的高亲脂性。(C)2014爱思唯尔公司All rights reserved.
Clioquinol (5-chloro-7-iodo-8-hydroxyquinoline) recently has shown promising results in the treatment of Alzheimer's disease and in cancer therapy, both of which also are thought to be due to clioquinol's ability as a lipophilic copper chelator. Previously, clioquinol was used as an anti-fungal and anti-protozoal drug that was responsible for an epidemic of subacute myelo-optic neuropathy (SMON) in Japan during the 1960s, probably a myeloneuropathy arising from a clioquinol-induced copper deficiency. Previous X-ray absorption spectroscopy of solutions of copper chelates of clioquinol suggested unusual coordination chemistry. Here we use a combination of electron paramagnetic, UV-visible and X-ray absorption spectroscopies to provide clarification of the chelation chemistry between clioquinol and copper. We find that the solution structures for the copper complexes formed with stoichiometric and excess clioquinol are conventional 8-hydroxyquinolate chelates. Thus, the promise of clioquinol in new treatments for Alzheimer's disease and in cancer therapy is not likely to be due to any novel chelation chemistry, but rather due to other factors including the high lipophilicity of the free ligand and chelate complexes. (C) 2014 Elsevier Inc. All rights reserved.