空间效应对含氨基喹啉衍生物的铜（II）配合物核酸酶活性的影响。

Steric effect on the nuclease activity of Cu(II) complexes with aminoquinoline derivatives.

作者信息

Shao Ying, Zhang Junyong, Tu Chao, Dai Chunhui, Xu Qiang, Guo Zijian

机构信息

State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, 210093 Nanjing, PR China.

出版信息

J Inorg Biochem. 2005 Jul;99(7):1490-6. doi: 10.1016/j.jinorgbio.2005.04.007.

DOI:10.1016/j.jinorgbio.2005.04.007

PMID:15919117

Abstract

Three copper(II) complexes of aminoquinoline derivatives, l-glycine-N'-8-quinolylamide (L1), l-alanine-N'-8-quinolylamide (L2), and N-(8-quinolyl) pyridine-2-carboxamide (L3) have been shown to cleave plasmid DNA pBR322 and pUC18 with or without the presence of H(2)O(2)/ascorbate. Crystallographic data reveal that the Cu(II) coordination plane in [Cu(L1)(Ac)(H(2)O)] (1) and [Cu(L2)(Ac)] (2) is nearly co-planar with the quinoline ring. The cleavage activity follows the order of complex 1>complex 2>complex 3, which is in agreement with the reverse order of the steric hindrance of the amino-substituent of the ligands. The presence of the standard radical scavengers does not have a clear effect on the cleavage efficiency of the Cu(II) complexes, suggesting the reactive species leading to DNA damage could be DNA-bound copper-centered radicals rather than the free diffusible ones.

摘要

三种氨基喹啉衍生物的铜（II）配合物，即L-甘氨酸-N'-8-喹啉酰胺（L1）、L-丙氨酸-N'-8-喹啉酰胺（L2）和N-（8-喹啉基）吡啶-2-甲酰胺（L3），已被证明在有或没有过氧化氢/抗坏血酸存在的情况下都能切割质粒DNA pBR322和pUC18。晶体学数据表明，[Cu（L1）（Ac）（H₂O）]（1）和[Cu（L2）（Ac）]（2）中的Cu（II）配位平面与喹啉环几乎共面。切割活性遵循配合物1>配合物2>配合物3的顺序，这与配体氨基取代基的空间位阻的相反顺序一致。标准自由基清除剂的存在对Cu（II）配合物的切割效率没有明显影响，这表明导致DNA损伤的活性物种可能是以DNA结合的铜为中心的自由基，而不是自由扩散的自由基。