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学科主题: 药学
题名:
Studies on the nuclease activity and interactions of the mixed-polypyridyl [Ni-2(1,3-tpbd)(diimine)(2)(H2O)(2)](4+) complexes with thioredoxin reductase
作者: Li, Dong-Dong1,2; Zeng, Hui-Hui1,2
关键词: mixed-polypyridyl complexes ; nuclease activity ; thioredoxin reductase inhibitors
刊名: APPLIED ORGANOMETALLIC CHEMISTRY
发表日期: 2013-02-01
DOI: 10.1002/aoc.2945
卷: 27, 期:2, 页:89-97
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Chemistry, Applied ; Chemistry, Inorganic & Nuclear
研究领域[WOS]: Chemistry
关键词[WOS]: CELL GROWTH-INHIBITION ; ORGANOTELLURIUM COMPOUNDS ; COPPER(II) COMPLEXES ; ANTITUMOR AGENTS ; NICKEL-COMPLEXES ; DNA OXIDATION ; BINDING ; FLUORESCENCE ; SELECTIVITY ; ETHIDIUM
英文摘要:

Three new nickel(II) complexes formulated as [Ni2(1,3-tpbd)(diimine)2(H2O)2]4+ [1,3-tpbd?=?N,N,N′,N′-tetrakis(2-pyridylmethyl)benzene-1,3-diamine, where diimine is an N,N-donor heterocyclic base like 1,10-phenanthroline (phen),2,2′-bipyridine (bpy), 4,5-diazafluoren-9-one (dafo)], have been synthesized and structurally characterized by X-ray crystallography: [Ni2(1,3-tpbd)(phen)2(H2O)2]4+ (1), [Ni2(1,3-tpbd)(bpy)2(H2O)2]4+(2) and [Ni2(1,3-tpbd)(dafo)2(H2O)2]4+ (3). Single-crystal diffraction reveals that the metal atoms in the complexes are all in a distorted octahedral geometry and in a trans arrangement around 1,3-tpbd ligand. The interactions of the three complexes with calf thymus DNA (CT-DNA) have been investigated by UV absorption, fluorescence spectroscopy, circular dichroism and viscosity. The apparent binding constant (Kapp) values are calculated to be 1.91 x 105? m-1 for 1, 1.18 x 105? m-1 for 2, and 1.35 x105? m-1 for 3, following the order 1?>?3?>?2. The higher DNA binding affinity of 1 is due to the involvement in partial insertion of the phen ring between the DNA base pairs. A decrease in relative viscosities of DNA upon binding to 13 is consistent with the DNA binding affinities. These complexes efficiently display oxidative cleavage of supercoiled DNA in the presence of H2O2 (250?mu m), with 3 exhibiting the highest nuclease activity. The rate constants for the conversion of supercoiled to nicked DNA are 5.28 x 10-5?s-1 (for 1), 6.67 x 10-5?s-1 (for 2) and 1.39 x 10-4?s-1 (for 3), also indicating that complex 3 shows higher catalytic activity than 1 and 2. Here the nuclease activity is not readily correlated to binding affinity. The inhibitory effect of complexes 13 on thioredoxin reductase has also been examined. The IC50 values are calculated to be 26.54?+/-?0.57, 31.03?+/-?3.33 and 8.69?+/-?2.54?mu m, respectively, showing a more marked inhibitory effect on thioredoxin reductase by complex 3 than the other two complexes. Copyright (c) 2012 John Wiley & Sons, Ltd.

语种: 英语
所属项目编号: 2011M500526
项目资助者: China Postdoctoral Science Foundation
WOS记录号: WOS:000313890200006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/55037
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
2.Tianjin Int Joint Acad Biotechnol & Med, Tianjin 300457, Peoples R China

Recommended Citation:
Li, Dong-Dong,Zeng, Hui-Hui. Studies on the nuclease activity and interactions of the mixed-polypyridyl [Ni-2(1,3-tpbd)(diimine)(2)(H2O)(2)](4+) complexes with thioredoxin reductase[J]. APPLIED ORGANOMETALLIC CHEMISTRY,2013,27(2):89-97.
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