Synthesis, structure and comparison of the DNA cleavage ability of metal complexes M(II)L with the N-(2-ethoxyethanol)bis(2-picolyl)amine ligand L (M = Co, Ni, Cu and Zn)

Synthesis, structure and comparison of the DNA cleavage ability of metal complexes M(II)L with the N-(2-ethoxyethanol)bis(2-picolyl)amine ligand L (M = Co, Ni, Cu and Zn)
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DOI:
10.1039/b313634e
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发表时间:
2004-01-01
影响因子:
4
通讯作者:
Metzler-Nolte, N
Metzler-Nolte, N
中科院分区:
化学2区
文献类型:
--
作者:
Kirin, SI;Happel, CM;Metzler-Nolte, N

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研究了含乙氧基乙醇侧链的N,N-双(2-甲基)胺(BPA)衍生物(BPA(CH2)(2)O(CH2)(2)OH)(1)与后二价过渡金属离子Co(II)、Ni(II)、Cu(II)和Zn(II)的配合物。所有络合物,[{BPA(CH2)(2)O(CH2)(2)OH}Co(NO3)](NO3)(1(Co)),[{BPA(CH2)(2)O(CH2)(2)OH}Ni(NO3)](NO3)(1(Ni)),对[{bpa(CH2)(2)O(CH2)(2)OH}Cu(H2O)(NO3)](NO3)(1(Cu))和[{bpa(CH2)(2)O(CH2)(2)OH}Zn(NO3)](NO3)(1(Zn))进行了全面的表征,并测定了它们的单晶结构。配合物呈六配位构型,其中1作为四齿(1(Cu))或五齿(1(Co),1(Ni)和1(Zn))配体。为了比较四种金属在同一配基环境中的切割效率,对超螺旋双链DNA载体进行了DNA切割实验。在本实验中,1(Co)和1(Cu)显示出最高的切割效率,而1(Ni)和1(Zn)几乎没有活性。昆蒂。凝胶电泳带的阳离子分析表明,在1(Cu)的情况下,80%以上的质粒遭受了至少一条单链的切割,约50%的质粒被1(Co)切割。讨论了1(Cu)的不同切割活性与结构的关系,并提出了1(Cu)的作用机理。
Complexes of a N,N-bis(2-picolyl) amine (bpa) derivative with a pendant ethoxyethanol side chain (bpa(CH2)(2)O( CH2)(2)OH) (1) with late divalent transition metal ions Co(II), Ni(II), Cu(II) and Zn(II) have been studied. All complexes, [{bpa(CH2)(2)O(CH2)(2)OH} Co(NO3)](NO3) (1(Co)), [{bpa(CH2)(2)O(CH2)(2)OH} Ni(NO3)](NO3) (1(Ni)), [{bpa(CH2)(2)O(CH2)(2)OH} Cu(H2O)(NO3)](NO3) (1(Cu)) and [{bpa(CH2)(2)O(CH2)(2)OH} Zn(NO3)](NO3) (1(Zn)), were comprehensively characterized and their X-ray single crystal structures have been determined. The complexes show hexacoordinated geometries, in which 1 acts as a tetradentate (1(Cu)) or pentadentate (1(Co), 1(Ni) and 1(Zn)) ligand. DNA cleavage experiments have been performed on supercoiled double stranded DNA plasmids in order to compare the cleavage efficiency of all four metals in the same ligand environment of 1. In this assay, 1(Co) and 1(Cu) showed the highest cleavage efficiency, whereas 1(Ni) and 1(Zn) were virtually inactive. Quanti. cation of the gel electrophoresis bands showed that more than 80% of the plasmid has suffered at least one single strand cut in the case of 1(Cu), and about 50% of the plasmid was nicked by 1(Co). The differential cleavage activity is discussed in relation to the structural findings and a mechanism is proposed for 1(Cu).