Comparison of the SOD-like activity of hexacoordinate Mn(II), Fe(II) and Ni(II) complexes having isoindoline-based ligands

Comparison of the SOD-like activity of hexacoordinate Mn(II), Fe(II) and Ni(II) complexes having isoindoline-based ligands
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DOI:
10.1016/j.jinorgbio.2011.01.016
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发表时间:
2011-06-01
影响因子:
3.9
通讯作者:
Speier, Gabor
Speier, Gabor
中科院分区:
生物学2区
文献类型:
--
作者:
Pap, Jozsef S.;Kripli, Balazs;Speier, Gabor

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近年来,本课题组合成了一系列含不同Ar-基团(吡啶基、4-甲基吡啶基、噻唑基、苯并咪唑基和N-甲基苯并咪唑基)的1,3-双(2 ′-Ar-亚氨基)异吲哚啉铁配合物。化合物的超氧阴离子清除活性与Fe(III)/Fe(II)氧化还原电位相关。本文报道了Mn(Ⅱ)和Ni(Ⅱ)在2:1配体:金属组成下的类似电中性螯合物。每个Mn(II)络合物表现出一个可逆的氧化还原波,其被指定为Mn(III)/Mn(II)氧化还原转变。取决于Ar-侧臂,E-1/2相对于Fc(+)/Fc跨越从-98(Ar = 3-甲基吡啶基)至82 mV(Ar =噻唑基)的180 mV范围。根据McCord-Fridovich方法测定所有复合物的SOD样(SOD =超氧化物歧化酶)活性。Mn(II)异吲哚酸盐的IC 50值-用50 μ M细胞色素c Fe(III)测定-范围为(3.22 +/- 0.39)x 10(-6)(Ar =苯并咪唑基)至(10.80 +/- 0.54)x 10(-6)M(Ar = N-甲基苯并咪唑基)。与Fe(II)络合物相比,IC 50浓度在此窄电位范围内对E-1/2值没有显着依赖性,强调氧化还原电位不是含Mn(II)清除剂中的主导因素。类似的Ni(II)化合物在化学相关电位范围(-0.40至0.65V vs. SCE)内没有显示氧化还原转变,因此,它们的超氧化物清除活性(如果有的话)低于检测水平。(C)2011 Elsevier Inc. All rights reserved.
Recently, a series of Fe(II) complexes have been published by our group with 3 N-donor 1,3-bis(2'-Ar-imino) isoindoline ligands containing various Ar-groups (pyridyl, 4-methylpyridyl, thiazolyl, benzimidazolyl and N-methylbenzimidazolyl). The superoxide scavenging activity of the compounds showed correlation with the Fe(III)/Fe(II) redox potentials. Analogous, electroneutral chelate complexes with Mn(II) and Ni(II) in 2:1 ligand: metal composition are reported here. Each Mn(II) complex exhibits one reversible redox wave that is assigned as the Mn(III)/Mn(II) redox transition. The E-1/2 spans a 180 mV range from -98 (Ar = 3-methylpyridyl) to 82 mV (Ar = thiazolyl) vs. the Fc(+)/Fc depending on the Ar-sidearm. The SOD-like (SOD = superoxide dismutase)activity of all complexes was determined according to the McCord-Fridovich method. The Mn(II) isoindolinates have IC50 values - determined with 50 mu M cytochrome c Fe(III) - that range from (3.22 +/- 0.39) x 10(-6) (Ar = benzimidazolyl) to (10.80 +/- 0.54) x 10(-6) M (Ar = N-methylbenzimidazolyl). In contrast with the Fe(II) complexes, the IC50 concentrations show no significant dependence on the E-1/2 values in this narrow potential range emphasizing that the redox potential is not the governing factor in the Mn(II)-containing scavengers. The analogous Ni(II) compounds show no redox transitions in the thermodynamically relevant potential range (-0.40 to 0.65 V vs. SCE) and accordingly, their superoxide scavenging activity (if any) is below the detection level. (C) 2011 Elsevier Inc. All rights reserved.