Superoxide dismutase activity enabled by a redox-active ligand rather than metal
Superoxide dismutase activity enabled by a redox-active ligand rather than metal
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DOI：
10.1038/s41557-018-0137-1
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发表时间：
2018-12-01
期刊：
影响因子：
21.8
通讯作者：
Goldsmith, Christian R.
中科院分区：
文献类型：
--
作者：
Ward, Meghan B.;Scheitler, Andreas;Goldsmith, Christian R.
活性氧在许多生理过程中都是不可或缺的。尽管它们的作用仍在阐明中，但它们似乎与各种疾病有关，可能代表着有希望的药物靶点。超氧化物歧化酶的模拟物催化O-2(中心圆点-)分解为H_2O_2和O-2，传统上使用氧化还原活性金属，这些金属在紧密配位的配体之外是有毒的。纯有机抗氧化剂也被研究过，但通常需要化学计量剂量，而不是催化剂量。在这里，我们证明了氧化还原不活跃的金属锌(II)与含有氧化还原活性的喹酚的六齿配体的络合物可以催化降解超氧化物，这一结果通过与O-2(中心点-)和锌(II)络合物的直接反应的反应性分析和停流动力学研究来证明。与以前报道的工作相比，观察到的超氧化物歧化酶催化有一个重要的优势，因为它会被磷酸盐的存在加速，而不是受到阻碍，磷酸盐的浓度在生理条件下很高。
Reactive oxygen species are integral to many physiological processes. Although their roles are still being elucidated, they seem to be linked to a variety of disorders and may represent promising drug targets. Mimics of superoxide dismutases, which catalyse the decomposition of O-2(center dot-) to H2O2 and O-2, have traditionally used redox-active metals, which are toxic outside of a tightly coordinating ligand. Purely organic antioxidants have also been investigated but generally require stoichiometric, rather than catalytic, doses. Here, we show that a complex of the redox-inactive metal zinc(II) with a hexadentate ligand containing a redox-active quinol can catalytically degrade superoxide, as demonstrated by both reactivity assays and stopped-flow kinetics studies of direct reactions with O-2(center dot-) and the zinc(II) complex. The observed superoxide dismutase catalysis has an important advantage over previously reported work in that it is hastened, rather than impeded, by the presence of phosphate, the concentration of which is high under physiological conditions.