Dicopper(II) Complexes of p-Cresol-2,6-Bis(dpa) Amide-Tether Ligands: Large Enhancement of Oxidative DNA Cleavage, Cytotoxicity, and Mechanistic Insight by Intracellular Visualization
Dicopper(II) Complexes of p-Cresol-2,6-Bis(dpa) Amide-Tether Ligands: Large Enhancement of Oxidative DNA Cleavage, Cytotoxicity, and Mechanistic Insight by Intracellular Visualization
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DOI：
10.1021/acs.inorgchem.0c02954
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发表时间：
2021-04-19
影响因子：
4.6
通讯作者：
Kodera, Masahito
中科院分区：
文献类型：
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作者：
Kadoya, Yuki;Hata, Machi;Kodera, Masahito
合成了一种新型对甲酚-2,6-双（dpa）酰胺系链配体（HL1） [Cu-2(mu-OH2)(mu-1,3-OAc)(L1)](ClO4)(2)(1)和[Cu-2(mu-1,1-OAc)(mu-1,3-OAc)(L1)]X (X = ClO4 （2a), OAc (2b)）的双铜配合物并进行了结构表征。2b通过在中性pH下激活H2O2，将超螺旋质粒DNA快速切割成线性DNA，与相关复合物相比，显示出显著的细胞毒性。由于2b比HL1具有更强的细胞毒性，diccopper核被保留在细胞中。合成了一种硼二吡咯（Bodipy）修饰的对甲酚-2,6-双（dpa）酰胺系链配体（HL2）的配合物[Cu-2(mu-OAc)(2)(L2)](OAc)(3)，以观察细胞内行为，表明2b攻击核核和线粒体。彗星试验清楚地表明2b不切割核DNA。流式细胞术证实凋亡细胞死亡。
Dicopper complexes of a new p-cresol-2,6-bis(dpa) amide-tether ligand (HL1), [Cu-2(mu-OH2)(mu-1,3-OAc)(L1)](ClO4)(2) (1) and [Cu-2(mu-1,1-OAc)(mu-1,3-OAc)(L1)]X (X = ClO4 (2a), OAc (2b)) were synthesized and structurally characterized. 2b rapidly cleaves supercoiled plasmid DNA by activating H2O2 at neutral pH to a linear DNA and shows remarkable cytotoxicity in comparison with related complexes. As 2b is more cytotoxic than HL1, the dicopper core is kept in the cell. A boron dipyrromethene (Bodipy)-modified complex of the p-cresol-2,6-bis(dpa) amide-tether ligand having a Bodipy pendant (HL2), [Cu-2(mu-OAc)(2)(L2)]( OAc) (3), was synthesized to visualize intracellular behavior, suggesting that 2b attacks the nucleolus and mitochondria. A comet assay clearly shows that 2b does not cleave nuclear DNA. The apoptotic cell death is evidenced from flow cytometry.