Department of Molecular Chemistry and Biochemistry , Doshisha University , Kyotanabe Kyoto 610-0321 , Japan.
Department of Life Science , University of Hyogo , Kouto 2-1 , Ako Kamigori Hyogo 678-1297 , Japan.
Inorg Chem. 2019 Nov 4;58(21):14294-14298. doi: 10.1021/acs.inorgchem.9b02093. Epub 2019 Oct 10.
Metal complexes to promote oxidative DNA cleavage by HO are desirable as anticancer drugs. A dicopper(II) complex of known -cresol-derived methylene-tether ligand Hbcc [Cu(bcc)] did not promote DNA cleavage by HO. Here, we synthesized a new -cresol-derived amide-tether one, 2,6-bis(1,4,7,10-tetrazacyclododecyl-1-carboxyamide)--cresol (Hbcamide). A dicopper(II) complex of the new ligand [Cu(μ-OH)(bcamide)] was structurally characterized. This complex promoted the oxidative cleavage of supercoiled plasmid pUC19 DNA (Form I) with HO at pH 6.0-8.2 to give Forms II and III. The reaction was largely accelerated in a high pH region. A μ-1,1-hydroperoxo species was formed as the active species and spectroscopically identified. The amide-tether complex is more effective in cytotoxicity against HeLa cells than the methylene-tether one.
金属配合物通过 HO 促进氧化 DNA 断裂，是理想的抗癌药物。一种已知的 -甲酚衍生的亚甲基 - 桥联配体 Hbcc 的二铜（II）配合物 [Cu(bcc)] 不能促进 HO 引发的 DNA 断裂。在这里，我们合成了一种新的 -甲酚衍生的酰胺 - 桥联配体 2,6-双（1,4,7,10-四氮杂环十二烷-1-羧酰胺）- -甲酚（Hbcamide）。新配体的二铜（II）配合物 [Cu(μ-OH)(bcamide)] 的结构进行了表征。该配合物在 pH 6.0-8.2 下通过 HO 促进超螺旋质粒 pUC19 DNA（形式 I）的氧化断裂，生成形式 II 和 III。该反应在高 pH 区域得到了很大的加速。形成了μ-1,1-过氧物种作为活性物种，并通过光谱学进行了鉴定。酰胺 - 桥联配合物在对 HeLa 细胞的细胞毒性方面比亚甲基 - 桥联配合物更有效。
