Institute of Inorganic Chemistry, University of Vienna, Währinger Strasse 42, A-1090 Vienna, Austria.
Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
Inorg Chem. 2021 Aug 2;60(15):11297-11319. doi: 10.1021/acs.inorgchem.1c01275. Epub 2021 Jul 19.
Three new thiosemicarbazones (TSCs) - as triapine analogues bearing a redox-active phenolic moiety at the terminal nitrogen atom were prepared. Reactions of - with CuCl·2HO in anoxic methanol afforded three copper(II) complexes, namely, (), [ (), and (), in good yields. Solution speciation studies revealed that the metal-free ligands are stable as - at pH 7.4, while being air-sensitive in the basic pH range. In dimethyl sulfoxide they exist as a mixture of and isomers. A mechanism of the isomerization with an inversion at the nitrogen atom of the Schiff base imine bond is proposed. The monocationic complexes are the most abundant species in aqueous solutions at pH 7.4. Electrochemical and spectroelectrochemical studies of , , and confirmed their redox activity in both the cathodic and the anodic region of potentials. The one-electron reduction was identified as metal-centered by electron paramagnetic resonance spectroelectrochemistry. An electrochemical oxidation pointed out the ligand-centered oxidation, while chemical oxidations of and as well as and afforded several two-electron and four-electron oxidation products, which were isolated and comprehensively characterized. Complexes and showed an antiproliferative activity in Colo205 and Colo320 cancer cell lines with half-maximal inhibitory concentration values in the low micromolar concentration range, while with the most closely related ligand to triapine displayed the best selectivity for cancer cells versus normal fibroblast cells (MRC-5). and in the presence of 1,4-dithiothreitol are as potent inhibitors of mR2 ribonucleotide reductase as triapine.
三种新型的硫代氨基甲酸盐（TSC）——作为三嗪类似物，在末端氮原子上带有一个氧化还原活性的酚部分——被制备出来。在缺氧甲醇中，与 CuCl·2HO 的反应以高产率得到了三种铜（II）配合物，即 ()、[()]和()。溶液形态研究表明，在 pH 7.4 下，金属游离配体作为稳定的 -，而在碱性 pH 范围内则对空气敏感。在二甲基亚砜中，它们以 -和 -异构体的混合物形式存在。提出了席夫碱亚胺键氮原子反转的异构化机制。在 pH 7.4 时，一价阳离子配合物是水溶液中最丰富的物种。电化学和光谱电化学研究证实了 、和的氧化还原活性，其电位范围在阴极和阳极区都存在。单电子还原被确定为金属中心的，通过电子顺磁共振光谱电化学。电化学氧化指出了配体中心的氧化，而 、和 以及 、的化学氧化得到了几个两电子和四电子氧化产物，这些产物被分离并进行了全面的表征。配合物 和 在 Colo205 和 Colo320 癌细胞系中表现出抗增殖活性，半数最大抑制浓度值在低微摩尔浓度范围内，而与三嗪最相关的配体 的选择性最好，对癌细胞比对正常成纤维细胞（MRC-5）更好。在 1,4-二硫苏糖醇存在下， 和 是 mR2 核糖核苷酸还原酶的有效抑制剂，与三嗪相当。
