School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong new area, Shanghai, 201210, P. R. China.
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, P. R. China.
Angew Chem Int Ed Engl. 2019 Apr 23;58(18):6070-6073. doi: 10.1002/anie.201814519. Epub 2019 Mar 26.
Aerobic organisms must rely on abundant intracellular thiols to reductively protect various vital functional units, especially ubiquitous zinc(II) thiolate sites of proteins, from deleterious oxidations resulting from oxidizing environments. Disclosed here is the first well-defined model study for reactions between zinc(II) thiolate complexes and copper(II) complexes. Among all the studied ligands of copper(II), diethyldithiocarbamate (DTC) displays a unique redox-tuning ability that enables copper(II) to resist the reduction by thiols while retaining its ability to oxidize zinc(II) thiolates to form disulfides. This work proves for the first time that it is possible to develop oxidants to discriminate between thiols and zinc(II) thiolates, alluding to a new chemical principle for how oxidants, especially universal anticancer Cu(DTC) , might circumvent the intracellular reductive defense around certain zinc(II) thiolate sites of proteins to kill malignant cells.
需氧生物必须依赖丰富的细胞内巯基来还原保护各种重要的功能单元，特别是蛋白质中普遍存在的锌(II)硫醇盐部位，使其免受氧化环境造成的有害氧化。这里首次公开了锌(II)硫醇配合物与铜(II)配合物之间反应的明确定义模型研究。在所研究的所有铜(II)配体中，二乙基二硫代氨基甲酸盐（DTC）显示出独特的氧化还原调谐能力，使铜(II)能够抵抗巯基的还原，同时保持氧化锌(II)硫醇盐形成二硫化物的能力。这项工作首次证明，有可能开发出氧化剂来区分巯基和锌(II)硫醇盐，这暗示了一种新的化学原理，即氧化剂（特别是通用抗癌 Cu(DTC)）如何绕过蛋白质中某些锌(II)硫醇盐部位周围的细胞内还原防御，从而杀死恶性细胞。
