临床上具有广谱抗癌活性的硫代胺基甲酸铜Cu(DTC)2可以克服细胞内还原性保护机制，通过选择性氧化锌硫蛋白的锌硫配位位点而导致癌细胞死亡。因此，研究这一特殊反应选择性与分子结构之间的关系，将为癌症化疗药物的开发提供新的科学基础。同步辐射X射线吸收谱技术可以准确地表征铜元素的氧化价态和配位模式，为研究Cu(DTC)2与锌硫配位化合物的相互作用机理提供了有效的手段。本项目将利用配合物对金属蛋白质的锌硫位点进行结构和反应活性模拟，探究Cu(DTC)2选择性氧化各种类型锌硫配位化合物的构效关系规律。利用先进的同步辐射停流X射线吸收谱技术，结合质谱、核磁和密度泛函计算等手段，准确地表征反应中间体和产物的结构，并跟踪模拟各种配合物氧化剂与锌硫配位化合物相互作用的分子动态过程。在系统测量反应动力学和计算模拟反应能量曲线的基础上，为发展新的具有潜在癌症化疗应用前景的金属配位化合物建立原创性的构效规律。

Universal anticancer Cu(DTC)2 can overcome intracellular reductive-protection mechanism and selectively oxidize Zn thiolates of Zn/S proteins to form disulfide, resulting in the death of cancerous cells. Thus, investigations of the structure-reactivity relationship underlying such a special selectivity can provide significant insights into development of new chemotherapeutic drugs for cancerous treatments. Synchrotron radiation X-ray absorption spectroscopy (XAS) is a powerful tool to characterize the oxidation state and the coordination structure of copper ions, which provide great information for the mechanistic understanding of the interactions between Cu(DTC)2 and Zn thiolates. The proposed research will develop small model coordination complexes to mimic the structure and reactivity of Zn-thiolate sites in proteins and establish the structure-reactivity relationship for selective oxidation of Zn thiolates by Cu(DTC)2. A combination of advanced synchrotron radiation stopped-flow XAS, mass spectroscopy, NMR, EPR and DFT will elucidate the structures of the reaction intermediates and products as well as the kinetic processes.