Kinetic characterization of the interactions of trans-dichloro-platinum(IV) anticancer prodrugs and a model compound with thiosulfate
Kinetic characterization of the interactions of trans-dichloro-platinum(IV) anticancer prodrugs and a model compound with thiosulfate
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DOI：
10.1007/s11243-013-9781-x
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发表时间：
2014-03
影响因子：
1.7
通讯作者：
Jingran Dong;S. Huo;C. Song;S. Shen;Yanli Ren;T. Shi
中科院分区：
文献类型：
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作者：
Jingran Dong;S. Huo;C. Song;S. Shen;Yanli Ren;T. Shi
硫代硫酸钠已被用作缓解顺铂和卡铂毒性作用的拯救剂。在这项工作中，我们表征了反式二氯铂（IV）配合物cis-[Pt（NH3）2Cl 4]，ormaplatin [Pt（dach）Cl 4]和trans-[PtCl 2（CN）4]2-的反应动力学（抗癌前药和模型化合物）与硫代硫酸盐在生物学上重要的pH值。建立了硫代硫酸盐还原反式-[PtCl 2（CN）4]2−的总体二级速率定律，pH从4.45变化到7.90对反应速率几乎没有影响。在硫代硫酸盐与cis-[Pt（NH3）2Cl 4]和[Pt（dach）Cl 4]的反应中，动力学迹线显示出快速还原步骤，随后是涉及中间体Pt（II）络合物的缓慢取代。还原步骤也遵循二级动力学。顺式-[Pt（NH3）2Cl 4]和[Pt（dach）Cl 4]被硫代硫酸盐还原的速率相似，可能是因为它们的构型相似，而反式-[PtCl 2（CN）4]2−的还原速度约快1,000倍。一个共同的还原机制的建议，并已划定的速率决定步骤的过渡态。的活化参数是一致的转移的Cl+从铂（IV）中心的攻击硫代硫酸盐的速率决定步骤。
Sodium thiosulfate has been utilized as a rescuing agent for relief of the toxic effects of cisplatin and carboplatin. In this work, we characterized the kinetics of reactions of thetrans-dichloro-platinum(IV) complexescis-[Pt(NH3)2Cl4], ormaplatin [Pt(dach)Cl4] andtrans-[PtCl2(CN)4]2−(anticancer prodrugs and a model compound) with thiosulfate at biologically important pH. An overall second-order rate law was established for the reduction oftrans-[PtCl2(CN)4]2−by thiosulfate, and varying the pH from 4.45 to 7.90 had virtually no influence on the reaction rate. In the reactions of thiosulfate withcis-[Pt(NH3)2Cl4] and with [Pt(dach)Cl4], the kinetic traces displayed a fast reduction step followed by a slow substitution involving the intermediate Pt(II) complexes. The reduction step also followed second-order kinetics. Reductions ofcis-[Pt(NH3)2Cl4] and [Pt(dach)Cl4] by thiosulfate proceeded with similar rates, presumably due to their similar configurations, whereas the reduction oftrans-[PtCl2(CN)4]2−was about 1,000 times faster. A common reduction mechanism is suggested, and the transition state for the rate-determining step has been delineated. The activation parameters are consistent with transfer of Cl+from the platinum(IV) center to the attacking thiosulfate in the rate-determining step.