Bouvet Diane, Michalowicz Alain, Crauste-Manciet Sylvie, Brossard Denis, Provost Karine
Laboratoire de Physique Structurale des Molécules et Matériaux, Université Paris XII, 61 avenue du Général De Gaulle, 94010 Créteil Cedex, France.
Inorg Chem. 2006 Apr 17;45(8):3393-8. doi: 10.1021/ic051904u.
Platinum compounds constitute a discrete class of DNA-damaging anticancer drug agents, including cisplatin, carboplatin, and oxaliplatin. The toxicity of such drugs raises the problem of waste detoxification. Diethyl dithiocarbamate (DDTC) is recommended by the World Heath Organization (WHO) for the destruction of cisplatin, but the degradation product has not been structurally characterized. This paper deals with the extended X-ray absorption fine structure (EXAFS) and IR structural study of the reaction products of DDTC with cisplatin, carboplatin, and oxaliplatin. Cisplatin and carboplatin give the same reaction product: Pt(DDTC)2. In the case of oxaliplatin, we observed the formation of [(diaminocyclohexane)(DDTC)Pt(II)]. In all cases, the replacement of labile ligands by strong ligands should lead to inactive compounds. Our results suggest that the WHO inactivation protocol might be extended to carboplatin and oxaliplatin. Nevertheless, this should be validated by toxicity tests of the degradation products.
铂化合物是一类独特的DNA损伤抗癌药物，包括顺铂、卡铂和奥沙利铂。这类药物的毒性引发了废物解毒的问题。世界卫生组织（WHO）推荐用二乙基二硫代氨基甲酸盐（DDTC）来销毁顺铂，但降解产物的结构尚未得到表征。本文研究了DDTC与顺铂、卡铂和奥沙利铂反应产物的扩展X射线吸收精细结构（EXAFS）和红外结构。顺铂和卡铂产生相同的反应产物：Pt(DDTC)2。对于奥沙利铂，我们观察到[(二氨基环己烷)(DDTC)Pt(II)]的形成。在所有情况下，不稳定配体被强配体取代应会导致化合物失去活性。我们的结果表明，WHO的灭活方案可能适用于卡铂和奥沙利铂。然而，这需要通过降解产物的毒性测试来验证。
