EXAFS and IR structural study of platinum-based anticancer drugs' degradation by diethyl dithiocarbamate.
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.
Bouvet
Diane
D
Laboratoire de Physique Structurale des Molécules et Matériaux, Université Paris XII, 61 avenue du Général De Gaulle, 94010 Créteil Cedex, France. bouvet@univ-paris12.fr
Michalowicz
Alain
A
Crauste-Manciet
Sylvie
S
Brossard
Denis
D
Provost
Karine
K
D000970:Antineoplastic Agents / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry; D004050:Ditiocarb / Q000737:chemistry; D004787:Environmental Pollution / Q000517:prevention & control; D052918:Environmental Restoration and Remediation; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry; D000077150:Oxaliplatin; D017671:Platinum Compounds / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013057:Spectrum Analysis; D014965:X-Rays
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D000077150:Oxaliplatin; D004050:Ditiocarb; D016190:Carboplatin; D002945:Cisplatin