title: EXAFS and IR structural study of platinum-based anticancer drugs' degradation by diethyl dithiocarbamate.
abstract: 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.
authors.affiliation: 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
authors.forename: Diane
authors.initials: D
authors.lastname: Bouvet
authors.forename: Alain
authors.initials: A
authors.lastname: Michalowicz
authors.forename: Sylvie
authors.initials: S
authors.lastname: Crauste-Manciet
authors.forename: Denis
authors.initials: D
authors.lastname: Brossard
authors.forename: Karine
authors.initials: K
authors.lastname: Provost
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D000077150:Oxaliplatin; D004050:Ditiocarb; D016190:Carboplatin; D002945:Cisplatin