title: Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin).
abstract: The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0°C and 1.0M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the five GSH species is the mainly responsible for the reduction of ormaplatin at the physiological pH of 7.4.
authors.affiliation: College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, People's Republic of China.
authors.forename: Jingran
authors.initials: J
authors.lastname: Dong
authors.affiliation: College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, People's Republic of China.
authors.forename: Shuying
authors.initials: S
authors.lastname: Huo
authors.affiliation: College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, People's Republic of China.
authors.forename: Shigang
authors.initials: S
authors.lastname: Shen
authors.affiliation: College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, People's Republic of China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Chemistry and Environmental Science, and the MOE Key Laboratory of Medicinal Chemistry and Molecular Diagnostics, Hebei University, Baoding 071002, Hebei Province, People's Republic of China. Electronic address: rock@hbu.edu.cn.
authors.forename: Tiesheng
authors.initials: T
authors.lastname: Shi
authors.affiliation: Center for Analysis and Synthesis, Department of Chemistry, Lund University, PO Box 124, SE 221 00 Lund, Sweden. Electronic address: lars_ivar.elding@chem.lu.se.
authors.forename: Lars I
authors.initials: LI
authors.lastname: Elding
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D005978:Glutathione / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D013058:Mass Spectrometry; D009944:Organoplatinum Compounds / Q000737:chemistry*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D011355:Prodrugs; D005978:Glutathione; C049777:ormaplatin
keywords: Anticancer; Glutathione; Kinetic analysis; Ormaplatin (tetraplatin); Reduction