Extended X-Ray Absorption Fine Structure Study on Reaction of Anti-tumor Platinum Complexes with Reduced Glutathione

Abstract

Reactions of cis-diamminedichloroplatinum(II) (cisplatin) and 1,1-cyclobutanedicarboxylatodiammineplatinum(II) (carboplatin) with reduced glutathione, a tripeptide that is abundant in cells, were studied by means of X-ray absorption spectroscopy. Back-scattering amplitudes F_i(k) and phase shifts Φ_i(k) were theoretically derived, and validated by applying them to calculate extended X-ray absorption fine structure (EXAFS) oscillations of cisplatin and K₂[Pt(SCN)₄] in the solid state. EXAFS oscillations of reaction mixtures of cisplatin or carboplatin with reduced glutathione were fitted to the standard EXAFS equation using the F_i(k) and Φ_i(k) functions to give the coordination numbers of N or O atoms (N_N/O) and of Cl or S atoms (N_Cl/S). For both cisplatin and carboplatin, the N_N/O value decreased and the N_Cl/S values increased monotonically as the reaction proceeded. However, the reaction rate for carboplatin was significantly slower than that for cisplatin.