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 Fi(k) and phase shifts Φi(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 Φi(k) functions to give the coordination numbers of N or O atoms (NN/O) and of Cl or S atoms (N Cl/S). For both cisplatin and carboplatin, the NN/O value decreased and the NCl/S values increased monotonically as the reaction proceeded. However, the reaction rate for carboplatin was significantly slower than that for cisplatin. © 2009 Pharmaceutical Society of Japan.