Photon Factory Activity Report 2004 #22 Part B (2005)
Chemistry

10B/2004G290

EXAFS Analysis of Coordination Structure ofGlycoconjugated Bioactive Complex
Makoto OBATA*1, Masafumi HARADA2, Yuko SUGAI1, Misaki NAKAI1 and Shigenobu Yano1
1
Division of Material Science, Graduate School of Humanities and Sciences, Nara Women’s
University, Nara 830-8506, Japan2
Department of Textile and Apparel Science, Faculty of Human Life and Environment, Nara
Women’s University, Nara 830-8506, Japan
Introduction
Inorganic pharmaceuticals have been developed in thefield such as anti-cancer, anti-rheumatism and antidiabetes treatments.
Medicinal inorganic chemist
improves the efficacy of these drugs by changing ligands.
cis-Diamminedichloroplatinum(II), namely cisplatin, is amost successful drug in the field of inorganic anti-cancerdrug. The mechanism of cisplatin in the tumor necrosis
has been investigated in vitro.
Nuclear magnetic
15195
resonance (NMR) of N and Pt is a powerful tool tostudy a coordination structure in the aqueous medium.
15195
However, this technique sometimes requires N or Ptenriched sample, which is quite difficult to prepareespecially for sophisticated inorganic pharmaceuticals.
As an alternative way, we have investigated the EXAFS
approach to study cisplatin derivatives in aqueousenvironment. In this report, we demonstrate the EXAFS
analysis of the decomposition of cisplatin withglutathione which is an abundant tripeptide in biologicalsystem (Chart 1).
H3N

NH2ClPt

H3NClcisplatin

HN

HO2C
OO
N
HSH

CO2H

Fig. 1 shows the Pt-LIII edge EXAFS Fourier transformsof the reaction between cisplatin and glutathione at thevarious reaction times. Before the addition of glutathione(t = 0 min), two peaks were found at 1.6 Å and 2.0 Å(before phase-shift correction). And these were assigned
to back-scattering contribution of nitrogen and chlorine
atoms coordination to platinum, respectively. While thepeak at 1.6 Å decreased, the peak at 2.0 Å increased
monotonically with the progress of the reaction. After 6hours, the Fourier transforms of Pt-LIII edge EXAFS
shows essentially one peak at 2.0 Å. The EXAFS
oscillation can be fitted using the back-scattering
amplitude FS(k) and the phase shift ΦS(k) functions
between Pt and S atoms derived from K2[Pt(SCN)4]. The
fittings were converged with the coordination number n =4.2, the atomic distance r = 2.32 Å and Debye-Waller
factor σ = 0.065. These observations were fairly agreed
with the earlier work reported by Berners-Price andKuchel by means of NMR technique [3].
This
encourages us to apply the EXAFS technique to tailormade inorganic pharmaceuticals. The investigation forglycoconjugated bioacive complex is in progress.

glutathione (GSH)

Chart 1
Experimentals
Cisplatin
andpotassium
tetrakis(thiocyanato)platinate(II) (K2[Pt(SCN)4]) was prepared according toliteratures [1,2]. Glutathione was purchased from Wako
Pure Chemicals Co. Cisplatin (150 mg) was dissolved in(50 mL) by heating. The solution was kept at 37 °C withstirring. To the solution was added glutathione (1.56 g) toinitiate decomposition of cisplatin. After appropriate time,a portion of the solution was poured into a cell (pathlength was 1.0 cm). Pt-LIII edge EXAFS spectra werecollected at BL-10B. The EXAFS measurements werecarried out at room temperature in transmittance mode.
The back-scattering amplitude FS(k) and the phase shiftΦS(k) functions between Pt and S atoms were derived
from the Pt-LIII edge EXAFS and X-ray crystallographyof K2[Pt(SCN)4]. All calculations were performed with
REX2000, version 2.0.7 (Rigaku Co.).
Results and Discussions

24Users' Report

Fig. 1 Fourier transforms of Pt-LIII edge for the mixtureof cisplatin and glutathione in water.
References[1] E. Biilman, A. C. Andersen, Ber., 36, 1568 (1903).
[2] W. Peters, Ber., 41, 3178 (1908).
[3] S. J. Berners-Price, P. W. Kuchel, J. Inorg. Biochem.,
38, 305 (1990).
*mobata@cc.nara-wu.ac.jp