Photon Factory Activity Report 2005 #23 Part B (2006)
Materials Science

7C/2004G290

EXAFS Study of Glycoconjugated Bioactive Complex in Aqueous Solution
Makoto OBATA*1, Shigenobu Yano 1 and Masafumi HARADA 2
Division of Functional Material Science, Graduate School of Human Culture,
Nara Women’s University, Nara 630-8506, Japan
2Department of Clothing Environmental Science, Faculty of Human Life and Environment,
Nara Women’s University, Nara 630-8506, Japan
1

Introduction
cis-Dichlorodiammineplatinum, i.e., cisplatin is mostpromising inorganic pharmaceuticals for anticancer
chemotherapy [1]. Several derivatives such as carboplatin,
nedaplatin and oxaliplatin, have been developed in order
to expand therapeutic spectrum and reduce side effects.
We have developed platinum complex havingcarbohydrate moieties which is well-known bioactive
molecules for cellular interaction (Chart 1).
The
anticancer effect of glycoconjugated platinum complex issignificantly depends on the carbohydrate moieties
attached [2]. One possibility of the glycoconjugation
effect is the difference in the affinities of abundant
proteins such as albumin, which is main preserver for
platinum pharmaceuticals in the circulation. Here we
report the EXAFS study on glycoconjugated platinumcomplexes 1 and 2 in water and cell culture such as
Dulbeco’s modified eagle medium (DMEM).
H3NClPt

H3NClHOOOOHOH N
H2 ClHONH2Pt Cl

glucose
cisplatin

1OHOO
OHOH

NH2ClN Pt
H2 Clxylose
2Chart 1
Experimentals
Cisplatin and glycoconjugated platinum complexes 1and 2 were prepared according to literatures [2].
Fluorescence EXAFS measurements at Pt LIII edge (11559eV) were performed at BL-7C at room temperature, using
double crystal Si(111) monochromator and Lytle detector.
The ring current was 300-450 mA, and the storage ring
was operated with an electron energy of 2.5 GeV. The
samples were prepared as water and DMEM solutions of3
cisplatin, 1 and 2 (1 mM), respectively. The resulting k weighted EXAFS oscillation was analyzed on the basis
single scattering and theoretical amplitude and phasefunctions calculated by means of the FEFF 8.2 program.
All calculations were performed with REX2000 ver. 2.0.7(Rigaku Co.).
Results and Discussion
3Figure 1 shows the representative k -weighted EXAFS
3oscillations (k χ(k)) and their Fourier transforms of 1 and
32 in water. The k χ(k) oscillations were quite resemble
each other, suggesting the similar coordination structure
3of Pt atom in water and DMEM solution. The k χ(k)oscillations were fitted with sum of two back-scattering

120

Users' Reportcontribution, namely, Pt-N (k χ(k)N) and Pt-Cl (k χ(k)Cl) toafford coordination number N, interatomic distance r andDebye-Waller factor σ. As previously reported, thetheoretical amplitude and phase functions calculated byFEFF 8.2 have enough quality to analyze these EXAFS
oscillations. The interatomic distances rN and rCl are ca.
2.0 and 2.3 Å for Pt-N and Pt-Cl, respectively, which arein good accordance with those derived from X-ray
crystallography. In water, the values of NN/NCl weredetermined to be 3/1 for all platinum complexes
examined. This may be caused by the hydrolysis ofplatinum complexes, i.e., substitution reaction of Cl
ligand by water molecules.
Hence no significant
differences between cisplatin and glycoconjugatedplatinum complexes was found in the EXAFS structure inaqueous solution. In the DMEM solution, however, thevalues of NN/NCl for cisplatin and 1 were same as those inwater, while the value for 2 was ca. 1/1 in DMEM. Thissuggests platinum complex 2 is in a different situationfrom cisplatin and 1 in DMEM. Serum albumin, which isa dominant protein in DMEM affords nucleophilic sulfur
ligand e.g, their cys-34. Since the Cl and S ligand is notdistinguishable in EXAFS, one plausible explanation isthat the enhanced affinity of 2 to serum albumin. Further
study on these platinum complexes is in progress at ourlaboratory.
3Figure 1 k χ(k) oscillations and their Fourier transformsof 1 (a) and 2 (b) in water.
3

3References[1] E. Wong et al., Chem. Rev. 99, 2451 (1999).
[2] Y. Mikata et al., Bioorg. Med. Chem. Lett. 11, 3045
(2001).
* mobata@cc.nara-wu.ac.jp