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Biotransformations of Anticancer Ruthenium(III) Complexes: An X‐Ray Absorption Spectroscopic Study
Author(s) -
Levina Aviva,
Aitken Jade B.,
Gwee Yee Yen,
Lim Zhi Jun,
Liu Mimi,
Singharay Anannya Mitra,
Wong Pok Fai,
Lay Peter A.
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201203127
Subject(s) - chemistry , x ray absorption spectroscopy , ruthenium , imidazole , absorption spectroscopy , stereochemistry , nuclear chemistry , inorganic chemistry , biochemistry , physics , quantum mechanics , catalysis
Abstract An anti‐metastatic drug, NAMI‐A ((ImH)[Ru III Cl 4 (Im)(dmso)]; Im=imidazole, dmso=S‐bound dimethylsulfoxide), and a cytotoxic drug, KP1019 ((IndH)[Ru III Cl 4 (Ind) 2 ]; Ind=indazole), are two Ru‐based anticancer drugs in human clinical trials. Their reactivities under biologically relevant conditions, including aqueous buffers, protein solutions or gels (e.g, albumin, transferrin and collagen), undiluted blood serum, cell‐culture medium and human liver (HepG2) cancer cells, were studied by Ru K‐edge X‐ray absorption spectroscopy (XAS). These XAS data were fitted from linear combinations of spectra of well‐characterised Ru compounds. The absence of XAS data from the parent drugs in these fits points to profound changes in the coordination environments of Ru III . The fits point to the presence of Ru IV/III clusters and binding of Ru III to S‐donor groups, amine/imine and carboxylato groups of proteins. Cellular uptake of KP1019 is approximately 20‐fold higher than that of NAMI‐A under the same conditions, but it diminishes drastically after the decomposition of KP1019 in cell‐culture media, which indicate that the parent complex is taken in by cells through passive diffusion.