EXAFS characterization of oxaliplatin anticancer drug and its degradation in chloride media

Abstract

Oxaliplatin is a second-generation platinum-based anticancer drug. Its degradation is studied in solution, in the presence of chloride ions (in neutral or acidic media) in excess. In both cases the degradation product precipitates immediately. The EXAFS spectra of these products show that they are identical. EXAFS modeling and refinement of the first coordination sphere shows that two light atoms are replaced by two chloride ions. The complete refinement of the local structure is possible by studying the multiple-scattering signal. The results show that the main multiple-scattering contribution is due to the binding oxalato group and that the degradation product is [Cl(2)-(diaminocyclohexane)-Pt(II)].

Characterizing Pt‐Derived Anticancer Drugs from First Principles: The Case of Oxaliplatin in Aqueous Solution

“…A recent contribution by Sarmah et al reports the optimized structure of oxaliplatin in vacuum and within the conductor-like screening model (COSMO) to take the solvent into account in the sense of a continuum using density functional theory (DFT). [18] In both phases they find bond lengths and bond angles close to the X-ray [17] and EXAFS [11,12] data and a chair configuration of the cyclohexane ring with the two amine groups in equatorial positions. In two classical molecular dynamics (CL-MD) simulations performed by Scheeff et al [19] and Sharma et al [20] the oxaliplatin-DNA adduct is characterized.…”

“…Data concerning the average structure of EDO-Pt in the gas phase, also obtained from CP-MD simulations, are included as well, along with selected structural parameters of both EDO-Pt and oxaliplatin complexes optimized in vacuum and other theoretical [18] and experimental [12,17] reference data.…”

“…The only structural determination of oxaliplatin in aqueous solution comes from the contributions of Provost and collaborators who have characterized it by means of EXAFS spectroscopy. [11,12] In their measurements, they find four equivalent first-shell PtÀO and PtÀN distances of 2.00 , as well as a PtÀC distance of 2.82 (C atoms belonging to both ethyldiamine and oxalate ligands) and a Pt···O distance of 4.00 for the outer O atoms in oxalate. These values are in good agreement with previous crystallographic data (of 2.03, 2.83 and 4.00 , respectively).…”

“…Several studies have appeared on the substitution kinetics and chemical stability of oxaliplatin in water solution, [9,10] in NaCl solution, [9] and in the presence of different chemical species (such as chloride anions, [11,12] diethyl dithiocarbamate, [13] carbonate buffers, [14] different nucleophiles, [15,16] etc.). The only structural determination of oxaliplatin in aqueous solution comes from the contributions of Provost and collaborators who have characterized it by means of EXAFS spectroscopy.…”

Rákellenes gallium- és platinafém komplexek oldatkémiája, kölcsönhatásuk vérszérum-fehérjékkel és DNS-sel

“…Csapadékképződést csak a NaCl-ot is tartalmazó mintáknál figyeltünk meg (23 mM NaCl jelenlétében 56 óra múlva). Feltehetőleg a metilcsoport jelenléte miatt a molekula lipofilebb karakterű lesz, és a sárga csapadék az oxalát ligandum cseréjével képződő dikloridokomplex [105,106].…”