Karine Provost

Carboplatin and oxaliplatin decomposition in chloride medium, monitored by XAS.

The stability of carboplatin and oxaliplatin aqueous solutions has been studied under different chloride ions concentration and pH conditions. For both compounds, we demonstrate the chloration of the platinum first coordination shell.

F‐test in EXAFS fitting of structural models

A. M i c h a l o w i c z * , K Provost * * , S. Larue l le ÷, A. M i m o u n i * a n d G. V la ic x The meaning and the way to estimate these quantities is discussed elsewhere (Lytle, S&C report, 1988 and present XAFS conference, 1998). We want to compare two fits noted AX2~ and AX22 with respectively the degrees of freedom v~ and v2. In order to avoid confusing notation we shall not use A%zv in the following formulas.

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

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)].

EXAFS structural study of platinum-based anticancer drugs degradation in presence of sulfur nucleophilic species

Three platinum complexes, cisplatin, carboplatin and oxaliplatin are currently used worldwide. Investigation of their main structural modifications in presence of sulfur nucleophiles is of particular interest because of the implication of thiol and thioether groups in biochemical mechanism of action, resistance mechanism and in vivo or in vitro detoxification. We present the main structural results we have obtained concerning the reaction of these drugs with diverse sulfur nucleophiles (cysteine, glutathione, methionine, thiosulfate and thiocyanate), monitored in solution or as precipitates by EXAFS spectroscopy. The reactivities of the carboxylate and amine ligands of both carboplatin and oxaliplatin are compared, on the basis of first-coordination sphere modeling. Among the new results of this EXAFS study, we present the first observation of oxaliplatin diaminocyclohexane ligand displacement by sulfur nucleophiles.

A square-planar di-N-carboxamido, dithiolato–cobalt(III) complex related to nitrile hydratase metallic site. Addition of axial ligands and EXAFS study of the derived dicyano and diisocyanido complexes

Abstract A square-planar cobalt(III) complex with a N2S2 di-N-carboxamido di-thiolato tetradentate ligand, mimics the metal core of the cobalt containing nitrile hydratases. It forms hexacoordinated complexes only upon addition of ligands like cyanide or isocyanides. An EXAFS analysis confirmed that two axial ligands get bound, and lead to a significant increase of the bond lengths between the cobalt(III) and the equatorial ligands. Whereas the planar complex is stable in the presence of air or hydrogen peroxide, its hexacoordinated derivatives with strong σ-donor axial ligands undergo an oxygenation of the equatorial thiolate ligands.

Carboplatin decomposition in aqueous solution with chloride ions monitored by X-ray absorption spectroscopy

Carboplatin n aqueous solutions, with chloride ions added at different concentrations, were studied by X-ray absorption spectroscopy (XAS). The comparison of solid and solution spectra shows that carboplatin and cisplatin spectra are strongly n different, and that the carboplatin ligands induce a specific structure of the spectrum, conserved in solution. n Hence, it is possible to study by XAS the evolution of carboplatin in solution. This study shows that carboplatin n is the major compound present in solution, even after 15 days, in neutral solutions with chloride concentration n less than 9%, exposed to light or not. On the contrary, with high chloride concentrations (18%) or in acidic n solutions (0.1 M HCl), the carboplatin is chlorolysed, the evolution n of the n solution composition can be followed by XAS and cisplatin formation is evidenced.

Composition and size dependence of hydrogen interaction with carbon supported bulk-immiscible Pd–Rh nanoalloys

In-depth clarification of hydrogen interaction with noble metal nanoparticles and nanoalloys is essential for further development and design of efficient catalysts and hydrogen storage nanomaterials. This issue becomes even more challenging for nanoalloys of bulk-immiscible metals. The hydrogen interaction with bulk-immiscible Pd-Rh nanoalloys (3-6 nm) supported on mesoporous carbon is studied by both laboratory and large scale facility techniques. X-ray diffraction (XRD) reveals a single phase fcc structure for all nanoparticles confirming the formation of nanoalloys in the whole composition range. In situ extended x-ray absorption fine structure (EXAFS) experiments suggest segregated local structures into Pd-rich surface and Rh-rich core coexisting within the nanoparticles. Hydrogen sorption can be tuned by chemical composition: Pd-rich nanoparticles form a hydride phase, whereas Rh-rich phases do not absorb hydrogen under ambient temperature and pressure conditions. The thermodynamics of hydride formation can be tailored by the composition without affecting hydrogen capacity at full hydrogenation. Furthermore, for hydrogen absorbing nanoalloys, in situ EXAFS reveals a preferential occupation of hydrogen for the interstitial sites around Pd atoms. To our knowledge, this is the first study providing insights into the hydrogen interaction mechanism with Pd-Rh nanoalloys that can guide the design of catalysts for hydrogenation reactions and the development of nanomaterials for hydrogen storage.

Experimental Challenges in Studying Hydrogen Absorption in Ultrasmall Metal Nanoparticles

Recent advances on synthesis, characterisation and hydrogen absorption properties of ultra-small metal nanoparticles (defined here as objects with average size ≤ 3 nm) are briefly reviewed in the first part of this work. The experimental challenges encountered in performing accurate measurements of hydrogen absorption in Mg- and noble metal-based ultra-small nanoparticles are addressed. The second part of this work reports original results obtained for ultra-small bulk immiscible Pd-Rh nanoparticles. Carbon supported Pd-Rh nanoalloys in the whole binary chemical composition range have been successfully prepared by liquid impregnation method followed by reduction at 300 °C. EXAFS investigations suggested that the local structure of these nanoalloys is partially segregated into Rh-rich core and Pd-rich surface coexisting within the same nanoparticles. Downsizing to ultra-small dimensions completely suppresses the hydride formation in Pd-rich nanoalloys at ambient conditions, contrary to bulk and larger nanosized (5-6 nm) counterparts. The ultra-small Pd90Rh10 nanoalloy can absorb hydrogen forming solid solutions under these conditions, as suggested by in situ XRD. Apart from this composition, common laboratory techniques such as, in situ XRD, DSC and PCI failed to clarify the hydrogen interaction mechanism : either adsorption on developed surfaces or both adsorption and absorption with formation of solid solutions. Concluding insights were brought by in situ EXAFS experiments at synchrotron: ultra-small Pd75Rh25 and Pd50Rh50 nanoalloys absorb hydrogen forming solid solutions at ambient conditions. Moreover, the hydrogen solubility in these solid solutions is higher with increasing Pd content and this trend can be understood in terms of hydrogen preferential occupation in the Pd-rich regions, as suggested by in situ EXAFS. The Rh-rich nanoalloys (Pd25Rh75 and Pd10Rh90) only adsorb hydrogen on the developed surface of ultra-small nanoparticles. In summary, in situ characterization techniques carried out at large scale facilities are unique and powerful tools for in-depth investigation of hydrogen interaction with ultra-small nanoparticles at local level.

CRYSTALFF - from crystallography to EXAFS multiple-scattering calculations with FEFF

CRYSTALFF is an alternative utility to ATOMS containing most of the features of this standard program for converting crystallographic data to FEFF input. In addition, it offers an interface with molecular modelling programs via the PDB format and new coordination sphere analysis options.

Investigation of the local structure of nanosized rhodium hydride

The local structure and the thermal stability of small and well-dispersed RhHx nanoparticles (average size of 1.4u202fnm) were studied by in situ X-ray Absorption Spectroscopy. The RhHx nanoparticles are stable at room temperature and undergo a structural transition from hydride (fcc) to metal phase (fcc) with a shrinking of the lattice volume due to the desorption of hydrogen. This phase transition occurs in the temperature range of 150-180u202f°C, in good agreement with the results from thermo-desorption spectroscopy. Above 180u202f°C, the desorbed nanoparticles undertake important coalescence. In situ transmission electron microscopy performed up to 300u202f°C proves that this process cannot be only thermal, thus it may be ascribed to a X-ray beam effect.