Axial structure of the Pd(II) aqua ion in solution.

Solution chemistry of Pd(II) and Pt(II) complexes is relevant to many fields of chemistry given the widespread applications of their compounds in homogeneous and heterogeneous catalysis, intermediate reaction synthesis, and antitumoral drugs. The well-defined square-planar arrangement of their complexes contrasts with the rather diffuse axial environment in solution. A theoretical proposal for a characteristic hydration shell in this axial region, called the meso-shell, stimulated further experimental and theoretical studies which have led to different pictures. The present work characterizes the structure of the axial region of the Pd(II) aqua ion in solution using a combination of neutron and X-ray diffraction and extended X-ray absorption fine structure (EXAFS) spectroscopy, with empirical potential structure refinement (EPSR). The results confirm the existence of the axial region and structurally characterize the water molecules within it. An important finding not previously reported is that the counterion, in this case the perchlorate anion, competes with water molecules for the meso-shell occupancy. The important role played by the axial region in many ligand substitution reactions is therefore intimately connected with the presence of the counterion and not just hydration water. This must call the attention of the experimental community to the important role that the counterion of the precursor salt must play in the synthesis.

Coupling CP-MD simulations and X-ray absorption spectroscopy: exploring the structure of oxaliplatin in aqueous solution.

A combined experimental-theoretical approach applying X-ray absorption spectroscopy and ab initio molecular dynamics (CP-MD) simulations is used to get insight into the structural determination of oxaliplatin, a third-generation anticancer drug of the cisplatin family, in aqueous solution. Experimental Pt L(III)-edge EXAFS and XANES spectra of oxaliplatin in water are compared with theoretical XAS spectra. The latter are obtained as statistically averaged spectra computed for a set of selected snapshots extracted from the MD trajectory of ethyldiamineoxalatoplatinum(II) (EDO-Pt) in liquid water. This compound is a simplified structure of oxaliplatin, where the outer part of the cyclohexane ring contained in the cyclohexanediamine ligand of oxaliplatin has been removed. We show that EDO-Pt is an appropriate model to simulate the spectroscopical properties of oxaliplatin given that the cyclohexane ring does not generate particular features in neither the EXAFS nor the XANES spectra. The computation of average EXAFS spectra using structures from the MD simulation in which atoms are selected according to different cutoff radii around the Pt center allows the assignment of spectral features to particular structural motifs, both in k and R-spaces. The outer oxygen atoms of the oxalate ligand (R(Pt-O(II)) = 3.97 +/- 0.03 A) are responsible for a well-defined hump at around 6.5 A(-1) in the k(2)-weighted EXAFS spectrum. The conventional EXAFS analysis data procedure is reexamined by its application to the simulated average EXAFS spectra. The structural parameters resulting from the fit may then be compared with those obtained from the simulation, providing an estimation of the methodological error associated with the global fitting procedure. A thorough discussion on the synergy between the experimental and theoretical XAS approaches is presented, and evidence for the detection of a slight hydration structure around the Pt complex is shown, leading to the suggestion of a new challenge to experimental XAS measurements.

Characterizing Pt-derived anticancer drugs from first principles: the case of oxaliplatin in aqueous solution.

The molecular compound ethyldiamine-oxalatoplatinum(II), EDO-Pt, is used as a model to study the oxaliplatin anticancer drug in aqueous solution by means of ab initio computer simulation. Gas-phase structure optimizations have been performed for both oxaliplatin and its EDO-Pt mimic along with Car-Parrinello molecular dynamics simulations of EDO-Pt in gas phase and in aqueous solution. The coordination of Pt(II) is square-planar on average, with Pt-N and Pt-O(I) distances of 2.04 A in solution. The diamine ligand has a bent structure, while the oxalate ligand is planar on average. The complex features a very rigid structure during the simulation and the charge distribution describes a dipole with its negative pole on the oxalate ligand and the positive pole on the Pt-diamine side. The solvation pattern of EDO-Pt is most well-defined around the amine and oxalate groups and is quantified by means of radial and spatial distribution functions of water molecules around the complex. Decomposition of radial distribution functions into their contributions from different regions (axial and equatorial) reveals an "anionic hydration" pattern of the metal cation by the solvent, which is analogous in nature to the bare Pt(II) aqua ion. A qualitative prediction on the kinetics of ligand exchange in oxaliplatin is derived based on its axial hydration pattern.