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Characterizing Pt‐Derived Anticancer Drugs from First Principles: The Case of Oxaliplatin in Aqueous Solution
Author(s) -
Beret Elizabeth C.,
Pappalardo Rafael R.,
Marx Dominik,
Sánchez Marcos Enrique
Publication year - 2009
Publication title -
chemphyschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.016
H-Index - 140
eISSN - 1439-7641
pISSN - 1439-4235
DOI - 10.1002/cphc.200900027
Subject(s) - chemistry , solvation , molecular dynamics , aqueous solution , oxalate , solvation shell , computational chemistry , crystallography , platinum , ligand (biochemistry) , ab initio , molecule , chemical physics , inorganic chemistry , organic chemistry , biochemistry , receptor , catalysis
Anionic hydration: Ab initio molecular dynamics simulations help to obtain a microscopic description of the behavior of oxaliplatin anticancer drug in bulk water (see picture). Its hydration structure is closely related to that previously found for Pt II aqua ion and derives from the presence of a square‐planar motif around the metal center.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 PtN and PtO I distances of 2.04 Å 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 Ptdiamine 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.