Beret Elizabeth C, Pappalardo Rafael R, Marx Dominik, Sánchez Marcos Enrique
Departamento de Química Física, Universidad de Sevilla, 41012 Sevilla, Spain.
Chemphyschem. 2009 May 11;10(7):1044-52. doi: 10.1002/cphc.200900027.
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.
分子化合物乙二胺草酸铂（II）（EDO-Pt）被用作模型，通过从头算计算机模拟研究奥沙利铂在水溶液中的抗癌药物作用。对奥沙利铂及其EDO-Pt模拟物进行了气相结构优化，并对EDO-Pt在气相和水溶液中进行了Car-Parrinello分子动力学模拟。Pt（II）的配位平均为平面正方形，在溶液中Pt-N和Pt-O（I）距离为2.04 Å。二胺配体具有弯曲结构，而草酸盐配体平均为平面结构。在模拟过程中，该配合物具有非常刚性的结构，电荷分布描述了一个偶极子，其负极在草酸盐配体上，正极在Pt-二胺一侧。EDO-Pt的溶剂化模式在胺基和草酸盐基团周围最为明确，并通过配合物周围水分子的径向和空间分布函数进行量化。将径向分布函数分解为其来自不同区域（轴向和赤道）的贡献，揭示了溶剂对金属阳离子的“阴离子水合”模式，其本质上类似于裸露的Pt（II）水合离子。基于其轴向水合模式，对奥沙利铂中配体交换动力学进行了定性预测。
