Monte Carlo Simulation of Cisplatin Molecule in Aqueous Solution

Abstract

The Lennard-Jones (12-6) parameters were obtained for all atoms of cisplatin molecule using the ab initio quantum mechanical potential energy surface for the water-cisplatin interaction as reference data. The parameters found were (epsilon/kcal.mol(-1) and sigma/angstroms) 1.0550, 3.6590 (Pt); 0.0381, 4.6272 (Cl); 0.0455, 3.3783 (N); and 0.0185, 0.0936 (H) and provided very good results for the description of the aqueous solution of cisplatin through Monte Carlo simulation. From statistical analysis of solute-solvent interactions, we observed that the NH3 groups are involved in 53% of the calculated hydrogen bonds with a significant contribution from chlorides (41%) and only 6% involving the Pt center. This is in agreement with the expected behavior for such molecules. Two hydration shells with 22 and 81 water molecules, respectively, centered around 4.6 and 7.3 angstroms were found from the center of mass pair correlation function analysis. The cisplatin atomic Lennard-Jones parameters are reported for the first time, and they might be useful for studying the structure, properties, and processes of cisplatin-like molecules in aqueous solution, including explicitly the solvent effect.

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

“…Lopes et al [24] have performed a Monte Carlo simulation of cisplatin in water analyzing the hydration pattern of the complex. We have previously studied the Pd II and Pt II aqua ions in water solution, which also show a square-planar first coordina-…”

An investigation of the BSSE effect on the evaluation of Ab Initio interaction energies for cisplatin-water complexes

“…A good example is the use of BSSE corrected potential energy curves for the generation of empirical parameters that feed the Lennard-Jones (12-6) potential function used in classical Monte Carlo simulation of liquids and also solvent effects. We have reported ε and σ Lennard-Jones parameters obtained for cisplatin using BSSE corrected 9 and uncorrected 10 potential energy curves in the fitting procedure. The results are presented in Table 3 (the TIP3P potential was used for the water molecule), 36 where it can be promptly seen that the difference is quite substantial.…”

“…1 The drug mechanism of action has been the subject of several experimental studies in chemical and biological areas, [2][3][4] along with a number of theoretical works. [5][6][7][8][9] In a recent study 10 we have emphasized the importance of the intermolecular interactions between cisplatin and water molecule as a pre-step to the hydrolysis reaction which plays an important role in the drug mechanism of action. In that work, the interest was devoted to the trend of theoretical methods used, with the focus on the electronic correlation and electrostatic effects for the interaction of cisplatin with water and their aquated species using ab initio correlated level of theory.…”

Comparison of hydration reactions for “piano-stool” RAPTA-B and [Ru(η6− arene)(en)Cl]+ complexes: Density functional theory computational study

“…Description of the reaction mechanisms and electronic properties of cisplatin and its analogs were examined in several papers. [27][28][29][30][31] Some studies concerned the aquation process of platinum complexes, which is crucial in the activation step, [32][33][34][35][36][37][38][39] interactions with nucleobases, [40][41][42][43][44][45][46][47][48][49][50][51] or other competitive reactions with cellular components, such as side chains of amino acids. [52][53][54][55][56] Ruthenium compounds also attract a lot of attention as can be noticed in recent computational chemistry literature.…”