Hydration of Two Cisplatin Aqua-Derivatives Studied by Quantum Mechanics and Molecular Dynamics Simulations

Abstract

The hydration of the cisplatin aqua-derivatives, cis-[PtCl(H2O)(NH3)2](+) (w-cisplatin) and cis-[Pt(H2O)2(NH3)2](2+) (w2-cisplatin), has been studied by means of classical molecular dynamics simulations. The new platinum complex-water interaction potential, w-cisplatin-W, has been built on the basis of the already obtained cisplatin-water interaction potential (cisplatin-W) [J. Chem. Theory Comput. 2013 9, 4562]. That potential has been then transferred to the w2-cisplatin-W potential. The w-cisplatin and w2-cisplatin atomic charges were specifically derived from their solute's wave functions. Bulk solvent effects on the complex-water interactions have been included by means of a continuum model. Classical MD simulations with 1 platinum complex and 1000 SPC/E water molecules have been carried out. Angle-solved radial distribution functions and spatial distribution functions have been used to provide detailed pictures of the local hydration structure around the ligands (water, chloride, and ammine) and the axial region. A novel definition of a multisite cavity has been employed to compute the hydration number of complexes in order to provide a consistent definition of their first-hydration shell. Interestingly, the hydration number decreases with the increase of the complex net charge from 27 for cisplatin to 23 and 18 for w-cisplatin and w2-cisplatin, respectively. In parallel to this hydration number behavior, the compactness of the hydration shell increases when going from the neutral complex, i.e. cisplatin, to the doubly charged complex, w2-cisplatin. Quantum mechanics estimation of the hydration energies for the platinum complexes allows the computation of the reaction energy for the first- and second-hydrolysis of cisplatin in water. The agreement with experimental data is satisfactory.

Cisplatin under oriented external electric fields: A deeper insight into electrochemotherapy at the molecular level

“…Herein, the calculated activation Gibbs free energy barrier for interchanging one anionic chloride ligand of cisplatin with water in field‐free state is 28.72 kcal/mol, which accords well with the literature values 4,8,51,52 . Besides, the reaction Gibbs free energy (16.37 kcal/mol) for the first hydrolysis of Cl − in cisplatin is nearly equal to that of 17.3 kcal/mol reported by Cossío and coworkers, 8 but is smaller than that of 23.15 kcal/mol reported by Miller et al 53 and larger than those of 6.4–10.3 kcal/mol from other studies 51,54,55 …”

“…Besides, the reaction Gibbs free energy (16.37 kcal/mol) for the first hydrolysis of Cl − in cisplatin is nearly equal to that of 17.3 kcal/mol reported by Cossío and coworkers, 8 but is smaller than that of 23.15 kcal/mol reported by Miller et al 53 and larger than those of 6.4-10.3 kcal/mol from other studies. 51,54,55 As is expected, the obtained activation barriers for cisplatin are gradually decreased from 28.72 to 26.62 kcal/mol as the strengths of Figure S5. It can be seen clearly that, under the considered OEEFs, all the transition F I G U R E 5 Isosurface maps of the electron density difference (EDD) for cisplatin under F y of −0.01 and 0.01 au with respect to the field-free state.…”

para-Aminosalicylic acid in the treatment of manganese toxicity. Complexation of Mn2+ with 4-amino-2-hydroxybenzoic acid and its N-acetylated metabolite

“…This suggests that the logβ values reported in Table 2, which show that the formation of the Mn-L complexes is more favorable following the AcPAS > SAL > PAS order, could not primarily influenced by the strength of the Mn-L interaction. Evidently this difference in stability could be due to a delicate balance of metalligand interaction and solvation properties of the reagents and products as previously observed [55][56][57].…”

Cu(i) and Ag(i) complex formation with the hydrophilic phosphine 1,3,5-triaza-7-phosphadamantane in different ionic media. How to estimate the effect of a complexing medium

“…This computational approach has been successfully employed to obtain reliable structural and thermochemical data for metal complex formation in the gas phase and aqueous solution. [24][25][26][27][28][29][30][31][32][33][34] The combined results from the thermodynamic studies and DFT calculations are used to propose a relationship between the stability in solution of the [M(PTA) 4 ][X] compounds (X = BF 4 − , PF 6 − , Fig. 1) and their cytotoxic activity.…”