The hydrolysis process of the cis-dichloro(ethylenediamine)platinum(II): A theoretical study

Abstract

The hydrolysis process of the cisplatin analog cis-dichloro(ethylenediamine)platinum(II) (cis-DEP) was theoretically investigated at the Hartree–Fock, density functional theory and the second order Møller–Plesset perturbation theory levels of calculation. The stationary points on the gas phase potential energy surface for the first and second hydrolysis steps were fully optimized and characterized. For the first aquation process the gas phase results are in satisfactory agreement with the experimental data. However in order to reproduce the observed rate constant for the second hydrolysis step it is essential to include the solvent effect. The structures and energetic properties are similar to the values found for the parent compound cisplatin, showing that the cis-DEP analog should be considered as a potential drug concerning its hydrolysis process.

An experimental and theoretical investigation into the hydrolysis of dichloro(ethylenediamine)platinum(II) via electrospray mass spectrometry and density functional theory

“…Costa et al have also reported theoretical gas-phase Gibbs energies at a variety of levels of theory for the reaction in eq 4, [19] where similar values were found with density functionals (B3P86 and B3PW91) closely related to that used here (B3LYP): ⌬G gas ϭ 5.5 and 6.0 kcal/mol, respectively. The authors did not, however, report theoretical aqueous values.…”

“…Our value is similar to that found by Figure 3 for theoretical structures. Costa et al : ⌬G gas ϭ 22.0 and 24.5 kcal/mol [19]. Costa et al also calculated an aqueous Gibbs energy for the reaction in eq 6 [20].…”

Hydrogen bonding, solvation, and hydrolysis of cisplatin: A theoretical study

“…The reaction is thought to proceed via a five-coordinate trigonal-bipyramidal transition state, with a reported barrier of around 24 kcal/mol, 29 well reproduced in a recent in vacuo DFT study by Zhang et al 30 Costa et al have recently reported a similar study of the hydrolysis of cis-dichloro(ethylenediamine)platinum(II), demonstrating the importance of solvent effects. 31 Because we have observed H-bonding to water to be important for the ground state of cisplatin, we have reexamined the potential energy surface for this reaction in the presence of explicit water molecules. Indeed, the most stable 1:1 complex found here is essentially identical to that reported by Zhang et al as the first stage of hydrolysis.…”

Hydration process as an activation of trans‐ and cisplatin complexes in anticancer treatment. DFT and ab initio computational study of thermodynamic and kinetic parameters

“…32,33 Other calculations devoted to the hydration of Pt complexes appeared recently. 34,35 Here, the authors gave a thorough insight on the effect of various contributions in multipole expansion of SCRF (Self-Consistent Reaction Field). Despite the fact that they have focused on dechlorination of the Pt(II)-ethylenediammine complex, the obtained hydration characteristics are very close to the cisplatin data.…”