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Blue moon ensemble simulation of aquation free energy profiles applied to mono and bifunctional platinum anticancer drugs
- Source :
- Journal of Computational Chemistry. 41:1973-1984
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Aquation free energy profiles of neutral cisplatin and cationic monofunctional derivatives, including triaminochloroplatinum(II) and cis-diammine(pyridine)chloroplatinum(II), were computed using state of the art thermodynamic integration, for which temperature and solvent were accounted for explicitly using density functional theory-based canonical molecular dynamics (DFT-MD). For all the systems, the "inverse-hydration" where the metal center acts as an acceptor of hydrogen bond has been observed. This has motivated to consider the inversely bonded solvent molecule in the definition of the reaction coordinate required to initiate the constrained DFT-MD trajectories. We found that there exists little difference in free enthalpies of activation, such that these platinum-based anticancer drugs are likely to behave the same way in aqueous media. Detailed analysis of the microsolvation structure of the square-planar complexes, along with the key steps of the aquation mechanism, is discussed.
- Subjects :
- Organoplatinum Compounds
010304 chemical physics
Hydrogen bond
Molecular Conformation
Thermodynamic integration
chemistry.chemical_element
Aquation
Antineoplastic Agents
General Chemistry
Molecular Dynamics Simulation
010402 general chemistry
01 natural sciences
0104 chemical sciences
Reaction coordinate
Computational Mathematics
chemistry.chemical_compound
Molecular dynamics
chemistry
Computational chemistry
0103 physical sciences
Thermodynamics
Density functional theory
Bifunctional
Platinum
Density Functional Theory
Subjects
Details
- ISSN :
- 1096987X and 01928651
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Journal of Computational Chemistry
- Accession number :
- edsair.doi.dedup.....c4928ed9e71a394e47da7c2a703d909a