Formation of chelate structure between His-Met dipeptide and diaqua-cisplatin complex; DFT/PCM computational study

  • Michal Maixner
  • Helio F. Dos Santos
  • Jaroslav V. Burda
Original Paper


Interaction of cisplatin in activated diaqua-form with His-Met dipeptide is explored using DFT approach with PCM model. First the conformation space of the dipeptide is explored to find the most stable structure (labeled 0683). Several functionals with double-zeta basis set are used for optimization and obtained order of conformers is confirmed by the CCSD(T) single-point calculations. Supermolecular model is used to determine reaction coordinate for the replacement of aqua ligands consequently by N-site of histidine and S-site of methionine and reversely. Despite the monoadduct of Pt–S(Met) is thermodynamically less stable this reaction passes substantially faster (by several orders of magnitude) than coordination of cisplatin to histidine. The consequent chelate formation occurs relatively fast with energy release up to 12 kcal mol−1.


Computational chemistry Density functional theory Thermodynamics Anticancer drug Heavy metal 



Authors (JVB and MM) are grateful for supporting this study to the Grant Agency of Czech Republic Project no 16-06240S. We would also like to acknowledge a generous access to computational facilities of the National Grid Infrastructure MetaCentrum, provided under the program ‘Projects of Large Infrastructure for Research, Development, and Innovations’ (LM2010005).

Supplementary material

775_2018_1536_MOESM1_ESM.pdf (97 kb)
Supplementary material 1 (PDF 97 kb)


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Copyright information

© SBIC 2018

Authors and Affiliations

  • Michal Maixner
    • 1
  • Helio F. Dos Santos
    • 2
  • Jaroslav V. Burda
    • 1
  1. 1.Department of Chemical Physics and Optics, Faculty of Mathematics and PhysicsCharles UniversityPrague 2Czech Republic
  2. 2.NEQC: Núcleo de Estudos em Química Computacional, Departamento de Química-ICEUniversidade Federal e Juiz de ForaJuiz de ForaBrazil

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