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.

• Klíčová slova
• Anticancer drug, Computational chemistry, Density functional theory, Heavy metal, Thermodynamics,
• MeSH
• chelátory chemie   MeSH
• cisplatina chemie   MeSH
• dipeptidy chemie   MeSH
• histidin chemie   MeSH
• kinetika MeSH
• methionin chemie   MeSH
• protinádorové látky chemie   MeSH
• teorie funkcionálu hustoty * MeSH
• termodynamika MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chelátory MeSH
• cisplatina MeSH
• dipeptidy MeSH
• histidin MeSH
• methionin MeSH
• protinádorové látky MeSH

In the study behavior of molecular electrostatic potential, averaged local ionization energy, and reaction electronic flux along the reaction coordinate of hydration process of three representative Ru(II) and Pt(II) complexes were explored using both post-HF and DFT quantum chemical approximations. Previously determined reaction mechanisms were explored by more detailed insight into changes of electronic properties using ωB97XD functional and MP2 method with 6-311++G(2df,2pd) basis set and CCSD/6-31(+)G(d,p) approach. The dependences of all examined properties on reaction coordinate give more detailed understanding of the hydration process.

• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The thermodynamics of cisplatin and transplatin hydration is studied within the model of constant pH solution. Several implicit solvation models were chosen for the determination of pK(a) and pK constants of the hydration reactions. The polarizable dielectric model (DPCM), integral equation formalism polarizable model (IEFPCM), and polarizable conductor model (CPCM) were combined with the 'united atom model for Hartree-Fock' (UAHF) method for cavity construction and the B3LYP/6-31++G(2dp,2pd) level of calculations for the determination of electronic energies. The results were compared with the COSMO-RS and SM8 model developed by Truhlar (with M06 and MPWX functionals and the charge model CM4). The RMS difference between experimental and calculated pK(a) values of cis/transplatin, water, HCl, and NH (4) (+) was used to evaluate accuracy of calculations. The DPCM model was confirmed to perform the best. The predicted pK(a) constants were used in Legendre transformation for the estimation of the ΔG' energies in the constant-pH model. The dependence of the pK constant on pH is plotted and compared with experimental value at pH=7.4. The influence of various chloride concentrations on the molar fractions of dissolved forms of cisplatin is examined for the DPCM model. The increased ratio of cisplatin active aqua-forms is clearly visible for 4 mM chloride solution in comparison with 104 mM Cl(-) concentration.

• MeSH
• algoritmy MeSH
• chemické modely MeSH
• chloridy chemie   MeSH
• cisplatina chemie   MeSH
• hydrolýza MeSH
• komplexní sloučeniny chemie   MeSH
• koncentrace vodíkových iontů MeSH
• kvantová teorie MeSH
• počítačová simulace MeSH
• termodynamika * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chloridy MeSH
• cisplatina MeSH
• komplexní sloučeniny MeSH
• transplatin MeSH Prohlížeč

Three potential anticancer agents {trans-[PtCl(2)(NH(3))(thiazole)], cis-[PtCl(2)(NH(3))(piperidine)], and PtCl(2)(NH(3))(cyclohexylamine) (JM118)} were explored and compared with cisplatin and the inactive [PtCl(dien)](+) complex. Basic electronic properties, bonding and stabilization energies were determined, and thermodynamic and kinetic parameters for the aquation reaction were estimated at the B3LYP/6-311++G(2df,2pd) level of theory. Since the aquation process represents activation of these agents, the obtained rate constants were compared with the experimental IC(50) values for several tumor cells. Despite the fact that the processes in which these drugs are involved and the way in which they affect cells are very complex, some correlations can be deduced.

• MeSH
• chemické modely * MeSH
• cisplatina chemie   farmakologie   MeSH
• elektrony MeSH
• inhibiční koncentrace 50 MeSH
• kinetika MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• organoplatinové sloučeniny chemie   farmakologie   MeSH
• počítačová simulace * MeSH
• protinádorové látky chemie   farmakologie   MeSH
• sloučeniny platiny chemie   MeSH
• termodynamika MeSH
• thiazoly chemie   farmakologie   MeSH
• voda chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• amminedichloro(cyclohexylamine)platinum(II) MeSH Prohlížeč
• cisplatina MeSH
• ligandy MeSH
• organoplatinové sloučeniny MeSH
• platinum chloride MeSH Prohlížeč
• protinádorové látky MeSH
• sloučeniny platiny MeSH
• thiazoly MeSH
• trans-(PtCl2(NH3)(thiazole)) MeSH Prohlížeč
• voda MeSH

In this study, various platinum cross-links in DNA bases were explored. Some of these structures occur in many cis/trans-platinated double-helixes or single-stranded adducts. However, in the models studied, no steric hindrance from sugar-phosphate backbone or other surroundings is considered. Such restrictions can change the bonding picture partially but hopefully the basic energy characteristics will not be changed substantially. The optimization of the structures explored was performed at the DFT level with the B3LYP functional and the 6-31G(d) basis set. Perturbation theory at the MP2/6-31++G(2df,2pd) level was used for the single-point energy and 6-31+G(d) basis set for the electron-property analyses. It was found that the most stable structures are the diguanine complexes followed by guanine-cytosine Pt-cross-links, ca 5 kcal mol(-1) less stable. The adenine-containing complexes are about 15 kcal mol(-1) below the stability of diguanine structures. This stability order was also confirmed by the BE of Pt-N bonds. For a detailed view on dative and electrostatic contributions to Pt-N bonds, Natural Population Analysis, determination of electrostatic potentials, and canonical Molecular Orbitals description of the examined systems were used.

• MeSH
• adenin chemie   MeSH
• cisplatina chemie   MeSH
• cytosin chemie   MeSH
• guanin chemie   MeSH
• heteroduplexy nukleové kyseliny chemie   MeSH
• jednovláknová DNA chemie   MeSH
• molekulární modely MeSH
• platina chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenin MeSH
• cisplatina MeSH
• cytosin MeSH
• guanin MeSH
• heteroduplexy nukleové kyseliny MeSH
• jednovláknová DNA MeSH
• platina MeSH