The kinetics of the hydration reaction on trans-[Pt(NH3)2(pyrX)Cl]+ (pyr = pyridine) complexes (X = OH-, Cl-, F-, Br-, NO2 -, NH2, SH-, CH3, C≡CH, and DMA) was studied by density functional theory calculations in the gas phase and in water solution described by the implicit polarizable continuum model method. All possible positions ortho, meta, and para of the substituent X in the pyridine ring were considered. The substitution of the pyr ligand by electron-donating X's led to the strengthening of the Pt-N1(pyrX) (Pt-NpyrX) bond and the weakening of the trans Pt-Cl or Pt-Ow bonds. The electron-withdrawing X's have exactly the opposite effect. The strengths of these bonds can be predicted from the basicity of sigma electrons on the NpyrX atom determined on the isolated pyrX ligand. As the pyrX ring was oriented perpendicularly with respect to the plane of the complex, the nature of the X···Cl electrostatic interaction was the decisive factor for the transition-state (TS) stabilization which resulted in the highest selectivity of ortho-substituted systems with respect to the reaction rate. Because of a smaller size of X's, the steric effects influenced less importantly the values of activation Gibbs energies ΔG ⧧ but caused geometry changes such as the elongation of the Pt-NpyrX bonds. Substitution in the meta position led to the highest ΔG ⧧ values for most of the X's. The changes of ΔG ⧧ because of electronic effects were the same in the gas phase and the water solvent. However, as the water solvent dampened electrostatic interactions, 2200 and 150 times differences in the reaction rate were observed between the most and the least reactive mono-substituted complexes in the gas phase and the water solvent, respectively. An additional NO2 substitution of the pyrNO2 ligand further decelerated the rate of the hydration reaction, but on the other hand, the poly-NH2 complexes were no more reactive than the fastest o-NH2 system. In the gas phase, the poly-X complexes showed the additivity of the substituent effects with respect to the Pt-ligand bond strengths and the ligand charges.

• Publikační typ
• časopisecké články 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

Hydration reactions of two anticancer Pt(IV) complexes JM149 and JM216 (Satraplatin) were studied computationally together with the hydration of the Pt(II) complex JM118, which is a product of the Satraplatin reduction. Thermodynamic and kinetic parameters of the reactions were determined at the B3LYP/6-311++G(2df.2pd)//B3LYP/6-31 + G(d)) level of theory. The water solution was modeled using the COSMO implicit solvation model, with cavities constructed using Klamt's atomic radii. It was found that hydration of the Pt(IV) complexes is an endergonic/endothermic reaction. It follows the (pseudo)associative mechanism is substantially slower (k ≈ 10(-11) s(-1)) than the corresponding reaction of Pt(II) analogues ((k ≈ 10(-5) s(-1)). Such a low value of the reaction constant signifies that the hydration of JM149 and Satraplatin is with high probability a kinetically forbidden reaction. Similarly to JM149 and Satraplatin, the hydration of JM118 is an endothermic/endoergic reaction. On the other hand, the kinetic parameters are similar to those of cisplatin Zimmermann et al. (J Mol Model 17:2385-2393, 2011), allowing the hydration reaction to occur at physiological conditions. These results suggest that in order to become active Satraplatin has to be first reduced to JM118, which may be subsequently hydrated to yield the active species.

• MeSH
• chemické modely MeSH
• kinetika MeSH
• kvantová teorie MeSH
• ligandy MeSH
• molekulární modely MeSH
• organoplatinové sloučeniny chemie   MeSH
• oxidace-redukce MeSH
• protinádorové látky chemie   MeSH
• termodynamika MeSH
• voda chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• amminedichloro(cyclohexylamine)platinum(II) MeSH Prohlížeč
• JM 335 MeSH Prohlížeč
• ligandy MeSH
• organoplatinové sloučeniny MeSH
• protinádorové látky MeSH
• satraplatin MeSH Prohlížeč
• voda 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