Interactions of hydrated cisplatin complexes with sulphur-containing amino acids cysteine and methionine were explored. The square-planar cis-[Pt(NH3)2(H2O)X]+ complexes (where X=Cl- and OH-) were chosen as mono- and dihydrated reactants. Calculations using density functional theory (DFT) techniques with B3LYP functional were performed. The isolated molecules and the supermolecular approaches were employed for the determination of the reaction energies. Bond dissociation energies (BDE) were estimated in the model of isolated molecules and supermolecules were used for the determination of the association energies between the two interacting parts. Formation of monodentate complexes by replacing the aqua-ligand with the S, N, and O-sites of both amino acids represents an exothermic process. The highest BDE was found in cysteine structures for the Pt-S coordination. The bonding energy is about 114 kcal/mol, which is comparable with cisplatin-guanine adducts. Analogous BDE for methionine complexes is smaller by about 40 kcal/mol. This correlates well with the known fact that cysteine forms irreversible cisplatin adducts while similar adducts in the methionine case are reversible. The formation of chelate structures is an exothermic reaction only for the hydroxo-form of reactants in the supermolecular approach where additional association interactions between the released water and chelate molecules sufficiently stabilize the final product.

• MeSH
• biochemie metody   MeSH
• cisplatina chemie   metabolismus   MeSH
• cystein chemie   metabolismus   MeSH
• methionin chemie   metabolismus   MeSH
• platina chemie   metabolismus   MeSH
• statická elektřina MeSH
• sulfan metabolismus   MeSH
• termodynamika MeSH
• výpočetní biologie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• cisplatina MeSH
• cystein MeSH
• methionin MeSH
• platina MeSH
• sulfan MeSH

In this paper we explore cisplatin interactions with sulfur-containing amino acids in a polarizable continuum model. Two cisplatin hydrated complexes were considered as reactants (chloro complex, cis-[Pt(NH3)2Cl(H2O)]+; hydroxo complex, cis-[Pt(NH3)2(OH)(H2O)]+). We considered the following reaction mechanism: first step, substitution of the aqua ligand by amino acid; second step, dissociative chelate formation. For the optimized complex (at the B3LYP/6-31+G(d)/COSMO level), the energy profile was determined using the B3LYP/6-311++G(2df,2pd) level and two different PCM models-COSMO and UAKS/DPCM methods which were adapted for use on transition metal complexes. The results show thermodynamic preference for bonding by cysteine sulfur followed by the amino group nitrogen, methionine thioether sulfur, and carboxyl-group oxygen. Methionine slightly prefers the Pt-N(Met) coordination in the chloro complex, but in the hydroxo complex it prefers the Pt-S(Met) coordination. A similar trend follows from the bonding energies: BE(Pt-S(Cys)) = 80.8 kcal/mol and BE(Pt-N(Met)) = 76 kcal/mol. According to the experimental observations, the most stable structures found are kappa2(S,N) chelates. In the case of methionine, the same thermodynamic stability is predicted also for the kappa2(N,O) chelate. This differs from the gas-phase results, where kappa2(S,N) and even kappa2(S,O) were found to be more stable than kappa2(N,O) complex.

• MeSH
• aminokyseliny chemie   MeSH
• chelátory chemie   MeSH
• cisplatina chemie   MeSH
• cystein chemie   MeSH
• dusík chemie   MeSH
• ligandy MeSH
• methionin chemie   MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• počítačová simulace MeSH
• software MeSH
• statistické modely MeSH
• teoretické modely MeSH
• termodynamika MeSH
• výpočetní biologie metody   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• chelátory MeSH
• cisplatina MeSH
• cystein MeSH
• dusík MeSH
• ligandy MeSH
• methionin MeSH