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
• Models, Chemical * MeSH
• Cisplatin chemistry   pharmacology   MeSH
• Electrons MeSH
• Inhibitory Concentration 50 MeSH
• Kinetics MeSH
• Humans MeSH
• Ligands MeSH
• Cell Line, Tumor MeSH
• Organoplatinum Compounds chemistry   pharmacology   MeSH
• Computer Simulation * MeSH
• Antineoplastic Agents chemistry   pharmacology   MeSH
• Platinum Compounds chemistry   MeSH
• Thermodynamics MeSH
• Thiazoles chemistry   pharmacology   MeSH
• Water chemistry   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• amminedichloro(cyclohexylamine)platinum(II) MeSH Browser
• Cisplatin MeSH
• Ligands MeSH
• Organoplatinum Compounds MeSH
• platinum chloride MeSH Browser
• Antineoplastic Agents MeSH
• Platinum Compounds MeSH
• Thiazoles MeSH
• trans-(PtCl2(NH3)(thiazole)) MeSH Browser
• Water 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
• Adenine chemistry   MeSH
• Cisplatin chemistry   MeSH
• Cytosine chemistry   MeSH
• Guanine chemistry   MeSH
• Nucleic Acid Heteroduplexes chemistry   MeSH
• DNA, Single-Stranded chemistry   MeSH
• Models, Molecular MeSH
• Platinum chemistry   MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Adenine MeSH
• Cisplatin MeSH
• Cytosine MeSH
• Guanine MeSH
• Nucleic Acid Heteroduplexes MeSH
• DNA, Single-Stranded MeSH
• Platinum MeSH