title: Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study.
abstract: The reduction mechanism of [Pt(IV) (dach)Cl4 ] (dach=diaminocyclohexyl) in the presence of dGMP was studied. The first step is substitution of a chloro ligand by dGMP, followed by nucleophilic attack of a phosphate or sugar oxygen atom to the C8-position of guanine. Subsequent reduction forms the [Pt(II) (dach)Cl2 ] complex. The whole process is completed by a hydrolysis. Two different pathways for the substitution reaction were examined: a direct associative and a Basolo-Pearson autocatalytic mechanism. All the explored structures were optimized at the B3LYP-D3/6-31G(d) level and by using the COSMO solvation model with Klamt's radii. Single-point energetics was determined at the B3LYP-GD3BJ/6-311++G(2df,2pd)/PCM/scaled-UAKS level. Activation barriers were used for an estimation of the rate constants and these were compared with experimental values. It was found that the rate-determining step is the nucleophilic attack with a slightly faster performance in the 3'-dGMP branch than in the case of 5'-dGMP with activation barriers of 21.1 and 20.4 kcal mol(-1) (experimental: 23.8 and 23.2 kcal mol(-1) ). The reduction reaction is connected with an electron flow from guanine. The product of the reduction reaction is a chelate structure, which dissociates within the last reaction step, that is, a hydrolysis reaction. The whole redox process (substitution, reduction, and hydrolysis) is exergonic by 34 and 28 kcal mol(-1) for 5'-dGMP and 3'-dGMP, respectively.
authors.affiliation: Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16, Prague 2, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Šebesta
authors.affiliation: Department of Chemical Physics and Optics, Faculty of Mathematics and Physics, Charles University, Ke Karlovu 3, 121 16, Prague 2, Czech Republic. burda@karlov.mff.cuni.cz.
authors.forename: Jaroslav V
authors.initials: JV
authors.lastname: Burda
mesh_terms: D002384:Catalysis; D006152:Cyclic GMP / Q000737:chemistry* / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000737:chemistry* / Q000378:metabolism; D006157:Guanosine Monophosphate / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000737:chemistry*; D010084:Oxidation-Reduction; D011789:Quantum Theory; D013237:Stereoisomerism; D013816:Thermodynamics
chemical_list: D003848:Deoxyguanine Nucleotides; D008024:Ligands; D009944:Organoplatinum Compounds; D006157:Guanosine Monophosphate; D006152:Cyclic GMP; C049777:ormaplatin
keywords: density functional calculations; kinetics; platinum; redox chemistry; thermodynamics