Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study

The reduction mechanism of [PtIV(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 [PtII(...

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Vydáno v:	Chemistry : a European journal Ročník 22; číslo 3; s. 1037 - 1047
Hlavní autoři:	Šebesta, Filip, Burda, Jaroslav V.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Germany Blackwell Publishing Ltd 18.01.2016 Wiley Subscription Services, Inc
Témata:	Activation Associative Catalysis Chemistry Computer applications Cyclic GMP - chemistry Cyclic GMP - metabolism density functional calculations Deoxyguanine Nucleotides - chemistry Deoxyguanine Nucleotides - metabolism Deoxyguanosine Guanine Guanines Guanosine Monophosphate - chemistry Guanosine Monophosphate - metabolism Hydrolysis Kinetics Ligands Mathematical models Molecular Structure Organoplatinum Compounds - chemistry Oxidation-Reduction Oxygen Pathways Phosphate platinum Quantum Theory Rate constants redox chemistry Reduction Solvation Stereoisomerism Substitution reactions Sugar Thermodynamics thermodynamics density functional calculations platinum kinetics redox chemistry
ISSN:	0947-6539, 1521-3765, 1521-3765
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Popis
Shrnutí:	The reduction mechanism of [PtIV(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 [PtII(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. Calculated reduction: The mechanism of [PtIV(dach)Cl4] (dach=diaminocyclohexyl) reduction by dGMP and its derivatives, which consists of three reaction steps (substitution, reduction, and hydrolysis), is investigated by using DFT calculations. Two different pathways for the substitution reaction (associative or autocatalytic), which is the rate‐ determining step, were compared.
Bibliografie:	Grant Agency of Czech Republic - No. P208/12/0622 ArticleID:CHEM201503555 istex:73B9FA3192F603457C987BCD7369C75B6F8FB7FE ark:/67375/WNG-BL94SV7K-J National Grid Infrastructure MetaCentrum - No. LM2010005 Grant Agency of Charles University - No. 532212 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0947-6539 1521-3765 1521-3765
DOI:	10.1002/chem.201503555