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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Bibliographic Details
Published in:Chemistry : a European journal Vol. 22; no. 3; pp. 1037 - 1047
Main Authors: Šebesta, Filip, Burda, Jaroslav V.
Format: Journal Article
Language:English
Published: Germany Blackwell Publishing Ltd 18.01.2016
Wiley Subscription Services, Inc
Subjects:
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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Summary: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.
Bibliography: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
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SourceType-Scholarly Journals-1
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ISSN:0947-6539
1521-3765
1521-3765
DOI:10.1002/chem.201503555