Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F16%3A10330432" target="_blank" >RIV/00216208:11320/16:10330432 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1002/chem.201503555" target="_blank" >http://dx.doi.org/10.1002/chem.201503555</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/chem.201503555" target="_blank" >10.1002/chem.201503555</a>
Alternative languages
Result language
angličtina
Original language name
Reduction Process of Tetraplatin in the Presence of Deoxyguanosine Monophosphate (dGMP): A Computational DFT Study
Original language description
The reduction mechanism of [Pt-IV(dach)Cl-4] (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)Cl-2] 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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
BJ - Thermodynamics
OECD FORD branch
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Result continuities
Project
<a href="/en/project/GAP208%2F12%2F0622" target="_blank" >GAP208/12/0622: Interactions of organometallic antitumor compounds with nucleic acids and proteins: study of sequence and substrate selectivity</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Chemistry - A European Journal
ISSN
0947-6539
e-ISSN
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Volume of the periodical
22
Issue of the periodical within the volume
3
Country of publishing house
DE - GERMANY
Number of pages
11
Pages from-to
1037-1047
UT code for WoS article
000368906200026
EID of the result in the Scopus database
2-s2.0-84954026415