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

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

BJ - Termodynamika

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP208%2F12%2F0622" target="_blank" >GAP208/12/0622: Interakce organokovových protinádorových komplexů s nukleovými kyselinami a proteiny: studium sekvenční a substrátové selektivity</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2016

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Chemistry - A European Journal

ISSN

0947-6539

e-ISSN

—

Svazek periodika

22

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

11

Strana od-do

1037-1047

Kód UT WoS článku

000368906200026

EID výsledku v databázi Scopus

2-s2.0-84954026415