Mechanism of the cis-[Pt(1R,2R-DACH)(H2O)(2)](2+) Intrastrand Binding to the Double-Stranded (pGpG)center dot(CpC) Dinucleotide in Aqueous Solution: A Computational DFT Study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11320%2F13%3A10173461" target="_blank" >RIV/00216208:11320/13:10173461 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/60076658:12310/13:43885379 RIV/60076658:12110/13:43885379

Výsledek na webu

<a href="http://dx.doi.org/10.1021/ic302654s" target="_blank" >http://dx.doi.org/10.1021/ic302654s</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/ic302654s" target="_blank" >10.1021/ic302654s</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Mechanism of the cis-[Pt(1R,2R-DACH)(H2O)(2)](2+) Intrastrand Binding to the Double-Stranded (pGpG)center dot(CpC) Dinucleotide in Aqueous Solution: A Computational DFT Study

Popis výsledku v původním jazyce

A mechanism of the intrastrand 1,2-cross-link formation between the double-stranded pGpG center dot CpC dinucleotide (ds(pGpG)) and fully aquated oxaliplatin cis-[Pt(DACH)(H2O)(2)](2+) (DACH = cyclohexane-1R,2R-diamine) is presented. All structures of the reaction pathways including the transition states (TSs) were fully optimized in water solvent using DFT methodology with dispersion corrections. Both 5' -> 3' and 3' -> 5' binding directions were considered. In the first step there is a slight kineticpreference for 5'-guanine (5'G) monoadduct formation with an activation Gibbs free energy of 18.7 kcal/mol since the N7 center of the 5'G base is fully exposed to the solvent. On the other hand, the N7 atom of 3'-guanine (3'G) is sterically shielded by 5'G. The lowest energy path for formation of the 3'G monoadduct with an activation barrier of 19.3 kcal/mol is connected with a disruption of the DNA like structure of ds(pGpG). Monoadduct formation is the rate-determining process. The sec

Název v anglickém jazyce

Mechanism of the cis-[Pt(1R,2R-DACH)(H2O)(2)](2+) Intrastrand Binding to the Double-Stranded (pGpG)center dot(CpC) Dinucleotide in Aqueous Solution: A Computational DFT Study

Popis výsledku anglicky

A mechanism of the intrastrand 1,2-cross-link formation between the double-stranded pGpG center dot CpC dinucleotide (ds(pGpG)) and fully aquated oxaliplatin cis-[Pt(DACH)(H2O)(2)](2+) (DACH = cyclohexane-1R,2R-diamine) is presented. All structures of the reaction pathways including the transition states (TSs) were fully optimized in water solvent using DFT methodology with dispersion corrections. Both 5' -> 3' and 3' -> 5' binding directions were considered. In the first step there is a slight kineticpreference for 5'-guanine (5'G) monoadduct formation with an activation Gibbs free energy of 18.7 kcal/mol since the N7 center of the 5'G base is fully exposed to the solvent. On the other hand, the N7 atom of 3'-guanine (3'G) is sterically shielded by 5'G. The lowest energy path for formation of the 3'G monoadduct with an activation barrier of 19.3 kcal/mol is connected with a disruption of the DNA like structure of ds(pGpG). Monoadduct formation is the rate-determining process. The sec

Druh

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

CEP obor

BJ - Termodynamika

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2013

Kód důvěrnosti údajů

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

Název periodika

Inorganic Chemistry

ISSN

0020-1669

e-ISSN

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Svazek periodika

52

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

5801-5813

Kód UT WoS článku

000319720400028

EID výsledku v databázi Scopus

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