Investigation of the acid-base and electromigration properties of 5-azacytosine derivatives using capillary electrophoresis and density functional theory calculations

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00474757" target="_blank" >RIV/61388963:_____/17:00474757 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.chroma.2016.11.058" target="_blank" >http://dx.doi.org/10.1016/j.chroma.2016.11.058</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.chroma.2016.11.058" target="_blank" >10.1016/j.chroma.2016.11.058</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Investigation of the acid-base and electromigration properties of 5-azacytosine derivatives using capillary electrophoresis and density functional theory calculations

Popis výsledku v původním jazyce

Capillary electrophoresis (CE) and quantum mechanical density functional theory (DFT) were applied to the investigation of the acid-base and electromigration properties of important compounds: newly synthesized derivatives of 5-azacytosine - analogs of efficient antiviral drug cidofovir. These compounds exhibit a strong antiviral activity and they are considered as potential new antiviral agents. For their characterization and application, it is necessary to know their acid-base properties, particularly the acidity constants (pK(a)) of their ionogenic groups (the basic N-3 atom of the triazine ring and the acidic phosphonic acid group in the alkyl chain). First, the mixed acidity constants (pK(a)(mix)) of these ionogenic groups and the ionic mobilities of these compounds were determined by nonlinear regression analysis of the pH dependence of their effective electrophoretic mobilities. Effective mobilities were measured by CE in a series of background electrolytes in a wide pH range (2.0-10.5), at constant ionic strength (25 mM) and constant temperature (25 degrees C). Subsequently, the pK(a)(mix) values were recalculated to thermodynamic pKa values using the Debye-Hilckel theory. The thermodynamic pKa value of the NH+ moiety at the N-3 atom of the triazine ring was found to be in the range 2.82-3.30, whereas the pK(a) of the hydrogenphosphonate group reached values from 7.19 to 7.47, depending on the structure of the analyzed compounds. These experimentally determined pKa values were in good agreement with those calculated by quantum mechanical DFT. In addition, DFT calculations revealed that from the four nitrogen atoms in the 5-azacytosine moiety, the N-3 atom of the triazine ring is preferentially protonated. Effective charges of analyzed compounds ranged from zero or close-to-zero values at pH 2 to -2 elementary charges at pH >= 9. Ionic mobilities were in the range (-16.7 to -19.1) x 10(-9) m(2) V-1 s(-1) for univalent anions and in the interval (-26.9 to -30.3) x 10(-9) m(2) V-1 s(-1) for divalent anions.

Název v anglickém jazyce

Investigation of the acid-base and electromigration properties of 5-azacytosine derivatives using capillary electrophoresis and density functional theory calculations

Popis výsledku anglicky

Capillary electrophoresis (CE) and quantum mechanical density functional theory (DFT) were applied to the investigation of the acid-base and electromigration properties of important compounds: newly synthesized derivatives of 5-azacytosine - analogs of efficient antiviral drug cidofovir. These compounds exhibit a strong antiviral activity and they are considered as potential new antiviral agents. For their characterization and application, it is necessary to know their acid-base properties, particularly the acidity constants (pK(a)) of their ionogenic groups (the basic N-3 atom of the triazine ring and the acidic phosphonic acid group in the alkyl chain). First, the mixed acidity constants (pK(a)(mix)) of these ionogenic groups and the ionic mobilities of these compounds were determined by nonlinear regression analysis of the pH dependence of their effective electrophoretic mobilities. Effective mobilities were measured by CE in a series of background electrolytes in a wide pH range (2.0-10.5), at constant ionic strength (25 mM) and constant temperature (25 degrees C). Subsequently, the pK(a)(mix) values were recalculated to thermodynamic pKa values using the Debye-Hilckel theory. The thermodynamic pKa value of the NH+ moiety at the N-3 atom of the triazine ring was found to be in the range 2.82-3.30, whereas the pK(a) of the hydrogenphosphonate group reached values from 7.19 to 7.47, depending on the structure of the analyzed compounds. These experimentally determined pKa values were in good agreement with those calculated by quantum mechanical DFT. In addition, DFT calculations revealed that from the four nitrogen atoms in the 5-azacytosine moiety, the N-3 atom of the triazine ring is preferentially protonated. Effective charges of analyzed compounds ranged from zero or close-to-zero values at pH 2 to -2 elementary charges at pH >= 9. Ionic mobilities were in the range (-16.7 to -19.1) x 10(-9) m(2) V-1 s(-1) for univalent anions and in the interval (-26.9 to -30.3) x 10(-9) m(2) V-1 s(-1) for divalent anions.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

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

2017

Kód důvěrnosti údajů

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

Název periodika

Journal of Chromatography A

ISSN

0021-9673

e-ISSN

—

Svazek periodika

1479

Číslo periodika v rámci svazku

Jan 6

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

9

Strana od-do

185-193

Kód UT WoS článku

000392681300021

EID výsledku v databázi Scopus

2-s2.0-85008256379