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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10406 - Analytical chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

Journal of Chromatography A

ISSN

0021-9673

e-ISSN

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Volume of the periodical

1479

Issue of the periodical within the volume

Jan 6

Country of publishing house

NL - THE KINGDOM OF THE NETHERLANDS

Number of pages

9

Pages from-to

185-193

UT code for WoS article

000392681300021

EID of the result in the Scopus database

2-s2.0-85008256379