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

0474757 - ÚOCHB 2018 RIV NL eng J - Článek v odborném periodiku
Geffertová, Denisa - Ali, Syed Tahir - Šolínová, Veronika - Krečmerová, Marcela - Holý, Antonín - Havlas, Zdeněk - Kašička, Václav
Investigation of the acid-base and electromigration properties of 5-azacytosine derivatives using capillary electrophoresis and density functional theory calculations.
Journal of Chromatography A. Roč. 1479, Jan 6 (2017), s. 185-193. ISSN 0021-9673. E-ISSN 1873-3778
Grant CEP: GA ČR(CZ) GA15-01948S; GA ČR(CZ) GA14-00522S
Institucionální podpora: RVO:61388963
Klíčová slova: acidity constant * 5-azacytosine * capillary electrophoresis * density functional theory * effective charge * ionic mobility
Obor OECD: Analytical chemistry
Impakt faktor: 3.716, rok: 2017

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.
Trvalý link: http://hdl.handle.net/11104/0271718