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Determination of acid–base dissociation constants of amino‐ and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis
Author(s) -
Šolínová Veronika,
Kašička Václav,
Koval Dušan,
Česnek Michal,
Holý Antonín
Publication year - 2006
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200500815
Subject(s) - chemistry , protonation , phosphonate , nucleoside , dissociation constant , acid dissociation constant , stereochemistry , amino acid , nucleotide , moiety , nucleobase , dissociation (chemistry) , organic chemistry , aqueous solution , biochemistry , dna , ion , receptor , gene
CZE has been applied for determination of acid–base dissociation constants (p K a ) of ionogenic groups of newly synthesized amino‐ and (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonate, acyclic nucleoside phosphonate diesters and other related compounds. These compounds bear characteristic pharmacophores contained in various important biologically active substances, such as cytostatics and antivirals. The p K a values of ionogenic groups of the above compounds were determined by nonlinear regression analysis of the experimentally measured pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by CZE performed in series of BGEs in a broad pH range (3.50–11.25), at constant ionic strength (25 mM) and temperature (25°C). p K a values were determined for the protonated guanidinyl group in (amino)guanidino 9‐alkylpurines and in (amino)guanidinopurine nucleotide analogs, such as acyclic nucleoside phosphonates and acyclic nucleoside phosphonate diesters, for phosphonic acid to the second dissociation degree (—2) in acyclic nucleoside phosphonates of amino and (amino)guanidino 9‐alkylpurines, and for protonated nitrogen in position 1 (N1) of purine moiety in acyclic nucleoside phosphonates of amino 9‐alkylpurines. Thermodynamic p K a of protonated guanidinyl group was estimated to be in the range of 7.75–10.32, p K a of phosphonic acid to the second dissociation degree achieved values of 6.64–7.46, and p K a of protonated nitrogen in position 1 of purine was in the range of 4.13–4.89, depending on the structure of the analyzed compounds.