Determination of acid–base dissociation constants of amino‐ and guanidinopurine nucleotide analogs and related compounds by capillary zone electrophoresis

Abstract

CZE has been applied for determination of acid-base dissociation constants (pKa) 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 pKa 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 degrees C). pKa 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 pKa of protonated guanidinyl group was estimated to be in the range of 7.75-10.32, pKa of phosphonic acid to the second dissociation degree achieved values of 6.64-7.46, and pKa 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.

Determination of thermodynamic acidity constants and limiting ionic mobilities of weak electrolytes by capillary electrophoresis using a new free software AnglerFish

“…Even though ionic mobilities are also obtained from the fit, Cai proposed no means of how to calculate limiting mobilities from the experimental data. Cai's approach has been further extended for multivalent substances and applied to wide variety of substances .…”

Chiral analysis of anti‐acquired immunodeficiency syndrome drug, 9‐(R)‐[2‐(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using β‐CD as chiral selector

“…All compounds contain one or two basic amino groups on the purine or pyrimidine base moiety, positively charged at low pH (ca pHo5), and an acidic phosphonic acid group, which possesses negative charge À2 at pH above 7. Taking into account a good solubility and chemical stability of the analyzed compounds in water and in alkaline buffers, and the estimated value of the second acidity constant of phosphonic acid (pK a (À2)$7), of the structurally related ANPs [36,37], the investigated ANPs were analyzed as anions in alkaline BGEs within a pH range 7.5-10.5. In these high-pH BGEs, the compounds are doubly negatively charged due to the deprotonated state of their basic amino groups and dissociation of hydrogenphosphonate (À1) to phosphonate (À2).…”

Enantiopurity analysis of new types of acyclic nucleoside phosphonates by capillary electrophoresis with cyclodextrins as chiral selectors

“…In this study, taking into account the prevalence of acidic groups in the molecules of the ANPs analyzed and considering the results of our previous chiral and achiral analyses of ANPs , first, several alkaline BGEs, such as Tris/Tricine, boric acid/NaOH, and sodium tetraborate/NaOH, in the pH range 8.1–10.5, were tested, using variable native and derivatized noncharged and charged CDs (α‐, β‐, and γ‐CDs, 2‐HP‐β‐CD, 2‐HP‐γ‐CD, heptakis(2,6‐dimethyl)‐β‐CD, and quaternary‐ammonium‐β‑cyclodextrin (QA‐β‐CD)) as chiral selectors. No or very low enantioseparations were observed when any of these CDs were added to the Tris/Tricine and boric acid/NaOH BGEs (data not shown).…”