Determination of acidity constants at 37 °C through the internal standard capillary electrophoresis (IS-CE) method: internal standards and application to polyprotic drugs

Lebanov, Leo; Fuguet, Elisabet; Melo, Javier Mauricio; Rosés, Martı́

doi:10.1039/d0an00918k

Cited by 10 publications

(7 citation statements)

References 32 publications

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“…For water-soluble compounds, the CZE determinations of pK a are carried out in aqueous BGEs. Recent applications include the determination of thermodynamic or apparent pK a values of variable compounds, for example, very weak zwitterionic heterocyclic bases [23], 3-nitro-tyrosine and 3-chloro-tyrosine [24], tetrabromophenolphthalein ethyl ester [25], polyprotic peptide hormones [26], triazole fungicides [27], coumarin derivatives [28], cathinones [29], and different types of pharmaceuticals [12,[30][31][32].…”

Section: Introductionmentioning

confidence: 99%

“…The former case is represented by estimation of pK a values of peptides in mixed solvents of water-2,2,2trifluoroethanol [33], water-ACN [34] or water-methanol (MeOH) [35], by determination of pK a of basic drugs in 50% v/v water-MeOH [36] and 28 organic compounds, mainly drugs, in 40-60% v/v water-MeOH by multiplex 96-channel CZE [37] and by rapid estimation of pK a of 24 active pharmaceutical ingredients in 10-20% v/v MeOH using the same multiplex 96-channel CZE device [38]. The recent innovations in pK a determination by CE include accelerated measurement of the EOF at acidic BGEs by pressure-assisted CE [27], application of pK a standards [32], more accurate measurement of effective mobilities [39], and a new software for pK a calculation from the CE data, the program Anglerfish [40,41]. It provides thermodynamic pK a s and limiting ionic mobilities of the studied compounds from their effective mobilities at various pH and from the composition of the BGEs used.…”

Section: Introductionmentioning

confidence: 99%

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Nonaqueous capillary electrophoresis and quantum chemical calculations applied to investigation of acid–base and electromigration properties of azahelicenes

et al. 2021

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Nonaqueous capillary electrophoresis (NACE) using methanol (MeOH) as a solvent of the BGEs and quantum mechanical density functional theory (DFT) have been applied to determine the thermodynamic acidity (ionization) constants (pK a ) of mono-and diaza[5]helicenes, mono-and diaza[6]helicenes, and their dibenzo derivatives in MeOH and water. First, the mixed acidity constants, pK mix a,MeOH , of ionogenic pyridinium groups of azahelicenes and their derivatives in MeOH were obtained by nonlinear regression analysis of pH dependence of their effective electrophoretic mobilities. The effective mobilities were measured by NACE in a large series of methanolic BGEs within a wide conventional pH range (pH MeOH 1.6-12.0) and at ambient temperature (21-26°C) in a home-made CE device. Prior to mixed acidity constant calculation, the effective mobilities were corrected to reference temperature (25°C) and constant ionic strength (25 mM). Then, the mixed acidity constants were recalculated to the thermodynamic acidity constants pK a,MeOH by the Debye-Hückel theory of nonideality of electrolyte solutions. Finally, from the methanolic thermodynamic pK a,MeOH values, the aqueous thermodynamic pK a,H 2 O constants were estimated using the empirical relations between methanolic and aqueous acidity constants derived for structurally related pyridine derivatives. Depending on the number and position of the nitrogen atoms in their molecules, the analyzed azahelicenes were found to be weak to moderate bases with methanolic pK a,MeOH in the range 2.01-8.75 and with aqueous pK a,H 2 O in the range 1.67-8.28. The thermodynamic pK a,MeOH obtained by the DFT calculations were in a good agreement with those determined experimentally by NACE.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nonaqueous capillary electrophoresis and quantum chemical calculations applied to investigation of acid–base and electromigration properties of azahelicenes

et al. 2021

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“…The choice of such BGEs is based on the analyte acidity constants. The acidity constants for the ester betulin derivatives are not available in literature but can be also determined by CE [28][29][30]. For this purpose, the electrophoretic mobilities of analytes are measured using BGEs with pH from 2 to 12, and pK a s are calculated from the dependencies obtained.…”

Section: Abbreviationsmentioning

confidence: 99%

Electrophoretic mobility of ester betulin derivatives and their complexation with γ‐cyclodextrin studied by capillary electrophoresis in aqueous solutions at different pH values

2021

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In this article, capillary electrophoresis was used to measure the effective electrophoretic mobility of ester betulin derivatives as a pH function and to study their complexation with γ-cyclodextrin (γ-CD). The electrophoretic mobility of betulin 3,28-diphthalate (DPhB) and 3,28-disuccinate (DScB) changed unusually with decreasing pH: instead of decreasing, it first increased and then decreased. This fact as well as the turbidity of sample solutions at pH from 2.5 to 6, broadening of electrophoretic peaks and a decrease in the surface tension of the solutions indicates that these betulin derivatives, being amphiphilic compounds and weak acids, exist as micelles in aqueous solutions at pH 6 and below. The inclusion complexation of betulin derivatives with γ-CD at pH 9.18 and 4.5 was studied by mobility shift affinity capillary electrophoresis. At pH 9.18, the apparent binding (stability) constant logarithms for 1:1 γ-CD complexes of DPhB, betulin 3,28-disulfate (DSB) and DScB with 95% confidence interval limits were equal to 7. 44 ± 0.02, 7.09 (7.01-7.19), and 6.97 (6.87-7.08) at 25°C, respectively. At pH 4.5, the binding constant for the DSB complex was slightly lower, while the micelle formation did not allow determining the exact values of the constants for the DPhB and DScB complexes.

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“…The determination of pK a values by means of CE has gained strong importance in recent years, and many innovations have been achieved in addition to the expansion of datasets of experimentally determined pK a values. Some work focused on the determination of pK a values at the physiologically relevant temperature of 37 • C [7] and approaches to tackle sparingly soluble chemicals by the application of a methanol-water extrapolation [8]. Šolínová et al even applied nonaqueous CE using methanol as solvent for the determination of pK a s of azahelicenes [9].…”

Section: Introductionmentioning

confidence: 99%

Determination of acidity constants of pyridines, imidazoles, and oximes by capillary electrophoresis

Hajduk,

Ulrich

2023

Electrophoresis

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The acidity constant in the form of pKa is one of the most important physicochemical quantities. There are prediction tools available for calculating the pKa, but they only deliver precise calculated values for a relatively small set of chemicals. For complex structures with multiple functional groups in particular, the error in the predicted pKa is high due to the application domain of the corresponding models. Thus, we aim to enlarge the dataset of experimentally determined pKa values using capillary electrophoresis. We, therefore, selected various pyridines, imidazoles, and oximes to determine the pKa values using the internal standard approach and the classical method. Especially oximes were not investigated in the past, and predictions for them include larger errors. Thus, our experimentally determined values could contribute to an improved understanding of various functional groups impacting the pKa values and serve as additional datasets to develop improved pKa prediction tools.

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Determination of acidity constants at 37 °C through the internal standard capillary electrophoresis (IS-CE) method: internal standards and application to polyprotic drugs

Abstract: This work provides the pKa at the biorelevant temperature of 37 °C for a set of compounds proposed as internal standards for the internal standard capillary electrophoresis method. The method is applied to pKa determination of polyprotic drugs.

Cited by 10 publications

References 32 publications

Nonaqueous capillary electrophoresis and quantum chemical calculations applied to investigation of acid–base and electromigration properties of azahelicenes

Nonaqueous capillary electrophoresis and quantum chemical calculations applied to investigation of acid–base and electromigration properties of azahelicenes

Electrophoretic mobility of ester betulin derivatives and their complexation with γ‐cyclodextrin studied by capillary electrophoresis in aqueous solutions at different pH values

Determination of acidity constants of pyridines, imidazoles, and oximes by capillary electrophoresis

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