Abstract
Complexation plays an important role in many biological phenomena, the analysis of different samples, optimization of separation processes, and increasing the pharmacological activity of drugs. This paper discusses the features of using mobility shift affinity capillary electrophoresis for studying strong complexation. Electrophoretic peaks for this case are often triangular. It was shown that the use of electrophoretic mobility obtained from the peak apex time to calculate binding constants leads to significant systematic and random errors, and the parameter a1 of the Haarhoff-Van der Linde function should be used instead of the apex time. Distorted triangular peaks with dips were shown to be observed at too high a ratio of analyte concentration in the sample to ligand concentration in the background electrolyte, and the peaks and parameter a1 significantly shifted. It was found that the permissible excess of analyte concentration over ligand concentration was approximately 10–35, provided that the parameter a1 was used, but the peak shape should be used as a landmark, and only triangular peaks without dips should be fitted with the function. The lowest possible analyte concentration should be utilized, which allows the use of a wider range of ligand concentration leading to higher precision of determining the binding constants values. Kinetically labile 1:1 complexes between (2-hydroxypropyl)-γ-cyclodextrin (HP-γ-CD) and betulin 3,28-diphthalate (DPhB) and betulin 3,28-disuccinate (DScB) were studied as an example. The binding constant logarithms at 25 °C are 7.23 ± 0.03 and 7.13 ± 0.10 for the HP-γ-CD complexes of DPhB and DScB, respectively.
Similar content being viewed by others
References
Crini G. Review: a history of cyclodextrins. Chem Rev. 2014;114:10940–75.
Jacob S, Nair AB. Cyclodextrin complexes: perspective from drug delivery and formulation. Drug Dev Res. 2018;79:201–17.
Mura P. Analytical techniques for characterization of cyclodextrin complexes in aqueous solution: a review. J Pharm Biomed Anal. 2014;101:238–50.
Olabi M, Stein M, Wätzig H. Affinity capillary electrophoresis for studying interactions in life sciences. Methods. 2018;146:76–92.
Dubský P, Dvořák M, Ansorge M. Affinity capillary electrophoresis: the theory of electromigration. Anal Bioanal Chem. 2016;408:8623–41.
Musile G, Cenci L, Andreetto E, Ambrosi E, Tagliaro F, Bossi AM. Screening of the binding properties of molecularly imprinted nanoparticles via capillary electrophoresis. Anal Bioanal Chem. 2016;408:3435–43.
Popova OV, Sursyakova VV, Burmakina GV, Levdansky VA, Rubaylo AI. Determination of stability constants of inclusion complexes of betulin derivatives with β-cyclodextrin by capillary electrophoresis. Dokl Chem. 2015;461:67–9.
Sursyakova VV, Levdansky VA, Rubaylo AI. Thermodynamic parameters for the complexation of water-soluble betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin determined by affinity capillary electrophoresis. J Mol Liq. 2019;283:325–31.
Sursyakova VV, Levdansky VA, Rubaylo AI. Strong complexation of water-soluble betulin derivatives with (2-hydroxypropyl)-γ-cyclodextrin studied by affinity capillary electrophoresis. Electrophoresis. 2020;41:112–5.
Stein M, Haselberg R, Mozafari-Torshizi M, Wätzig H. Experimental design and measurement uncertainty in ligand binding studies by affinity capillary electrophoresis. Electrophoresis. 2019;40:1041–54.
Pangavhane S, Makrlík E, Ruzza P, Kašička V. Affinity capillary electrophoresis employed for determination of stability constants of antamanide complexes with univalent and divalent cations in methanol. Electrophoresis. 2019;40:2321–8.
Nevídalová H, Michalcová L, Glatz Z. Capillary electrophoresis-based approaches for the study of affinity interactions combined with various sensitive and nontraditional detection techniques. Electrophoresis. 2019;40:625–42.
Neaga IO, Hambye S, Bodoki E, Palmieri C, Ansseau E, Belayew A, et al. Affinity capillary electrophoresis for identification of active drug candidates in myotonic dystrophy type 1. Anal Bioanal Chem. 2018;410:4495–507.
Neaga IO, Hambye S, Bodoki E, Palmieri C, Eynde JJV, Ansseau E, et al. Correction to: Affinity capillary electrophoresis for identification of active drug candidates in myotonic dystrophy type 1. Anal Bioanal Chem. 2019;411:545.
Ansorge M, Dubský P, Ušelová K. Into the theory of the partial-filling affinity capillary electrophoresis and the determination of apparent stability constants of analyte-ligand complexes. Electrophoresis. 2018;39:742–51.
Konášová R, Koval D, Jaklová Dytrtová J, Kašička V. Comparison of two low flow interfaces for measurement of mobilities and stability constants by affinity capillary electrophoresis–mass spectrometry. J Chromatogr A. 2018;1568:197–204.
Aizpurua-Olaizola O, Torano JS, Pukin A, Fu O, Boons GJ, de Jong GJ, et al. Affinity capillary electrophoresis for the assessment of binding affinity of carbohydrate-based cholera toxin inhibitors. Electrophoresis. 2018;39:344–7.
Kanizsová L, Ansorge M, Zusková I, Dubský P. Using single-isomer octa(6-O-sulfo)-γ-cyclodextrin for fast capillary zone electrophoretic enantioseparation of pindolol: determination of complexation constants, software-assisted optimization, and method validation. J Chromatogr A. 2018;1568:214–21.
Mofaddel N, Fourmentin S, Guillen F, Landy D, Gouhier G. Ionic liquids and cyclodextrin inclusion complexes: limitation of the affinity capillary electrophoresis technique. Anal Bioanal Chem. 2016;408:8211–20.
Holm R, Hartvig RA, Nicolajsen HV, Westh P, Østergaard J. Characterization of the complexation of tauro and glyco-conjugated bile salts with γ-cyclodextrin and 2-hydroxypropyl-γ-cyclodextrin using affinity capillary electrophoresis. J Incl Phenom Macrocycl Chem. 2008;61:161–9.
Sursyakova VV, Rubaylo AI. Stability constants of adducts of succinate copper(II) complexes with β-cyclodextrin determined by capillary electrophoresis. Electrophoresis. 2018;39:1079–85.
Pangavhane S, Böhm S, Makrlík E, Ruzza P, Kašička V. Affinity capillary electrophoresis and quantum mechanical calculations applied to investigation of [Gly6]-antamanide binding with sodium and potassium ions. Electrophoresis. 2017;38:1551–9.
Sursyakova VV, Burmakina GV, Rubaylo AI. Composition and stability constants of copper(II) complexes with succinic acid determined by capillary electrophoresis. J Coord Chem. 2017;70:431–40.
Tůmová T, Monincová L, Čeřovský V, Kašička V. Estimation of acidity constants, ionic mobilities and charges of antimicrobial peptides by capillary electrophoresis. Electrophoresis. 2016;37:3186–95.
Sursyakova VV, Burmakina GV, Rubaylo AI. Influence of analyte concentration on stability constant values determined by capillary electrophoresis. J Chromatogr Sci. 2016;54:1253–62.
Sladkov V. Affinity capillary electrophoresis in studying the complex formation equilibria of radionuclides in aqueous solutions. Electrophoresis. 2016;37:2558–66.
Ehala S, Kašička V, Makrlík E. Determination of stability constants of valinomycin complexes with ammonium and alkali metal ions by capillary affinity electrophoresis. Electrophoresis. 2008;29:652–7.
Jiang C, Armstrong DW. Use of CE for the determination of binding constants. Electrophoresis. 2010;31:17–27.
Dubský P, Ördögová M, Malý M, Riesová M. CEval: all-in-one software for data processing and statistical evaluations in affinity capillary electrophoresis. J Chromatogr A. 2016;1445:158–65.
Šlampová A, Malá Z, Gebauer P. Recent progress of sample stacking in capillary electrophoresis (2016–2018). Electrophoresis. 2019;40:40–54.
Vespalec R, Boček P. Calculation of stability constants for the chiral selector–enantiomer interactions from electrophoretic mobilities. J Chromatogr A. 2000;875:431–45.
Hruška V, Svobodová J, Beneš M, Gaš B. A nonlinear electrophoretic model for PeakMaster: part III. Electromigration dispersion in systems that contain a neutral complex-forming agent and a fully charged analyte. Theory. J Chromatogr A. 2012;1267:102–8.
Svobodová J, Beneš M, Hruška V, Ušelová K, Gaš B. Simulation of the effects of complex-formation equilibria in electrophoresis: II. Experimental verification. Electrophoresis. 2012;33:948–57.
Beneš M, Svobodová J, Hruška V, Dvořák M, Zusková I, Gaš B. A nonlinear electrophoretic model for PeakMaster: part IV. Electromigration dispersion in systems that contain a neutral complex-forming agent and a fully charged analyte. Experimental verification. J Chromatogr A. 2012;1267:109–15.
Galbusera C, Thachuk M, De Lorenzi E, Chen DDY. Affinity capillary electrophoresis using a low-concentration additive with the consideration of relative mobilities. Anal Chem. 2002;74:1903–14.
Le Saux T, Varenne A, Gareil P. Peak shape modeling by Haarhoff-Van der Linde function for the determination of correct migration times: a new insight into affinity capillary electrophoresis. Electrophoresis. 2005;26:3094–104.
Dubský P, Dvořák M, Műllerová L, Gaš B. Determination of the correct migration time and other parameters of the Haarhoff–van der Linde function from the peak geometry characteristics. Electrophoresis. 2015;36:655–61.
Erny GL, Bergström ET, Goodall DM. Electromigration dispersion in capillary zone electrophoresis. Experimental validation of use of the Haarhoff–Van der Linde function. J Chromatogr A. 2002;959:229–39.
Erny GL, Bergström ET, Goodall DM. Predicting peak shape in capillary zone electrophoresis: a generic approach to parametrizing peaks using the Haarhoff-Van der Linde (HVL) function. Anal Chem. 2001;73:4862–72.
Rekharsky MV, Inoue Y. Complexation thermodynamics of cyclodextrins. Chem Rev. 1998;98:1875–917.
Connors KA. The stability of cyclodextrin complexes in solution. Chem Rev. 1997;97:1325–58.
Holm R, Nicolajsen HV, Hartvig RA, Westh P, Østergaard J. Complexation of tauro- and glyco-conjugated bile salts with three neutral β-CDs studied by ACE. Electrophoresis. 2007;28:3745–52.
François Y, Varenne A, Sirieix-Plenet J, Gareil P. Determination of aqueous inclusion complexation constants and stoichiometry of alkyl(methyl)-methylimidazolium-based ionic liquid cations and neutral cyclodextrins by affinity capillary electrophoresis. J Sep Sci. 2007;30:751–60.
Le Saux T, Varenne A, Perreau F, Siret L, Duteil S, Duhau L, et al. Determination of the binding parameters for antithrombin–heparin fragment systems by affinity and frontal analysis continuous capillary electrophoresis. J Chromatogr A. 2006;1132:289–96.
Tolstikova TG, Sorokina IV, Tolstikov GA, Tolstikov AG, Flekhter OB. Biological activity and pharmacological prospects of lupane terpenoids: I. natural lupane derivatives. Rus J Bioorg Chem. 2006;32:37–49.
Popova OV, Sursyakova VV, Burmakina GV, Maksimov NG, Levdansky VA, Rubaylo AI. Solubility study of betulonic acid in the presence of hydroxypropyl-γ-cyclodextrin by capillary electrophoresis. J Sib Fed Univ Chem. 2016;9:171–6.
Sursyakova VV, Maksimov NG, Levdansky VA, Rubaylo AI. Combination of phase-solubility method and capillary zone electrophoresis to determine binding constants of cyclodextrins with practically water-insoluble compounds. J Pharm Biomed Anal. 2018;160:12–8.
Sursyakova VV, Levdansky VA, Rubaylo AI. Thermodynamic parameters for the complexation of water-insoluble betulin derivatives with (2-hydroxypropyl)-γ-cyclodextrin determined by phase-solubility technique combined with capillary zone electrophoresis. Electrophoresis. 2019;40:1656–61.
Levdanskii VA, Levdanskii AV, Kuznetsov BN. Synthesis of betulin dibenzoate and diphthalate. Chem Nat Compound. 2017;53:310–1.
Levdanskij VA, Levdanskij AV, Kuznetsov BN. Method for producing betulinol diphtalate. Russ Patent. № RU 2614149 C1. 23.03.2017.
Levdanskij VA, Levdanskij AV, Kuznetsov BN. Method of producing betulinol disuccinate. Russ Patent. № RU 2638160 C1. 12.12.2017.
Funding
This work was conducted within the framework of the budget project АААА-А17-117021310221-7 for Institute of Chemistry and Chemical Technology SB RAS using the equipment of Krasnoyarsk Regional Research Equipment Centre of SB RAS.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 425 kb)
Rights and permissions
About this article
Cite this article
Sursyakova, V.V., Levdansky, V.A. & Rubaylo, A.I. Determination of binding constants for strong complexation by affinity capillary electrophoresis: the example of complexes of ester betulin derivatives with (2-hydroxypropyl)-γ-cyclodextrin. Anal Bioanal Chem 412, 5615–5625 (2020). https://doi.org/10.1007/s00216-020-02777-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-020-02777-4