Skip to main content
SpringerLink
Log in

The Microscopic and Tautomeric Protonation Constants of Some α-Amino Acids in Dioxane–Water Mixtures

  • Published:
Journal of Solution Chemistry Aims and scope Submit manuscript

Abstract

Knowledge of the protonation constants of α-amino acids is important, interesting and necessary for complete understanding of the physiochemical behavior of the acids. The acid–base chemistry of zwitterionic compounds such as α-amino acids has been characterized in terms of the macroscopic constants; K1, K2; the microscopic constants; k11, k12, k21, k22 and the tautomeric constant; kz. The compounds may exist in four different microforms; a cation, zwitterion (dipolarion), neutral species and anion. In this study, both to demonstrate whether the predominant species are zwitterion or the neutral form and to predict the change of dipolar form to neutral form ratio in dioxane–water mixtures, the macroscopic protonation constants of the α-amino acids, glycine, DL-alanine, DL-valine, L-leucine, DL-phenylalanine and L-serine, and their esters, were determined potentiometrically using a combined pH electrode system calibrated as the concentration of hydrogen ion and later the microscopic and tautomeric constants of the amino acids were calculated in dioxane–water mixtures (20, 40, and 60% dioxane (v/v)). Titrations were performed at 25.0 ± 0.1 °C and the ionic strength of the medium was maintained at 0.10 mol·dm−3 using sodium chloride. The protonation constants were influenced by changes in solvent composition and the effects of solvent composition on the protonation constants are discussed. Also, the variation of microscopic constants and the ratio of zwitterionic form to neutral form are discussed on the basis of solute–solvent interactions of amino acids in dioxane–water mixtures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Dogan, A., Demirel, A., Kılıç, E.: The protonation equilibria of selected glycine dipeptides in ethanol–water mixture: solvent composition effect. Amino Acids 36, 373–379 (2009)

    Article  CAS  PubMed  Google Scholar 

  2. Albert, A., Serjeant, E.P.: The Determination of Ionization Constants. Chapman & Hall, New York (1984)

    Book  Google Scholar 

  3. Pandit, N.K., Sisco, J.M.: The determination of microscopic ionization constants of a substituted piperazine using estimates from model compounds. Pharm. Res. 6(2), 177–181 (1989)

    Article  CAS  PubMed  Google Scholar 

  4. Szakacs, Z., Krazni, M., Noszal, B.: Determination of microscopic acid–base parameters from NMR–pH titrations. Anal. Bioanal. Chem. 378, 1428–1448 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. Tager, H.S.: Solute translocations: an overview of biological transport. In: Colombett, L.G. (ed.) Biological Transport of Radionucleides. CRC Press, Boca Raton (1982)

    Google Scholar 

  6. Stein, W.D., Lieb, W.R.: Transport and Diffusion Across Cell Membranes. Academic Press, Orlando (1986)

    Google Scholar 

  7. Hughes, A.B.: Amino Acids, Peptides and Proteins in Organic Chemistry, Analysis and Function of Amino Acids and Peptides. Wiley-VCH, Hoboken (2012)

    Google Scholar 

  8. Nikaido, H., Thanassi, D.G.: Penetration of lipophilic agents with multiple protonation sites into bacterial cells. Antimicrob. Agents Chem. 37, 1393–1399 (1993)

    Article  CAS  Google Scholar 

  9. Martin, R.B., Edsall, J.T., Wetlaufer, D.B., Hollingworth, B.R.: A complete ionization scheme for tyrosine, and the ionization constants of some tyrosine derivatives. J. Biol. Chem. 233, 1429–1435 (1958)

    Article  CAS  PubMed  Google Scholar 

  10. Hughes, D.L., Bergan, J., Grabowski, E.J.: Amino acid chemistry in dipolar aprotic solvents; dissociation constants and ambident reactivity. J. Org. Chem. 51, 2579–2585 (1986)

    Article  CAS  Google Scholar 

  11. D’Angelo, J.C., Collette, T.W.: A method for the measurement of site-specific tautomeric and zwitterionic microspecies equilibrium constants. Anal. Chem. 69, 1642–1650 (1997)

    Article  Google Scholar 

  12. Martin, B.: Zwitterions formation upon deprotonation in L-3,4-dihidroxyphenylalanine and other phenolic amines. J. Phys. Chem. 75, 2657–2661 (1971)

    Article  CAS  PubMed  Google Scholar 

  13. Novak, T., Kökösi, J., Podanyi, B., Nozsal, B., Tsai, R.S., Lisa, G., Corrupt, P.A., Testa, B.: Microscopic protonation/deprotanation equilibria of the anti-inflammatory agent piroxicam. Helv. Chim. Acta 78, 553–563 (1995)

    Article  Google Scholar 

  14. Noszal, B., Szaka, Z.: Microscopic protonation equilibria of oxidized glutathione. J. Phys. Chem. B 107, 5074–5080 (2003)

    Article  CAS  Google Scholar 

  15. Zapała, L., Woznicka, E., Kalembkiewicz, J.: Tautomeric and microscopic protonation equilibria of anthranilic acid and its derivatives. J. Solution Chem. 43, 1167–1183 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Carty, R.P., Hirs, C.H.W.: Modification of bovine pancreatic ribonuclease A with 4-sulfonyloxy-2-nitrofluorobenzene. Isolation and identification of modified proteins. J. Biol. Chem. 243, 5256–5265 (1968)

    Article  CAS  Google Scholar 

  17. Schmidt, D.E., Westheimer, F.H.: pK of the lysine amino group at the active site of acetoacetate decarboxylase. Biochemistry 10, 249–1253 (1971)

    Google Scholar 

  18. Crosby, J., Stone, R., Lienhard, G.E.: Mechanisms of thiamine-catalyzed reactions. Decarboxylation of 2-(1-carboxy-1-hydroxyetyl)-3,4-dimethylthiazolium chloride. J. Am. Chem. Soc. 92, 2891–2900 (1970)

    Article  CAS  PubMed  Google Scholar 

  19. Bester-Rogac, M., Neueder, R., Barthel, J.: Conductivity of sodium chloride in water +1,4-dioxane mixtures at temperatures from 5 to 35 °C – I. Dilute solutions. J. Solution Chem. 28, 1071–1086 (1999)

    Article  CAS  Google Scholar 

  20. Perrin, D.D., Armerega, W.L.F.: Purification of Laboratory Chemicals. Pergamon Press, Elmsford (1991)

    Google Scholar 

  21. Gran, G.: Determination of the equivalent point in potentiometric titrations Part II. Analyst 77, 661–671 (1952)

    Article  CAS  Google Scholar 

  22. Martell, A.E., Motekaitis, R.J.: The Determination and Use of Stability Constants. VCH, Weinheim (1988)

    Google Scholar 

  23. Meloun, M., Havel, J., Högfelt, H.: Computation of Solution Equilibria. Wiley, New York (1988)

    Google Scholar 

  24. Woolley, E.M., Hukot, D.G., Hepler, L.G.: Ionization constant for water in aqueous organics mixture. J. Phys. Chem. 74, 3908–3913 (1970)

    Article  Google Scholar 

  25. Rondinini, S., Mussini, T., Mussini, P.R., Longhi, P.: Autoprotolysis constants in nonaqueous solvent and aqueous organic-solvent mixtures. Pure Appl. Chem. 59, 1693–1702 (1987)

    Article  CAS  Google Scholar 

  26. Motekaitis, R.J., Martell, A.E.: BEST-a new program for rigorous calculation of equilibrium parameters of complex multi-component systems. Can. J. Chem. 60, 2403–2409 (1982)

    Article  CAS  Google Scholar 

  27. Doğan, A., Aslan, N., Canel, E., Kılıç, E.: Solvent effect on the protonation constants of some amino acid esters in 1,4-dioxan–water mixtures. J. Solution Chem. 39(11), 1589–1596 (2010)

    Article  CAS  Google Scholar 

  28. Köseoğlu, F., Kılıç, E., Doğan, A.: Studies on the protonation constants and solvation of α-amino acids in dioxan– water mixtures. Anal. Biochem. 277, 243–246 (2000)

    Article  PubMed  CAS  Google Scholar 

  29. Pagliara, A., Carrupt, P.A., Caron, G., Gaillard, P., Testa, B.: Lipophilicity profiles of ampholytes. Chem. Rev. 97, 3385–3400 (1997)

    Article  CAS  PubMed  Google Scholar 

  30. Metzler, D.E., Snell, E.E.: Spectra and ionization constants of the vitamin B6 group and related 3-hydroxypyridine derivatives. J. Am. Chem. Soc. 77, 2431–2437 (1955)

    Article  CAS  Google Scholar 

  31. Takas-Novak, K., Avdeef, A., Box, K.J., Podanyi, B., Szasz, G.: Determination of protonation macro and microconstants and octanol/water partition coefficient of the anti-inflammatory drug niflumic acid. J. Pharm. Biomed. Anal. 12, 1369–1377 (1994)

    Article  Google Scholar 

  32. Takas-Novak, K., Tam, K.Y.: Multiwavelength spectrophotometric determination of acid dissociation constants. Part V: Microconstants and tautomeric ratios of diprotic amphoteric drugs. J. Pharm. Biomed. Anal. 21, 1171–1182 (2000)

    Article  Google Scholar 

  33. Mandic, Z., Gabelica, V.: Ionization, lipohpilicity and solubility properties of repaglinide. J. Pharm. Biomed. Anal. 41, 866–871 (2006)

    Article  CAS  PubMed  Google Scholar 

  34. Rossotti, H.: The Study of Ionic Equilibria. Longman, London, New York (1978)

    Google Scholar 

  35. Benesch, R.E., Benesch, R.: The acid strength of the –SH group in cysteine and related compounds. J. Am. Chem. Soc. 77(5), 877–5881 (1955)

    Google Scholar 

  36. Rochester, C.H.: Ionization of phenol, the cresols, and the xylenols in methanol. J. Chem. Soc. Faraday Trans. I 62, 355–358 (1966)

    Article  CAS  Google Scholar 

  37. Dogan, A., Aslan, N., Erden, P., Canel, E., Kılıç, E.: Macroscopic and microscopic protonation equilibria of some α-amino acids in dimethyl sulfoxide–water mixtures. J. Solution Chem. 44, 1705–1722 (2015)

    Article  CAS  Google Scholar 

  38. Robinson, R.A., Stokes, R.H.: Electrolyte Solutions. Academic Press, New York (1959)

    Google Scholar 

  39. Gharib, F., Naeej, N.B., Nouri, N.: Tautomeric and microscopic protonation constants of alanine and valine in different aqueous solutions of methanol and tetrahydrofuran. J. Solution Chem. 44, 1655–1672 (2015)

    Article  CAS  Google Scholar 

  40. Headley, A.D., Starnes, S.D.: Effects of branching on the tautomeric equilibrium of amino acids. J. Am. Chem. Soc. 117, 9309–9313 (1995)

    Article  CAS  Google Scholar 

  41. Dogan, A., Kılıç, E.: Tautomeric and microscopic protonation equilibria of some α-amino acids. Anal. Biochem. 365, 7–13 (2007)

    Article  CAS  PubMed  Google Scholar 

  42. Gündüz, T., Kılıç, E., Köseoğlu, F., Canel, E.: Protonation constants of some substituted salicylideneanilines in dioxan–water mixtures. Anal. Chim. Acta 282, 489–495 (1993)

    Article  Google Scholar 

  43. Chattopadhyay, A.K., Lahiri, S.C.: Studies on the solvation of amino acids in ethanol and water mixtures. Electrochim. Acta 27, 269–272 (1982)

    Article  CAS  Google Scholar 

  44. Kılıç, E., Köseoğlu, F., Başgut, Ö.: Protonation constants of some pyridine derivatives in ethanol–water mixtures. Anal. Chim. Acta. 294, 215–220 (1994)

    Article  Google Scholar 

  45. Kılıç, E., Gökçe, G., Canel, E.: The protonation constants of some aliphatic alkylamines in ethanol–water mixtures. Turk. J. Chem. 26, 843–849 (2002)

    Google Scholar 

  46. Dogan, A., Kılıç, E.: Potentiometric studies on the protonation constants and solvation of some α-amino acid benzyl- and t-butyl- esters in ethanol–water mixtures. Turk. J. Chem. 29, 41–47 (2005)

    CAS  Google Scholar 

  47. Takamuku, T., Yamaguchi, A., Tabata, M., Nishi, N., Yoshida, K., Wakita, H., Yamaguchi, T.: Structure and dynamics of 1,4-dioxane–water binary solutions studied by X-ray diffraction, mass spectrometry and NMR relaxation. J. Mol. Liq. 83, 163–177 (1999)

    Article  CAS  Google Scholar 

  48. Marcus, Y.: Preferential solvation in mixed solvents X. Completely miscible aqueous co-solvent binary mixtures at 298.15K. Monatsh. Chem. 132, 1387–1411 (2001)

    Article  CAS  Google Scholar 

  49. Bates, R.G.: Solute–solvent interactions and acid–base dissociation in mixed solvent systems. J. Electroanal. Chem. 29, 1–19 (1971)

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Health Service Vocational School, University of Gazi, Golbası, Ankara, Turkey

    Tugce Deniz Tanalp

  2. Department of Science Education, Faculty of Gazi Education, University of Gazi, 06500, Teknikokullar, Ankara, Turkey

    Alev Doğan

Authors
  1. Tugce Deniz Tanalp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alev Doğan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alev Doğan.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tanalp, T.D., Doğan, A. The Microscopic and Tautomeric Protonation Constants of Some α-Amino Acids in Dioxane–Water Mixtures . J Solution Chem 50, 983–994 (2021). https://doi.org/10.1007/s10953-021-01099-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-021-01099-y

Keywords

Search

Navigation