Skip to main content
SpringerLink
Log in

Thermodynamic Study on the Protonation and Complexation of the Neuroleptic Drug, Gabapentin with Na+, Ca2+ and Mg2+ at Various Temperatures and Ionic Strengths

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

Abstract

The current work investigates the protonation constants of gabapentin (GP), 2-[1-(aminomethyl)cyclohexyl]acetic acid and the stability constants for the binding of GP to Ca2+ and Mg2+ in a wide range of temperature and ionic strength conditions [283.15 ≤ T/K ≤ 318.15 and ionic strengths of NaCl(aq), 0.12 ≤ I/mol·dm−3 ≤ 4.84]. The pH-potentiometric titration method was applied for gathering experimental data and determination of solution equilibrium constants. The ΔpK method was used for the determination of calcium and magnesium stability constants due to the low values which were predicted. A Debye–Hückel type equation, Specific Ion Interaction Theory, Pitzer and van’t Hoff equations were used for the modeling of ionic strength and temperature effects. Two species, ML and MHL, were found according to the best model for Ca2+ and Mg2+. Both protonation processes are exothermic based on the enthalpy values at 298.15 K and infinite dilution. A case study has been performed taking into account the speciation of GP in seawater.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Scheme 1
Fig. 1
Fig. 2 

Similar content being viewed by others

References

  1. Glorian, H., Börnick, H., Sandhu, C., Grischek, T.: Water quality monitoring in northern India for an evaluation of the efficiency of bank filtration sites. Water 10, 1804–1818 (2018)

    Article  CAS  Google Scholar 

  2. Kümmerer, K.: Pharmaceuticals in the Environment, Sources, Fate, Effects and Risks, 3rd edn. Springer, Berlin (2008)

    Book  Google Scholar 

  3. Dasgupta, A., Krasowski, M.D.: Antiepileptic drugs. In: Dasgupta, A., Krasowski, M.D. (eds.) Therapeutic Drug Monitoring Data, 4th edn, pp. 99–158. Academic Press, Cambridge (2020)

    Chapter  Google Scholar 

  4. Mahmoud, M.A., Helal, M.A., Ammar, A.M.: Zinc ternary complexes with gabapentin and neurotransmitters: synthesis, spectral, thermal and molecular docking studies. J. Mol. Struct. 1199, 126951 (2020)

    Article  CAS  Google Scholar 

  5. Mahmoud, M.A., Abbas, A.M., Zaitone, S.A., Ammar, A.M., Sallam, S.A.: Copper(II) ternary complexes with gabapentin and neurotransmitters as antiepileptic drug. J. Mol. Struct. 1180, 861–877 (2019)

    Article  CAS  Google Scholar 

  6. Zaid, A.A., Farooqui, M., Janrao, D.M.: Study of stability constant of binary and ternary complexes of gabapentin with transition metal ions using potentiometric titration. Asian J. Biochem. Pharm. Res. 1, 22–27 (2011)

    CAS  Google Scholar 

  7. Jalali, F., Shahbazi, A.R.: pH-metric study of some transition metal complexes of gabapentin and homocycloleucine. Pol. J. Chem. 82, 2207–2213 (2008)

    CAS  Google Scholar 

  8. Yang, L.X., Li, D.X., Liu, B.L., Guo, B.S., Wei, D.Q.: Improvement in the stability of gabapentin by the complexation of gabapentin with different metal ions: a DFT study. Chin. J. Struct. Chem. 38, 695–705 (2019)

    CAS  Google Scholar 

  9. Kumar, A., Malik, A.K.: Potentiometric studies on the complexes of Cu(II), Cd(II), Co(II), Ni(II), Pb(II) and Zn(II) with gabapentin. J. Electrochem. Soc. India 56, 33–35 (2007)

    CAS  Google Scholar 

  10. Jalali, F., Dorraji, P.S.: Electrochemical and spectroscopic studies of the interaction between the neuroleptic drug, gabapentin, and DNA. J. Pharm. Biomed. Anal. 70, 598–601 (2012)

    Article  CAS  PubMed  Google Scholar 

  11. Hadidi, S., Shiri, F., Norouzibazaz, M.: Theoretical mechanistic insight into the gabapentin lactamization by an intramolecular attack: degradation model and stabilization factors. J. Pharm. Biomed. Anal. 178, 112900 (2020)

    Article  CAS  PubMed  Google Scholar 

  12. Zambon, E., Giovanetti, R., Cotarca, L., Pasquato, L.: Mechanistic investigation on 2-aza-spiro[4,5]decan-3-one formation from 1-(aminomethyl)cyclohexylacetic acid (gabapentin). Tetrahedron 64, 6739–6743 (2008)

    Article  CAS  Google Scholar 

  13. Robinson, R.A., Stokes, R.H.: Electrolyte Solutions. Butterworths Scientific Publication, London (1959)

    Google Scholar 

  14. De Robertis, A., De Stefano, C., Sammartano, S., Rigano, C.: The determination of formation constants of weak complexes by potentiometric measurements: experimental procedures and calculation methods. Talanta 34, 933–938 (1987)

    Article  PubMed  Google Scholar 

  15. Brønsted, J.N.: Calculation of the osmotic and activity functions in solutions of uni-univalent salts. J. Am. Chem. Soc. 44, 938–948 (1922)

    Article  Google Scholar 

  16. Ciavatta, L.: The specific interaction theory in evaluating ionic equilibria. Ann. Chim. (Rome) 70, 551–567 (1980)

    CAS  Google Scholar 

  17. Grenthe, I., Puigdomenech, I. In: Modelling in Aquatic Chemistry. OECD, Paris (1997)

  18. Guggenheim, E.A., Turgeon, J.C.: Specific interaction of ions. Trans. Faraday Soc. 51, 747–761 (1955)

    Article  CAS  Google Scholar 

  19. Biederman, G.: Ionic media. In: Dahlem Workshop on the Nature of Seawater. Dahlem Konferenzen, Berlin, pp. 339–362 (1975)

  20. Pitzer, K.S. (ed.): Activity Coefficients in Electrolyte Solutions. CRC Press, Boca Raton (1991)

    Google Scholar 

  21. Daniele, P.G., Foti, C., Gianguzza, A., Prenesti, E., Sammartano, S.: Weak alkali and alkaline earth metal complexes of low molecular weight ligands in aqueous solution. Coord. Chem. Rev. 252, 1093–1107 (2008)

    Article  CAS  Google Scholar 

  22. Bretti, C., De Stefano, C., Lando, G., Sammartano, S.: Thermodynamic properties of melamine (2,4,6-triamino-1,3,5-triazine) in aqueous solution. Effect of ionic medium, ionic strength and temperature on the solubility and acid–base properties. Fluid Phase Equilib. 355, 104–113 (2013)

    Article  CAS  Google Scholar 

  23. Pytkowicz, R.M. (ed.): Activity Coefficients in Electrolyte Solutions, vol. 1. CRC Press Inc., Boca Raton (1979)

    Google Scholar 

  24. Bretti, C., Millero, F.J., Sammartano, S.: Modeling of protonation constants of linear aliphatic dicarboxylates containing -S-groups in aqueous chloride salt solutions, at different ionic strengths, using the SIT and Pitzer equations and empirical relationships. J. Solution Chem. 37, 763–784 (2008)

    Article  CAS  Google Scholar 

  25. Bretti, C., Cigala, R.M., Crea, F., Foti, C., Sammartano, S.: Solubility and activity coefficients of acidic and basic non-electrolytes in aqueous salt solutions. 3. Solubility and activity coefficients of adipic and pimelic acids in NaCl(aq), (CH3)4NCl(aq) and (C2H5)4NI(aq) at different ionic strengths and at t = 25 °C. Fluid Phase Equilib. 263, 43–54 (2008)

    Article  CAS  Google Scholar 

  26. Bretti, C., Giuffrè, O., Lando, G., Sammartano, S.: Solubility, protonation and activity coefficients of some aminobenzoic acids in NaClaq and (CH3)4NClaq, at different salt concentrations, at T = 298.15 K. J. Mol. Liq. 212, 825–832 (2015)

    Article  CAS  Google Scholar 

  27. Bretti, C., Giuffrè, O., Lando, G., Sammartano, S.: Modeling solubility and acid–base properties of some amino acids in aqueous NaCl and (CH3)4NCl aqueous solutions at different ionic strengths and temperatures. SpringerPlus 5, 928 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bretti, C., Cigala, R.M., Giuffrè, O., Lando, G., Sammartano, S.: Modeling solubility and acid–base properties of some polar side chain amino acids in NaCl and (CH3)4NCl aqueous solutions at different ionic strengths and temperatures. Fluid Phase Equilib. 459, 51–64 (2018)

    Article  CAS  Google Scholar 

  29. Long, F.A., McDevit, W.F.: Activity coefficients of nonelectrolyte solutes in aqueous salt solutions. Chem. Rev. 51, 119–169 (1952)

    Article  CAS  Google Scholar 

  30. De Stefano, C., Sammartano, S., Mineo, P., Rigano, C.: Computer tools for the speciation of natural fluids. In: Gianguzza, A., Pelizzetti, E., Sammartano, S. (eds.) Marine Chemistry—An Environmental Analytical Chemistry Approach, pp. 71–83. Kluwer Academic Publishers, Amsterdam (1997)

    Google Scholar 

  31. Martell, A.E., Smith, R.M., Motekaitis, R.J.: NIST Standard Reference Database 46, vers.8, Gaithersburg (2004)

  32. Cardiano, P., Giacobello, F., Giuffrè, O.: Thermodynamic and spectroscopic study of Al3+ interaction with glycine, l-cysteine and tranexamic acid in aqueous solution. Biophys. Chem. 230, 10–19 (2017)

    Article  CAS  PubMed  Google Scholar 

  33. Majlesi, K., Bretti, C., De Stefano, C., Lando, G., Majlesi, K., Sammartano, S.: Thermodynamic study on the interaction of nicotinic acid with H+, Na+, Ca2+ and Mg2+ at different temperatures and ionic strengths. J. Solution Chem. 48, 1671–1684 (2019)

    Article  CAS  Google Scholar 

  34. Bretti, C., Crea, F., Rey-Castro, C., Sammartano, S.: Interaction of acrylic-maleic copolymers with H+, Na+, Mg2+ and Ca2+: Thermodynamic parameters and their dependence on medium. React. Funct. Polym. 65, 329–342 (2005)

    Article  CAS  Google Scholar 

  35. De Robertis, A., De Stefano, C., Sammartano, S., Gianguzza, A.: Equilibrium studies in natural fluids: a chemical speciation model for the major constituents of sea water. Chem. Speciation Bioavailab. 6, 65–84 (1994)

    Article  Google Scholar 

  36. Millero, F.J.: Chemical Oceanography, 2nd edn. Taylor & Francis, Boca Raton (1996)

    Google Scholar 

  37. De Stefano, C., Foti, C., Gianguzza, A., Rigano, C., Sammartano, S.: Chemical speciation of amino acids in electrolyte solutions containing major components of natural fluids. Chem. Spec. Bioavailab 7, 1–8 (1995)

    Article  Google Scholar 

Download references

Acknowledgements

Kavosh Majlesi thanks Ms. Yeganeh Mousavian, Quality Control Manager at Damavand Darou Company (Tehran, Iran) for providing gabapentin and some useful information about the gabapentin assay.

Author information

Authors and Affiliations

  1. Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran

    Kavosh Majlesi

  2. Dipartimento di Scienze Chimiche, Biologiche, Farmaceutiche ed Ambientali, Università degli Studi di Messina, Viale Ferdinando Stagno d’Alcontres, 31, 98166, Messina (Vill. S. Agata), Italy

    Clemente Bretti, Concetta De Stefano & Silvio Sammartano

Authors
  1. Kavosh Majlesi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Clemente Bretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Concetta De Stefano
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvio Sammartano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kavosh Majlesi.

Additional information

This work is dedicated to the memory of Prof. Silvio Sammartano, who passed away on September 27th, 2020. He was a mentor, colleague and a friend for all of us.

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

Majlesi, K., Bretti, C., De Stefano, C. et al. Thermodynamic Study on the Protonation and Complexation of the Neuroleptic Drug, Gabapentin with Na+, Ca2+ and Mg2+ at Various Temperatures and Ionic Strengths. J Solution Chem 49, 1225–1236 (2020). https://doi.org/10.1007/s10953-020-01022-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10953-020-01022-x

Keywords

Search

Navigation