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Solvent Effects on Acid–Base Equilibria of Propranolol and Atenolol in Aqueous Solutions of Methanol: UV-Spectrophotometric Titration and Theory

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Abstract

The pK a values of two important drugs were determined in different binary aqueous/organic solutions, which mimic a range of industrial solvents and biological fluids encountered during drug synthesis and end use. Titrations of monoprotic (propranolol) and diprotic (atenolol) drugs were determined using a combination of potentiometric and spectroscopic methods at constant temperature and ionic strength. Single-parameter correlations between the measured pK a values (at 25 °C) and hydrogen-bond acidity/basicity or solvent polarity parameters were poor in all cases. However, analysis using the multi-parameter method of Kamlet, Abboud, and Taft represents significant improvement enabling better interpretation of the solvent effects on the acid−base equilibria of the drugs. As a validation step and for a deeper understanding of the origins of the solvent effects on the drugs, all pK a values were predicted by DFT calculations. Finally, acidity constants were determined by correlations between experimental and theoretical measurements. The developed method will measure and accurately simulate the effect of the solvent environment on pK a values and represent advancement for questions related to drug synthesis and drug compound’s behavior in biological fluids.

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References

  1. Mozayani, A., Raymon, L.: Handbook of Drug Interactions: A Clinical and Forensic Guide, 1st edn. Springer, New Jersey (2004)

    Book  Google Scholar 

  2. Narasimham, L., Barhate, V.D.: Physico-chemical characterization of some beta blockers and anti-diabetic drugs-potentiometric and spectrophotometric pK a determination in different co-solvents. Chem-Eur J. 2, 36–46 (2011)

    Article  CAS  Google Scholar 

  3. Uzel, S.G., Pavesi, A., Kamm, R.D.: Microfabrication and microfluidics for muscle tissue models. Prog. Biophys. Mol. Biol. 115, 279–293 (2014)

    Article  CAS  Google Scholar 

  4. Maitra, A., Bagchi, S.: Study of solute–solvent and solvent–solvent interactions in pure and mixed binary solvents. J. Mol. Liq. 137, 131–137 (2008)

    Article  CAS  Google Scholar 

  5. Soleimani, F., Karimi, R., Gharib, F.: Thermodynamic studies on protonation constant of acyclovir at different ionic strengths. J. Solution Chem. 45, 920–931 (2016)

    Article  CAS  Google Scholar 

  6. Atanassova, M., Billard, I.: Determination of pK a IL values of three chelating extractants in ILs: consequences for the extraction of 4f elements. J. Solution Chem. 44, 606–620 (2015)

    Article  CAS  Google Scholar 

  7. Dávila, Y.A., Sancho, M.I., Almandoz, M.C., Blanco, S.E.: Solvent effects on the dissociation constants of hydroxyflavones in organic–water mixtures. Determination of the thermodynamic pK a values by UV–visible spectroscopy and DFT calculations. J. Chem. Eng. Data 58, 1706–1716 (2013)

    Article  Google Scholar 

  8. Signore, G., Nifosì, R., Albertazzi, L., Storti, B., Bizzarri, R.: Polarity-sensitive coumarins tailored to live cell imaging. J. Am. Chem. Soc. 132, 1276–1288 (2010)

    Article  CAS  Google Scholar 

  9. Kudo, K., Momotake, A., Tanaka, J.K., Miwa, Y., Arai, T.: Environmental polarity estimation in living cells by use of quinoxaline-based full-colored solvatochromic fluorophore PQX and its derivatives. Photech. Photobio. Sci. 11, 674–678 (2012)

    Article  CAS  Google Scholar 

  10. Giusti, L.A., Marini, V.G., Machado, V.G.: Solvatochromic behavior of 1-(p-dimethylaminophenyl)-2-nitroethylene in 24 binary solvent mixtures composed of amides and hydroxylic solvents. J. Mol. Liq. 150, 9–15 (2009)

    Article  CAS  Google Scholar 

  11. Farajtabar, A., Jaberi, F., Gharib, F.: Preferential solvation and solvation shell composition of free base and protonated 5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin in aqueous organic mixed solvents. Spectrochim. Acta A 83, 213–220 (2011)

    Article  CAS  Google Scholar 

  12. Takamuku, T., Saisho, K., Nozawa, S., Yamaguchi, T.: X-ray diffraction studies on methanol–water, ethanol–water, and 2-propanol–water mixtures at low temperatures. J. Mol. Liq. 119, 133–146 (2005)

    Article  CAS  Google Scholar 

  13. Jaberi, F., Gharib, F.: Spectrophotometric determination of equilibrium constants of dimethyl and diethyltin(IV) dichloride with 5,10,15,20-tetrakis(4-trimethyl-ammonio-phenyl)-prophine eetratosylate. J. Solution Chem. 44, 34–44 (2015)

    Article  CAS  Google Scholar 

  14. Naderi, F., Farajtabar, A., Gharib, F.: Solvatochromic and preferential solvation of fluorescein in some water–alcoholic mixed solvents. J. Mol. Liq. 190, 126–132 (2014)

    Article  CAS  Google Scholar 

  15. Gharib, F., Abbaszadeh, M., Pousti, M.: Acid–base properties of adenosine 5′-monophosphate, guanosine 5′-monophosphate, and inosine 5′-monophosphate in aqueous solutions of methanol. Helv. Chim. Acta 96, 1134–1145 (2013)

    Article  CAS  Google Scholar 

  16. Naderi, F., Farajtabar, A., Gharib, F.: Protonation of tetrakis(4-sulfonatophenyl) porphyrin in aqueous solutions of scetonitrile and dioxane. J. Solution Chem. 41, 1033–1043 (2012)

    Article  CAS  Google Scholar 

  17. Jabbari, M., Gharib, F.: Solvent dependence on antioxidant activity of some water-insoluble flavonoids and their cerium(IV) complexes. J. Mol. Liq. 168, 36–41 (2012)

    Article  CAS  Google Scholar 

  18. Avdeef, A.: Absorption and drug development: solubility, permeability, and charge state. Wiley, New York (2012)

    Book  Google Scholar 

  19. Beale, J.M., Block, J., Hill, R.: Organic Medicinal and Pharmaceutical Chemistry, 12th edn. Lippincott Williams and Wilkins, Philadelphia (2010)

    Google Scholar 

  20. Leggett, D.J.: Computation Methods for the Determination of Formation Constants. Plenum Press, New York (1985)

    Book  Google Scholar 

  21. Meloun, M., Javůrek, M., Havel, J.: Multiparametric curve fitting—X: a structural classification of programs for analysing multicomponent spectra and their use in equilibrium-model determination. Talanta 33, 513–524 (1986)

    Article  CAS  Google Scholar 

  22. Gordon, M.S., Schmidt, M.W.: Advances in electronic structure theory Gamess a decade later. In: Dykstra, C.E., Frenking, G., Kim, K.S., G.E. Scuseria, G.E. (eds.) Theory and Applications of Computational Chemistry, pp. 1185–1189. Elsevier, Amsterdam (2005)

  23. Pliego, J.R., Riveros, J.M.: Theoretical calculation of pK a using the cluster-continuum model. J. Phys. Chem. A 106, 7434–7439 (2002)

    Article  CAS  Google Scholar 

  24. Jacquemin, D., Perpète, E.A.: Ab initio calculations of the colour of closed-ring diarylethenes: TD-DFT estimates for molecular switches. Chem. Phys. Lett. 429, 147–152 (2006)

    Article  CAS  Google Scholar 

  25. Allouche, A.R.: Gabedit—A graphical user interface for computational chemistry softwares. J. Comput. Chem. 32, 174–182 (2011)

    Article  CAS  Google Scholar 

  26. Hanson, R.M., Prilusky, J., Renjian, Z., Nakane, T., Sussman, J.L.: JSmol and the next-generation web-based representation of 3D molecular structure as applied to Proteopedia. Isr. J. Chem. 53, 207–216 (2013)

    Article  CAS  Google Scholar 

  27. Bode, B.M., Gordon, M.S.: MacMolPlt: a graphical user interface for GAMESS. J. Mol. Graph. Model. 16, 133–138 (1998)

    Article  CAS  Google Scholar 

  28. Kiani, F., Rostami, A.A., Sharifi, S., Bahadori, A., Chaichi, M.J.: Determination of acidic dissociation constants of glycine, valine, phenylalanine, glycylvaline, and glycylphenylalanine in water using ab initio methods. J. Chem. Eng. Data 55, 2732–2740 (2010)

    Article  CAS  Google Scholar 

  29. Maleki, N., Haghighi, B., Safavi, A.: Evaluation of formation constants, molar absorptivities of metal complexes, and protonation constants of acids by nonlinear curve fitting using microsoft excel solver and user-defined function. Microchem. J. 62, 229–236 (1999)

    Article  CAS  Google Scholar 

  30. Babić, S., Horvat, A.J., Pavlović, D.M., Kaštelan-Macan, M.: Determination of pK a values of active pharmaceutical ingredients. Trac-Trend Anal. Chem. 26, 1043–1061 (2007)

    Article  Google Scholar 

  31. Schurmann, W., Turner, P.: Membrane model of the human oral mucosa as derived from buccal absorption performance and physicochemical properties of the beta-blocking drugs atenolol and propranolol. J. Pharm. Pharmacol. 30, 137–147 (1978)

    Article  CAS  Google Scholar 

  32. Völgyi, G., Ruiz, R., Box, K., Comer, J., Bosch, E., Takács-Novák, K.: Potentiometric and spectrophotometric pK a determination of water-insoluble compounds: validation study in a new cosolvent system. Anal. Chim. Acta 583, 418–428 (2007)

    Article  Google Scholar 

  33. Sanli, S., Altun, Y., Guven, G.: Solvent effects on pK a values of some anticancer agents in acetonitrile–water binary mixtures. J. Chem. Eng. Data 59, 4015–4020 (2014)

    Article  CAS  Google Scholar 

  34. Farajtabar, A., Gharib, F.: Spectral analysis of naringenin deprotonation in aqueous ethanol solutions. Chem. Pap. 67, 538–545 (2013)

    Article  CAS  Google Scholar 

  35. Reichardt, C.: Solvents and Solvent Effects in Organic Chemistry, 3rd edn. Wiley-VCH, Weinheim (2004)

    Google Scholar 

  36. Marcus, Y.: Water structure enhancement in water-rich binary solvent mixtures. Part II. The excess partial molar heat capacity of the water. J. Mol. Liq. 166, 62–66 (2012)

    Article  CAS  Google Scholar 

  37. Kamlet, M.J., Gal, J.F., Maria, P.C., Taft, R.W.: Linear solvation energy relationships. Part 32. A co-ordinate covalency parameter, ξ, which, in combination with the hydrogen bond acceptor basicity parameter, β, permits correlation of many properties of neutral oxygen and nitrogen bases (including aqueous pK a). J. Chem. Soc. Perkin Trans. 2, 1583–1589 (1985)

    Article  Google Scholar 

  38. Kamlet, M.J., Carr, P.W., Taft, R.W., Abraham, M.H.: Linear solvation energy relationships. 13. Relationship between the Hildebrand solubility parameter, ∆H, and the solvatochromic parameter, π*. J. Am. Chem. Soc. 103, 6062–6066 (1981)

    Article  CAS  Google Scholar 

  39. Kamlet, M.J., Abboud, J.L.M., Abraham, M.H., Taft, R.W.: Linear solvation energy relationships. 23. A comprehensive collection of the solvatochromic parameters, π*, α, and β, and some methods for simplifying the generalized solvatochromic equation. J. Org. Chem. 48, 2877–2887 (1983)

    Article  CAS  Google Scholar 

  40. Taft, R.W., Abboud, J.L.M., Kamlet, M.J.: Linear solvation energy relationships. An analysis of Swain’s solvent” acity” and” basity” scales. J. Org. Chem. 49, 2001–2005 (1984)

    Article  CAS  Google Scholar 

  41. Deb, N., Shannigrahi, M., Bagchi, S.: Use of fluorescence probes for studying Kamlet-Taft solvatochromic parameters of micellar system formed by binary mixture of sodium dodecyl sulfate and Triton-X 100. J. Phys. Chem. B 112, 2868–2873 (2008)

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Département de Chimie, Université Laval, 1045 Avenue de La Médecine, Québec, QC, G1V0A6, Canada

    Mehran Abbaszadeh Amirdehi, Mohammad Pousti, Farnaz Asayesh & Jesse Greener

  2. Chemistry Department, Shahid Beheshti University, G. C., Evin, Tehran, Iran

    Farrokh Gharib

Authors
  1. Mehran Abbaszadeh Amirdehi
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  2. Mohammad Pousti
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  3. Farnaz Asayesh
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  4. Farrokh Gharib
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  5. Jesse Greener
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Correspondence to Jesse Greener.

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Amirdehi, M.A., Pousti, M., Asayesh, F. et al. Solvent Effects on Acid–Base Equilibria of Propranolol and Atenolol in Aqueous Solutions of Methanol: UV-Spectrophotometric Titration and Theory. J Solution Chem 46, 720–733 (2017). https://doi.org/10.1007/s10953-017-0595-x

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  • DOI: https://doi.org/10.1007/s10953-017-0595-x

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