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Journal of Solution Chemistry

, Volume 46, Issue 3, pp 720–733 | Cite as

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

  • Mehran Abbaszadeh Amirdehi
  • Mohammad Pousti
  • Farnaz Asayesh
  • Farrokh Gharib
  • Jesse GreenerEmail author
Article
  • 209 Downloads

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.

Graphical Abstract

Keywords

Protonation constant Propranolol Atenolol Solvent effect Kamlet and Taft Solvatochromic parameters DFT 

Supplementary material

10953_2017_595_MOESM1_ESM.docx (124 kb)
Supplementary material 1 (DOCX 124 kb)

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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Mehran Abbaszadeh Amirdehi
    • 1
  • Mohammad Pousti
    • 1
  • Farnaz Asayesh
    • 1
  • Farrokh Gharib
    • 2
  • Jesse Greener
    • 1
    Email author
  1. 1.Département de ChimieUniversité LavalQuébecCanada
  2. 2.Chemistry DepartmentShahid Beheshti University, G. C.TehranIran

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