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

Autor: Mohammad Pousti, Mehran Abbaszadeh Amirdehi, Farrokh Gharib, Farnaz Asayesh, Jesse Greener
Rok vydání: 2017
Předmět:
Zdroj: Journal of Solution Chemistry. 46:720-733
ISSN: 1572-8927
0095-9782
DOI: 10.1007/s10953-017-0595-x
Popis: 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.
Databáze: OpenAIRE
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