@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Popović, Gordana and Nikolić, Katarina",
year = "2024",
abstract = "Membrane mimicking approach is based on the philosophy of compartmentalization of molecules in systems
which may affect reaction rates, properties and stereochemistry that, in turn, differ from those observed in “pure”
aqueous solutions [1]. There is no ideal model that fully reproduces all the complexities of biomembranes, but a
large variety of membrane mimetics are available [2]. Since their properties are well understood at the chemical
level, micellar solutions of differently charged surfactants are systems the most commonly used to mimic the
desired functions of cells membranes [1]. In our previous studies we showed that protolytic equilibria of
ionizable drugs may significantly shift in micellar solutions [3, 4]. Our results suggest that is not possible to
predict the direction and intensity of the shift which requires comprehensive experimental consideration of every
single compound. Drug compounds containing two or more ionizable centers represent the greatest challenge,
especially if the pKa values are close and the ionization processes are overlapped. Estimation of the
pharmacological behavior and pharmacokinetic properties of these drugs, based on the pKa values exclusively
defined in “pure” aqueous solution, can be misleading, as possible interactions with biomolecules may
significantly change the assumed ionization patterns. In this study, the protolytic equilibria of cetirizine, a
second-generation antihistamine used to treat various allergy symptoms has been examined in micellar solutions
of differently charged surfactants, anionic (SDS), cationic (CTAB), and nonionic (TX-100). The pKa values of
cetirizine were determined potentiometrically under the same conditions in the “pure” water and in the micellar
solutions. Complex system of protolytic equilibria which includes 3 ionizable centers was resolved by program
HYPERQUAD [5]. The shift in equilibria affected by the presence of micelles was observed from (- 1.41) pKa
unit (cationic micelles) to (+ 2.01) pKa unit (anionic micelles). Interaction with micelles indicates on possible
interactions with biomolecules which may affect assumed distribution of equilibrium forms under the conditions
of absorption.
References
1) Fendler, J.H., Chem Rev., 1987, 87(5):877-899.
2) Klöpfer, K., Hagn, F., Prog Nucl Magn Reson Spectrosc., 2019, 114:271-283.
3) Popović-Nikolić, M.R., et al., J Chem Eng Data., 2018, 63(8):3150-3156.
4) Popović, M. R., et al., J ChemEng Data., 2013, 58(9):2567-2573.
5) Gans, P., et al., Talanta., 1996:43:1739.",
publisher = "EFMC, Societa Chimica Italiana",
journal = "EFMC-ISMC 2024, XXVIII EFMC International Symposium on Medicinal Chemistry, Rome, Italy, September 1-5, 2024, Book of Abstracts",
title = "Application of membrane mimetic systems approach in investigation of ionizable drugs: a case of cetirizine",
pages = "468-468",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5746"
}