Modelling of chromatographic and electrophoretic behaviour of imidazoline and alpha adrenergic receptors ligands under different acid-base conditions

Slavica Oljacic; Mitja Križman; Marija Popovic-Nikolic; Irena Vovk; Katarina Nikolic; Danica Agbaba

doi:10.5599/admet.2278

Authors

Slavica Oljacic University of Belgrade-Faculty of Pharmacy, Deparment of Pharmaceutical Chemistry https://orcid.org/0000-0001-9128-6072
Mitja Križman Laboratory of Food Chemistry, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia https://orcid.org/0009-0001-3859-7338
Marija Popovic-Nikolic Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia https://orcid.org/0000-0002-8902-3211
Irena Vovk Laboratory of Food Chemistry, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia https://orcid.org/0000-0002-4738-2849
Katarina Nikolic Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia https://orcid.org/0000-0002-3656-9245
Danica Agbaba Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11000 Belgrade, Serbia https://orcid.org/0000-0001-5907-9823

DOI:

https://doi.org/10.5599/admet.2278

Keywords:

Quantitative structure-retention relationship, quantitative structure-mobility relationship, liquid chromatography, capillary electrophoresis

Abstract

Background and Purpose: The ligands of the imidazoline and α-adrenergic receptors are mainly imidazoline and guanidine derivatives, known as centrally-acting antihypertensives and compounds with potential use in various neurological disorders. The extent of their ionisation has a major influence on their behaviour in the different analytical systems. The main objective of this work was to compare the mechanism of chromatographic retention and electrophoretic mobility under acidic, neutral and basic conditions. Experimental Approach: Multiple Linear Regression and Partial Least Squares Regression were applied for the QSRR (quantitative structure-retention relationship) and QSMR (quantitative structure-mobility relationship) modelling and to select the most important molecular parameters describing the chromatographic and electrophoretic behaviour of the investigated compounds. Key Results: The most important molecular descriptors, such as the chemical composition of the compounds, lipophilicity, polarizability and molecular branching, in the selected QSRR models showed that an important insight into the retention behaviour can be derived from the 0D-, 1D- and 2D-descriptors. The electrophoretic mobility could be explained by 2D- and 3D-descriptors, which provide information on the molecular mass, size and complexity, as well as on the influence of charge transfer and electronic properties on the migration behaviour. Conclusion: All created QSRR/QSMR models met the stringent validation criteria and showed high potential in describing the chromatographic and electrophoretic behaviour of investigated compounds.

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