Biomimetic Electrochromatography for Rapid Solute–Solvent Interaction Mapping

To better characterize solute-solvent interactions in electrokinetic systems, Universitat de Barcelona (Spain) researchers tested a new method based around the Abraham’s solvation parameter model. Their findings were published in the Journal of Chromatography A (1).

Liquid chromatography (LC), which relies on a solution partitioning between two immiscible phases, can effectively be used for physicochemical profiling and characterizing the binding properties of compounds. Biomimetic chromatography, which is a type of high-performance liquid chromatography (HPLC) method that applies stationary phases containing proteins and phospholipids that can mimic the biological environment where drug molecules distribute, is typically used in drug discovery to forecast how drug candidates will interact in biological processes (2). Such processes include blood and brain distribution, plasma protein binding, tissue partitioning, skin penetration, and toxicity.

Biomimetic separation in electrokinetic capillary chromatography is mainly assayed with liposomes, which may mimic biological membranes. However, the required lipids are expensive, liposome preparation is complex, and the systems involved can often face issues with homogeneity and stability. The potential use of alternate electrochromatographic approaches with common non-lipidic dispersed phases has largely been unexplored for biomimetic applications. According to the scientists, this likely stems from a lack of a reliable and rapid method for characterizing the main solute-solvent interactions affecting the chromatographic behavior.

In this research, a fast method for characterizing solute-solvent interactions in micellar and microemulsion electrokinetic chromatography was presented. The method was based off the Abraham’s solvation parameter model, which allows the accurate characterization of the selectivity of chromatographic systems according to solute-solvent interactions (polarizability, dipolarity, hydrogen bonding, and cavity formation) (3). The magnitude of different types of interactions between solutes and chromatographic phases was determined through the differences in migration observed for pairs of solutes. The effect of the different cohesion of the dispersed phase and the dispersive medium is determined from the injection of a mixture of homologous compounds, using nonanophenone as a dispersed phase marker in all injections.

For excess polarizability interactions (e), the compounds 8-hydroxyquinoline and 1,2-dimethoxybenzene were used. The dipolarity/polarizability coefficient (s) is assessed with 1,4- or 1,2-dicyanobenzene and 2-methylbenzaldehyde. To evaluate the solute hydrogen bond acceptor capacity (a), 3-ethoxyphenol and 2-chloroacetophenone are employed, and the hydrogen bond donor capacity (b) is characterized using 2,3,5,6-tetramethylpyrazine and 2,6-dimethylanisole. Finally, the cavity term (v) is determined using a mixture of n-alkyl phenone homologues in the range of acetophenone to heptanophenone, depending on the nature of the electrokinetic system.

This new approach allows for results similar to conventional methodologies, which are based on the injection of a relatively large number of solutes and subsequent analysis using multiple linear regressions. However, the new course of action significantly reduces the time and resources invested into characterizing electrokinetic chromatography systems. The novel method was assayed with micellar solutions prepared from bile salts (SC, SDC), anionic surfactants (SDS, LDS), and cationic surfactants (CTAB, TTAB), and microemulsions consisting of heptane, 1-butanol, and surfactants (SDS, SC, and TTAB) at different concentrations and pH values.

This new approach displayed promise as a more efficient alternative to conventional characterization of electrokinetic chromatography (EKC) systems through means of multilinear regression analysis of a relatively large set of test compounds. Further, the technique is said to align with the Green Chemistry principles of waste prevention and energy efficiency. According to the researchers, implementing their proposed methodology will allow increases in the pace of EKC systems, raising the possibilities of developing chromatographic configurations suitable for biomimetic applications in pharmaceutical and environmental sciences.

References

(1) Idrees, R.; Subirats, X.; Amézqueta, S.; Rosés, M. Towards Biomimetic Electrochromatography: Fast Method for the Abraham’s Characterization of Solute-Solvent Interactions in Micellar and Microemulsion Electrokinetic Systems. J. Chromatogr. A 2025, 1758, 466176. DOI: 10.1016/j.chroma.2025.466176

(2) Valko, K. L. Biomimetic Chromatography—A Novel Application of the Chromatographic Principles. Anal. Sci. Adv. 2022, 3 (3–4), 146–153. DOI: 10.1002/ansa.202200004

(3) Redón, L.; Beiranvand, M. S.; Subirats, X.; Rosés, M. Characterization of Solute-Solvent Interactions in Liquid Chromatography Systems: A Fast Method Based on Abraham’s Linear Solvation Energy Relationships. Anal. Chim. Acta 2023, 1277, 341672. DOI: 10.1016/j.aca.2023.341672