Developing efficient ways to study small molecule interactions with lipid bilayers is instrumental in cost effective drug development. Nanodiscs composed of phospholipid bilayers and synthetic maleic acid-styrene copolymers have been introduced as a pseudostationary phase (PSP) in electrokinetic chromatography in order to study these interactions. The nanodiscs provide an adequate migration range and high theoretical plate counts. Using these nanodisc PSPs, the affinity of the bilayer structures for probe solutes was determined and characterized; this characterization was done using linear solvation energy relationships. Nanodiscs consisting of phospholipids with varying degrees of unsaturation were determined to provide a solvation environment with weak hydrogen bond donating ability, and provide relatively strong hydrogen bond acceptor strength. Good correlation is observed between retention factors and octanol water partition coefficients for particular categories of solutes, but the general correlation is weak primarily because the nanodiscs show stronger affinity than octanol for hydrogen bond donors. Retention factors were also compared to computational D<sub>pH7.0</sub> values, although in general the retention factor results correlate better to experimental P<sub>o/w</sub> values. This suggests that a more appropriate application of this technology is to measure and characterize interactions between solutes and lipid bilayers directly.

Characterization of phospholipid bilayers in copolymer belted nanodiscs by electrokinetic chromatography

253rd National Meeting (2017)

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