Interactions of helquats with chiral acidic aromatic analytes investigated by partial-filling affinity capillary electrophoresis

- Interactions of helquats (helical extended diquats) with chiral analytes were studied.
- Weak to medium strong non-chiral and chiral interactions were observed.
- Binding constants of analyte-helquat complexes were determined by PF-ACE.
- Helquats provided best chiral separations for analytes with helical structure.
- The interactions are mediated by electrostatic, hydrophobic and π-π interactions.

Noncovalent molecular interactions between helquats, a new class of dicationic helical extended diquats, and several chiral acidic aromatic drugs and catalysts have been investigated using partial-filling affinity capillary electrophoresis (PF-ACE). Helquats dissolved at 1 mM concentration in the aqueous background electrolyte (40 mM Tris, 20 mM acetic acid, pH 8.1) were introduced as ligand zones of variable length (0-130 mm) into the hydroxypropylcellulose coated fused silica capillary whereas 0.1 mM solutions of negatively charged chiral drugs or catalysts (warfarin, ibuprofen, mandelic acid, etodolac, binaphthyl phosphate and 11 other acidic aromatic compounds) were applied as a short analyte zone at the injection capillary end. After application of electric field, analyte and ligand migrated against each other and in case of their interactions, migration time of the analyte was increasing with increasing length of the ligand zone. From the tested compounds, only isomers of those exhibiting helical chirality and/or possessing conjugated aromatic systems were enantioselectively separated through their differential interactions with helquats. Some compounds with conjugated aromatic groups interacted with helquats moderately strongly but non-enantiospecifically. Small compounds with single benzene ring exhibited no or very weak non-enantiospecific interactions. PF-ACE method allowed to determine binding constants of the analyte-helquat complexes from the changes of migration times of the analytes. Binding constants of the weakest complexes of the analytes with helquats were less than 50 L/mol, whereas binding constants of the strongest complexes were in the range 1 000-1 400 L/mol.