Complexation between low‐molecular‐weight cationic ligands and negatively charged polymers as studied by capillary electrophoresis frontal analysis

Abstract

The potential of using capillary electrophoresis frontal analysis for the study of low-molecular-weight ligand-polyelectrolyte interactions was assessed. The interaction of the ligands 1-propylpyridinium bromide, 2-propylisochinolinium bromide, and paraquat with the polymer dextran sulfate was investigated as a function of polymer concentration and ionic strength of the buffer solution. Linear binding isotherms were obtained and association constants were determined. The complex formation was independent of the dextran sulfate concentration at low ionic strength. Ligand-polyelectrolyte interactions were strongly dependent on the ionic strength. The interaction of the divalent cation paraquat with the dextran sulfate was much stronger than the interactions of the monovalent cationic ligands with the polyelectrolyte. The binding data obtained were in accord with results obtained by equilibrium dialysis. Capillary electrophoresis frontal analysis has the potential to become a valuable tool for characterization of ligand-polyelectrolyte interactions in drug design as well as in other areas.

Binding of Low-Molecular-Weight Cationic Ligands to Chondroitin Sulfate as Studied by Capillary Electrophoresis Frontal Analysis

“…In line with previous studies [19], strong adsorption to the fused silica capillary wall was observed for methyl viologen (paraquat). Methyl viologen adsorbed onto PVA coated capillaries to a lesser extent indicating that the PVA coated capillary should be applied in the affinity studies encompassing methyl viologen.…”

“…The construction of binding isotherms for determination of the apparent association constant K app has been described previously [19]. Briefly, the binding density, , was calculated from the measured free ligand concentration [L] free , the total ligand concentration [L] total, and the molar concentration of chondroitin sulfate disaccharide units, C CS :…”

“…In all cases was less than 0.01. It is known that for 0, the binding equations reduce to /[L] free = K app [19,54]. Thus, the apparent association constant K app was determined form the slopes of the binding isotherms.…”

“…A range of methods have been applied to the study of low-molecular-weight ligand-polyelectrolyte complexation including equilibrium dialysis [11][12][13], isothermal titration calorimetry [14][15][16], ion selective electrodes [17,18], and capillary electrophoresis (CE) [19][20][21][22]. CE has been established as an efficient micromethod for studying molecular interactions [23][24][25][26][27][28].…”

“…[29,[34][35][36][37][38][39][40][41][42][43]. Also drug binding to *Address correspondence to this author at the Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark; Tel: +45 35336138; Fax: +45 35336030; E-mail: joe@farma.ku.dk 1 -acid glycoprotein [35,36], lipoproteins [44][45][46], liposomes [47,48], and the polyelectrolyte dextran sulfate [19,20] has been investigated by CE-FA.…”