Complexation between Amylodextrin Oligomers and Selected Pharmaceuticals Measured through Capillary Electrophoresis

Abstract

The amylodextrin oligomers, tagged fluorescently at their reducing ends for laser fluorescence detection, were used as model solutes to investigate certain carbohydrate-drug interactions through capillary electrophoresis. The separation patterns of some oligomers were found to be altered significantly by the presence of selected pharmaceuticals used as buffer additives. The selectivity of complexation at a particular size of an oligomer could be judged from alterations in migration times and peak shapes. The formation of complex was influenced substantially by solutes' chemical environment (pH, ionic strength, and the nature and concentration of organic additives). The chemical nature of the guest molecules also played an important role in complexation. Using amylodextrins as chiral selectors, enantiomeric resolution of several pharmaceuticals was achieved electrophoretically. The conclusions drawn from electrophoretic data were found to be in close agreement with the results of a (13)C NMR study.

Affinity capillary electrophoretic studies of complexation between dextrin oligomers and polyiodides

“…1, using iodine/iodide-free buffer as a control. Just as with the previous study of hydrophobic ligand binding [18], we observe an accelerated migration beyond the ªcritical oligomerº, in this case, a component with a degree of polymerization (DP) of 20. This result indicates that the well-known complexation between amylose and the polyiodide entities can be observed during our CZE experiment (in spite of the fact that a previous study estimates this to happen around DP 40 [7]).…”

“…In the study of complexation, the same fraction was dissolved in D 2 O, as described above, except that 0.52 mg/mL KI and 0.05 mg/mL I 2 were also included in the solution. Since our previous work on dextrin-drug complexation [18] established that the fluorescent tag has no appreciable effect on the behavior of the remaining oligosaccharide chain, the NMR study was conducted with underivatized samples. A mixture of small oligosaccharides (DE-20), which does not contain oligomers large enough to complex with polyiodides (see Section 3 below), was used as a control.…”

“…As shown in our previous study [18] on binding of small pharmaceutical molecules to amylodextrin, the combination of affinity principles with CZE is highly desirable to observe oligomer-specific interactions, i.e., information that clearly is unavailable from bulk physical measurements. An easily observable fluorophore has been placed at the oligosaccharide reducing end, so that a large part of the molecule participating in the complexation process remains unperturbed.…”

“…In more general terms, this approach also adds to a series of techniques used previously to probe the amylose conformation in solutions and its versatility to complex with a variety of other molecules: 13 C-NMR spectrometry [13], circular dichroism [14], viscometry [8], calorimetry [15], potentiometry [16], and surface tension measurements [17]. In describing the complexation phenomena between the amylose oligomers and various pharmaceuticals [18], we have recently demonstrated the value of this electrophoretic approach: (i) it provides ªoligomer-specific informationº, for which the bulk measurements are not informative; (ii) capillary zone electrophoresis (CZE) is inherently a sensitive technique, necessitating only minute quantities of studied materials; and (iii) CZE overcomes any potential problems with a limited solubility of amylose and its complexes that may complicate less sensitive bulk measurements.…”

“…The affinity/CZE strategy described in a previous communication [18] first involves the end-labeling of the reducing end of polysaccharide molecules with a fluorophore. Subsequently, the labeled molecules are electrophoresed through a capillary containing a buffer and the ligand, whose concentration may be varied (if necessary) and, finally, detected at high sensitivity through laser-induced fluorescence.…”