Evaluation of three neutral capillary coatings for the determination of analyte-cyclodextrin binding constants by affinity capillary electrophoresis. Application to N,N⿲-disubstituted piperazine derivatives

• Published in: Journal of Chromatography A 2016-07, Vol.1455, p.163-171
• Main Authors: Danel, Cécile, Melnyk, Patricia, Azaroual, Nathalie, Larchanché, Paul-Emmanuel, Goossens, Jean-François, Vaccher, Claude
• Format: Article
• Language: English
• Subjects: Affinity; Affinity capillary electrophoresis; Analytical chemistry; Binding; Capillarity; Chemical Sciences; Coatings; Constants; Cyclodextrin; Cyclodextrins; Derivatives; Electrophoresis; Hydroxypropyl cellulose; Neutral coating; Poly(N,N-dimethylacrylamide); Polyethylene oxide
• ISSN: 0021-9673; 1873-3778
• DOI: 10.1016/j.chroma.2016.05.090

⿢Three neutral coatings are evaluated to avoid the analyte and CD adsorption.⿢CD adsorption on the HPC and PEO coatings is proved.⿢PDMA coating allows to determine polycationic analyte-CD binding constants.⿢Complex structure is elucidated through structure-binding constant relationships. The performances of three neutral static coatings (hydroxypropyl cellulose, polyethylene oxide and poly(N,N-dimethylacrylamide) have been evaluated in order to determine the binding constants of the complexes formed between four polycationic compounds (piperazine derivatives) and four cyclodextrins of pharmaceutical interest (β-CD, HP-β-CD, Me-β-CD and sulfobutyl ether-β-CD) by affinity capillary electrophoresis. The physically-adsorbed poly(N,N-dimethylacrylamide) coating proves to be the more efficient to mask the silanol groups of the capillary wall since the lowest electroosmotic flow was measured for this coating. Moreover, it drastically reduces the adsorption of the compounds since it allows a correct repeatability of their migration time, higher efficiencies of the peaks and no baseline shift. Then, it was verified for four complexes that this coating allows a correct determination of the binding constants avoiding the CD adsorption which is responsible of an undervaluation of binding constants. The highest binding constants are obtained using the anionic sulfobutyl ether-β-CD (SBE-β-CD). The structure of the complex formed between the tacrine derivative and the SBE-β-CD was further investigated through 2D ROESY NMR experiments and structure-binding constant relationships. Results suggest that the inclusion in the SBE-β-CD cavity occurs through the aliphatic ring portion of the tacrine moiety.