A new example of reversal of the order of migration of enantiomers, as a function of cyclodextrin concentration and pH, by cyclodextrin-modified capillary zone electrophoresis: enantioseparation of 6,6′-dibromo-1,1′-binaphthyl-2,2′-diol

Abstract

Enantioseparation of 6,6'-dibromo-1,1'-binaphthyl-2,2'-diol (DBBD) by cyclodextrin-modified capillary zone electrophoresis (CD-CZE) was studied using the three native alpha, beta, and gamma cyclodextrins, the three hydroxypropylated cyclodextrins (2-hydroxypropyl-alpha, beta, and gamma), heptakis-2,6-di-O-methyl-beta-CD (DM-beta-CD), and heptakis-2,3,6-tri-O-methyl-beta-cyclodextrin (TM-beta-CD). First, the acidity constants of DBBD were determined using capillary electrophoresis, before performing enantioseparation. The influence of the concentrations of the studied cyclodextrins on the enantioseparation was explored and the experimental optimal concentrations were determined and compared to the theoretical optimal concentrations. Moreover, the apparent complexation constants between each studied cyclodextrin and the two DBBD enantiomers were evaluated using a non-linear curve fitting method and three linear plotting methods (x-reciprocal, y-reciprocal and double reciprocal). For TM-beta-CD, the order of migration of the enantiomers of DBBD reversed as a function of TM-beta-CD concentration. The influence of the nature of methylated cyclodextrin derivatives (methyl-beta-CD (M-beta-CD) and DM-beta-CD) was then studied. Inversion of the order of migration of the enantiomers of DBBD was observed for DM-beta-CD, whereas the S enantiomer of DBBD always migrated first for M-beta-CD.

Application of cyclodextrins in chiral capillary electrophoresis

“…Randomly substituted CDs often provide a compromise between native and persubstituted CDs and, in some cases, they are actually mixtures of native and substituted CDs, as it is obvious for instance with use of 2‐hydroxypropylated CDs of the average degree of substitution below 1 . Randomly substituted CDs are frequently employed in electromigration methods.…”

“…Nevertheless, these randomly substituted CDs can be very useful in enantioseparations because their separation ability is different from single isomers . Sometimes, the migration order of enantiomers can be reversed as a consequence of the change of the degree of substitution .…”

“…Wide range of CD derivatives with exactly known numbers and positions of substituents on CD glucose units is also used in electromigration methods. The most common derivatives have the same substituents on all the given carbon atoms of the glucose units (persubstituted derivatives at a given position or persubstituted derivatives where all the hydroxyl groups are replaced with the same functional group), for example, heptakis(2‐ O ‐sulfo‐3‐ O ‐methyl‐6‐ O ‐acetyl)‐β‐CD and per‐ O ‐methyl‐β‐CD .…”

“…Jasmonic acid [203]; norephedrine [128]; ANDA-CC-penicillamine [204]; trimipramine [205]; tryptophan [206]; vincamine, vinpocetine, and vincadifformine [122]; four basic compounds [58]; five N,S exo-heterodisubstituted O-carborane ligands [207]; Tic-hydantoin derivatives [208]; binaphthol and its mono derivatives [174,209]; acyclic nucleoside phosphonate [210] ␤-CD Amisulpride [211]; DTAF-aspartic acid [212]; baclofen [138]; catechin, chlorpheniramine, and promethazine [213]; ephedrine [130]; epicatechin [214]; fluvastatin [215]; ANSA-fucose and FMOC-pipecolic acid [216]; metoprolol [217]; binaphthol and its mono derivatives [209]; 6,6 -dibromo-1,1 -binaphthyl-2,2 -diol [218]; norephedrine [128]; penicillamine [202]; ANDA-CC-penicillamine [204]; 1,4-bis(9-O-quininyl)phthalazine [219]; dioxopromethazine [220]; propranolol [221]; salsolinol and its derivatives [136]; NBD-F-serine [194]; Tröger's base derivatives [222,223]; DNS-tyrosine and DNS-threonine [195]; vincamine, vinpocetine, and vincadifformine [122]; zopiclone [224]; ␤-agonists [225][226][227]; nine amino acids [228]; three amino acids and 13 DNS amino acids ...…”

Analysis of Binding Equilibrium of Phenylalkylamines to Brij 58 Micelle through the Measurement of Electrophoretic Mobility by CZE

“…Acidity constants in 50% methanol/water [10] and in 100% methanol [11] were determined. Changes in electrophoretic mobility of analytes were also utilized to investigate the chemical equilibria of complex formation [2], ion-association [2,[12][13], and inclusion to cyclodextrins [14][15][16].…”