A Persubstituted Cationic β-Cyclodextrin for Chiral Separations

Abstract

The applications of a novel polycationic derivative of beta-cyclodextrin (beta-CD), heptakis(6-hydroxyethylamino-6-deoxy-beta-cyclodextrin) (beta-CD-EA), as a chiral host--guest additive for the enantioseparation of various classes of chiral anionic analytes are presented. The cationic beta-CD described in this paper is persubstituted with seven ethanolamine side arms at the primary rim of each cyclodextrin (CD) molecule. It is found that the electrophoretic mobility of beta-CD-EA can be adjusted to influence the chiral selectivity by changing the pH of the background electrolyte. Most of the observed CD capillary zone electrophoresis (CZE) separations of anionic drugs and herbicides were accomplished in the pH range of 4.0-7.0 with a reverse polarity configuration. At pH 5.0, enantioseparation of a mixture of three structurally related antiinflammatory agents (fenoprofen, flurbiprofen, and ibuprofen) was possible in about 30 min. However, other chiral acids, such as a series of phenoxypropionic acid herbicides and dansylated amino acids (glutamic acid and aspartic acids), were best separated at pH 6.0 or 7.0. An impressive separation of a mixture of six structurally related anionic herbicides [(+/-)-2-phenoxypropionic acid, (+/-)-2-(2-chlorophenoxy)propionic acid, (+/-)-2-(3-chlorophenoxy)propionic acid, (+/-)-2-(4-chlorophenoxy)propionic acid, (+/-)-2-(2,4-dichlorophenoxy)propionic acid, and (+/-)-2-(2,4,5-trichlorophenoxy)propionic acid] was achieved for the first time in about 15 min during a single run with 20 mM beta-CD-EA. The analytical applicability of this cationic CD molecule for chiral separations is discussed in detail.

Chiral separation by chromatographic and electromigration techniques. A Review

“…Cationic CDs such as 6-[(3-aminoethyl)amino]-6-deoxy-b-CD, 6 A -methylamino-b-CD, 6 A ,6 D -dimethylamino-b-CD, a hepta-substituted methylamino-b-CD, mono (6-amino-6-deoxy)-b-CD were the first cationic CDs described that found application to the chiral separation of various acidic and neutral compounds [13,15,16]. A polycationic CD derivative, heptakis(6-hydroxyethylamino-6-deoxyb-CD) (beta-CD-EA) was developed by O'Keeffe et al [359] and applied to acidic compounds such as NSAIDs, Dns-amino acids, and phenoxypropionic acid herbicides.…”

Nonaqueous capillary electrophoretic separation of basic enantiomers using heptakis(2,3-dimethyl-6-sulfato)-β-cyclodextrin

“…Though the majority of these enantiomer separations were achieved with randomly substituted CDs [9,10], containing many isomers with different numbers of ionic or ionizable functional groups, recent efforts led to the successful synthesis of well characterized, single-isomer hepta-substituted, anionic CDs [11±13] and cationic CDs [14,15]. Nonaqueous capillary electrophoretic (NACE) separations of enantiomers with native and derivatized b-and g-CDs have been reported recently using formamide [16], N-methylformamide [ 16± 18] and N,N-dimethylformamide [16] as background electrolyte (BGE) solvents.…”

Comparison of charged cyclodextrin derivatives for the chiral separation of atropisomeric polychlorinated biphenyls by capillary electrophoresis

“…Besides the oftenused neutral CDs, the use of charged CD derivatives has expanded the range of applicability of this technique for chiral analysis [6]. The growing use of charged CDs for the enantioseparation of a wide range of enantiomers can be attributed to three important facts: (i) their ability to perform fast chiral separations at low concentrations; (ii) the possible chiral separation of neutral and charged racemates; and (iii) the effect that the introduction of ionogenic groups on the CD rim, or connected to it via a short alkyl chain, has on the enhancement of the solubility of charged CDs in aqueous media [7,8]. In addition, the enantioseparation of neutral analytes, which can be performed using charged micelles mixed with neutral CDs, can be carried out using charged CDs, which confers a nonzero mobility, without micelles.…”

“…However, the use of cationic CDs has not been extensively reported probably due to the high price and low commercial availability. About 20 papers have been published using cationic CDs as chiral selectors [7,8, since in 1989 Terabe [10] was the first to introduce a cationic CD for chiral separation by CE. All of them have shown the possibilities of these CDs to perform the enantiomeric separation of analytes in pharmaceutical analysis, being the most common application the separation of carboxylic acids or amino acids.…”