Danuta Sybilska

Resolution of some chiral mandelic acid derivatives into enantiomers by reversed-phase high-performance liquid chromatography via α- and β-cyclodextrin inclusion complexes

Abstract The resolution of mandelic acid derivatives (differing in the kind of functional group and in the position of its substitution in the aromatic ring) into enantiomers in a reversed-phase high-performance liquid chromatographic system via α- and β-cyclodextrin inclusion complexes was studied. Of the mandelic acid derivatives investigated (o-, m- and p-OH, o-CH3, o-OCH3, o- and m-Cl), only the chloro derivatives showed high enantioselectivity in the processes of complex formation with β- cyclodextrin (separation factors: αo-C1 = 1.8 at pH 2.1 and αo-Cl = 1.15 and αm-Cl = 1.15 at pH 6.8). In contrast, the enantioselectivity for complex formation between α-cyclodextrin and mandelic acid and the derivatives investigated was low.

Resolution of Mephenytoin and Some Chiral Barbiturates into Enantiomers by Reversed Phase High Performance Liquid Chromatography via β-Cyclodextrin Inclusion Complexes

Abstract β-Cyclodextrin as the chiral mobile phase component was used for resolution of mephenytoin and some barbiturates (antidepressant drugs) into enantiomers on LiChrosorb RP 18 column. The effects of β-cyclodextrin concentration on the capacity factors were investigated and the stability constants as well as capacity factors of β-cyclodextrin complexes were calculated. It has been found that β-cyclodextrin complexation results in a distinct enantioselectivity in the case of mephenytoin and barbiturates containing a chiral center in the pyrimidine ring. Results are discussed in the light of two phenomena influencing resolution: adsorption of inclusion complexes on the stationary phase and complexation process in the mobile phase solution.

Application of α- and β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin as mobile phase components for the separation of some chiral barbiturates into enantiomers by reversed-phase high-performance liquid chromatography

Abstract Using LiChrosorb RP-18 as the stationary phase, systematic studies were performed on the changes in the capacity factors of a series of hydantoin and barbituric acid derivatives (including some therapeutically useful drugs) with variation in the concentrations of α- and β-cyclodextrin and heptakis(2,6-di-O-methyl)-β-cyclodextrin in the mobile phase.It has been found that both β-cyclodextrin and its dimethyl derivative exhibit enantioselectivities towards hydantoins and barbiturates that contain a chiral carbon atom in the heterocyclic ring. No selectivity was observed with α-cyclodextrin. Owing to the strong adsorption of dimethylated β-cyclodextrin from its dilute solutions on an ODS surface, a new mechanism for the separation of enantiomeric barbiturates was established.

The resolution of some chiral compounds in reversed-phase high-performance liquid chromatography by means of β-cyclodextrin inclusion complexes

Summaryβ-Cyclodextrin is applied as the chiral component of the mobile phase in a systematic study of the resolution —into enantiomers — of mandelic acid and its derivatives by reversed-phase liquid chromatography. It is found that the stereoselectivity arising from inclusion in β-cyclodextrin molecules is significant (α=1.02÷1.05) only for the compounds showing at the asymmetric carbon atom the presence of first, an intact carboxylic group and second, a functional group capable of hydrogen bonding with the hydroxyl groups of β-cyclodextrin. Results are discussed in the light of the three-point attachment model of stereoselectivity as well as of the structure of the inclusion complexes.

Enantiomers of monoterpenic hydrocarbons in essential oils from Juniperus communis

An investigation of the chiral and achiral composition of monoterpenic hydrocarbons in juniper oils has been undertaken. Samples were collected from different locations in Poland in two seasons (spring and autumn) and included needles, berries and wood. Surprisingly, large variations in the monoterpenic hydrocarbon compositions were observed.

α-and β-cyclodextrin complexation as a tool for the separation of o-, m- and p-nitro-cis and trans-cinnamic acids by reversed-phase high-performance liquid chromatography

The capacity factors of o-, m- and p-nitro-cis- and trans-cinnamic acids on reversed-phase columns at various pH values of the mobile phase and concentrations of α- and/or β-cyclodextrin were determined. Attempts to calculate the stability constants, Ko and K−, as well as the capacity factors, k′, of all individual species (neutral and anionic, free and bound to β-cyclodextrin) were made on the basis of experimental data. It was found that β-cyclodextrin enhances the selectivity of the system towards m- and p-nitrocinnamic acids, of whether cis- or trans-configuration2. Under optimum conditions, attempts were made to separate all the compounds investigated.

Comparative study on camphor enantiomers behavior under the conditions of gas-liquid chromatography and reversed-phase high-performance liquid chromatography systems modified with α- and β-cyclodextrins

The dependence of retention and selectivity parameters of camphor enantiomers on the concentration of alpha- and beta-cyclodextrins were studied under conditions of GLC (matrix solvent: Glycerol, 95 degrees C) and RP-HPLC (matrix solvent: Aqueous methanolic, 20 degrees C). It has been found that beta-cyclodextrin forms complex of 1:1 stoichiometry and does not recognize enantiomers of camphor. In contrast alpha-CD forming complexes of 1:2 stoichiometry appeared to be very efficient chiral selector of (+) and (-)-camphor. Relatively considerable differences have been observed between stability constants determined by GLC and RP-HPLC, what may be explained by the various natures of the matrix solvents and the various temperatures of the measurements. On the contrary, the enantioseparation factor alpha observed at higher concentrations of alpha-cyclodextrin stabilizes on the very similar value alpha+/-(GLC) approximately = alpha-/+(HPLC) approximately = 1.6. Simple theoretical considerations focusing on the differences in the mechanisms of the studied processes have been performed. According to them the enantiomer forming the more stable complex with the cyclodextrin should be eluted from the RP-HPLC column first and GLC column last. This fact has been confirmed experimentally.

Resolution of chiral barbiturates into enantiomers by reversed-phase high-performance liquid chromatography using methylated β-cyclodextrins

The correlation between the capacity factors of enantiomers of chiral barbiturates and the concentrations of beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin and heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin dissolved in the mobile phase was studied using LiChrosorb RP-18 as the stationary phase. Owing to the very strong adsorption of permethylated beta-cyclodextrin on the ODS surface a chiral stationary phase is generated dynamically and forms complexes with the solutes; this mechanism has been found to be the only factor responsible for the chiral recognition of the investigated compounds at all applied concentrations. The inclusion of barbiturates in the cavities of permethylated beta-cyclodextrin involves a distinct and entirely new kind of enantioselectivity compared with that observed for beta-cyclodextrin and its dimethyl derivative. Using permethylated beta-cyclodextrin baseline resolutions have been obtained with barbiturates containing a chiral centre in the heterocyclic ring or in the aliphatic side-chain.

Joint use of cyclodextrin additives in chiral discrimination by reversed-phase high-performance liquid chromatography: temperature effects

The temperature dependence of chiral separations was investigated in combined system of reversed-phase (RP) liquid chromatography using two chiral additives: single α or β native cyclodextrins and their permethylated derivatives. The model tested compounds of pharmaceutical interest were: methylphenobarbital, mephenytoin, morsuximide and camphor. Taking the localization of a complexation process as a criterion – the combined system with two selectors has been rationalized as occurring in three stages. The influence of temperature (in narrow range of 20°C) on retention and enantioselectivity was studied in; System I (complexation occurs in the mobile phase), in System II (complexation on the stationary phase) and in System III (complexation in both phases together). In System III (as for System I) it has been found that the model compounds could be classified into three groups based on their retention dependence on temperature: retention decrease with temperature decrease, retention increase with temperature decrease or no influence of temperature on retention. For all the compounds investigated, decrease in temperature increases the selectivity. Standard enthalpy (ΔH0) and entropy (ΔS0) changes of solute transfer between the mobile and the stationary phase and standard enthalpy (ΔH0CD) and entropy (ΔS0CD) changes of complex formation were also calculated. In Systems I and III, if the complexation in the mobile phase is favored process compared with interaction with the stationary phases (RP or covered by permethylated cyclodextrin), the shortest retention time and the best selectivity is observed at low temperature.

New chromatographic method for the determination of the enantiomeric purity of terpenoic hydrocarbons

Abstract The application of a very selective chiral stationary phase (Celite coated with α-cyclodextrin in formamide solution) to gas—liquid chromatography is described. A new convenient method for determination of the enantiomeric purity of terpenoic hydrocarbons, e.g., α-pinene, β-pinene, cis-pinane, trans-pinane and 2-carene, based on complete chromatographic separation of the enantiomers, is presented.