Julianna Szemán

Cyclodextrins in Analytical Chemistry: Host–Guest Type Molecular Recognition

Cyclodextrins are utilized in many diverse fields of analytical chemistry, due to their propensity to form reversible inclusion complexes and recognize analytes selectively. This Feature shows how these nanocavities can serve analysts in sample preparation, sensitivity and selectivity improvement, enantio-separation, creating single-molecule sensors, and automatizing DNA sequencing.

Effect of the degree of substitution of cyclodextrin derivatives on chiral separations by high-performance liquid chromatography and capillary electrophoresis

Optical isomers of some basic racemic drugs (oxprenolol, AMEBD, ephedrine) were separated by high-performance liquid chromatography (HPLC) and/or capillary electrophoresis (CE) using carboxymethyl-beta-cyclodextrin (CMBCD) with various degree of substitution (DS). The effects of the separation conditions (pH, concentration and DS of CMBCD) were studied and compared using CE and HPLC. The degree of substitution had a significant effect on the resolution of the optical isomers and the ionic strength of the separation media, hence the use of well characterized CD derivatives is crucial. Different optimum DS values for the same test samples were obtained when HPLC or CE was used.

Fatty acid-cyclodextrin complexes: Properties and applications

The complexation of fatty acids (both saturated and unsaturated) with various cyclodextrins and cyclodextrin derivatives greatly modifies their properties. Inclusion complex formation — depending upon the type of host cyclodextrin — may result in protection against the environment, in improved water solubility and bioavailability. Thus lipid complexation enables the preparation of more reliable diagnostic reagents, better chromatographic separations and higher yields in biotechnological processes. The relevant literature is reviewed with particular emphasis on the practical utility of the molecular encapsulation of fatty acids with cyclodextrins.

Water Soluble Cyclodextrin Polymers: Their Interaction with Drugs

The complex forming ability of a water-soluble β-cyclodextrin epichlorohydrin, polymer (CDPS) and its different molecular weight fractions was studied and compared with the complexing properties of β-cyclodextrin (βCD) and dimethyl-βCD (DM-βCD). CDPS was separated into two main fractions. CDPS and its fractions formed well soluble inclusion compounds with the studied drugs. The low molecular weight fraction formed rather stable complexes with small guest molecules, the high molecular weight fraction was found to be more efficient in binding larger substrates. Structural studies of furosemide-CD complexes were attempted by NMR spectroscopy.

Enantiomeric separation of antimalarial drugs by capillary electrophoresis using neutral and negatively charged cyclodextrins

Capillary electrophoresis (CE) methods for chiral resolution of five antimalarial drugs (primaquine, tafenoquine, mefloquine, chloroquine and quinacrine) were developed by using a wide selection of neutral and anionic cyclodextrin (CD) derivatives. The use of sulfobutyl-β-CD and carboxymethyl-β-CD (CMBCD) resulted in good resolution of quinacrine and tafenoquine, respectively. New results are presented for resolutions of chloroquine and mefloquine. Application of carboxyalkyl- and sulfobutyl-CD derivatives provided improved resolution for primaquine. The impurity in primaquine sample detected by CE was identified as quinocide by MS and NMR. CMBCD provided not only the best separation of primaquine from quinocide but also the simultaneous complete resolution of both compounds.

Systematic approach to cost- and time-effective method development with a starter kit for chiral separations by capillary electrophoresis☆

Abstract In capillary electrophoresis, the use of cyclodextrins (CDs) as additive in the background electrolyte plays a very important role in achieving enantiomeric resolution. The wide range of available CD derivatives contained in commercial kits provides several possibilities for method development (LC·GC Int., 9 (1996) 88. [1]). The advantage of the large selection of CD derivatives and the application guidelines provided by the kits make method development versatile. A disadvantage, however, is often the difficulty at the starting point to choose which CD or modified CD to use. Most of the guidelines suggest complicated multistep selection methods assuming that all information about the analyte is available. In this paper the Elphodextrin starter kit from Cyclolab, Hungary has been evaluated. An easy, step-by-step protocol is developed to speed up the CD selection procedure and the analytical method development, even if the character of the analyte is unknown. The applicability of the Elphodextrin starter kit for the separation of neutral, acidic and basic enantiomers is demonstrated.

Efficacy and ototoxicity of different cyclodextrins in Niemann–Pick C disease

Niemann–Pick type C (NPC) disease is a fatal, neurodegenerative, lysosomal storage disorder characterized by intracellular accumulation of unesterified cholesterol (UC) and other lipids. While its mechanism of action remains unresolved, administration of 2‐hydroxypropyl‐β‐cyclodextrin (HPβCD) has provided the greatest disease amelioration in animal models but is ototoxic. We evaluated other cyclodextrins (CDs) for treatment outcome and chemical interaction with disease‐relevant substrates that could pertain to mechanism.

Chiral separation by a monofunctionalized cyclodextrin derivative: From selector to permethyl-β-cyclodextrin bonded stationary phase

Preparation of (6-monoureido-6-monodeoxy) permethylated beta-cyclodextrin bonded chiral stationary phase from permethylated 6-monoamino-6-monodeoxy-beta-cyclodextrin is described. The optimized chiral stationary phase was evaluated by using HPLC separation of racemates of coumarin derivatives. Column characterization was performed by solid-state (13)C, (15)N, (29)Si NMR using cross-polarization at the magic angle spinning. The development process was supported by CE experiments where the complex formation between cyclodextrins and warfarin was investigated. The results demonstrate good enantio-discrimination for coumarin derivatives.

“Back to the Future”: A New Look at Hydroxypropyl Beta-Cyclodextrins

Since the discovery about 30 years ago (2-hydroxypropyl) beta-cyclodextrin, a highly soluble derivative of beta-cyclodextrin, has become an approved excipient of drug formulations included both in the United States and European Pharmacopoeias. It is recommended to use as solubilizer and stabilizer for oral and parenteral formulations. Recently, its pharmacological activity has been recognized in various diseases. The increasing applications require a closer look to the structure-activity relationship. As (2-hydroxypropyl) beta-cyclodextrin (HPBCD) is always a mixture of isomers with various degrees and pattern of hydroxypropylation, no wonder that the products of different manufacturers are often different. Several HPBCDs were compared applying a battery of analytical tools including thin layer chromatography, high performance liquid chromatography (HPLC), HPLC-mass spectrometry (MS), and matrix-assisted laser desorption MS. We studied how the average degree of substitution affects the aggregation behavior, the toxicity, and the solubilizing effect on poorly soluble drugs. We found that the products with low average degree of substitution are more prone to aggregation. The samples studied are nontoxic to Caco-2 cells and have low hemolytic activity. The solubility enhancement of poorly soluble drugs decreases or increases with increasing degree of substitution or shows a maximum curve depending on the properties of the guest.

Ruggedness of enantiomeric separation by capillary electrophoresis and high-performance liquid chromatography with methylated cyclodextrins as chiral selectors

Abstract When applying cyclodextrin (CD) derivatives as chiral selectors for enantiomeric separation in different separation methods, the difference in degree of substitution (DS) and substitution pattern of the CD derivative may lead to complications. Seven different methylated β-cyclodextrin derivatives were tested as additives in the background electrolyte in capillary electrophoresis (CE) and as an additive to the mobile phase in high-performance liquid chromatography (HPLC). The substitution patterns of heptakis(2,6-di-O-methyl)-β-CD (DIMEB) and randomly methylated β-CD samples were compared using a simple thin-layer chromatography method. The CE method was sensitive to the quality of the chiral selector and it was solute dependent. While the enantiomeric separation of N-methylephedrine and terbutaline was excellent with all DIMEBs, in the case of hexobarbital, the separation failed with one DIMEB sample. The HPLC method was less sensitive to the quality of the chiral selector than the CE method.