Water-insoluble β-cyclodextrin–epichlorohydrin polymers for removal of pollutants from aqueous solutions by sorption processes using batch studies: A review of inclusion mechanisms

Evolution of Cyclodextrin Nanosponges.

The stereoselective recognition of chiral molecules is an important aspect in nature as the basis of the interaction of chiral bioactive compounds with their target structures. In separation sciences such as chromatographic and capillary electromigration techniques, the formation of transient diastereomeric complexes between chiral analytes and chiral selectors via hydrogen and halogen bonds, ionic, ion-dipole, dipole-dipole, van der Waals as well as π-π interactions is the basis for chiral separations. Spectroscopic techniques, especially nuclear magnetic resonance spectroscopy, as well as molecular modeling and molecular dynamics simulations have contributed to the understanding of the structure of the diastereomeric complexes, complexation thermodanymics and the visualization of their structures. As part 1, the present review highlights contributions to the understanding of the enantiorecognition mechanisms of polysaccharide as well as cyclodextrin chiral selectors published between 2016 and mid 2019.

Chiral recognition in separation sciences. Part I: Polysaccharide and cyclodextrin selectors

This report covers advances in capillary electrophoresis (CE) from January 2018 through September 2019. A summary of the literature during this time period is insightful. A search performed using the SciFinder Scholar database for journal reports (limited to English) using the term capillary electrophoresis returned approximately 1,800 publications. Further analysis of this list provided a snapshot of activity in biomolecular research. Classes of biomolecules most frequently associated with CE publications were proteins, drugs, DNA and metabolites. Another measure of the impact of CE is the translation of this technology into society. A search of patent activity illustrating this process of CE technology transfer returned 346 patents published in all languages, with a substantial contribution reported only in Chinese (198 patents) or English (98 patents). Established applications of CE continued to serve as the gold standard for molecular separations providing analytical assays, enantiomeric resolution a...

Challenging Bioanalyses with Capillary Electrophoresis.

Cyclodextrins are natural oligosaccharides obtained from starch. They were discovered in 1891 by Villiers, and attracted major scientific and industrial interests from the late 1970s. Actually, cyclodextrins are among the most remarkable macrocyclic molecules with major theoretical and practical interest for chemistry and biology. Cyclodextrins belong to the family of cage molecules due to their structure, which is composed of a hydrophobic cavity that can encapsulate other molecules. Indeed, the most characteristic feature of cyclodextrins is their ability to form inclusion complexes with various molecules through host-guest interactions. Cyclodextrins and their derivatives have a wide variety of practical applications including pharmacy, medicine, foods, cosmetics, toiletries, catalysis, chromatography, biotechnology, nanotechnology, and textile production. Cyclodextrins are also the object of numerous fundamental studies. Between 2011 and 2015, 18,430 cyclodextrin-related publications have been published. In this chapter, after a brief description of cyclodextrin basics, we highlight selected works on cyclodextrins published over the last 5 years by various research groups.

Fundamentals and Applications of Cyclodextrins

The fluorescent tagging of cyclodextrin derivatives enlarges their spectroscopic properties thus generating chemosensors, biological tools for visualization and sophisticated photoresponsive devices. Cyclodextrin polymers, due to the cooperative interactions, exhibit additional properties compared to their monomeric counterpart. These macromolecules can be prepared either in well water-soluble form or as gels of high swelling. Two versatile synthetic strategies for introducing a fluorescent tag (rhodamine, fluorescein, nitrobenzofuran or coumarin) into the water-soluble epichlorohydrin branched cyclodextrin polymers were worked out and compared. The fluorescent labeling was realized in three steps: 1) building in azido moieties, 2) transforming the azido groups into amino groups and 3) coupling the proper fluorescent compound to the amino groups. The other strategy started by functionalization of the monomer prior to the branching. Either the fluorescent-labeled monomer or the intermediate azido derivative of the monomer was branched. Further tuning of the properties of the polymer was achieved via branching of the methylated cyclodextrin derivative. The key intermediates and the fluorescent final products were characterized by various spectroscopic techniques and capillary electrophoresis. The applied synthetic routes were evaluated based on the molecular weight, cyclodextrin content of the products and the efficiency of labeling.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-10-319.pdf

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers.

Xanthene dyes can be appended to cyclodextrins via an ester or amide bridge in order to switch the fluorescence on or off. This is made possible through the formation of nonfluorescent lactones or lactams as the fluorophore can reversibly cyclize. In this context we report a green approach for the synthesis of switchable xanthene-dye-appended cyclodextrins based on the coupling agent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). By using 6-monoamino-β-cyclodextrin and commercially available inexpensive dyes, we prepared rhodamine- and fluorescein-appended cyclodextrins. The compounds were characterized by NMR and IR spectroscopy and MS spectrometry, their UV–vis spectra were recorded at various pH, and their purity was determined by capillary electrophoresis. Two potential models for the supramolecular assembly of the xanthene-dye-appended cyclodextrins were developed based on the set of data collected by the extensive NMR characterization.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-12-53.pdf

New synthetic strategies for xanthene-dye-appended cyclodextrins

The exhaustive primary-side alkylation of cyclodextrins has never been achieved directly. The undesired and simultaneous derivatization of the secondary hydroxyl moieties generates intricate isomeric mixtures that are challenging to purify, analyse and characterize. The aim of this study was to develop a chromatography-free and up-scalable strategy towards the preparation of per-6-O-methylated cyclodextrin and to test the compound as potential chiral selector. The target molecule was prepared according to a five-step synthesis by using methyltriphenylphosphonium bromide as catalyst under heterogeneous conditions. The removal of benzyl moieties, used as temporary secondary-side protecting groups, was attained by applying hydrazine-carbonate in the presence of Pd/C. All the intermediates were obtained in high yields, thoroughly characterized and their purity was assessed by ad-hoc developed HPLC methods. The per-6-O-methylated β-cyclodextrin showed promising chiral recognition ability as background electrolyte additive in cyclodextrin-modified capillary electrophoresis using the recreational drug methylene-dioxypyrovalerone as model compound. Additionally, a model for the inclusion geometry between the single isomer host and the selected drug was developed based on the extensive 2D NMR analysis. The versatility of the proposed synthetic strategy opens the way to the industrial production of homogeneously primary-alkylated cyclodextrins and to their wide application in chiral separation of various drugs.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/elps.201900065

Synthesis of the chiral selector heptakis(6-O-methyl)-β-cyclodextrin by phase-transfer catalysis and hydrazine-mediated transfer-hydrogenation

The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physicochemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6A,6X-ditosyl-β-CDs afforded hetero-difunctionalized 6A-monoazido-6X-tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6A,6X-ditosyl-, 6A,6X-diazido- and 6A-monoazido-6X-monotosyl-β-CD were prepared in one or two steps and purified in multigram scale thus opening the way towards further selective and orthogonal functionalizations of β-CD hosts.

https://www.beilstein-journals.org/bjoc/content/pdf/1860-5397-15-66.pdf

Mihály Bálint

Papers

Synthetic strategies for the fluorescent labeling of epichlorohydrin-branched cyclodextrin polymers.

New synthetic strategies for xanthene-dye-appended cyclodextrins

Synthesis of the chiral selector heptakis(6-O-methyl)-β-cyclodextrin by phase-transfer catalysis and hydrazine-mediated transfer-hydrogenation

Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry