Mirror-image cyclodextrins

today’s cyclodextrin:
Do you often take a good look in the mirror?

Nobel laureate Sir Fraser Stoddard, Daniel W. Armstrong, and their team report the syntheses of three mirror-image CDs—namely, α-, β- and γ-L-CDs, which are composed of six, seven and eight α-1,4-linked L-glucopyranosyl residues, respectively.

The availability of L-CDs has enabled the elucidation of an unprecedented chiral self-sorting of a racemic modification of β-CDs in the solid state and an investigation of the chiral recognition of enantiomeric fenchone by α-L-CD. This research identifies a missing piece of the cyclodextrin jigsaw and sets the stage for scientists to explore the mirror-image world of naturally occurring CDs.

Mirror-image cyclodextrins | Nature Synthesis

Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs

We have a nice read to propose for the week-started coffee, the most recent work of Szabolcs Béni from our advisory board and András DohárszkyFejős IdaEszter Kalydi and Gergely Völgyi.
A comprehensive investigation of the stability of cathinone derivatives and their cyclodextrin complexes.

Molecules | Free Full-Text | Cyclodextrin-Enabled Enantioselective Complexation Study of Cathinone Analogs (mdpi.com)

Analysis of Peptides and Proteins by Native and SDS Capillary Gel Electrophoresis Coupled to Electrospray Ionization Mass Spectrometry via a Closed-Circuit Coaxial Sheath Flow Reactor Interface

today’s cyclodextrin:
CD-supported capillary gel electrophoresis analysis of proteins and peptides including SDS–protein complexes, by Dániel Sárközy and Andras Guttman from the University of Debrecen. Addition of γ-cyclodextrin to the sheath liquid efficiently removed the SDS content of the sample and the background electrolyte in the flow reactor section by inclusion complexation, while maintaining good separation efficiency and decreasing ion suppression.

See the full article here

Avoiding Interferences in Advance: Cyclodextrin Polymers to Enhance Selectivity in Extraction of Organic Micropollutants for Carbon Isotope Analysis

today’s cyclodextrin:
CDs in carbon isotope analysis
Compound-specific isotope analysis (CSIA) of organic water contaminants can provide important information about their sources and fate in the environment. Analyte enrichment from water remains nonetheless a critical yet inevitable step before measurement. Commercially available solid-phase extraction (SPE) sorbents are inherently nonselective leading to co-extraction of concurrent dissolved organic matter and in turn to analytical interferences, especially for low-occurring contaminants. Using cyclodextrin polymers (α-, β-, γ-CDP) as SPE sorbents (i) extraction selectivity was increased, (ii) their applicability to carbon isotope analysis for a selection of pesticides was assessed, and (iii) they were compared with commonly used commercial sorbents. Extraction with β-CDP significantly reduced backgrounds in gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and enhanced sensitivity by a factor of 7.5, which was further confirmed by lower carbon-normalized CDOM/Canalyte ratios in corresponding extracts as derived from dissolved organic carbon (DOC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The present study highlights the benefit of selecting innovative extraction sorbents to avoid interferences in advance. This strategy in combination with existing cleanup approaches offers new prospects for CSIA at field concentrations of tens to hundreds of nanograms per liter.

Martin Elsner and Rani Bakkour et al

See the full article here

The electrochemical quantitation method for sugammadex via a molecularly imprinted polymer-based sensor

Sugammadex (SUG) is a synthetically modified γ-cyclodextrin derivative used in hospitals after surgeries to reverse the neuromuscular blockade induced by rocuronium or vecuronium. Who has experience in the field knows that analysis (in particular those human samples) of carbohydrates and cyclodextrin are very challenging.
In this study, Ankara University and DEVA Holding A.Ş. present the first electroanalytical quantification method for sugammadex by using molecular imprinting (MIP) via the electropolymerization (EP) technique. An EP-MIP film was formed by EP on a screen-printed gold electrode (SPAuE) and a new electrochemical sensor, EP-MIP(SUG)/SPAuE, was fabricated using the 4-aminophenol monomer with copper ions to enhance the MIP-binding site. Surface and electrochemical characterization of the EP-MIP(SUG)/SPAuE sensor have been done via scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). The specificity/selectivity of the developed sensor has been shown by using common interferents found in the biological fluids and also molecules having similar structures, such as α-cyclodextrin, β-cyclodextrin, and γ-cyclodextrin. As a result, a quantitative analysis method has been developed and validated by using the EP-MIP(SUG)/SPAuE sensor in the concentration range of 0.1–1.0 pM with very high sensitivity (limit of detection: 27.3 fM). The applicability of the method has been shown for bulk drug substances, pharmaceutical dosage forms, and commercial serum samples.

See the full article here

Effect of Substitution Degree and Homogeneity on Cyclodextrin-Ligand Complex Stability: Comparison of Fenbufen and Fenoprofen Using CD and NMR Spectroscopy

today’s cyclodextrin:
is a rarely applied analytical technique for the analysis of CD-complexes: circular dichroism, presented by the group at Semmelweis University where I got my PhD, so close to my heart.
The stability of host–guest complexes of two NSAID drugs with similar physicochemical properties, fenbufen and fenoprofen, was investigated by comparing induced circular dichroism and 1H nuclear magnetic resonance methods using eight cyclodextrins of different degrees of substitution and isomeric purity as guest compounds. These cyclodextrins include native β-cyclodextrin (BCyD), 2,6-dimethyl-β-cyclodextrin 50 (DIMEB50), 80 (DIMEB80) and 95% (DIMEB95) isomerically pure versions, low-methylated CRYSMEB, randomly methylated β-cyclodextrin (RAMEB) and 4.5 and 6.3 average substitution grade hydroxypropyl-β-cyclodextrin (HPBCyD). The stability constants obtained by the two methods show good agreement in most cases. For fenbufen complexes, there is a clear trend that the stability constant increases with the degree of substitution, while isomer purity has a smaller effect on the magnitude of stability constants.
Mazákné Dr. Kraszni MártaFerenc AghDaniel HorvathArash MirzahosseiniHorváth Péter

See the full article here: Effect of Substitution Degree and Homogeneity on Cyclodextrin-Ligand Complex Stability: Comparison of Fenbufen and Fenoprofen Using CD and NMR Spectroscopy


today’s cyclodextrin:
if you wish to learn more about the role of CD’s in chiral analysis and enantioseparation, this recent book chapter is for you:
Chiral Separations and Stereochemical Elucidation – Cyclodextrins
This chapter focuses on CDs in separation sciences covering also fundamental aspects including chiral recognition mechanisms as well as the use of CDs in the major separation technologies including gas chromatography, thin-layer chromatography, high-performance liquid chromatography, supercritical fluid chromatography, and capillary electrophoresis.
#analysis #analyticalchemistry
Gerhard Scriba, Dr. Mari-luiza KonjariaDr. Sulaiman Krait

See this book chapter here: Cyclodextrins

Investigation of 2-Hydroxypropyl-β-Cyclodextrin Treatment in a Neuronal-Like Cell Model of Niemann–Pick Type C Using Quantitative Proteomics

There are multiple challenges in developing carbohydrate/cyclodextrin-based drugs that we also face at CarboHyde every day. One is to develop proper analytical techniques, which are especially difficult for biological samples and if the drug is not a single compound but a mixture of components (just like HP-b-CD used in Niemann-Pick C). While HP-b-CD has been promising in vitro and in vivo, a clear understanding of the mechanism(s) of action is lacking.
That being said, we particularly welcome the study disclosing method for a large-scale mass-spectrometry-based proteomic study to evaluate proteome changes upon treatment with these small molecules. Investigation of HP-b-CD treatment was performed where we observe that, although HP-b-CD reduces cholesterol storage, levels of NPC1 and NPC2 are not normalized to control levels. The following changes in the proteome suggest that HP-b-CD promotes exocytosis in this neuron-like model. Utilizing state-of-the-art mass spectrometry analysis, these data demonstrate newly reported changes with pharmacological perturbations related to NPC disease and provide insight into the mechanisms of HP-b-CD as a potential therapeutic.
Antony Cougnoux, (Karolinska Institutet), Melissa Pergande, Fidel Serna-Perez, and Stephanie Cologna (University of Illinois Chicago)

See the full article here: Investigation of 2-Hydroxypropyl-β-Cyclodextrin Treatment in a Neuronal-Like Cell Model of Niemann–Pick Type C Using Quantitative Proteomics