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

Preparation of 6-Monohalo-β-cyclodextrin Derivatives with Selectively Methylated Rims via Diazonium Salts

Great cyclodextrin chemistry by Konstantin Lebedinskii and Jindřich Jindřich preparing a series of 6-monohalo (Cl, Br, and I) β-cyclodextrin derivatives with various types of methylations. This new method opens the way for preparing poorly investigated monofunctionalized selectively methylated cyclodextrins.

Preparation of 6-Monohalo-β-cyclodextrin Derivatives with Selectively Methylated Rims via Diazonium Salts | ACS Omega

Reversible Light-Induced Dimerization of Secondary Face Azobenzene-Functionalized β-Cyclodextrin Derivatives

Fantastic cyclodextrin chemistry by Carmen Ortiz Mellet, Jose Manuel Garcia Fernandez, and Francisco Mendicuti et al.
β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example.

See the full article here!

Functional group polarity-modulated formation of liquid crystals of amphiphilic cyclodextrins

Today’s cyclodextrin:
At CarboHyde, we also deal with amphiphilic CDs; this application from this Canadian collaboration caught my attention.
Pseudo-face-to-face symmetry in the native CDs represents a distinctive advantage to designing amphiphilic materials capable of self-assembly into liquid crystals. In this work, a new family of amphiphilic β-CD derivatives possessing 14 stearoyl chains (non-polar) and 7 functionalized tetraethylene glycols were synthesized using an improved design and more efficient chemistry, and the synthetic targets showed excellent ability to form stable hexagonal columnar mesophases. Studies of a lithium composite revealed fast local Li-ion exchange processes with very low activation energies, suggesting the benefit of using these materials as potential electrolytes for high ionic conductions. The results from this work can guide the design of future generations of CD-based LC materials for ion conduction.

University of Calgary – Austin Che, Simon Trudel-LachanceJayar EspejoChang-Chun Ling
University of Alberta – Diganta SarkarVladimir Michaelis
Simon Fraser University – Carson ZellmanVance Williams

See the full article here: Functional group polarity-modulated formation of liquid crystals of amphiphilic cyclodextrins

Well-Defined Heparin Mimetics Can Inhibit Binding of the Trimeric Spike of SARS-CoV-2 in a Length-Dependent Manner

Well-defined heparin mimetics that could inhibit the binding of the SARS-CoV-2 spike or RBD to immobilized heparin or to Vero E6 cells. The inhibitory potency increased with increasing chain length, and a compound composed of four sulfated hexasaccharides linked by triazoles had a similar potency as unfractionated heparin. The heparin mimetics exhibit no or reduced binding to antithrombin-III and platelet factor 4, respectively, which are associated with side effects.

Utrecht University – Roosmarijn van der WoudeRobert de Vries et al
The University of Georgia – Lin Liu et al

See the full article here

Cyclodextrin polymers functionalized with histidine and carcinine as chelating therapeutics for copper dyshomeostasis

Fascinating breaking application of cyclodextrin polymer proposed by Noemi Bognanni, Francesco Bellia and Graziella Vecchio from Università di Catania. Based on the features of cyclodextrins, they derivatized cross-linked cyclodextrin polymers with histidine or carcinine moieties and found that amylase enzymes do not hydrolyze cyclodextrin polymers. The new polymers can form copper(II) complexes and may act as nanochelators to counteract copper(II) dyshomeostasis-related diseases. Furthermore, the copper(II) complexes show superoxide dismutase activity, similar to free carcinine and histidine complexes. The antioxidant biological activity of the copper(II) complex formed in situ may protect cells from oxidative damage related to #copper dyshomeostasis.

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Templated Enzymatic Synthesis of δ-Cyclodextrin

Recently, I tried to summarize in a blog post, how CDs are made from starch. Although such technologies have been used for decades, there is room for improvement for some derivatives. Sophie Beeren, Andreas Erichsen and Günther Peters at DTU – Technical University of Denmark explore this room using bolaamphiphile templates to produce δ-CD with unprecedented yields in an enzyme-mediated dynamic combinatorial library of cyclodextrins. This technology can open a new and more efficient way to produce some native cyclodextrins. Or even derivatives

See the article here.

See the Cyclodextrin Tales: From Starch to Cyclodextrins: Understanding the Production Process

A cyclodextrin polymer as supramolecular matrix for scalable green photooxygenation of hydrophobic substrates in homogeneous phase

We are proud of the fruit of our most recent collaboration with Consiglio Nazionale delle Ricerche and Semmelweis University.

Complexation of the hydrophobic substrates within a hydrophilic cyclodextrin polymer allowed their photooxygenation in a homogeneous aqueous environment. These results hold great potential for the launch of CD polymers both as reaction vessels for green, homogeneous photocatalysis and as a drug delivery carrier of oxygen-releasing agents in tissues.

Marco Agnes, Arianna Mazza, Eszter KalydiSzabolcs BéniMilo MalangaIlse Manet

See the full article here.

Comparison of the Efficacy and Safety of Adamgammadex with Sugammadex for Reversal of Rocuronium-Induced Neuromuscular Block: Results of a Phase II Clinical Trial

The success of Sugammadex inspired several further cyclodextrin research, including the development of other antidotes and discovering “follow-up” compounds for the same indication. The most advanced candidate in this field is Adamgammadex (developed by Adamerck) with its efficacy recently compared to SGM in a Phase II trial lead by Sichuan University. Although it was used in 2-3 times higher concentrations, the previously reported adverse effects were not observed in this study, including anaphylaxis, haemorrhage, recurarization, abnormal basic vital signs, or lengthened QRS intervals and QT intervals. Adamgammadex was found to be effective for reversing rocuronium-induced neuromuscular block as sugammadex.

See the full article here