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Herein, we describe the confinement of a N-Heterocyclic Carbene (NHC) organocatalyst in the cavity of cyclodextrins (CDs). These confined organocatalysts allow the formylation of amines through CO2 hydrosilylation. The presence of the cavity of the CDs leads to substrate-selectivity between amines in competition reactions. The use of the smallest α-CD induces the best selectivities but also to increased reactivity compared to the bigger β-CD. A careful study conducted by NMR and DFT revealed that in α-CD, the complexed CO2 interacts with the cavity through hydrogen bonds. These H-bonds destabilize the NHC-CO2 adduct and are accountable for the higher reactivity observed using α-CD., (© 2024 Wiley‐VCH GmbH.)

Enantioconvergent transformations from racemic mixtures are attractive since they allow the generation of optically active products with full conversion despite the possibly adverse kinetic resolution process. When dealing with gold(I)-catalyzed cycloisomerizations, chirality transfer from the precursor is another possible diverting pathway, which renders enantioconvergence challenging. Not surprisingly, enantioconvergent Au(I)-catalyzed processes have remained extremely rare. Herein we show that cavity-driven catalysis using β-cyclodextrin-NHC-Au(I) complexes brings opportunities to conduct highly enantioconvergent cycloisomerizations of 1,5-enynes, -enynols, and, -enynyl esters.

Ganglioside GM3 is one of the most common membrane-bound glycosphingolipids. The over-expression of GM3 on tumor cells makes it defined as a tumor-associated carbohydrate antigen (TACA). The specific expression property in cancers, especially in melanoma, make it become an important target to develop anticancer vaccines or immunotherapies. However, in the manner akin to most TACAs, GM3 is an autoantigen facing with problems of low immunogenicity and easily inducing immunotolerance, which means itself only cannot elicit a powerful enough immune response to prevent or treat cancer. With a comparative understanding of the mechanisms that how immune system responses to the carbohydrate vaccines, this review summarizes the studies on the recent efforts to development GM3-based anticancer vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Regioselective di-functionalization of a cyclodextrin allows hydrophobic domains to be directed in a geometrically controlled manner. This controlled orientation ultimately gives access to an original hierarchical assembly in the solid state. This assembly spans over three levels of hierarchy which are governed by synergistic host-guest inclusions, directed hydrophobic effect and hydrogen bonding. This combination of interactions precisely positioned in space through regioselective functionalization of a cyclodextrin creates a porous organic architecture., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

β-Cyclodextrin (β-CD) and derivatives are approved therapeutics in >30 clinical settings. β-CDs have also shown promise as therapeutics for treatment of some lysosomal storage disorders, such as Niemann-Pick disease type C, and other disease states which involve metabolite accumulation in the lysosome. In these cases, β-CD activity relies on transport to the lysosome, wherein it can bind hydrophobic substrate and effect extraction. The post-translational attachment of N-glycans terminated in mannose-6-phosphate (M6P) residues is the predominant method by which lysosomal enzymes are targeted to the lysosome. In this work we covalently attach a synthetic biantennary bis-M6P-terminated N-glycan to β-CD and study the effect of the added glycans in a mammalian cell line. The formation of a host guest complex with a Cy5 fluorophore allows study of both cellular internalisation and transport to the lysosome by fluorescence microscopy. Results indicate that the rates of both internalisation and lysosomal transport are increased by the attachment of M6P-glycans to β-CD, indicating that M6P-glycan conjugation may improve the therapeutic effectiveness of β-CD for the treatment of disorders involving hydrophobic metabolite accumulation in the lysosome., (© 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

The development of organometallic catalysis has greatly expanded the synthetic chemist toolbox compared to only exploiting "classical" organic chemistry. Although more widely used in organic solvents, metal-based catalysts have also emerged as efficient tools for developing organic transformations in water, thus paving the way for further development of bio-compatible reactions. However, performing metal-catalysed reactions within living cells or organisms induces additional constraints to the design of reactions and catalysts. In particular, metal complexes must exhibit good efficiency in complex aqueous media at low concentrations, good cell specificity, good cellular uptake and low toxicity. In this review, we focus on the presentation of discrete metal complexes that catalyse or photocatalyse reactions within living cells or living organisms. We describe the different reaction designs that have proved to be successful under these conditions, which involve very few metals (Ir, Pd, Ru, Pt, Cu, Au, and Fe) and range from in cellulo deprotection/decaging/activation of fluorophores, drugs, proteins and DNA to in cellulo synthesis of active molecules, and protein and organelle labelling. We also present developments in bio-compatible photo-activatable catalysts, which represent a very recent emerging area of research and some prospects in the field., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

In the last few years, nanomaterials based on fullerene have begun to be considered promising tools in the development of efficient adjuvant/delivery systems for vaccination, thanks to their several advantages such as biocompatibility, size, and easy preparation and modification. In this work we reported the chemoenzymatic synthesis of natural polymannan analogues (di- and tri-mannan oligosaccharides characterized by α1,6man and/or α1,2man motifs) endowed with an anomeric propargyl group. These sugar derivatives were submitted to 1,3 Huisgen dipolar cycloaddition with a malondiamide-based chain equipped with two azido terminal groups. The obtained sugar-modified malondiamide derivatives were used to functionalize the surface of Buckminster fullerene (C 60 ) in a highly controlled fashion, and yields (11-41%) higher than those so far reported by employing analogue linkers. The same strategy has been exploited to obtain C 60 endowed with natural and unnatural amino acid derivatives. Finally, the first double functionalization of fullerene with both sugar- and amino acid-modified malondiamide chains was successfully performed, paving the way to the possible derivatization of fullerenes with immunogenic sugars and more complex antigenic peptides.

Bis-azolium salts with one azolium capping a perbenzylated α-cyclodextrin have been designed to generate Janus-type bimetallic complexes with various combinations of copper, silver, gold or palladium salts. Encapsulation of one metal center inside the cavity allowed (trans)metalation and oxidation reactions to be controlled at selected positions. In particular, it was possible to oxidize Au I into Au III selectively on the position outside the cavity of the cyclodextrin on the bis-Au I Janus complex.

The encapsulation of guests in a confined space enables unusual conformations and reactivities. In particular, the compression of akyl chains has been obtained by self-assembled molecular capsules but such an effect has not been reported in solution for pseudorotaxane architectures. By exploiting the tendency of cyclodextrin (CD) to form head to head [3]pseudorotaxanes and the hydrogen bonding abilities of phosphate groups, we have studied the effect of the CD dimer cavity on the conformation of threaded α,ω-alkyl-diphosphate axles. The formation of [2]pseudorotaxanes and [3]pseudorotaxanes was investigated by a combination of NMR, ITC and X-ray diffraction techniques. In the solid state, the [3]pseudorotaxane with a C 8 axle presents a fully extended conformation with both terminal phosphate groups interacting with hydroxyl groups of the primary rim of CDs. Such hydrogen bonding interactions are also present with the C 9 and C 10 axles resulting in a compression of the alkyl chain with gauche conformations in the solid state. NMR studies have shown that this effect is maintained in solution resulting in a size-dependent progressive compression of the alkyl chain by the CD [3]pseudorotaxane architecture for C 9 , C 10 and C 11 axles., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A family of cyclodextrins functionalized with zero, one, two, or six amines was shown to control the rate of their threading and dethreading on a molecular axle depending on the pH and their substitution pattern. The originality of this system lies in the rate control of the switch by operating the stimulus directly on the macrocycle.

Mucopolysaccharidosis type IIIB is a devastating neurological disease caused by a lack of the lysosomal enzyme, α-N-acetylglucosaminidase (NAGLU), leading to a toxic accumulation of heparan sulfate. Herein we explored a pharmacological chaperone approach to enhance the residual activity of NAGLU in patient fibroblasts. Capitalizing on the three-dimensional structures of two modest homoiminosugar-based NAGLU inhibitors in complex with bacterial homolog of NAGLU, CpGH89, we have synthesized a library of 17 iminosugar C-glycosides mimicking N-acetyl-D-glucosamine and bearing various pseudo-anomeric substituents of both α- and β-configuration. Elaboration of the aglycon moiety results in low micromolar selective inhibitors of human recombinant NAGLU, but surprisingly it is the non-functionalized and wrongly configured β-homoiminosugar that was proved to act as the most promising pharmacological chaperone, promoting a 2.4 fold activity enhancement of mutant NAGLU at its optimal concentration., (© 2021 Wiley-VCH GmbH.)

What happens when a C-H bond is forced to interact with unpaired pairs of electrons at a positively charged metal? Such interactions can be considered as "contra-electrostatic" H-bonds, which combine the familiar orbital interaction pattern characteristic for the covalent contribution to the conventional H-bonding with an unusual contra-electrostatic component. While electrostatics is strongly stabilizing component in the conventional C-H⋅⋅⋅X bonds where X is an electronegative main group element, it is destabilizing in the C-H⋅⋅⋅M contacts when M is Au(I), Ag(I), or Cu(I) of NHC-M-Cl systems. Such remarkable C-H⋅⋅⋅M interaction became experimentally accessible within (α-ICyD Me )MCl, NHC-Metal complexes embedded into cyclodextrins. Computational analysis of the model systems suggests that the overall interaction energies are relatively insensitive to moderate variations in the directionality of interaction between a C-H bond and the metal center, indicating stereoelectronic promiscuity of fully filled set of d-orbitals. A combination of experimental and computational data demonstrates that metal encapsulation inside the cyclodextrin cavity forces the C-H bond to point toward the metal, and reveals a still attractive "contra-electrostatic" H-bonding interaction., (© 2021 Wiley-VCH GmbH.)

Cyclodextrin poly-functionalization has fueled progress in their use in multiple applications such as enzyme mimicry, but also in the polymer sciences, luminescence, as sensors or for biomedical applications. However, regioselective access to a given pattern of functions on β-cyclodextrin is still very limited. We uncover a new orienting group, the thioacetate, that expands the toolbox available for cyclodextrin poly-hetero-functionalization using diisobutylaluminum hydride (DIBAL-H) promoted debenzylation. The usefulness of this group is illustrated in the first synthesis of a precisely hepta-hetero-functionalized β-cyclodextrin. By way of comparison, a random hepta-functionalization would give 117655 different molecules. This synthesis is not simply the vain quest for the Holy Grail of CD hetero-functionalization, but it illustrates the versatility of the DIBAL-H oriented hetero-functionalization strategy, opening the way to a multitude of useful functionalization patterns for new practical applications., (© 2021 Wiley-VCH GmbH.)

Glycosphingolipids (GSLs) are ubiquitous components on animal cell membranes, and exposed on the outer surface. Various studies have demonstrated that they play key roles in cell proliferation, adhesion, motility and differentiation. Usually, the specific types of GSLs are expressed more highly in tumors than in normal tissues, which are known as tumorassociated antigens. It has been revealed that most tumor cells show altered GSLs patterns on their surface, abnormal GSLs signaling and biosynthesis, which together play a major role in tumor development. Tumor-associated GSL antigens have been used in the development of antitumor vaccines. There is no doubt that GSLs play a crucial role in tumor progression and would be a promising target for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)