Hypervalent Iodine Compounds in Carbohydrate Chemistry: Glycosylation, Functionalization and Oxidation.

This mini review article provides an overview on the use of hypervalent iodine compounds (HICs) in carbohydrate synthesis, focusing on their chemistry and recent applications. HICs are similar to transition metals in their reactivity but have the added benefit of being environmentally benign, and are therefore commonly used as selective oxidants and eco-friendly reagents in organic synthesis. Herein, we summarize various synthetic uses of hypervalent iodine reagents in reactions such as glycosylation, oxidations, functionalization, and C-C bond-forming reactions. The goal of this review is to illustrate the advantages and versatility of using HICs as an environmentally sustainable alternative to heavy metals in carbohydrate chemistry.

Diphosphine Bioconjugates via Pt(0)-Catalyzed Hydrophosphination. A Versatile Chelator Platform for Technetium-99m and Rhenium-188 Radiolabeling of Biomolecules.

The ability to append targeting biomolecules to chelators that efficiently coordinate to the diagnostic imaging radionuclide, 99mTc, and the therapeutic radionuclide, 188Re, can potentially enable receptor-targeted "theranostic" treatment of disease. Here we show that Pt(0)-catalyzed hydrophosphination reactions are well-suited to the derivatization of diphosphines with biomolecular moieties enabling the efficient synthesis of ligands of the type Ph2PCH2CH2P(CH2CH2-Glc)2 (L, where Glc = a glucose moiety) using the readily accessible Ph2PCH2CH2PH2 and acryl derivatives. It is shown that hydrophosphination of an acrylate derivative of a deprotected glucose can be carried out in aqueous media. Furthermore, the resulting glucose-chelator conjugates can be radiolabeled with either 99mTc(V) or 188Re(V) in high radiochemical yields (>95%), to furnish separable mixtures of cis- and trans-[M(O)2L2]+ (M = Tc, Re). Single photon emission computed tomography (SPECT) imaging and ex vivo biodistribution in healthy mice show that each isomer possesses favorable pharmacokinetic properties, with rapid clearance from blood circulation via a renal pathway. Both cis-[99mTc(O)2L2]+ and trans-[99mTc(O)2L2]+ exhibit high stability in serum. This new class of functionalized diphosphine chelators has the potential to provide access to receptor-targeted dual diagnostic/therapeutic pairs of radiopharmaceutical agents, for molecular 99mTc SPECT imaging and 188Re systemic radiotherapy.

Carbon-based glyco-nanoplatforms: towards the next generation of glycan-based multivalent probes.

Cell surface carbohydrates mediate a wide range of carbohydrate-protein interactions key to healthy and disease mechanisms. Many of such interactions are multivalent in nature and in order to study these processes at a molecular level, many glycan-presenting platforms have been developed over the years. Among those, carbon nanoforms such as graphene and their derivatives, carbon nanotubes, carbon dots and fullerenes, have become very attractive as biocompatible platforms that can mimic the multivalent presentation of biologically relevant glycosides. The most recent examples of carbon-based nanoplatforms and their applications developed over the last few years to study carbohydrate-mediate interactions in the context of cancer, bacterial and viral infections, among others, are highlighted in this review.

Accurate Determination of Hubble Attenuation and Amplification in Expanding and Contracting Cold-Atom Universes.

In the expanding universe, relativistic scalar fields are thought to be attenuated by "Hubble friction," which results from the dilation of the underlying spacetime metric. By contrast, in a contracting universe this pseudofriction would lead to amplification. Here, we experimentally measure, with fivefold better accuracy, both Hubble attenuation and amplification in expanding and contracting toroidally shaped Bose-Einstein condensates, in which phonons are analogous to cosmological scalar fields. We find that the observed attenuation or amplification depends on the temporal phase of the phonon field, which is only possible for nonadiabatic dynamics. The measured strength of the Hubble friction disagrees with recent theory [Gomez Llorente et al., Phys. Rev. A 100, 043613 (2019)PLRAAN2469-992610.1103/PhysRevA.100.043613 and Eckel et al., SciPost Phys. 10, 64 (2021)SPCHCW2542-465310.21468/SciPostPhys.10.3.064].

Structure-activity relationship studies on divalent naphthalene diimide G quadruplex ligands with anticancer and antiparasitic activity.

Naphthalene diimide (NDI) is a central scaffold that has been commonly used in the design of G-quadruplex (G4) ligands. Previous work revealed notable anticancer activity of a disubstituted N-methylpiperazine propyl NDI G4 ligand. Here, we explored structure-activity relationship studies around ligand bis-N,N-2,7-(3-(4-methylpiperazin-1-yl)propyl)-1,4,5,8-naphthalenetetracarboxylic diimide, maintaining the central NDI core whilst modifying the spacer and the nature of the cationic groups. We prepared new disubstituted NDI derivatives of the original compound and examined their in vitro antiproliferative and antiparasitic activity. Several N-methylpiperazine propyl NDIs showed sub-micromolar activity against Trypanosoma brucei and Leishmania major parasites with up to 30 fold selectivity versus MRC-5 cells. The best compound was a dimorpholino NDI with an IC50 of 0.17 µM against T.brucei and 40 fold selectivity versus MRC-5 cells. However, no clear correlation between G4 binding of the new NDI derivatives and antiproliferative or antiparasitic activity was observed, indicating that other mechanisms of action may be responsible for the observed biological activity.

Photosynthesis and crop productivity are enhanced by glucose-functionalised carbon dots.

From global food security to textile production and biofuels, the demands currently made on plant photosynthetic productivity will continue to increase. Enhancing photosynthesis using designer, green and sustainable materials offers an attractive alternative to current genetic-based strategies and promising work with nanomaterials has recently started to emerge. Here we describe the in planta use of carbon-based nanoparticles produced by low-cost renewable routes that are bioavailable to mature plants. Uptake of these functionalised nanoparticles directly from the soil improves photosynthesis and also increases crop production. We show for the first time that glucose functionalisation enhances nanoparticle uptake, photoprotection and pigment production, unlocking enhanced yields. This was demonstrated in Triticum aestivum 'Apogee' (dwarf bread wheat) and resulted in an 18% increase in grain yield. This establishes the viability of a functional nanomaterial to augment photosynthesis as a route to increased crop productivity.

Imide Condensation as a Strategy for the Synthesis of Core-Diversified G-Quadruplex Ligands with Anticancer and Antiparasitic Activity*.

A facile imide coupling strategy for the one-step preparation of G-quadruplex ligands with varied core chemistries is described. The G-quadruplex stabilization of a library of nine compounds was examined using FRET melting experiments, and CD, UV-Vis, fluorescence and NMR titrations, identifying several compounds that were capable of stabilizing G-quadruplex DNA with interesting selectivity profiles. The best G4 ligand was identified as compound 3, which was based on a perylene scaffold and exhibited 40-fold selectivity for a telomeric G-quadruplex over duplex DNA. Surprisingly, a tetra-substituted flexible core, compound 11, also exhibited selective stabilization of G4 DNA over duplex DNA. The anticancer and antiparasitic activity of the library was also examined, with the lead compound 3 exhibiting nanomolar inhibition of Trypanosoma brucei with 78-fold selectivity over MRC5 cells. The cellular localization of this compound was also studied via fluorescence microscopy. We found that uptake was time dependant, with localization outside the nucleus and kinetoplast that could be due to strong fluorescence quenching in the presence of small amounts of DNA.

A promiscuous glycosyltransferase generates poly-ß-1,4-glucan derivatives that facilitate mass spectrometry-based detection of cellulolytic enzymes.

Promiscuous activity of a glycosyltransferase was exploited to polymerise glucose from UDP-glucose via the generation of ß-1,4-glycosidic linkages. The biocatalyst was incorporated into biocatalytic cascades and chemo-enzymatic strategies to synthesise cello-oligosaccharides with tailored functionalities on a scale suitable for employment in mass spectrometry-based assays. The resulting glycan structures enabled reporting of the activity and selectivity of celluloltic enzymes.

A Vibration-Induced-Emission-Based Fluorescent Chemosensor for the Selective and Visual Recognition of Glucose.

The development of chemosensors to detect analytes in biologically relevant solutions is a challenging task. We report the synthesis of a fluorescent receptor that combines vibration-induced emission (VIE) and dynamic covalent chemistry for the detection of glucose in aqueous media. We show that the bis-2-(N-methylaminomethyl)phenylboronic acid-decorated N,N'-diphenyl-dihydrodibenzo[a,c]phenazine (DPAC) receptor 1 can detect glucose and discriminate between closely related monosaccharides including those commonly found in blood. Preliminary studies suggest monosaccharides bind to the DPAC-receptor with a 1:1 stoichiometry to produce pseudomacrocyclic complexes, which in turn leads to distinct optical changes in the fluorescent emission of the receptor for each host. Moreover, the complexation-induced change in emission can be detected visually and quantified in a ratiometric way. Our results highlight the potential of VIE-type receptors for the quantitative determination of saccharides in biological samples.

Stiff-Stilbene Ligands Target G-Quadruplex DNA and Exhibit Selective Anticancer and Antiparasitic Activity.

G-quadruplex nucleic acid structures have long been studied as anticancer targets whilst their potential in antiparasitic therapy has only recently been recognized and barely explored. Herein, we report the synthesis, biophysical characterization, and in vitro screening of a series of stiff-stilbene G4 binding ligands featuring different electronics, side-chain chemistries, and molecular geometries. The ligands display selectivity for G4 DNA over duplex DNA and exhibit nanomolar toxicity against Trypasanoma brucei and HeLa cancer cells whilst remaining up to two orders of magnitude less toxic to non-tumoral mammalian cell line MRC-5. Our study demonstrates that stiff-stilbenes show exciting potential as the basis of selective anticancer and antiparasitic therapies. To achieve the most efficient G4 recognition the scaffold must possess the optimal electronics, substitution pattern and correct molecular configuration.

Conformationally Constrained Glycosyl Donors as Tools to Control Glycosylation Outcomes.

The stereoselective synthesis of oligosaccharides remains one of the biggest challenges in carbohydrate chemistry. Many factors, including reaction conditions and the type of glycosyl donor and acceptor used, can affect the outcome of glycosylation reactions. In this Perspective, we discuss methods aimed to control the reactivity and stereoselectivity of glycosylation reactions using conformationally constrained glycosyl donors, with a focus on more recently developed chemistry.

Stereoselective Synthesis of Iminosugar 2-Deoxy(thio)glycosides from Bicyclic Iminoglycal Carbamates Promoted by Cerium(IV) Ammonium Nitrate and Cooperative Brønsted Acid-Type Organocatalysis.

The first examples of iminosugar-type 2-deoxy(thio)glycoside mimetics are reported. The key step is the activation of a bicyclic iminoglycal carbamate to generate a highly reactive acyliminium cation. Cerium(IV) ammonium nitrate efficiently promoted the formation of 2-deoxy S-glycosides in the presence of thiols, probably by in situ generation of catalytic HNO3, with complete α-stereoselectivity. Cooperative phosphoric acid/Schreiner's thiourea organocatalysis proved better suited for generating 2-deoxy O-glycosides, significantly broadening the scope of the approach.

Pseudo-enantiomeric carbohydrate-based N-heterocyclic carbenes as promising chiral ligands for enantiotopic discrimination.

The practical synthesis of carbohydrate-based NHC-Rh complexes bearing C1 or C3 sterically differentiated positions, accessed by glycosylation or SNAr strategies, is reported. These catalysts exhibit pseudo-enantiomeric behaviour in the hydrosilylation of acetophenone. We show that steric bulk at C1 gives preference for (S)-phenyl-1-ethanol, while bulk at C3 leads to the (R)-enantiomer. These results represent the first example of pseudo-enantiomeric carbohydrate-based NHC ligands leading to enantiotopic discrimination.

Biochemical characterisation of an α1,4 galactosyltransferase from Neisseria weaveri for the synthesis of α1,4-linked galactosides.

The human cell surface trisaccharide motifs globotriose and P1 antigen play key roles in infections by pathogenic bacteria, which makes them important synthetic targets as antibacterial agents. Enzymatic strategies to install the terminal α1,4-galactosidic linkage are very attractive but have only been demonstrated for a limited set of analogues. Herein, a new bacterial α1,4 galactosyltransferase from N. weaveri was cloned and produced recombinantly in E. coli BL21 (DE3) cells, followed by investigation of its substrate specificity. We demonstrate that the enzyme can tolerate galactosamine (GalN) and also 6-deoxygalactose and 6-deoxy-6-fluorogalactose as donors, and lactose and N-acetyllactosamine as acceptors, leading directly to analogues of Gb3 and P1 that are valuable chemical probes and showcase how biocatalysis can provide fast access to a number of unnatural carbohydrate analogues.

Methods for 2-Deoxyglycoside Synthesis.

Deoxy-sugars often play a critical role in modulating the potency of many bioactive natural products. Accordingly, there has been sustained interest in methods for their synthesis over the past several decades. The focus of much of this work has been on developing new glycosylation reactions that permit the mild and selective construction of deoxyglycosides. This Review covers classical approaches to deoxyglycoside synthesis, as well as more recently developed chemistry that aims to control the selectivity of the reaction through rational design of the promoter. Where relevant, the application of this chemistry to natural product synthesis will also be described.

Bioremediation of emerging micropollutants in irrigation water. The alternative of microalgae-based treatments.

The present study evaluated the efficiency of a semi-closed horizontal tubular photobioreactor (PBR) at demonstrative scale to remove a total of 35 target compounds, including benzotriazoles, benzophenones, antibiotics and different pharmaceuticals present in irrigation water in a peri-urban rural area. This water run through an open channel and was a mixture of reclaimed wastewater from a nearby wastewater treatment plant (WWTP) and run-off from the different agricultural fields in the area. Most of the compounds studied are usually not fully eliminated during conventional wastewater treatment, which justifies the need to investigate alternative treatment strategies. A total of 21 of these compounds were detected in the irrigation water. Benzotriazoles were only partially removed after the microalgae treatment, with elimination rates similar to those of conventional WWTPs. The UV filter benzophenone-3 (BP3) showed variable removals, ranging from no elimination to 51%, whereas 4-methylbenzilidenecamphor (4MBC) was completely eliminated. Regarding pharmaceuticals, average removals were higher, in the range of 60-100%, with the exception of the antibiotics sulfamethoxazole (46%) and sulfapyridine, which was not removed. Despite the low biomass productivity of the PBR, parameters such as the size of the reactors, the specific mixed cultures developed and the high temperatures and pH in the closed system may account for the overall good results, The efficiency and sustainability of these systems make them a solid, feasible treatment choice.

Design method for compact, achromatic, high-performance, solid catadioptric system (SoCatS), from visible to IR.

Maresse described a classical solid catadioptric system (SoCatS) for a lens comprising a solid body and a single-focal Maksutov type construction, characterized by two refractive and two reflective surfaces. Due to ray propagation through the solid block twice, the design is feasible at a single wavelength, otherwise suffering on chromatic aberration induced by dispersion. We design a SoCatS for a telescope and describe a class of solutions to reduce and control chromatic and some spherical aberration in the solid catadioptric system.

Substrate-Controlled Direct α-Stereoselective Synthesis of Deoxyglycosides from Glycals Using B(C6F5)3 as Catalyst.

B(C6F5)3 enables the metal-free unprecedented substrate-controlled direct α-stereoselective synthesis of deoxyglycosides from glycals. 2,3-Unsaturated α- O-glycoside products are obtained with deactivated glycals at 75 °C in the presence of the catalyst, while 2-deoxyglycosides are formed using activated glycals that bear no leaving group at C-3 at lower temperatures. The reaction proceeds in good to excellent yields via concomitant borane activation of glycal donor and nucleophile acceptor. The method is exemplified with the synthesis of a series of rare and biologically relevant glycoside analogues.

Enzymatic synthesis of N-acetyllactosamine from lactose enabled by recombinant ß1,4-galactosyltransferases.

Utilising a fast and sensitive screening method based on imidazolium-tagged probes, we report unprecedented reversible activity of bacterial ß1,4-galactosyltransferases to catalyse the transgalactosylation from lactose to N-acetylglucosamine to form N-acetyllactosamine in the presence of UDP. The process is demonstrated by the preparative scale synthesis of pNP-ß-LacNAc from lactose using ß1,4-galactosyltransferase NmLgtB-B as the only biocatalyst.

Exploring ultraviolet photoinduced charge-transfer dynamics in a model dinucleotide of guanine and thymine.

An understanding of the initial photoexcited states of DNA is essential to unravelling deleterious photoinduced chemical reactions and the intrinsic ultrafast photoprotection of the genetic code for all life. In our combined experimental and theoretical study, we have elucidated the primary non-radiative relaxation dynamics of a model nucleotide of guanine and thymine (2'-deoxyguanosine 3'-monophosphate 5'-thymidine, d(GpT)) in buffered aqueous solution. Experimentally, we unequivocally demonstrate that the Franck-Condon excited states of d(GpT) are significantly delocalised across both nucleobases, and mediate d(G+pT-) exciplex product formation on an ultrafast (<350 fs) timescale. Theoretical studies show that the nature of the vertical excited states is very dependent on the specific geometry of the dinucleotide, and dictate the degree of delocalised, charge-transfer or localised character. Our mechanism for prompt exciplex formation involves a rapid change in electronic structure and includes a diabatic surface crossing very close to the Franck-Condon region mediating fast d(G+pT-) formation. Exciplexes are quickly converted back to neutral ground state molecules on a ∼10 ps timescale with a high quantum yield, ensuring the photostability of the nucleotide sequence.