Ion Mobility Mass Spectrometry to Probe Sequences in Supramolecular Copolymers.

The analysis of the microstructure of supramolecular copolymers is difficult because of their dynamic character. Here, benzene-1,3,5-tricarboxamide (BTA) co-assemblies are analysed by ion mobility - mass spectrometry (IM-MS) to reveal the presence of various sequences. For example, the IM-MS mobilogram for hexamers composed of 4 units from a first monomer and 2 units from a second monomer is a broad distribution due to the presence of 9 possible isomeric sequences, which can be sorted out based on calculated collision cross-sections.

Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry.

The human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Recently, HSulf-2 was shown to exhibit an unusual post-translational modification consisting of a sulfated glycosaminoglycan chain. This study describes the structural characterization of this glycosaminoglycan (GAG) and provides new data on its impact on the catalytic properties of HSulf-2.

Ion mobility mass spectrometry enables the discrimination of positional isomers and the detection of conformers from cyclic oligosaccharides-metals supramolecular complexes.

Cyclic oligosaccharides are well known to interact with various metals, able to form supramolecular complexes with distinct sizes and shapes. However, the presence of various isomers in a sample, including positional isomers and conformers, can significantly impact molecular recognition, encapsulation ability and chemical reactivity. Therefore, it is crucial to have tools for deep samples probing and correlation establishments.

[Evaluation of the tele-expertise project in the management of common dermatoses in Togo].

Introduction: Tele-expertise in dermatology represents an opportunity to change medical practice in response to the need for cost savings in the health sector. The aim of this study was to evaluate the medical activities of the pilot phase of the tele-expertise project in Togo.

Method: A cross-sectional study was conducted in October 2020 on the 20 sites of the pilot phase.

Probing topology of supramolecular complexes between cyclodextrins and alkali metals by ion mobility-mass spectrometry.

In this study, the size and shape of supramolecular assemblies between cyclo-oligosaccharides and proton, ammonium or a series of alkali metals by electrospray coupled to trapped ion mobility-mass spectrometry (ESI-TIMS) have investigated. Native cyclodextrins (CD) were selected as models, and collision cross section (CCS) values were deducted for the main positive singly and doubly charged species. Experimental CCS values were in good agreement with those obtained from molecular modeling.

Enhanced Gene Delivery Triggered by Dual pH/Redox Responsive Host-Guest Dimerization of Cyclooligosaccharide Star Polycations.

A robust strategy is reported to build perfectly monodisperse star polycations combining a trehalose-based cyclooligosaccharide (cyclotrehalan, CT) central core onto which oligoethyleneimine radial arms are installed. The architectural perfection of the compounds is demonstrated by a variety of physicochemical techniques, including NMR, MS, DLS, TEM, and GPC. Key to the strategy is the possibility of customizing the cavity size of the macrocyclic platform to enable/prevent the inclusion of adamantane motifs.

Cytotoxic BODIPY-Appended Half-Sandwich Iridium(III) Complex Forms Protein Adducts and Induces ER Stress.

Half-sandwich complexes of iridium(III) are currently being developed as anticancer drug candidates. In this context, we introduce for which the C^N chelating phenyloxazoline ligand carries a fluorescent and lipophilic BODIPY reporter group, designed for intracellular tracking and hydrophobic compartment tropism. High-resolution analysis of cells cultured with showed that it quickly permeates the plasma membrane and accumulates in the mitochondria and endoplasmic reticulum (ER), generating ER stress, dispersal of the Golgi apparatus, cell proliferation arrest and apoptotic cell death.

Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery.

Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo.

Programmed Synthesis of Hepta-Differentiated β-Cyclodextrin: 1 out of 117655 Arrangements.

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.

Experimental and computational diagnosis of the fluxional nature of a benzene-1,3,5-tricarboxamide-based hydrogen-bonded dimer.

Precise characterization of the hydrogen bond network present in discrete self-assemblies of benzene-1,3,5-tricarboxamide monomers derived from amino-esters (ester BTAs) is crucial for the construction of elaborated functional co-assemblies. For all ester BTA dimeric structures previously reported, ester carbonyls in the side chain acted as hydrogen bond acceptors, yielding well-defined dimers stabilized by six hydrogen bonds. The ester BTA monomer derived from glycine (BTA Gly) shows a markedly different self-assembly behaviour.

First Steps to Rationalize Host-Guest Interaction between α-, β-, and γ-Cyclodextrin and Divalent First-Row Transition and Post-transition Metals (Subgroups VIIB, VIIIB, and IIB).

Cyclodextrins (CDs) are cyclic oligosaccharides mainly composed of six, seven, and eight glucose units, so-called α-, β-, and γ-CDs, respectively. They own a very particular molecular structure exhibiting hydrophilic features thanks to primary and secondary rims and delimiting a hydrophobic internal cavity. The latter can encapsulate organic compounds, but the former can form supramolecular complexes by hydrogen-bonding or electrostatic interactions.

Investigation of action pattern of a novel chondroitin sulfate/dermatan sulfate 4-O-endosulfatase.

Recently, a novel CS/DS 4-O-endosulfatase was identified from a marine bacterium and its catalytic mechanism was investigated further (Wang, W., et. al (2015) J.

Discrimination of isomeric trisaccharides and their relative quantification in honeys using trapped ion mobility spectrometry.

Carbohydrates play a myriad of critical roles as key intermediaries for energy storage, cell wall constituents, or also fuel for organisms. The deciphering of multiple structural isomers based on the monosaccharides composition (stereoisomers), the type of glycosidic linkages (connectivity) and the anomeric configuration (α and β), remains a major analytical challenging task. The possibility to discriminate 13 underivatized isomeric trisaccharides were reported using electrospray ionization coupled to trapped ion mobility spectrometry (ESI-TIMS).

Interactions of Calcium with Chlorogenic and Rosmarinic Acids: An Experimental and Theoretical Approach.

Chlorogenic (CA) and rosmarinic (RA) acids are two natural bioactive hydroxycinnamic acids whose antioxidant properties can be modulated by the chelation of metal ions. In this work, the interactions of these two carboxylic phenols with calcium ions and the impact of such interactions on their antioxidant activity were investigated. UV-Vis absorbance, mass spectroscopy and H and C liquid NMR were used to identify complexes formed by CA and RA with calcium.

First step to the improvement of the blood brain barrier passage of atazanavir encapsulated in sustainable bioorganic vesicles.

The blood - brain barrier (BBB) prevents the majority of therapeutic drugs from reaching the brain following intravenous or oral administration. In this context, polymer nanoparticles are a promising alternative to bypass the BBB and carry drugs to brain cells. Amphiphilic cyclodextrins can form self-assemblies whose nanoparticles have a 100-nm-diameter range and are thus able to encapsulate drugs for controlled release.

Cyclodextrin complexation studies as the first step for repurposing of chlorpromazine.

The antipsychotic drug chlorpromazine (CPZ) has potential for the treatment of acute myeloid leukemia, if central nervous system side-effects resulting from its passage through the blood-brain barrier can be prevented. A robust drug delivery system for repurposed CPZ would be drug-in-cyclodextrin-in-liposome that would redirect the drug away from the brain while avoiding premature release in the circulation. As a first step, CPZ complexation with cyclodextrin (CD) has been studied.

A method for quantifying pigment position in retinal pigment epithelium.

In wildtype mice, the pigment granules in the retinal pigment epithelium aggregate in the dark towards Bruch's membrane and disperse towards the photoreceptors in the light. We have developed a repeatable method amenable for quantifying pigment position in the RPE from wild type mice by estimating the population density of pigment granules, or pigment density, within 4 μm areas in the basal part of cells examined by transmission electron microscopy. To measure pigment position, 2 μm × 2 μm squares were aligned along the apical ends of the basal microvilli.

Surface plasmon resonance imaging coupled to on-chip mass spectrometry: a new tool to probe protein-GAG interactions.

A biosensor device for the detection and characterization of protein-glycosaminoglycan interactions is being actively sought and constitutes the key to identifying specific carbohydrate ligands, an important issue in glycoscience. Mass spectrometry (MS) hyphenated methods are promising approaches for carbohydrate enrichment and subsequent structural characterization. In the study herein, we report the analysis of interactions between the glycosaminoglycans (GAGs) heparin (HP) and heparan sulfate (HS) and various cytokines by coupling surface plasmon resonance imaging (SPRi) for thermodynamic analysis method and MALDI-TOF MS for structural determination.

Photosensitized oxidative addition to gold(I) enables alkynylative cyclization of o-alkylnylphenols with iodoalkynes.

The well-established oxidative addition-reductive elimination pathway is the most followed one in transition metal-catalysed cross-coupling reactions. While readily occurring with a series of transition metals, gold(I) complexes have shown some reluctance to undergo oxidative addition unless special sets of ligands on gold(I), reagents or reaction conditions are used. Here we show that under visible-light irradiation, an iridium photocatalyst triggers-via triplet sensitization-the oxidative addition of an alkynyl iodide onto a vinylgold(I) intermediate to deliver C(sp)-C(sp) coupling products after reductive elimination.

The uncommon strong inhibition of α-glucosidase by multivalent glycoclusters based on cyclodextrin scaffolds.

The homeostasis disruption of d-glucose causes diabetes, a dramatic chronic disease worldwide. Type 1 diabetes is a successfully treatable form, where blood d-glucose is regulated by insulin treatment. In contrast type 2 diabetes, the non-insulin dependent kind, is problematic.

Large-Ring Cyclodextrins as Chiral Selectors for Enantiomeric Pharmaceuticals.

Large-ring cyclodextrins (CD) are cyclic glucans composed of 9 or more α-1,4-linked glucose units. They are minor side products of bacterial glucanotransferases (CGTases, EC 2.4.

Dynamic Control of the Self-Assembling Properties of Cyclodextrins by the Interplay of Aromatic and Host-Guest Interactions.

The presence of a doubly-linked naphthylene clip at the -2 and -3 positions in the secondary ring of β-cyclodextrin (βCD) derivatives promoted their self-assembly into head-to-head supramolecular dimers in which the aromatic modules act either as cavity extension walls (if the naphthalene moiety is 1,8-disubstituted) or as folding screens that separate the individual βCD units (if 2,3-disubstituted). Dimer architecture is governed by the conformational properties of the monomer constituents, as determined by NMR, fluorescence, circular dichroism, and computational techniques. In a second supramolecular organization level, the topology of the assembly directs host-guest interactions and, reciprocally, guest inclusion impacts the stability of the supramolecular edifice.