Selectivity among two lectins: probing the effect of topology, multivalency and flexibility of "clicked" multivalent glycoclusters

The design of multivalent glycoconjugates has been developed over the past decades to obtain high-affinity ligands for lectin receptors. While multivalency frequently increases the affinity of a ligand for its lectin through the so-called "glycoside cluster effect", the binding profiles towards different lectins have been much less investigated. We have designed a series of multivalent galactosylated glycoconjugates and studied their binding properties towards two lectins, from plant and bacterial origins, to determine their potential selectivity. The synthesis was achieved through copper(I)-catalysed azide-alkyne cycloaddition (CuAAC) under microwave activation between propargylated multivalent scaffolds and an azido-functionalised carbohydrate derivative. The interactions of two galactose-binding lectins from Pseudomonas aeruginosa (PA-IL) and Erythrina cristagalli (ECA) with the synthesized glycoclusters were studied by hemagglutination inhibition assays (HIA), surface plasmon resonance (SPR) and isothermal titration microcalorimetry (ITC). The results obtained illustrate the influence of the scaffold's geometry on the affinity towards the lectin and also on the relative potency in comparison with a monovalent galactoside reference probe.     

Triazoles and tetrazoles: Prime ligands to generate remarkable coordination materials

The current great interest in preparing functional metal-organic materials is inevitably associated with tremendous research efforts dedicated to the design and synthesis of new families of sophisticated multi-nucleating ligands. In this context, the N-donor triazole and tetrazole rings represent two categories of ligands that are increasingly used, most likely as the result of the recent dramatic development of “click chemistry” and Zeolitic Imidazolate Frameworks (ZIFs). Thus, azole-based complexes have found numerous applications in coordination chemistry.In the present review, we focus on the utilization of 1,2,3-triazole, 1,2,4-triazole and tetrazole ligands to create coordination polymers, metal complexes and spin-crossover compounds, reported to the end of 2009. In the first instance, we present a compendium of all the relevant ligands that have been employed to generate coordination polymers and Metal-Organic Frameworks (MOFs). Due to the huge amount of reported MOFs and coordination polymers bearing these azole rings, three representative examples for each category (therefore nine in total) are described in detail. The second section is devoted to the use of the bridging abilities of these azole ligands to prepare metal complexes (containing at least two metal centers). Given the large number and the great structural diversity of the polynuclear compounds found in the literature, these have been grouped according to their nuclearity. Finally, in the last section, the triazole- and tetrazole-containing coordination compounds exhibiting spin-crossover properties are presented.     

Correlation between the structure and wettability of photoswitchable hydrophilic azobenzene monolayers on silicon

Photoresponsive monolayers of hydrophilically substituted azobenzenes have been prepared by reaction on aminosilane monolayers on silicon surfaces. Grafting densities in the 0.2-1.0 molecule/nm(2) range were determined by X-ray reflectometry. The monolayers exhibit reversible photoisomerization, switching from a more hydrophilic trans state to a less hydrophilic cis state upon UV irradiation, in contrast with the usual behavior of most azobenzene monolayers that switch from a less to a more hydrophilic state. This indicates that the wettability is not dominated by the change in the dipole moment of the azobenzene moiety but originates from variations in the composition of the outer surface of the monolayers resulting from the reorientation of the substituent groups. The light-driven change in the water contact angle correlates linearly with the grafting density but remains small. However, the wettability contrast can be increased by forcing the molecules to stand in an improved vertical orientation, either by densifying the underlying aminosilane monolayer or by filling the voids left at the bottom of the layer of grafted azobenzene molecules.     

The excited state dipole moments of betaine pyridinium investigated by an innovative solvatochromic analysis and TDDFT calculations

This work reports on the solvatochromic properties of a simple heterocyclic betaine pyridinium, 2-(1-pyridinio)benzimidazolate (SBPa), having promising potentialities in non-linear optics. From advanced PCM-TDDFT calculations, the solvatochromism of SBPa was found to be unusual, involving two different electronic states for absorption (S(0)→ S(2)) and emission (S(1)→S'(0)). To account for this behavior, we developed an innovative physical treatment which consists in a non-linear fit of the solvatochromic data using the Bilot-Kawski theoretical model and visualizing the least-square coefficient χ(2) on a 2D map as a function of the solute polarizability and gas phase absorption energy. In parallel, Kamlet-Taft correlations were undertaken to select a propitious set of electrostatic solvents usable in this treatment. Protic solvents that lead to specific interactions and nonpolar solvents that favor dimerization processes were excluded. From a choice of aprotic solvents with sufficiently high polarity, 4 dipole moments μ(g)(S(0)) = +9.1 D, μ(e)(S(2)) = -1.5 D, μ(e)(S(1)) = 0 D and μ(g)(S'(0)) = +3.31 D were determined, the 3 former values being in close agreement with TDDFT values, although the solute polarizability values seem underestimated. Anyhow, disregarding this discrepancy, we evaluated the static hyperpolarizability to β(0) = -64 × 10(-30) esu from the solvatochromic data in close agreement with DFT calculations.     

Size dependence of the folding of multiply charged sodium cationized polylactides revealed by ion mobility mass spectrometry and molecular modelling

Ion mobility spectrometry coupled with mass spectrometry was used to experimentally determine the three-dimensional structure of multiply charged sodium cationized polylactides (PLA). In particular, the experiments were conducted to evaluate the influence of the charge state and the size on the gas-phase conformation of cationized PLA. The measured collision cross sections were then compared to calculated values obtained by computational chemistry methods. The most striking feature was the experimental and theoretical observation of a breaking point in the quasilinear relationship between the average collision cross sections and the number of monomer units for the triply charged cations. This breaking point was theoretically demonstrated, for the doubly and triply charged cations, to be associated with a significant folding of the polymer chains around the cationizing agents. The occurrence of such breaking points could be exploited to correlate the charge state of the most intense ion series observed upon electrospray ionization with the number-average molecular mass of a polymer.     

Selection of a synthetic glycan oligomer from a library of DNA-templated fragments against DC-SIGN and inhibition of HIV gp120 binding to dendritic cells

We report the synthesis of a nucleic acid-encoded carbohydrate library, its combinatorial self-assembly into 37,485 pairs and a screen against DC-SIGN leading to the identification of consensus ligand motifs. A prototypical example from the selected pairs was shown to have enhanced binding. A dendrimer incorporating the selected motifs inhibited gp120's binding to dendritic cells with higher efficiency than mannan.     

Synthesis of polycyclic molecules by double C(sp2)-H/C(sp3)-H arylations with a single palladium catalyst

Polycyclic molecules were obtained in good yields by double C(sp(2))-H/C(sp(3))-H arylations mediated by a single palladium/phosphine catalyst. Both double intermolecular/intramolecular and intramolecular/intramolecular C-C couplings were performed successfully, which indicates that this concept has a broad applicability for the rapid construction of molecular complexity.     

Stereoselective rhodium-catalyzed amination of alkenes

The first stereoselective rhodium-catalyzed intermolecular aziridination and C-H amination of alkenes to produce chiral carbamate-protected aziridines and allylic amines is described. Good yields and diastereoselectivities were achieved using a readily available chiral N-tosyloxycarbamate and stoichiometric amount of the alkene substrate. Furthermore the protecting group is easy to cleave under mild reaction conditions.