A "green" strategy to construct non-covalent, stable and bioactive coatings on porous MOF nanoparticles.

Nanoparticles made of metal-organic frameworks (nanoMOFs) attract a growing interest in gas storage, separation, catalysis, sensing and more recently, biomedicine. Achieving stable, versatile coatings on highly porous nanoMOFs without altering their ability to adsorb molecules of interest represents today a major challenge. Here we bring the proof of concept that the outer surface of porous nanoMOFs can be specifically functionalized in a rapid, biofriendly and non-covalent manner, leading to stable and versatile coatings. Cyclodextrin molecules bearing strong iron complexing groups (phosphates) were firmly anchored to the nanoMOFs' surface, within only a few minutes, simply by incubation with aqueous nanoMOF suspensions. The coating procedure did not affect the nanoMOF porosity, crystallinity, adsorption and release abilities. The stable cyclodextrin-based coating was further functionalized with: i) targeting moieties to increase the nanoMOF interaction with specific receptors and ii) poly(ethylene glycol) chains to escape the immune system. These results pave the way towards the design of surface-engineered nanoMOFs of interest for applications in the field of targeted drug delivery, catalysis, separation and sensing.

Human galectin-3 selective and high affinity inhibitors. Present state and future perspectives.

Over the last decade an increasing number of studies have been published reporting on the inhibitory potency or selectivity that several types of ligands show against human galectin-3 (hGal-3). The reason for this interest lies in the many important roles galectins play both in intra and extra-cellular functions. Among galectins, galectin-3 stands out because it is the only known member of its subfamily in mammals, is small and monomeric but capable of aggregating, and is known to be involved in a large number of disease processes, from cancer to heart failure. These characteristics and roles make hGal-3 an ideal target for drugs. Since it binds ß-galactosides, like the rest of the galectin family of proteins, the search and design of potent and at the same time selective inhibitors for it is not an easy task. Herein we discuss the chemical features of the most potent inhibitors described so far, as well as the structural basis of their exhibited selectivity, in order to shed light on the rational design of drugs against this target.

Application of gas chromatography-hybrid chemical ionization mass spectrometry to the analysis of diclofenac in wastewater samples.

Hybrid chemical ionization (HCI), a new and useful alternative to conventional chemical ionization mass spectrometry, has been applied to the analysis of the pharmaceutical diclofenac in wastewater samples. This technique takes advantage of the high versatility of ion trap (IT) spectrometers combined with external ionization sources. In hybrid configuration, reagent ions are generated in the external source through electron ionisation (EI) of a reagent gas. These reagent ions are then drawn into the ion trap and only those selected are allowed to react with analytes eluting from the GC column. These ion-molecule reactions create analyte ions which are held in the ion trap. In this study ion-molecule reactions between C(3)F(5)(+) cations, generated from perfluorotributylamine (FC43), and diclofenac molecules have been investigated. The observed reaction products were [M+C(3)F(5)-H(2)O](+) adduct ions, which result from the initial electrophilic addition of C(3)F(5)(+) cations to the diclofenac molecule followed by the rapid loss of H(2)O. Further fragmentation of these ions by MS/MS yielded enough daughter ions for a reliable identification of diclofenac in complex matrices. The GC-HCI-MS/MS method applied to wastewater samples provided highly enhanced selectivity and sensibility, with a detection limit in real samples of 3.0 ng/L, for a solid-phase extraction (SPE) pre-concentration factor of 400. Other performance characteristics of the method, such as linearity and precision were also satisfactory. Finally, the method was successfully applied to the analysis of wastewater samples taken from the effluent of an urban sewage treatment plant (STP).

Structure of concanavalin A at pH 8: bound solvent and crystal contacts.

Concanavalin A has been crystallized in the presence of the ligand (6-S-beta-D-galactopyranosyl-6-thio)-cyclomaltoheptaose. The crystals are isomorphous to those reported for ConA complexed with peptides at low resolution (3.00-2.75 angstroms). The structure was solved at 1.9 angstroms, with free R and R values of 0.201 and 0.184, respectively. As expected, no molecules of the ligand were bound to the protein. Soaking in the cryobuffer left its fingerprint as 25 molecules of glycerol in the bound solvent, most of them at specific positions. The fact that a glycerol molecule is located in the sugar-binding pocket of each of the four subunits in the asymmetric unit and another is located in two of the peptide-binding sites suggests a recognition phenomenon rather than a displacement of water molecules by glycerol. Crystal contact analysis shows that a relation exists between the residues that form hydrogen bonds to other asymmetric units and the space group: contact Asp58-Ser62 is a universal feature of ConA crystals, while Ser66-His121, Asn69-Asn118 and Tyr100-His205 contacts are general features of the C222(1) crystal form.

Binding affinity properties of dendritic glycosides based on a beta-cyclodextrin core toward guest molecules and concanavalin A.

The inclusion behavior and concanavalin A binding properties of hepta-antennated and newly synthesized tetradeca-antennated C-6-branched mannopyranosyl and glucopyrannosyl cyclomaltoheptaose (beta-cyclodextrin) derivatives have been evaluated by isothermal titration microcalorimetry and enzyme-linked lectin assay (ELLA), respectively. The synthesis of three first-order dendrimers based on a beta-cyclodextrin core containing 14 1-thio-beta-D-glucose, 1-thio-beta-mannose, and 1-thio-beta-rhamnose residues was performed following a convergent approach and involving (1) preparation of a thiolated bis-branched glycoside building block and (2) attachment of the building block onto heptakis(6-deoxy-6-iodo)-beta-cyclodextrin. Calorimetric titrations performed at 25 degrees C in buffered aqueous solution (pH 7.4) gave the affinity constants and the thermodynamic parameters for the inclusion complex formation of these beta-cyclodextrin derivatives with guests sodium 8-anilino-1-naphthalensulfonate (ANS) and 2-naphthalenesulfonate. The host capability of the persubstituted beta-cyclodextrins decreased with respect to the native beta-CD when sodium 2-naphthalenesulfonate was used as a guest and improved when ANS was used as a guest molecule. Heptavalent mannoclusters based on beta-CD cores enhance the lectin binding affinity due to the cluster effect; however, the increase of the valency from 7 to 14 ligands did not contribute to the improvement of the concanavalin A binding affinity. In addition, the synthesized hyperbranched mannoCDs lost completely the capability as a host molecules.

Selective pivaloylation and diphenylacetylation of cyclomalto-oligosaccharides.

Regioselective acylation of cyclomalto-oligosaccharides was achieved using pivaloyl and diphenylacetyl chlorides. The reaction of cyclomaltohexaose (1) with pivaloyl chloride gave the hexakis(2,6-di-O-pivaloyl) derivative 19 in 66% yield. Similar reaction with cyclomalto-heptaose (2) led to the octakis(2I,6I,6II,6III,6IV,6V,6VI ,6VII-O-pivaloyl) 26 and the 17 heptakis(6-O-pivaloyl) derivatives in 34 and 26% yields, respectively. The octakis(6-O-pivaloyl) derivative 18 was the only compound isolated (72%) in the reaction of pivaloyl chloride with cyclomalto-octaose (3). Diphenylacetylation of 1-3 gave the symmetrical (20-22) and the non-symmetrical (27-29) per(6-O-diphenylacetyl) esters as major and minor products, respectively.