Human Lectins, Their Carbohydrate Affinities and Where to Find Them.

Lectins are a class of proteins responsible for several biological roles such as cell-cell interactions, signaling pathways, and several innate immune responses against pathogens. Since lectins are able to bind to carbohydrates, they can be a viable target for targeted drug delivery systems. In fact, several lectins were approved by Food and Drug Administration for that purpose. Information about specific carbohydrate recognition by lectin receptors was gathered herein, plus the specific organs where those lectins can be found within the human body.

Nanoparticles Based on Novel Carbohydrate-Functionalized Polymers.

Polymeric nanoparticles can be used for drug delivery systems in healthcare. For this purpose poly(lactic-co-glycolic acid) (PLGA) and poly(ethylene glycol) (PEG) offer an excellent polymeric matrix. In this work, PLGA and PEG polymers were functionalized with coumarin and carbohydrate moieties such as thymidine, glucose, galactose, and mannose that have high biological specificities. Using a single oil in water emulsion methodology, functionalized PLGA nanoparticles were prepared having a smooth surface and sizes ranging between 114-289 nm, a low polydispersity index and a zeta potential from -28.2 to -56.0 mV. However, for the corresponding PEG derivatives the polymers obtained were produced in the form of films due to the small size of the hydrophobic core.

An electrospray ionization mass spectrometry study of azidoacetic acid/transition metal complexes.

RATIONALE: The complexation behavior of transition metals with organic azides by electrospray ionization (ESI) tandem mass spectrometry (MS/MS) is not completely understood. In this study, fragmentation patterns of complex ions having azidoacetic acid coordinated to Ni/Co/Fe were elucidated. The role of transition metals in the mediation of ligand rearrangements in gas phase is experimentally supported. METHODS: The complexation of some transition metals, nickel, cobalt and iron, by azidoacetic acid was studied by means of ESI and MS/MS. Fragmentation patterns were discerned via consecutive MS/MS experiments on an ion trap mass spectrometer and confirmed by high-resolution (HR) Fourier transform ion cyclotron resonance MS. Density functional theory (DFT) calculations were used to characterize the major ions observed in MS. RESULTS: Only singly positively charged complex ions were detected presenting various stoichiometries. MS/MS and theoretical calculations allowed us to confirm assignments and coordination sites. Structural evidence suggested that the azidoacetic acid can behave as monodentate and/or bidentate and coordination through the oxygen and nitrogen atoms are both possible. Experimental evidence strongly points to a role of Ni/Co/Fe, in oxidative state (I), in mediating C-C bond activation in the gas phase. CONCLUSIONS: MS/MS and HRMS experiments were able to elucidate azidoacetic acid complexation with Ni/Co/Fe and several gas-phase processes involving metal reduction and rearrangements. The definition of the coordination pattern dictated by the competition between the nitrogen and the oxygen atoms is also dependent on the metal centre in a very dynamic process. Copyright © 2017 John Wiley & Sons, Ltd.

Antimicrobial and cytotoxic activities of 1,2,3-triazole-sucrose derivatives.

A library of 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-1,2,3-triazoles have been investigated for their antibacterial, antifungal and cytotoxic activities. Most of the target compounds showed good inhibitory activity against a variety of clinically and food contaminant important microbial pathogens. In particular, 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-pentylphenyl)-1,2,3-triazole (5) was highly active against all the tested bacteria with minimal inhibitory concentrations (MICs) ranging between 1.1 and 4.4 µM and bactericidal concentrations (MBCs) from 2.2 and 8.4 µM. The compound 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-(4-bromophenyl)-1,2,3-triazole (3) showed antifungal activity with MICs from 0.6 to 4.8 µM and minimal fungicidal concentrations (MFCs) ranging between 1.2 and 8.9 µM. Furthermore, some of the compounds possessed moderate cytotoxicity against human breast, lung, cervical and hepatocellular carcinoma cell lines, without showing toxicity for non-tumor liver cells. The above mentioned derivatives represent promising leads for the development of new generation of sugar-triazole antifungal agents.

The mechanism of pyrolysis of benzyl azide: spectroscopic evidence for benzenemethanimine formation.

We study the gas-phase pyrolysis of benzyl azide (BA, C6H5CH2N3) using ultraviolet photoelectron spectroscopy (UVPES) and matrix-isolation infrared (IR) spectroscopy, together with electronic structure calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) calculations. It is found that BA decomposes via N2 elimination at ca. 615 K, primarily yielding benzenemethaninime. Other end products include HCN and C6H6. N-Methyleneaniline is not detected, although its formation at higher temperature is foreseen by RRKM calculations.

Formation of spherical and core-shell polymeric microparticles from glycopolymers.

6-O-methacryloyl-α-d-glucoside 2 and 4-bromophenyl-6-O-methacryloyl-d-glucothioside 7, obtained by enzyme-catalyzed synthesis, have been homo-polymerized and copolymerized with styrene by a free radical process, yielding polymer materials with sugar moieties, attached to the polymer backbone via ester linkages. The results demonstrated that modifying the structural features of the monomers greatly affected the thermal and rheological properties of the polymers. The polymer materials obtained have been characterized by NMR, MALDI-MS, DSC, AFM, and EWC (equilibrium water content). The AFM images indicated the formation of spherical and core-shell polymeric microparticles.

Recent progress in the field of glycoconjugates.

The ubiquity of glycoconjugates in nature and their role in different biological processes, has led to the development of several methodologies to synthesize these molecules. Synthetic glycoconjugates are now used to answer a variety of glycoconjugate-related biological questions and have provided new potential vaccines against cancer, viral, and bacterial infections and new biotechnological tools. This review aims to collect and compile the recent advances in the field of glycopeptides, glycoproteins, and glycolipid synthesis and also to update the previous reviews made on this subject. Finally, by highlighting the successes and failures of past research, we hope that this review will inspire fruitful research in this important medicinal chemistry field.

Amide-linked N-methacryloyl sucrose containing polymers.

1',2,3,3',4,4',6-Hepta-O-benzyl-6'-N-methacryloyl-6'-deoxysucrose 1, 6'-deoxy-6'-N-methacryloyloxyethylureido sucrose 2 and 6,6'-dideoxy-6,6'-N-dimethacryloyloxyethylureido sucrose 3 have been homo-polymerized and copolymerized with styrene by a free radical process, yielding polymer materials with pendant sucrose moieties, attached to the polymer backbone via amide linkages. The results demonstrated that varying the structural features of the monomers, greatly affected the thermal and rheological properties of the polymers. The polymer materials obtained have been characterized by NMR, MALDI-TOF, DSC, AFM and EWC (equilibrium water content). The efficient synthesis of the three novel, regioisomerically pure, N-methacryloylamide sucrose-containing monomers (1, 2 and 3) have been described.

Surfactant-free polymeric nanoparticles composed of PEG, cholic acid and a sucrose moiety.

Polymer-based nanomedicine is a large and fast growing field that has gained plenty of research attention during recent decades. In the present study, new amphiphilic polymers were designed and synthesized by chemical modification of poly(ethylene glycol) (PEG) conjugated with sucrose and a cholic acid moiety (abbreviated as Suc-PEG-Chol). Two series of polymers with different PEG chain lengths were synthesized and their structures were confirmed by 1H-NMR, 13C-NMR and MALDI-TOF analysis. The fluorescence spectroscopy data of these conjugates showed that they are able to self-assemble in water and the critical association concentration (CAC) value was found to be in the range of 0.06-0.13 g L-1. Owing to their amphiphilic characteristics in aqueous solution, polymeric nanoparticles (PNPs) of Suc-PEG-Chol polymers were prepared by a nanoprecipitation method without any surfactants. The particle size distribution was determined by dynamic light scattering (DLS) and the result was 117 nm for the Suc-PEG2000-Chol conjugate and 96 nm for the PEG4000 analog, both with relatively narrow particle size distribution. All of the obtained PNPs showed a negative surface charge and no size dependence on the polymer concentration forming stable nanoparticle suspensions. From the atomic force microscopy (AFM) and scanning electron microscopy (SEM) observations, the PNPs were spherically shaped with a relatively smooth surface. Our results suggest that these PEGylated nanoparticles formulated with cholic acid and sucrose as biocompatible building blocks can be considered a potential candidate for biomedical applications.

Efficient microwave assisted synthesis of novel 1,2,3-triazole-sucrose derivatives by cycloaddition reaction of sucrose azides and terminal alkynes.

Novel 1-(1',2,3,3',4,4',6-hepta-O-acetyl-6'-deoxy-sucros-6'-yl)-4-substituted-1,2,3-triazoles were synthesized by microwave assisted copper catalyzed 1,3-dipolar cycloaddition of sucrose derived azides with terminal alkynes in excellent yields and in short reaction times. The compound 1',2,3,3',4,4',6-hepta-O-acetyl-6'-azido-6'-deoxy-sucrose was regioselectively synthesized from sucrose by improved procedure and used for the cycloadditions. By combining carbohydrate and 1,2,3-triazole structural motifs, a library of 1,2,3-triazole-sucrose conjugates have been obtained.

Metal-free direct amination/aromatization of 2-cyclohexenones to iodo-N-arylanilines and N-arylanilines promoted by iodine.

An iodine mediated aromatization leading to a one-pot synthesis of iodo-N-arylanilines and N-arylanilines is reported. This highly regioselective aliphatic-aromatic transformation can be performed with various combinations of 2-cyclohexenones and anilines. The presence of a directing group is crucial for achieving high yields.

Azidoacetone as a complexing agent of transition metals Ni2+/Co2+ promoted dissociation of the C-C bond in azidoacetone.

The relevance of metal interactions with azides has led us to the study of the complexation of some transition metals, nickel and cobalt, by azidoacetone by means of electrospray ionization mass spectrometry (ESI-MS). Complexes were obtained from solutions of NiCl(2) and CoCl(2) , in methanol/water. Nickel was electrosprayed with other counter ion, bromide (Br), as well as other solvent (ethanol/water). For nickel and cobalt, the complexes detected were single positively charged, with various stoichiometries, some resulted from the fragmentation of the ligand, the loss of N(2) being quite common. The most abundant species were [Ni(II)Az(2)X](+) where X = Cl, Br and Az = azidoacetone. Some of the complexes showed solvation with the solvent components. Metal reduction was observed in complexes where a radical was lost, resulting from the homolytic cleavage of a metal coordination bond. Collision-induced dissociation (CID) experiments followed by tandem mass spectrometry (MS-MS) analysis were not absolutely conclusive about the coordination site. However, terminal ions of the fragmentation routes were explained by a gas-phase mechanism proposed where a C-C bond was activated and the metal inserted subsequently. Density functional theory calculations provided structures for some complexes. In [Ni(II)Az(2)X](+) species, one azidoacetone ligand is monodentate and the dominant binding location is the alkylated nitrogen and not the carbonyl group. The other azidoacetone ligand is bidentate showing coordination through alkylated nitrogen and the carbonyl group. These are also the preferential binding sites for the most stable isomer of [Ni(II)AzX](+) species.

Competing channels in the thermal decomposition of azidoacetone studied by pyrolysis in combination with molecular beam mass spectrometric techniques.

The thermal decomposition of azidoacetone (CH3COCH2N3) was studied using a combined experimental and computational approach. Flash pyrolysis at a range of temperatures (296-1250 K) was used to induce thermal decomposition, and the resulting products were expanded into a molecular beam and subsequently analyzed using electron bombardment ionization coupled to a quadrupole mass spectrometer. The advantages of this technique are that the parent molecules spend a very short time in the pyrolysis zone (20-30 mus) and that the subsequent expansion permits the stabilization of thermal products that are not observable using conventional pyrolysis methods. A detailed analysis of the mass spectra as a function of pyrolysis temperature revealed the participation of five thermal decomposition channels. Ab initio calculations on the stable structures and transition states of the azidoacetone system in combination with an analysis of the dissociative ionization pattern of each channel allowed the identity and mechanism of each channel to be elucidated. At low temperatures (296-800 K) the azide decomposes principally by the loss of N2 to yield the imine (CH3COCHNH), which can further decompose to CH3CO and CHNH. At low and intermediate temperatures a process involving the loss of N2 to yield CH3CHO and HCN is also open. Finally, at high temperatures (800-1250 K) a channel in which the azide decomposes to a stable cyclic amine (CO(CH2)2NH) (after loss of N2) is active. The last channel involves subsequent thermal decomposition of this cyclic amine to ketene (H2CCO) and methanimine (H2CNH).

Study of doubly charged alkaline earth metal and 3-azidopropionitrile complexes by electrospray ionization mass spectrometry.

The present work describes a study of the complexation of calcium and magnesium by 3-azidopropionitrile by means of electrospray ionization mass spectrometry (ESI-MS). Complexes were obtained from solutions of calcium and magnesium salts of the type CaX2 and MgX2 (where X = Cl or NO3) in water and methanol/water. The complexes detected were mainly double positively charged, with various stoichiometries not depending on the solvent, since water and 3-azidopropionitrile were always the main ligands. Solvation with methanol was not observed unlike in a previous study of complexation of nickel and cobalt by 3-azidopropionitrile. The complex ions [M(II)Az4(H2O)](2+), [M(II)Az5](2+) (where M = Ca and Mg) are the most abundant for both metals, and both counter ions. Tandem mass spectrometric (MS/MS) analysis showed that, under collision-induced dissociation (CID) conditions, the most important processes occurring were loss of neutral ligands and the replacement of 3-azidopropionitrile by water. A complex species containing reduced alkaline earth metal was due to radical loss, resulting from homolytic cleavage in the azide ligand. Some terminal ions, in the fragmentation sequences, point to the nitrile group as the coordination site in the 3-azidopropionitrile. Density functional theory (DFT) calculations confirmed this coordination site and proved that 3-azidopropionitrile behaves as a monodentate ligand in the systems under study. Moreover, the theoretical study proved that the presence of water ligand introduces stability through a hydrogen bond established between the water molecule and one nitrogen atom of the azido group. In addition, the strong dipole moment of 3-azidopropionitrile (4.76 D), which is mainly related to presence of the nitrile group, favors the stabilization of the metal-ligand complexes through charge-dipole interactions and the coordination of the metal to the nitrile group.

Complexation of transition metals by 3-azidopropionitrile. An electrospray ionization mass spectrometry study.

Most complexes of azides and transition metals involve the N(3)(-) azide anion as a ligand other than an organic azide. Complexes of organic azides with metals are involved in biological applications and in the deposition of nitrenes on metal surfaces, producing nitride layers for semi-conductors preparation; this makes the study of these interactions an important issue. This work describes a study of the complexation of nickel and cobalt by 3-azidopropionitrile by means of electrospray ionization mass spectrometry (ESI-MS). Complexes were obtained from solutions of NiCl(2) and CoCl(2) in methanol/water. In the case of nickel, other NiX(2) salts were investigated (where X = Br or NO(3)) and other solvents were also studied (notably ethanol/water). All complexes detected were single positively charged, with various stoichiometries, some resulted from the fragmentation of the ligand, the loss of N(2), and HCN being quite common. The most abundant cations observed were [Ni(II)AzAzX](+), where X = Cl, Br, NO(3). Some of the complexes showed solvation with methanol/ethanol/water. Metal reduction was observed in complexes where a radical was lost, resulting from the homolytic cleavage of a metal-nitrogen bond. Collision induced dissociation (CID) experiments followed by tandem mass spectrometry (MS-MS) analysis were not absolutely conclusive about the coordination site. However, terminal ions observed from the fragmentation routes were explained by a proposed gas-phase mechanism. Density functional theory calculations were carried out and provided structures for some complexes, pointing to the possibility of 3-azidopropionitrile acting as a mono- or a bidentate ligand.

Synthesis of new chiral amines with a cyclic 1,2-diacetal skeleton derived from (2R, 3R)-(+)-tartaric acid.

The syntheses of new chiral cyclic 1,2-diacetals from (2R, 3R)-( )-tartaric acid are described. C(2)-symmetrical diamines were prepared via direct amidation of the tartrate or from the corresponding bismesylate via reaction with sodium azide. For C1-symmetrical compounds, the Appel reaction was used to form the key intermediate, a monochlorocarbinol, from the diol. Some of the new chiral compounds, produced in good to high yields, may be potentially useful as asymmetric organocatalysts or as nitrogen and sulfur chelating ligands for asymmetric metal catalyzed reactions. Thus, a bis-N-methyl-methanamine derivative, used in substoichiometric amounts, was found to catalyze the enantioselective addition of cyclohexanone to (E)-beta-nitrostyrene with high diastereoselectivity (syn / anti = 92:8), albeit giving moderate optical purity (syn: 30 %).

Contrasting behavior in azide pyrolyses: an investigation of the thermal decompositions of methyl azidoformate, ethyl azidoformate and 2-azido-N, N-dimethylacetamide by ultraviolet photoelectron spectroscopy and matrix isolation infrared spectroscopy.

The thermal decompositions of methyl azidoformate (N3COOMe), ethyl azidoformate (N3COOEt) and 2-azido-N,N-dimethylacetamide (N3CH2CONMe2) have been studied by matrix isolation infrared spectroscopy and real-time ultraviolet photoelectron spectroscopy. N2 appears as an initial pyrolysis product in all systems, and the principal interest lies in the fate of the accompanying organic fragment. For methyl azidoformate, four accompanying products were observed: HNCO, H2CO, CH2NH and CO2, and these are believed to arise as a result of two competing decomposition routes of a four-membered cyclic intermediate. Ethyl azidoformate pyrolysis yields four corresponding products: HNCO, MeCHO, MeCHNH and CO2, together with the five-membered-ring compound 2-oxazolidone. In contrast, the initial pyrolysis of 2-azido-N,N-dimethyl acetamide, yields the novel imine intermediate Me2NCOCH=NH, which subsequently decomposes into dimethyl formamide (HCONMe2), CO, Me2NH and HCN. This intermediate was detected by matrix isolation IR spectroscopy, and its identity confirmed both by a molecular orbital calculation of its IR spectrum, and by the temperature dependence and distribution of products in the PES and IR studies. Mechanisms are proposed for the formation and decomposition of all the products observed in these three systems, based on the experimental evidence and the results of supporting molecular orbital calculations.

Highly stereoselective aldol reaction for the synthesis of gamma-lactones starting from tartaric acid.

A simple stereoselective process for the synthesis of highly substituted gamma-lactones was developed based on aldol reactions between the enolate of dioxanes derived from tartaric acid and aldehydes. A range of aromatic and aliphatic aldehydes were reacted, in most cases achieving good yields and stereoselectivity. The limitations of this reaction were identified and a transition state is proposed.