Stereocontrolled synthesis of new iminosugar lipophilic derivatives and evaluation of biological activities.

Iminosugars' similarity to carbohydrates determines the exceptional potential for this class of polyhydroxylated alkaloids to serve as potential drug candidates for a wide variety of diseases such as diabetes, lysosomal storage diseases, cancer, bacterial and viral infections. The presence of lipophilic substituents has a significant impact on their biological activities. This work reports the synthesis of three new pyrrolidine lipophilic derivatives O-alkylated in C-6 position. The biological activities of our iminosugars' collection were tested in two cancer cell lines and, due to the pharmaceutical potential, in the model yeast system Saccharomyces cerevisiae to assess their toxicity.

4,4'-(Anthracene-9,10-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) Lead Iodide C30H22N2Pb2I6: A Highly Luminescent, Chemically and Thermally Stable One-Dimensional Hybrid Iodoplumbate.

A new one-dimensional hybrid iodoplumbate, namely, 4,4'-(anthracene-9,10-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) lead iodide C30H22N2Pb2I6 (AEPyPbI), is reported here for the first time with its complete characterization. The material exhibits remarkable thermal stability (up to 300 °C), and it is unreactive under ambient conditions toward water and atmospheric oxygen, due to the quaternary nature of the nitrogen atoms present in the organic cation. The cation exhibits strong visible fluorescence under ultraviolet (UV) irradiation, and when its iodide is combined with PbI2, it forms AEPyPb2I6, an efficient light-emitting material, with a photoluminescence emission intensity comparable to that of high-quality InP epilayers. The structure determination was obtained using three-dimensional electron diffraction, and the material was extensively studied by using a wide range of techniques, such as X-ray powder diffraction, diffuse reflectance UV-visible spectroscopy, thermogravimetry-differential thermal analysis, elemental analysis, Raman and infrared spectroscopies, and photoluminescence spectroscopy. The emissive properties of the material were correlated with its electronic structure by using state-of-the-art theoretical calculations. The complex, highly conjugated electronic structure of the cation interacts strongly with that of the Pb-I network, giving rise to the peculiar optoelectronic properties of AEPyPb2I6. The material, considering its relatively easy synthesis and stability, shows promise for light-emitting and photovoltaic devices. The use of highly conjugated quaternary ammonium cations may be useful for the development of new hybrid iodoplumbates and perovskites with optoelectronic properties tailored for specific applications.

Synthesis, Structure, and Characterization of 4,4'-(Anthracene-9,10-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) Bismuth Iodide (C30H22N2)3Bi4I18, an Air, Water, and Thermally Stable 0D Hybrid Perovskite with High Photoluminescence Efficiency.

4,4'-(Anthracene-9,10-diylbis(ethyne-2,1-diyl))bis(1-methyl-1-pyridinium) bismuth iodide (C30H22N2)3Bi4I18 (AEPyBiI) was obtained as a black powder by a very simple route by mixing an acetone solution of BiI3 and an aqueous solution of C30H22N2I2. This novel perovskite is air and water stable and displays a remarkable thermal stability up to nearly 300 °C. The highly conjugated cation C30H22N2 2+ is hydrolytically stable, being nitrogen atoms quaternarized, and this accounts for the insensitivity of the perovskite toward water and atmospheric oxygen under ambient conditions. The cation in aqueous solution is highly fluorescent under UV irradiation (emitting yellow-orange light). AEPyBiI as well is intensely luminescent, its photoluminescence emission being more than 1 order of magnitude greater than that of high-quality InP epilayers. The crystal structure of AEPyBiI was determined using synchrotron radiation single-crystal X-ray diffraction. AEPyBiI was extensively characterized using a wide range of techniques, such as X-ray powder diffraction, diffuse reflectance UV-vis spectroscopy, Fourier transform infrared (FTIR) and Raman spectroscopies, thermogravimetry-differential thermal analysis (TG-DTA), elemental analysis, electrospray ionization mass spectroscopy (ESI-MS), and photoluminescence spectroscopy. AEPyBiI displays a zero-dimensional (0D) perovskite structure in which the inorganic part is constituted by binuclear units consisting of two face-sharing BiI6 octahedra (Bi2I9 3- units). The C30H22N2 2+ cations are stacked along the a-axis direction in a complex motif. Considering its noteworthy light-emitting properties coupled with an easy synthesis and environmental stability, and its composition that does not contain toxic lead or easily oxidable Sn(II), AEPyBiI is a promising candidate for environmentally friendly light-emitting devices.

Total stereocontrolled synthesis of a novel pyrrolizidine iminosugar.

Herein we describe a versatile approach to the pyrrolizidine alkaloids skeleton by tailoring our original strategy already used for the pyrrolidine iminosugars synthesis. The key steps are the regio- and stereoselective azidolysis of the suitable chiral vinyl epoxide and then asymmetric dihydroxylation of the corresponding azido alcohol by using (DHQ)2AQN as the ligand. Further optimized elaborations addressed to the closure of the two rings allowed us to achieve the target iminosugar with complete stereocontrol. The wide range of pyrrolizidine iminosugars' biological properties make them a key focus of new drug research and therefore the development of synthetic strategies for obtaining them is of decisive importance.

Brightly Luminescent and Moisture Tolerant Phenyl Viologen Lead Iodide Perovskites for Light Emission Applications.

Lead halide perovskites are outstanding materials for optoelectronics, but they typically feature low stability against external agents. To overcome this drawback, LHPs based on quaternary ammonium cations, such as phenyl viologen lead iodide (PhVPI), were found to be promising candidates, being water-resistant and thermally stable. In this Letter, the optoelectronic properties of the PhVPI are investigated by a combined experimental-theoretical approach. Although the as-prepared material is photoluminescence-inactive, a short thermal (5 min @ 290 °C) or laser annealing turns PhVPI into a highly luminescent material, in the 600-1000 nm range. The PhVPI PL emission was characterized at different annealing conditions, and the structural evolution following thermal treatments was investigated by means of X-ray diffraction, Raman, and NMR spectroscopies. Besides this, the electronic structure and emission properties were investigated by density functional theory simulations. The intense optical emission and high stability make PhVPI an intriguing material for applications related to light-emitting devices.

Deoxycholic acid and l-Phenylalanine enrich their hydrogel properties when combined in a zwitterionic derivative.

HYPOTHESIS: Sodium Deoxycholate (NaDC) and Phenylalanine (Phe) are important biological hydrogelators. NaDC hydrogels form by lowering the pH or by increasing the ionic strength. Phe gels form from saturated solution by thermal induction and slow kinetics. The resulting gels hold great potential in medicine and biology as drug carriers and models for fundamental self-assembly in pathological conditions. Based on this background it was hypothesized that a Phe substituted NaDC could provide a molecule with expanded gelling ability, merging those of the precursors. EXPERIMENTS: We coupled both building blocks in a zwitterionic derivative bearing a Phe residue at the C3 carbon of NaDC. The specific zwitterionic structure, the concurrent use of Ca2+ ions for the carboxyl group coordination and the pH control generate conditions for the formation of hydrogels. The hydrogels were analyzed by combining UV and circular dichroism spectroscopies, rheology, small angle X-ray scattering and atomic force microscopy. FINDINGS: Hydrogel appearance occurs in conditions that are uncovered in the case of the pure Phe and NaDC: self-standing gels form instantaneously at room temperature, in the 10-12 pH range and down to concentration of 0.17 wt%. Both thixotropic and shake resistant gels can form depending on the derivative concentration. The gels show an uncommon thermal stability in the scanned range of 20-60 °C. The reported system concurrently enriches the hydrogelation properties of two relevant building blocks. We anticipate some potential applications of such gels in materials science where coordination of metal ions can be exploited for templating inorganic nanostructures.

Synthesis, physico-chemical characterization and structure of the elusive hydroxylammonium lead iodide perovskite NH3OHPbI3.

The synthesis of hydroxylammonium lead iodide NH3OHPbI3 was accomplished by means of the reaction between water solutions of HI and NH2OH with PbI2 in sulfolane in conjunction with either crystallization by CH2Cl2 vapor diffusion or sulfolane extraction with toluene. The appropriate choice of the solvent was found to be crucial in order to attain the desired material. The synthesized compound was extensively characterized by single crystal and powder X-ray diffraction, UV-Vis diffuse reflectance spectroscopy, FT-IR spectroscopy, 1H-NMR spectroscopy, TG-DTA-QMS EGA (Evolved Gas Analysis), ESI-MS, and CHNS analysis. NH3OHPbI3 is an extremely reactive, deliquescent solid that easily oxidizes in air releasing iodine. Furthermore, it is the first reported perovskite to melt (m.p. around 80 °C) before decomposing exothermally at 103 °C. Such a chemical behavior, together with its optical absorption properties (i.e. yellow-colored perovskite), renders this material totally unsuitable for photovoltaic applications. The deliquescence of the material is to be ascribed to the strong hydrophilicity of hydroxylammonium ion. On the other hand, the relatively high Brønsted acidity of hydroxylammonium (pKa = 5.97) compared to other ammonium cations, promotes the reduction of atmospheric oxygen to water and the NH3OHPbI3 oxidation. The crystal structure, determined by single crystal X-ray diffraction with synchrotron radiation, is orthorhombic, but differs from the prototypal perovskite structure. Indeed it comprises infinite chains of face-sharing PbI6 octahedra along the c-axis direction with hydroxylammonium cations positioned between the columns, forming layers on the ac plane. The solvent intercalates easily between the layers. The crystal structure is apparently anomalous considering that the expected Goldschmidt's tolerance factor for the system (0.909) lies in the range of a stable prototypal perovskite structure. Therefore, the strong hydrogen bond forming tendency of hydroxylamine is likely to account for the apparent structural anomaly.

Twisted nanoribbons from a RGD-bearing cholic acid derivative.

In light of the biomedical interest for self-assembling amphiphiles bearing the tripeptide Arg-Gly-Gly (RGD), a cholic acid derivative was synthesized by introducing an aromatic moiety on the steroidal skeleton and the RGD sequence on the carboxylic function of its chain 17-24, thus forming a peptide amphiphile with the unconventional rigid amphiphilic structure of bile salts. In aqueous solution, the compound self-assembled into long twisted ribbons characterized by a very low degree of polydispersity in terms of width (≈25nm), thickness (≈4.5nm) and pitch (≈145nm). It was proposed that in the ribbon the molecules are arranged in a bilayer structure with the aromatic moieties in the interior, strongly involved in the intermolecular interaction, whereas the RGD residues are located at the bilayer-water interface. The nanostructure is significantly different from those generally provided by RGD-containing amphiphiles with the conventional peptide-tail structure, for which fibers with a circular cross-section were observed, and successfully tested as scaffolds for tissue regeneration. From previous work on the use of this kind of nanostructures, it is known that features like morphology, rigidity, epitope spacing and periodicity are important factors that dramatically affect cell adhesion and signaling. Within this context, the reported results demonstrate that bile salt-based peptide surfactants are promising building blocks in the preparation of non-trivial RGD-decorated nanoaggregates with well-defined morphologies and epitope distributions.

AuNPs-functionalized PANABA-MWCNTs nanocomposite-based impedimetric immunosensor for 2,4-dichlorophenoxy acetic acid detection.

In this work, we developed an impedimetric label-free immunosensor for the detection of 2,4-Dichlorophenoxy Acetic Acid (2,4-D) herbicide either in standard solution and spiked real samples. For this purpose, we prepared by electropolymerization a conductive polymer poly-(aniline-co-3-aminobenzoic acid) (PANABA) then we immobilized anti-2,4-D antibody onto a nanocomposite AuNPs-PANABA-MWCNTs employing the carboxylic moieties as anchor sites. The nanocomposite was synthesized by electrochemical polymerization of aniline and 3-aminobenzoic acid, in the presence of a dispersion of gold nanoparticles, onto a multi-walled carbon nanotubes-based screen printed electrode. Aniline-based copolymer, modified with the nanomaterials, allowed to enhance the electrode conductivity thus obtaining a more sensitive antigen detection. The impedimetric measurements were carried out by electrochemical impedance spectroscopy (EIS) in faradic condition by using Fe(CN)63-/4- as redox probe. The developed impedimetric immunosensor displayed a wide linearity range towards 2,4-D (1-100ppb), good repeatability (RSD 6%), stability and a LOD (0.3ppb) lower than herbicide emission limits.

Crystal structure of a lithium salt of a glucosyl derivative of lithocholic acid.

The crystal structure of a Li(+) salt of a glucosyl derivative of lithocholic acid (lithium 3α-(α-d-glucopyranosyl)-5ß-cholan-24-oate) has been solved. The crystal belongs to the orthorhombic system, P212121 spatial group, and includes acetone and water in the structure with a 1:1:2 stoichiometry. Monolayers, having a hydrophobic interior and hydrophilic edges, are recognized in the crystal structure. Li(+) is coordinated to three hydroxyl groups of three different glucose residues, with two of them belonging to the same monolayer. A fourth molecule, located in this monolayer, is involved in the coordination of the cation through the carboxylate ion by an electrostatic interaction, thus completing a distorted tetrahedron. All Li(+)-oxygen distances values are very close to the sum of the ionic radius of Li(+) and van der Waals radius of oxygen. Each steroid molecule is linked to other five steroid molecules through hydrogen bonds. Water and acetone are also involved in the hydrogen bond network. A hierarchical organization can be recognized in the crystal, the helical assembly along 21 screw axes being left-handed.

On the self-assembly of a tryptophan labeled deoxycholic acid.

Self-assembly of peptides and bile acids has been widely investigated because of their biological role and their potential as a tool for the preparation of nanostructured biomaterials. We herein report both the synthesis and the self-association behavior of a compound that combines the aggregation properties of bile acid- and amino acid-based molecules. The derivative has been prepared by introducing a L-tryptophan residue into the C-3 position of the deoxycholic acid skeleton and resulted in an amphoteric fluorescent labeled bile acid that shows a pH-dependent self-assembly. Under alkaline conditions it assembles into 28 nm diameter tubules, thus showing a completely different behavior compared to the precursor bile acid, which forms micelles under similar conditions. Upon heating the tubules break and turn into micelles, leading to an increase in the exposure to water of the tryptophan residue. On the other hand, in acidic solutions it aggregates into elongated micelles that further self-assemble forming a gel network, when an electrolyte is added.

Sugar-bile acid-based bolaamphiphiles: from scrolls to monodisperse single-walled tubules.

The introduction of a mannose residue on carbon 3 of lithocholic acid gives rise to an asymmetric and rigid bolaamphiphilic molecule, which self-assembles in water to form elongated tubular aggregates with an outer diameter of about 20 nm. These tubular structures display a temporal evolution, where the average tube diameter decreases with time, which can be followed by time-resolved small-angle X-ray scattering experiments. Cryogenic transmission electron microscopy images collected as a function of time show that at short times after preparation tubular scrolls are formed via the rolling of layers, after which a complex transformation of the scrolls into single-walled tubules takes place. At long time scales, a further evolution occurs where the tubules both elongate and become narrower. The observed self-assembly confirms the tendency of bile acids and their derivatives to form supramolecular aggregates with an ordered packing of the constituent molecules. It also demonstrates that scrolls can be formed as intermediate structures in the self-assembly process of monodisperse single-walled tubules.

Between peptides and bile acids: self-assembly of phenylalanine substituted cholic acids.

Biocompatible molecules that undergo self-assembly are of high importance in biological and medical applications of nanoscience. Peptides and bile acids are among the most investigated due to their ability to self-organize into many different, often stimuli-sensitive, supramolecular structures. With the aim of preparing molecules mixing the aggregation properties of bile acid and amino acid-based molecules, we report on the synthesis and self-association behavior of two diastereomers obtained by substituting a hydroxyl group of cholic acid with a l-phenylalanine residue. The obtained molecules are amphoteric, and we demonstrate that they show a pH-dependent self-assembly. Both molecules aggregate in globular micelles at high pH, whereas they form tubular superstructures under acid conditions. Unusual narrow nanotubes with outer and inner cross-section diameters of about 6 and 3 nm are formed by the derivatives. The diasteroisomer with α orientation of the substituent forms in addition a wider tubule (17 nm cross-section diameter). The ability to pack in supramolecular tubules is explained in terms of a wedge-shaped bola-form structure of the derivatives. Parallel or antiparallel face-to-face dimers are hypothesized as fundamental building blocks for the formation of the narrow and wide nanotubes, respectively.

Amino acid-bile acid based molecules: extremely narrow surfactant nanotubes formed by a phenylalanine-substituted cholic acid.

An amino acid-substituted bile acid forms tubular aggregates with inner and outer diameters of about 3 and 6 nm. The diameters are unusually small for surfactant self-assembled tubes. The results enhance the spectrum of applications of supramolecular tubules and open up possibilities for investigating a novel class of biological amphiphiles.

Nanostructured materials based on the integration of ferrocenyl-tethered dendrimer and redox proteins on self-assembled monolayers: an efficient biosensor interface.

In this paper we report the use of ferrocenyl-tethered dendrimer (Fc-D) as an electrode modifier supported by a self-assembled monolayer coated gold surface. The pretreatment of electrodes with Fc-D allows the covalent immobilization of glucose oxidase. The resulting integrated hybrid system provides electrical contact between the redox center of the enzyme and the electrode, and improves the overall bioelectrocatalyzed oxidation of glucose. Cyclic voltammetry combined with surface plasmon resonance (SPR) is used to investigate the redox-induced orientation changes of ferrocene-tethered dendrimers and the optimal electrical wiring of the enzyme, depending on the length of the alkyl chain of the ferrocene-tethered groups. The amount of substrate controls the steady-state concentration ratio of Fc/Fc(+) in the film composition. Therefore, the SPR spectrum of the film is controlled by the reversible change in the refractive index of the enzyme-integrated redox film. The proposed method demonstrates a new procedure for developing a stable amperometric redox enzyme-based sensor by designing a new nanostructured material that control the biosensing performance.

Ferrocenyl alkanethiols-thio beta-cyclodextrin mixed self-assembled monolayers: evidence of ferrocene electron shuttling through the beta-cyclodextrin cavity.

This paper reports the preparation and characterization of an Au electrode modified with self-assembled alkane ferrocenes, in the absence and in the presence of beta-cyclodextrins (betaCD). Electrode modification with ferrocene derivatives was achieved through a self-assembled monolayer (SAM) approach, using ferrocenyl hexane thiol (FcC6) and ferrocenyl undecane thiol (FcC11); the same was also done using per-6-thio-beta-cyclodextrin. The different SAMs prepared were characterized by both cyclic voltammetry and electrochemical surface plasmon resonance (EC-SPR). The behavior of both single and binary monolayers including their interfacial reorganization was investigated and critically discussed, according to the nature of the SAM used. Cyclic voltammetry combined with SPR measurements revealed the reorientation of the SAM concomitant with the oxidation of ferrocene moieties. In particular, the electron shuttling of FcC11 through the betaCD cavity (mixed SAM) was also evidenced by both SPR and the electrocatalytic oxidation of ferro(II)cyanide.

Synthesis of alkyl-substituted six-membered lactones through ring-closing metathesis of homoallyl acrylates. An easy route to pyran-2-ones, constituents of tobacco flavor.

The ring-closing metathesis (RCM) reactions of homoallylic acrylates bearing alkyl substituents on various positions of their skeleton afford the corresponding pentenolides in the presence of carbene ruthenium catalysts. For R3 = R4 = H, or R3 = Me, R4 = H, the reactions are catalyzed by complex [RuCl2(PCy3)2(=CHPh)], while a second-generation Grubbs catalyst is required when R3 = H and R4 = Me, R3 = R4 = Me, or R3 = i-Pr and R4 = H. Alkyl substitution at the homoallylic carbon (R1, R2) increases the yield of the reaction when both the acrylic and/or homoallylic double bonds are methyl-substituted. The interaction of the catalyst with the substrate in the initiation stage involves the homoallylic double bond rather than the acrylic moiety, and the resulting alkylidene species from the first-generation Grubbs catalyst can be observed by 1H and 31P NMR. The racemic tobacco constituents 4-isopropyl-5,6-dihydropyran-2-one and 4-isopropyltetrahydropyran-2-one are prepared via a short reaction sequence, involving the RCM reaction as the key transformation.

Glutamate receptor incorporated in a mixed hybrid bilayer lipid membrane array, as a sensing element of a biosensor working under flowing conditions.

The realization of a reliable receptor biosensor requires stable, long-lasting, reconstituted biomembranes able to supply a suitable biomimetic environment where the receptor can properly work after incorporation. To this end, we developed a new method for preparing stable biological membranes that couple the biomimetic properties of BLMs (bilayer lipid membranes) with the high stability of HBMs (hybrid bilayer membranes); this gives rise to an innovative assembly, named MHBLM (mixed hybrid bilayer lipid membrane). The present work deals with the characterization of biosensors achieved by embedding an ionotropic glutamate receptor (GluR) on MHBLM. Thanks to signal (transmembrane current) amplification, which is typical of natural receptors, the biosensor here produced detects glutamate at a level of nmol L(-1). The transmembrane current changes linearly vs glutamate up to 100 nmol L(-1), while the limit of detection is 1 nmol L(-1). In addition, the biosensor response can be modulated both by receptor agonists (glycine) and antagonists (Mg(2+)) as well, and by exploiting the biosensor response, the distribution of different kinds of ionotropic GluR present in the purified sample, and embedded in MHBLM, was also evaluated. Finally, one of the most important aspects of this investigation is represented by the high stability of the biomimetic system, which allows the use of biosensor under flowing conditions, where the solutions flow on both biomembrane faces.

Synthesis of alpha,beta-unsaturated 4,5-disubstituted gamma-lactones via ring-closing metathesis catalyzed by the first-generation Grubbs' catalyst.

[reaction: see text] 4-Methyl-5-alkyl-2(5H)-furanones have been prepared by ruthenium-catalyzed ring-closing metathesis of the suitable methallyl acrylates. Despite the electron deficiency of the conjugated double bond and of the gem-disubstitution of the allylic alkene moiety in the starting acrylates, the first-generation Grubbs' catalyst I proved to be an effective promoter for the ring closure, affording the expected butenolides in good to high yields.