Regioselectivity Control in Spirobifluorene Nitration under Mild Conditions: Explaining the Crivello's Reagent Mechanism.

The regioselective nitration of 9,9'-spirobifluorene under mild conditions is reported for the first time by operating under Menke's and Crivello's conditions. The optimized protocol allows obtaining 2-nitro and 2,2'-dinitro-9,9'-spirobifluorene in yields of 79 and 95% and, for the first time, 2,2',7-trinitro-9,9'-spirobifluorene with 66% yield. Besides, the role of dinitrate salt in Crivello's protocol has been now clarified, which opens novel scenarios in the preparation of functional materials.

Thermally Activable Bistetrazoles for Elastomers Crosslinking.

Sulfur vulcanization is the most used method for curing of natural and synthetic rubbers. The crosslinking degree achieved is usually controlled by adding proper quantities of accelerants, activators, co-activators, retardants, and inhibitors, and influences the hardness, elasticity, hysteresis of elastomers and, consequently, the properties and behavior of the materials that incorporate them. Despite the fine tuning pursued over the years, sulfur crosslinking is still difficult to control both in terms of degree and homogeneity of cross-link. Addition of thermally activable bifunctional reagents able to crosslink the polymer matrix through covalent bonds could be a strategy to modulate and control finely the reticulation grade of elastomers. Tetrazoles can form highly reactive nitrilimines by thermal treatment at appropriate temperature, which can react with the vinyl double bonds present in the rubber. In this work a set of bis-tetrazoles were synthesized and those with the right activation temperatures were used for the curing of styrene-butadiene rubber, acting both as single crosslinkers and together with classic sulfur-based ones. The addition of bistetrazoles simplified and made more efficient the compounding process, allowing to prolong the mixing until optimum dispersion and homogeneity were obtained. Moreover, they led to an improvement in the hysteretic properties of the compound and to the reduction of the non-linearity of the dynamic behavior (Payne effect).

Pushing Down the Limit of NH3 Detection of Graphene-Based Chemiresistive Sensors through Functionalization by Thermally Activated Tetrazoles Dimerization.

An easy and cost-effective method is presented to functionalize graphene through thermally activated dimerization of 2,5-diaryltetrazoles. Consistently with the experimental spectroscopic results, theoretical calculations demonstrate that during the thermal treatment a dimerization process to tetrazine is energetically more favorable than covalent grafting. Since both the functionalization method by thermal activation and the use of tetrazoles have never been considered before to prepare graphene-based chemiresistors, this represents a promising approach to develop graphene-related sensing platforms. Five different 2,5-diaryltetrazoles have been tested here for the effective functionalization of low-defect graphene layers on silicon nitride. Based on these layers, an array of sensors has been prepared for testing upon ammonia exposure. The tests on the sensing performances clearly show sensitivity to ammonia, extending the current range of ammonia detection with a graphene-based chemiresistor down to the sub-ppm range, as results from a benchmarking with data available in the literature. Furthermore, all sensors perform better than bare graphene. Density functional theory (DFT) calculations, carried out on a model of the best performing layer of the array, provided the theoretical framework to rationalize the sensing mechanism and disclose a dual role played by the tetrazine molecules, (i) acting as ammonia concentrators and (ii) mediating the electron transfer between ammonia and graphene.

Bypassing the statistical limit of singlet generation in sensitized upconversion using fluorinated conjugated systems.

The photon upconversion based on triplet-triplet annihilation (TTA) is a mechanism that converts the absorbed low-energy electromagnetic radiation into higher energy photons also at extremely low excitation intensities, but its use in actual technologies is still hindered by the limited availability of efficient annihilator moieties. We present here the results obtained by the synthesis and application of two new fluorinated chromophores based on phenazine and acridine structures, respectively. Both compounds show upconverted emission demonstrating their ability as TTA annihilator. More interesting, the acridine-based chromophore shows an excellent TTA yield that overcomes the one of some of best model systems. By correlating the experimental data and the quantum mechanical modeling of the investigated compound, we propose an alternative efficient pathway for the generation of the upconverted emissive states involving the peculiar high-energy triplet levels of the dye, thus suggesting a new development strategy for TTA annihilators based on the fine tuning of their high-energy excited states properties.

Modular Synthetic Routes to Fluorine-Containing Halogenated Phenazine and Acridine Agents That Induce Rapid Iron Starvation in Methicillin-Resistant Staphylococcus aureus Biofilms.

During infection, bacteria use an arsenal of resistance mechanisms to negate antibiotic therapies. In addition, pathogenic bacteria form surface-attached biofilms bearing enriched populations of metabolically dormant persister cells. Bacteria develop resistance in response to antibiotic insults; however, nonreplicating biofilms are innately tolerant to all classes of antibiotics. As such, molecules that can eradicate antibiotic-resistant and antibiotic-tolerant bacteria are of importance. Here, we report modular synthetic routes to fluorine-containing halogenated phenazine (HP) and halogenated acridine (HA) agents with potent antibacterial and biofilm-killing activities. Nine fluorinated phenazines were rapidly accessed through a synthetic strategy involving (1) oxidation of fluorinated anilines to azobenzene intermediates, (2) SNAr with 2-methoxyaniline, and (3) cyclization to phenazines upon treatment with trifluoroacetic acid. Five structurally related acridine heterocycles were synthesized using SNAr and Buchwald-Hartwig approaches. From this focused collection, phenazines 5g, 5h, 5i, and acridine 9c demonstrated potent antibacterial activities against Gram-positive pathogens (MIC = 0.04-0.78 µM). Additionally, 5g and 9c eradicated Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis biofilms with excellent potency (5g, MBEC = 4.69-6.25 µM; 9c, MBEC = 4.69-50 µM). Using real-time quantitative polymerase chain reaction (RT-qPCR), 5g, 5h, 5i, and 9c rapidly induce the transcription of iron uptake biomarkers isdB and sbnC in methicillin-resistant S. aureus (MRSA) biofilms, and we conclude that these agents operate through iron starvation. Overall, fluorinated phenazine and acridine agents could lead to ground-breaking advances in the treatment of challenging bacterial infections.

Photoinduced Porcine Gelatin Cross-Linking by Homobi- and Homotrifunctional Tetrazoles.

Gelatin is a costless polypeptide material of natural origin, able to form hydrogels that are potentially useful in biomaterial scaffold design for drug delivery, cell cultures, and tissue engineering. However, gelatin hydrogels are unstable at physiological conditions, losing their features only after a few minutes at 37 °C. Accordingly, treatments to address this issue are of great interest. In the present work, we propose for the first time the use of bi- and trifunctional tetrazoles, most of them unknown to date, for photoinduced gelatin cross-linking towards the production of physiologically stable hydrogels. Indeed, after UV-B irradiation, aryl tetrazoles generate a nitrilimine intermediate that is reactive towards different functionalities, some of them constitutively present in the amino acid side chains of gelatin. The efficacy of the treatment strictly depends on the structure of the cross-linking agent used, and substantial improved stability was observed by switching from bifunctional to trifunctional cross-linkers.

Morphological characterization and electronic properties of pristine and oxygen-exposed graphene nanoribbons on Ag(110).

Graphene nanoribbons (GNRs) are at the frontier of research on graphene materials since the 1D quantum confinement of electrons allows for the opening of an energy gap. GNRs of uniform and well-defined size and shape can be grown using the bottom-up approach, i.e. by surface assisted polymerization of aromatic hydrocarbons. Since the electronic properties of the nanostructures depend on their width and on their edge states, by careful choice of the precursor molecule it is possible to design GNRs with tailored properties. A key issue for their application in nanoelectronics is their stability under operative conditions. Here, we characterize pristine and oxygen-exposed 1.0 nm wide GNRs with a well-defined mixed edge-site sequence (two zig-zag and one armchair) synthesized on Ag(110) from 1,6-dibromo-pyrene precursors. The energy gap and the presence of quantum confined states are investigated by scanning tunneling spectroscopy. The effect of oxygen exposure under ultra-high vacuum conditions is inferred from scanning tunneling microscopy images and photoemission spectra. Our results demonstrate that oxygen exposure deeply affects the overall system by interacting both with the nanoribbons and with the substrate; this factor must be considered for supported GNRs under operative conditions.

Gelatin-Based Hydrogels through Homobifunctional Triazolinediones Targeting Tyrosine Residues.

Gelatin is a biopolymer with interesting properties that can be useful for biomaterial design for different applications such as drug delivery systems, or 3D scaffolds for tissue engineering. However, gelatin suffers from poor mechanical stability at physiological temperature, hence methods for improving its properties are highly desirable. In the present work, a new chemical cross-linking strategy based on triazolinedione ene-type chemistry towards stable hydrogel is proposed. Two different homobifunctional 1,2,4-triazoline-3,5(4H)-diones, namely 4,4'-hexane-1,6-diylbis(3H-1,2,4-triazoline-3,5(4H)-dione) 1 and 4,4'-[methylenebis(4,1-phenylene)]bis(3H-1,2,4-triazoline-3,5(4H)-dione) 2 were used as cross-linkers in different ratio to tyrosine residues in gelatin. The reaction was proved effective in all experimented conditions and hydrogels featured with different thermal stability were obtained. In general, the higher the cross-linker/tyrosine ratio, the more thermostable the hydrogel. The swelling properties are strictly dependent upon the chemical nature of the cross-linker.

Synthesis of corrugated C-based nanostructures by Br-corannulene oligomerization.

The structure and electronic properties of carbon-based nanostructures obtained by metal surface assisted synthesis is highly dependent on the nature of the precursor molecule. Here, we report on a combined scanning tunneling microscopy, soft X-ray spectroscopy and density functional theory investigation on the surface assisted polymerization of Br-corannulene at Ag(110) and on the possibility of building a mesh of π-conjugated polymers starting from buckyball shaped molecules. Indeed, the corannulene units form one-molecule-wide ribbons in which the natural concavity of the precursor molecule is maintained. These C-based nanostructures are corrugated and merge into a covalent network on the surface.

Synthesis of graphene nanoribbons with a defined mixed edge-site sequence by surface assisted polymerization of (1,6)-dibromopyrene on Ag(110).

By a combination of scanning tunneling microscopy, X-ray spectroscopic techniques and density functional theory calculations, we prove the formation of extended patterns of parallel, graphene nanoribbons with alternate zig-zag and armchair edges and selected width by surface-assisted Ullmann coupling polymerization and dehydrogenation of 1,6-dibromopyrene (C16H8Br2). Besides the relevance of these nanostructures for their possible application in nanodevices, we demonstrate the peculiarity of halogenated pyrene derivatives for the formation of nanoribbons, in particular on Ag(110). These results open the possibility of tuning the shape and dimension of nanoribbons (and hence the correlated electronic properties) by choosing suitably tailored or on-purpose designed molecular precursors.

On-surface photo-dissociation of C-Br bonds: towards room temperature Ullmann coupling.

The surface-assisted synthesis of gold-organometallic hybrids on the Au(111) surface both by thermo- and light-initiated dehalogenation of bromo-substituted tetracene is reported. Combined X-ray photoemission (XPS) and scanning tunneling microscopy (STM) data reveal a significant increase of the surface order when mild reaction conditions are combined with 405 nm light irradiation.

Control of the intermolecular coupling of dibromotetracene on Cu(110) by the sequential activation of C-Br and C-H bonds.

Dibromotetracene molecules are deposited on the Cu(110) surface at room temperature. The complex evolution of this system has been monitored at different temperatures (i.e., 298, 523, 673, and 723 K) by means of a variety of complementary techniques that range from STM and temperature-programmed desorption (TPD) to high-resolution X-ray spectroscopy (XPS) and near-edge X-ray absorption fine structure spectroscopy (NEXAFS). State-of-the-art density-functional calculations were used to determine the chemical processes that take place on the surface. After deposition at room temperature, the organic molecules are transformed into organometallic monomers through debromination and carbon-radical binding to copper adatoms. Organometallic dimers, trimers, or small oligomers, which present copper-bridged molecules, are formed by increasing the temperature. Surprisingly, further heating to 673 K causes the formation of elongated chains along the Cu(110) close-packed rows as a consequence of radical-site migration to the thermodynamically more stable molecule heads. Finally, massive dehydrogenation occurs at the highest temperature followed by ring condensation to nanographenic patches. This study is a paradigmatic example of how intermolecular coupling can be modulated by the stepwise control of a simple parameter, such as temperature, through a sequence of domino reactions.

CHOLINE TRANSPORTER-LIKE1 is required for sieve plate development to mediate long-distance cell-to-cell communication.

Phloem, a plant tissue responsible for long-distance molecular transport, harbours specific junctions, sieve areas, between the conducting cells. To date, little is known about the molecular framework related to the biogenesis of these sieve areas. Here we identify mutations at the CHER1/AtCTL1 locus of Arabidopsis thaliana. The mutations cause several phenotypic abnormalities, including reduced pore density and altered pore structure in the sieve areas associated with impaired phloem function. CHER1 encodes a member of a poorly characterized choline transporter-like protein family in plants and animals. We show that CHER1 facilitates choline transport, localizes to the trans-Golgi network, and during cytokinesis is associated with the phragmoplast. Consistent with its function in the elaboration of the sieve areas, CHER1 has a sustained, polar localization in the forming sieve plates. Our results indicate that the regulation of choline levels is crucial for phloem development and conductivity in plants.

Thiol-ene mediated neoglycosylation of collagen patches: a preliminary study.

Despite the relevance of carbohydrates as cues in eliciting specific biological responses, the covalent surface modification of collagen-based matrices with small carbohydrate epitopes has been scarcely investigated. We report thereby the development of an efficient procedure for the chemoselective neoglycosylation of collagen matrices (patches) via a thiol-ene approach, between alkene-derived monosaccharides and the thiol-functionalized material surface. Synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), Fourier transform-infrared (FT-IR), and enzyme-linked lectin assay (ELLA) confirmed the effectiveness of the collagen neoglycosylation. Preliminary biological evaluation in osteoarthritic models is reported. The proposed methodology can be extended to any thiolated surface for the development of smart biomaterials for innovative approaches in regenerative medicine.

Electroless silver plating of the surface of organic semiconductors.

The integration of nanoscale processes and devices demands fabrication routes involving rapid, cost-effective steps, preferably carried out under ambient conditions. The realization of the metal/organic semiconductor interface is one of the most demanding steps of device fabrication, since it requires mechanical and/or thermal treatments which increment costs and are often harmful in respect to the active layer. Here, we provide a microscopic analysis of a room temperature, electroless process aimed at the deposition of a nanostructured metallic silver layer with controlled coverage atop the surface of single crystals and thin films of organic semiconductors. This process relies on the reaction of aqueous AgF solutions with the nonwettable crystalline surface of donor-type organic semiconductors. It is observed that the formation of a uniform layer of silver nanoparticles can be accomplished within 20 min contact time. The electrical characterization of two-terminal devices performed before and after the aforementioned treatment shows that the metal deposition process is associated with a redox reaction causing the p-doping of the semiconductor.

Polarized absorption, spontaneous and stimulated blue light emission of J-type tetraphenylbutadiene monocrystals.

Blue amplified spontaneous emission at room temperature is demonstrated from the exposed face of the strongly emitting organic semiconductor 1,1,4,4-tetraphenyl-1,3-butadiene in single crystal form. The symmetry of the crystal and calculation of lattice sums indicate the J-type organization of the molecular transition moments. The minimum in the lowest exciton dispersion branch, from which emission takes place, is found at the edge of the Brillouin zone leading to a dominant vibronic emission since the zero-phonon line is forbidden. The observed gain narrowed line is attributed to the vibronic replica which becomes amplified with increased pumping. The reported emission is along the normal to the exposed crystal face, important for the development of vertical cavity geometry lasers based on organic single crystals. The threshold excitation fluence of 400 microJ cm(-2) is comparable to other organic crystalline systems, even if the amplification path is much reduced as a consequence of the vertical geometry. Considering these relevant aspects, the optical characterization of this material is provided. The polarized absorption spectra are reported and the properties of the lowest-energy excitonic state investigated. Calculation of the electronic transitions for the isolated molecule, lattice sums for the transition at lowest energy, and the symmetry of the crystal allow attributing the largest face of the samples and the observed optical bands in the spectra. Polarized time-resolved spectra are also reported allowing to identify the intrinsic excitonic emission.

Hyaluronic acid in hydrophilic contact lenses: spectroscopic investigation of the content and release in solution.

Two experimental spectroscopic methods for the determination of the content of hyaluronic acid in solution are provided based on the formation of complexes between the hyaluronic acid and cationic dyes with sensitivity down to concentrations of either 0.25 or 2.5 microg/ml. These techniques were applied to commercial hydrophilic contact lenses and allowed (i) distinguishing among contact lenses either loaded or non-loaded with hyaluronic acid, (ii) determining, for the loaded ones, the content of hyaluronic acid, (iii) evaluating the release of hyaluronic acid by the lens in solution, and (iv) determining the role of the hyaluronic acid in preventing the adsorption and the successive release by the contact lens of other components which can be present, for example, in the conservation solutions and/or in the blisters of the lenses. The results represent new physical chemistry insights for the field of contact lenses with impact on the advancement of current technology.

Organic-organic epitaxy of incommensurate systems: quaterthiophene on potassium hydrogen phthalate single crystals.

Hot-wall epitaxy and molecular-beam epitaxy have been employed for growing quaterthiophene thin films on the (010) cleavage face of potassium hydrogen phthalate, and the results are compared in terms of film properties and growth mode. Even if there is no geometrical match between substrate and overlayer lattices, these films are epitaxially oriented. To investigate the physical rationale for this strong orientation effect, optical microscopy, atomic force microscopy, and X-ray diffraction are employed. A clear correlation between the morphology of the thin films and the crystallographic orientation is found. The results are also validated by surface potential calculations, which demonstrate the primary role played by the corrugation of the substrate surface.

Choline and phosphatidylcholine fluorescent derivatives localization in carcinoma cells studied by laser scanning confocal fluorescence microscopy.

In this study, we have shown the intracellular distribution of choline and phosphatidylcholine fluorescent derivatives in human breast carcinoma cells using confocal microscopy. The fluorescent choline derivatives ethanamimium 2-hydroxy-N,N-dimethyl-N-[2-N-(2,1,3-benzoxadiazol-4-amine,-N-methyl,-7- nitro)-ethyl] bromide (NBD-choline) and C(6)-NBD-phosphatidylcholine (C(6)-NBD-PC) were used in this work. NBD-choline was easily internalised into drug sensitive MCF-7 and in multidrug resistant MCF-7/DX cells. The probe was found to localise in the endoplasmic reticulum of sensitive cells and in the Golgi of multidrug resistant cells. In contrast, very low accumulation was found in normal MCF10A cells. For C(6)-NBD-PC, a similar pattern of localisation was found in tumour cells, but a significant uptake was also observed in normal cells. Unlike NBD-choline, C(6)-NBD-PC appears not to discriminate between normal and tumour cells. These results are consistent with previously published results showing higher levels of (11)C-choline uptake in malignant lesions seen with positron emission tomography (PET) in vivo imaging. Our results suggest that using NBD-choline and laser scanning confocal fluorescence microscopy (LSCFM) could be a useful tool to study choline metabolism in cancer cells and to consolidate PET imaging findings.