Complex structures arising from the self-assembly of a simple organic salt.

Molecular self-assembly is the spontaneous association of simple molecules into larger and ordered structures1. It is the basis of several natural processes, such as the formation of colloids, crystals, proteins, viruses and double-helical DNA2. Molecular self-assembly has inspired strategies for the rational design of materials with specific chemical and physical properties3, and is one of the most important concepts in supramolecular chemistry. Although molecular self-assembly has been extensively investigated, understanding the rules governing this phenomenon remains challenging. Here we report on a simple hydrochloride salt of fampridine that crystallizes as four different structures, two of which adopt unusual self-assemblies consisting of polyhedral clusters of chloride and pyridinium ions. These two structures represent Frank-Kasper (FK) phases of a small and rigid organic molecule. Although discovered in metal alloys4,5 more than 60 years ago, FK phases have recently been observed in several classes of supramolecular soft matter6-11 and in gold nanocrystal superlattices12 and remain the object of recent discoveries13. In these systems, atoms or spherical assemblies of molecules are packed to form polyhedra with coordination numbers 12, 14, 15 or 16. The two FK structures reported here crystallize from a dense liquid phase and show a complexity that is generally not observed in small rigid organic molecules. Investigation of the precursor dense liquid phase by cryogenic electron microscopy reveals the presence of spherical aggregates with sizes ranging between 1.5 and 4.6 nanometres. These structures, together with the experimental procedure used for their preparation, invite interesting speculation about their formation and open different perspectives for the design of organic crystalline materials.

Nanoporous Au Behavior in Methyl Orange Solutions.

Nanoporous (NP) gold, the most extensively studied and efficient NP metal, possesses exceptional properties that make it highly attractive for advanced technological applications. Notably, its remarkable catalytic properties in various significant reactions hold enormous potential. However, the exploration of its catalytic activity in the degradation of water pollutants remains limited. Nevertheless, previous research has reported the catalytic activity of NP Au in the degradation of methyl orange (MO), a toxic azo dye commonly found in water. This study aims to investigate the behavior of nanoporous gold in MO solutions using UV-Vis absorption spectroscopy and high-performance liquid chromatography. The NP Au was prepared by chemical removal of silver atoms of an AuAg precursor alloy prepared by ball milling. Immersion tests were conducted on both pellets and powders of NP Au, followed by examination of the residual solutions. Additionally, X-ray photoelectron spectroscopy and electrochemical impedance measurements were employed to analyze NP Au after the tests. The findings reveal that the predominant and faster process involves the partially reversible adsorption of MO onto NP Au, while the catalytic degradation of the dye plays a secondary and slower role in this system.

ADAM10 hyperactivation acts on piccolo to deplete synaptic vesicle stores in Huntington's disease.

Synaptic dysfunction and cognitive decline in Huntington's disease (HD) involve hyperactive A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). To identify the molecular mechanisms through which ADAM10 is associated with synaptic dysfunction in HD, we performed an immunoaffinity purification-mass spectrometry (IP-MS) study of endogenous ADAM10 in the brains of wild-type and HD mice. We found that proteins implicated in synapse organization, synaptic plasticity, and vesicle and organelles trafficking interact with ADAM10, suggesting that it may act as hub protein at the excitatory synapse. Importantly, the ADAM10 interactome is enriched in presynaptic proteins and ADAM10 co-immunoprecipitates with piccolo (PCLO), a key player in the recycling and maintenance of synaptic vesicles. In contrast, reduced ADAM10/PCLO immunoprecipitation occurs in the HD brain, with decreased density of synaptic vesicles in the reserve and docked pools at the HD presynaptic terminal. Conditional heterozygous deletion of ADAM10 in the forebrain of HD mice reduces active ADAM10 to wild-type level and normalizes ADAM10/PCLO complex formation and synaptic vesicle density and distribution. The results indicate that presynaptic ADAM10 and PCLO are a relevant component of HD pathogenesis.

Surface Compositional Change of Iron Oxide Porous Nanorods: A Route for Tuning their Magnetic Properties.

The capability of synthesizing specific nanoparticles (NPs) by varying their shape, size and composition in a controlled fashion represents a typical set of engineering tools that tune the NPs magnetic response via their anisotropy. In particular, variations in NP composition mainly affect the magnetocrystalline anisotropy component, while the different magnetic responses of NPs with isotropic (i.e., spherical) or elongated shapes are mainly caused by changes in their shape anisotropy. In this context, we propose a novel route to obtain monodispersed, partially hollow magnetite nanorods (NRs) by colloidal synthesis, in order to exploit their shape anisotropy to increase the related coercivity; we then modify their composition via a cation exchange (CE) approach. The combination of a synthetic and post-synthetic approach on NRs gave rise to dramatic variations in their magnetic features, with the pores causing an initial magnetic hardening that was further enhanced by the post-synthetic introduction of a manganese oxide shell. Indeed, the coupling of the core and shell ferrimagnetic phases led to even harder magnetic NRs.

Increased Antibacterial and Antibiofilm Properties of Silver Nanoparticles Using Silver Fluoride as Precursor.

Silver nanoparticles were produced with AgF as the starting Ag(I) salt, with pectin as the reductant and protecting agent. While the obtained nanoparticles (pAgNP-F) have the same dimensional and physicochemical properties as those already described by us and obtained from AgNO3 and pectin (pAgNP-N), the silver nanoparticles from AgF display an increased antibacterial activity against E. coli PHL628 and Staphylococcus epidermidis RP62A (S. epidermidis RP62A), both as planktonic strains and as their biofilms with respect to pAgNP-N. In particular, a comparison of the antimicrobial and antibiofilm action of pAgNP-F has been carried out with pAgNP-N, pAgNP-N and added NaF, pure AgNO3, pure AgF, AgNO3 and added NaF and pure NaNO3 and NaF salts. By also measuring the concentration of the Ag+ cation released by pAgNP-F and pAgNP-N, we were able to unravel the separate contributions of each potential antibacterial agent, observing an evident synergy between p-AgNP and the F- anion: the F- anion increases the antibacterial power of the p-AgNP solutions even when F- is just 10 µM, a concentration at which F- alone (i.e., as its Na+ salt) is completely ineffective.

Evolution of nanomechanical properties and crystallinity of individual titanium dioxide nanotube resonators.

Herein a complete characterization of single TiO2 nanotube resonator was reported for the first time. The modal vibration response analysis allows a non-invasive indirect evaluation of the mechanical properties of the TiO2 nanotube. The effect of post-grown thermal treatments on nanotube mechanical properties was investigated and carefully correlated to the chemico-physical parameters evolution. The Young's modulus of TiO2 nanotube rises linearly from 57 GPa up to 105 GPa for annealing at 600 °C depending on the compositional and crystallographic evolution of the nanostructure. Considering the growing interest in single nanostructure devices, the reported findings allow a deeper understanding of the properties of individual titanium dioxide nanotubes extrapolated from their standard arrayed architecture.

Pharmacological Modulation of AMPAR Rescues Intellectual Disability-Like Phenotype in Tm4sf2-/y Mice.

Intellectual disability affects 2-3% of the world's population and typically begins during childhood, causing impairments in social skills and cognitive abilities. Mutations in the TM4SF2 gene, which encodes the TSPAN7 protein, cause a severe form of intellectual disability, and currently, no therapy is able to ameliorate this cognitive impairment. We previously reported that, in cultured neurons, shRNA-mediated down-regulation of TSPAN7 affects AMPAR trafficking by enhancing PICK1-GluA2 interaction, thereby increasing the intracellular retention of AMPAR. Here, we found that loss of TSPAN7 function in mice causes alterations in hippocampal excitatory synapse structure and functionality as well as cognitive impairment. These changes occurred along with alterations in AMPAR expression levels. We also found that interfering with PICK1-GluA2 binding restored synaptic function in Tm4sf2-/y mice. Moreover, potentiation of AMPAR activity via the administration of the ampakine CX516 reverted the neurological phenotype observed in Tm4sf2-/y mice, suggesting that pharmacological modulation of AMPAR may represent a new approach for treating patients affected by TM4SF2 mutations and intellectual disability.

Lipid droplets: a new player in colorectal cancer stem cells unveiled by spectroscopic imaging.

The cancer stem cell (CSC) model is describing tumors as a hierarchical organized system and CSCs are suggested to be responsible for cancer recurrence after therapy. The identification of specific markers of CSCs is therefore of paramount importance. Here, we show that high levels of lipid droplets (LDs) are a distinctive mark of CSCs in colorectal (CR) cancer. This increased lipid content was clearly revealed by label-free Raman spectroscopy and it directly correlates with well-accepted CR-CSC markers as CD133 and Wnt pathway activity. By xenotransplantation experiments, we have finally demonstrated that CR-CSCs overexpressing LDs retain most tumorigenic potential. A relevant conceptual advance in this work is the demonstration that a cellular organelle, the LD, is a signature of CSCs, in addition to molecular markers. A further functional characterization of LDs could lead soon to design new target therapies against CR-CSCs.

Manganese doped-iron oxide nanoparticle clusters and their potential as agents for magnetic resonance imaging and hyperthermia.

A simple, one pot method to synthesize water-dispersible Mn doped iron oxide colloidal clusters constructed of nanoparticles arranged into secondary flower-like structures was developed. This method allows the successful incorporation and homogeneous distribution of Mn within the nanoparticle iron oxide clusters. The formed clusters retain the desired morphological and structural features observed for pure iron oxide clusters, but possess intrinsic magnetic properties that arise from Mn doping. They show distinct performance as imaging contrast agents and excellent characteristics as heating mediators in magnetic fluid hyperthermia. It is expected that the outcomes of this study will open up new avenues for the exploitation of doped magnetic nanoparticle assemblies in biomedicine.

Writing and functionalisation of suspended DNA nanowires on superhydrophobic pillar arrays.

Nanowire arrays and networks with precisely controlled patterns are very interesting for innovative device concepts in mesoscopic physics. In particular, DNA templates have proven to be versatile for the fabrication of complex structures that obtained functionality via combinations with other materials, for example by functionalisation with molecules or nanoparticles, or by coating with metals. Here, the controlled motion of the a three-phase contact line (TCL) of DNA-loaded drops on superhydrophobic substrates is used to fabricate suspended nanowire arrays. In particular, the deposition of DNA wires is imaged in situ, and different patterns are obtained on hexagonal pillar arrays by controlling the TCL velocity and direction. Robust conductive wires and networks are achieved by coating the wires with a thin layer of gold, and as proof of concept conductivity measurements are performed on single suspended wires. The plastic material of the superhydrophobic pillars ensures electrical isolation from the substrate. The more general versatility of these suspended nanowire networks as functional templates is outlined by fabricating hybrid organic-metal-semiconductor nanowires by growing ZnO nanocrystals onto the metal-coated nanowires.

Tuning light emission of PbS nanocrystals from infrared to visible range by cation exchange.

Colloidal semiconductor nanocrystals, with intense and sharp-line emission between red and near-infrared spectral regions, are of great interest for optoelectronic and bio-imaging applications. The growth of an inorganic passivation layer on nanocrystal surfaces is a common strategy to improve their chemical and optical stability and their photoluminescence quantum yield. In particular, cation exchange is a suitable approach for shell growth at the expense of the nanocrystal core size. Here, the cation exchange process is used to promote the formation of a CdS passivation layer on the surface of very small PbS nanocrystals (2.3 nm in diameter), blue shifting their optical spectra and yielding luminescent and stable nanostructures emitting in the range of 700-850 nm. Structural, morphological and compositional investigation confirms the nanocrystal size contraction after the cation-exchange process, while the PbS rock-salt crystalline phase is retained. Absorption and photoluminescence spectroscopy demonstrate the growth of a passivation layer with a decrease of the PbS core size, as inferred by the blue-shift of the excitonic peaks. The surface passivation strongly increases the photoluminescence intensity and the excited state lifetime. In addition, the nanocrystals reveal increased stability against oxidation over time. Thanks to their absorption and emission spectral range and the slow recombination dynamics, such highly luminescent nano-objects can find interesting applications in sensitized photovoltaic cells and light-emitting devices.

Dipolar rotors orderly aligned in mesoporous fluorinated organosilica architectures.

New mesoporous covalent frameworks, based on hybrid fluorinated organosilicas, were prepared to realize a periodic architecture of fast molecular rotors containing dynamic dipoles in their structure. The mobile elements, designed on the basis of fluorinated p-divinylbenzene moieties, were integrated into the robust covalent structure through siloxane bonds, and showed not only the rapid dynamics of the aromatic rings (ca. 10(8) Hz at 325 K), as detected by solid-state NMR spectroscopy, but also a dielectric response typical of a fast dipole reorientation under the stimuli of an applied electric field. Furthermore, the mesochannels are open and accessible to diffusing in gas molecules, and rotor mobility could be individually regulated by I2 vapors. The iodine enters the channels of the periodic structure and reacts with the pivotal double bonds of the divinyl-fluoro-phenylene rotors, affecting their motion and the dielectric properties.

Hybrid assemblies of fluorescent nanocrystals and membrane proteins in liposomes.

Because of the growing potential of nanoparticles in biological and medical applications, tuning and directing their properties toward a high compatibility with the aqueous biological milieu is of remarkable relevance. Moreover, the capability to combine nanocrystals (NCs) with biomolecules, such as proteins, offers great opportunities to design hybrid systems for both nanobiotechnology and biomedical technology. Here we report on the application of the micelle-to-vesicle transition (MVT) method for incorporation of hydrophobic, red-emitting CdSe@ZnS NCs into the bilayer of liposomes. This method enabled the construction of a novel hybrid proteo-NC-liposome containing, as model membrane protein, the photosynthetic reaction center (RC) of Rhodobacter sphaeroides. Electron microscopy confirmed the insertion of NCs within the lipid bilayer without significantly altering the structure of the unilamellar vesicles. The resulting aqueous NC-liposome suspensions showed low turbidity and kept unaltered the wavelengths of absorbance and emission peaks of the native NCs. A relative NC fluorescence quantum yield up to 8% was preserved after their incorporation in liposomes. Interestingly, in proteo-NC-liposomes, RC is not denatured by Cd-based NCs, retaining its structural and functional integrity as shown by absorption spectra and flash-induced charge recombination kinetics. The outlined strategy can be extended in principle to any suitably sized hydrophobic NC with similar surface chemistry and to any integral protein complex. Furthermore, the proposed approach could be used in nanomedicine for the realization of theranostic systems and provides new, interesting perspectives for understanding the interactions between integral membrane proteins and nanoparticles, i.e., in nanotoxicology studies.

Increased genomic instability and reshaping of tissue microenvironment underlie oncogenic properties of Arid1a mutations.

Oncogenic mutations accumulating in many chromatin-associated proteins have been identified in different tumor types. With a mutation rate from 10 to 57%, ARID1A has been widely considered a tumor suppressor gene. However, whether this role is mainly due to its transcriptional-related activities or its ability to preserve genome integrity is still a matter of intense debate. Here, we show that ARID1A is largely dispensable for preserving enhancer-dependent transcriptional regulation, being ARID1B sufficient and required to compensate for ARID1A loss. We provide in vivo evidence that ARID1A is mainly required to preserve genomic integrity in adult tissues. ARID1A loss primarily results in DNA damage accumulation, interferon type I response activation, and chronic inflammation leading to tumor formation. Our data suggest that in healthy tissues, the increased genomic instability that follows ARID1A mutations and the selective pressure imposed by the microenvironment might result in the emergence of aggressive, possibly immune-resistant, tumors.

Direct imaging of DNA fibers: the visage of double helix.

Direct imaging becomes important when the knowledge at few/single molecule level is requested and where the diffraction does not allow to get structural and functional information. Here we report on the direct imaging of double stranded (ds) λ-DNA in the A conformation, obtained by combining a novel sample preparation method based on super hydrophobic DNA molecules self-aggregation process with transmission electron microscopy (TEM). The experimental breakthrough is the production of robust and highly ordered paired DNA nanofibers that allowed its direct TEM imaging and the double helix structure revealing.

Engineering the structural and electrical interplay of nanostructured Au resistive switching networks by controlling the forming process.

Networks of random-assembled gold clusters produced in the gas phase show resistive switching (RS) activity at room temperature and they are suitable for the fabrication of devices for neuromorphic data processing and classification. Fully connected cluster-assembled nanostructured Au films are characterized by a granular structure rich of interfaces, grain boundaries and crystalline defects. Here we report a systematic characterization of the electroforming process of the cluster-assembled films demonstrating how this process affects the interplay between the nano- and mesoscale film structure and the neuromorphic characteristics of the resistive switching activity. The understanding and the control of the influence of the resistive switching forming process on the organization of specific structures at different scales of the cluster-assembled films, provide the possibility to engineer random-assembled neuromorphic architectures for data processing task.

Thermally Promoted Cation Exchange at the Solid State in the Transmission Electron Microscope: How It Actually Works.

Cation exchange offers a strong postsynthetic tool for nanoparticles that are unachievable via direct synthesis, but its velocity makes observing the onset of the reaction in the liquid state almost impossible. After successfully proving that cation exchange reactions can be triggered, performed, and followed live at the solid state by an in situ transmission electron microscopy approach, we studied the deep mechanisms ruling the onset of cation exchange reactions, i.e., the adsorption, penetration, and diffusion of cations in the host matrices of two crystal phases of CdSe. Exploiting an in situ scanning transmission electron microscopy approach with a latest generation heating holder, we were able to trigger, freeze, and image the initial stages of cation exchange with much higher detail. Also, we found a connection between the crystal structure of CdSe, the starting temperature, and the route of the cation exchange reaction. All the experimental results were further reviewed by molecular dynamics simulations of the whole cation exchange reaction divided in subsequent steps. The simulations highlighted how the cation exchange mechanism and the activation energies change with the host crystal structures. Furthermore, the simulative results strongly corroborated the activation temperatures and the cation exchange rates obtained experimentally, providing a deeper understanding of its phenomenology and mechanism at the atomic scale.

Synthesis and Characterization of Gd-Functionalized B4C Nanoparticles for BNCT Applications.

Inorganic nanoparticles of boron-rich compounds represent an attractive alternative to boron-containing molecules, such as boronophenylalanine or boranes, for BNCT applications. This work describes the synthesis and biological activity of multifunctional boron carbide nanoparticles stabilized with polyacrylic acid (PAA) and a gadolinium (Gd)-rich solid phase. A fluorophore (DiI) was included in the PAA functionalization, allowing the confocal microscopy imaging of the nanoparticles. Analysis of the interaction and activity of these fluorescent Gd-containing B4C nanoparticles (FGdBNPs) with cultured cells was appraised using an innovative correlative microscopy approach combining intracellular neutron autoradiography, confocal, and SEM imaging. This new approach allows visualizing the cells, the FGdBNP, and the events deriving from the nuclear process in the same image. Quantification of 10B by neutron autoradiography in cells treated with FGdBNPs confirmed a significant accumulation of NPs with low levels of cellular toxicity. These results suggest that these NPs might represent a valuable tool for achieving a high boron concentration in tumoral cells.

The big impact of a small detail: cobalt nanocrystal polymorphism as a result of precursor addition rate during stock solution preparation.

The control of nanocrystal structures at will is still a challenge, despite the recent progress of colloidal synthetic procedures. It is common knowledge that even small modifications of the reaction parameters during synthesis can alter the characteristics of the resulting nano-objects. In this work we report an unexpected factor which determines the structure of cobalt nanoparticles. Nanocrystals of distinctly different sizes and shapes have resulted from stock solutions containing exactly the same concentrations of [Co{N(SiMe(3))(2)}(2)(thf)], hexadecylamine, and lauric acid. The reduction reaction itself has been performed under identical conditions. In an effort to explain these differences and to analyze the reaction components and any molecular intermediates, we have discovered that the rate at which the cobalt precursor is added to the ligand solution during the stock solution preparation at room temperature becomes determinant by triggering off a nonanticipated side reaction which consumes part of the lauric acid, the main stabilizing ligand, transforming it to a silyl ester. Thus, an innocent mixing, apparently not related to the main reaction which produces the nanoparticles, becomes the parameter which in fine defines nanocrystal characteristics. This side reaction affects in a similar way the morphology of iron nanoparticles prepared from an analogous iron precursor and the same long chain stabilizing ligands. Side reactions are potentially operational in a great number of systems yielding nanocrystals, despite the fact that they are very rarely mentioned in the literature.

Controlled synthesis of gold nanostars by using a zwitterionic surfactant.

By replacing cetyltrimethylammonium bromide (CTAB) with the zwitterionic lauryl sulfobetaine (LSB) surfactant in the classical seed-growth synthesis, monocrystalline gold nanostars (m-NS) and pentatwinned gold asymmetric nanostars (a-NS) were obtained instead of nanorods. The main product under all synthetic conditions was a-NS, which have branches with high aspect ratios (AR), thus leading to LSPR absorptions in the 750-1150 nm range. The percentage of m-NS versus a-NS, the aspect ratio of the a-NS branches, and consequently the position of their LSPR absorption can be finely tuned simply by regulating the concentration of reductant, the concentration of surfactant, or the concentration of the "catalytic" Ag(+) cation. The m-NS have instead shorter and larger branches, the AR of which is poorly influenced by synthetic conditions and displays an LSPR positioned around 700 nm. A growth mechanism that involves the direct contact of the sulfate moiety of LSB on the surface of the nano-object is proposed, thereby implying preferential coating of the {111} Au faces with weak interactions. Consistent with this, we also observed the straightforward complete displacement of the LSB surfactant from the surface of the nanostars. This was obtained by the simple addition of thiols in aqueous solution to yield extremely stable coated a-NS and m-NS that are resistant to highly acidic, basic, and in similar to in vivo conditions.