Synthesis of Photoluminescent 2D Self-Assembled Silver Thiolate Nanoclusters for Sensors and Biomolecule Support.

Silver thiolate nanoclusters (Ag NCs) show distinctive optical properties resulting from their hybrid nature, metallic and molecular, exhibiting size-, structure-, and surface-dependent photoluminescence, thus enabling the exploitation of Ag NCs for potential applications in nanobiotechnology, catalysis, and biomedicine. However, tailoring Ag NCs for specific applications requires achieving long-term stability and may involve modifying surface chemistry, fine-tuning ligand composition, or adding functional groups. In this study, we report the synthesis of novel Ag NCs using 2-ethanephenylthiolate (SR) as a ligand, highlight critical points addressing stability, and characterize their optical and structural properties. A preliminary electrical characterization revealed high anisotropy, well suited for potential use in electronics/sensing applications. We also present the synthesis and characterization of Ag NCs using 10-carboxylic 2-ol thiolate (SR'COOH) having a terminal carboxylic group for conjugation with amine-containing molecules. We present a preliminary assessment of its bioconjugation capability using bovine serum albumin as a model protein indicating its prospective application as a biomolecule support.

Stereoselectivity in electrosprayed confined volumes: asymmetric synthesis of warfarin by diamine organocatalysts in microdroplets and thin films.

The asymmetric synthesis of warfarin in microdroplets and thin films generated by an electrospray ionization (ESI) source is reported. This is one of the first examples of an enantioselective organocatalyzed reaction in electrosprayed confined volumes. The optimal conditions in terms of system setting were established for this reaction.

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.

Antigravitropic PIN polarization maintains non-vertical growth in lateral roots.

Lateral roots are typically maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles are intriguing because their maintenance requires that roots are able to effect growth response both with and against the gravity vector, a phenomenon previously attributed to gravitropism acting against an antigravitropic offset mechanism. Here we show how the components mediating gravitropism in the vertical primary root-PINs and phosphatases acting upon them-are reconfigured in their regulation such that lateral root growth at a range of angles can be maintained. We show that the ability of Arabidopsis lateral roots to bend both downward and upward requires the generation of auxin asymmetries and is driven by angle-dependent variation in downward gravitropic auxin flux acting against angle-independent upward, antigravitropic flux. Further, we demonstrate a symmetry in auxin distribution in lateral roots at gravitropic setpoint angle that can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella. These auxin fluxes are shifted by altering PIN protein phosphoregulation in the columella, either by introducing PIN3 phosphovariant versions or via manipulation of levels of the phosphatase subunit PP2A/RCN1. Finally, we show that auxin, in addition to driving lateral root directional growth, acts within the lateral root columella to induce more vertical growth by increasing RCN1 levels, causing a downward shift in PIN3 localization, thereby diminishing the magnitude of the upward, antigravitropic auxin flux.

Synthesis of 3-substituted 2,3-dihydropyrazino[1,2-a]indol-4(1H)-ones by sequential reactions of 2-indolylmethyl acetates with α-amino acids.

The synthesis of 2,3-dihydropyrazino[1,2-a]indol-4(1H)-ones from the sequential reaction of amino acid methyl esters with readily available indole-2-ylmethyl acetates is described. The reaction proceeds in situ under basic conditions of highly unstable and reactive 2-alkylideneindolenines followed by Michael-type addition of α-amino acid methyl esters/intramolecular cyclization.

Silver thiolate nanoclusters as support for chiral ligands: application in heterogeneous phase asymmetric catalysis.

Silver thiolate nanoclusters have been functionalized with a chiral amino alcohol ligand that has previously shown high catalytic efficiency in different asymmetric reactions. The as-developed nanostructured catalyst, which can be easily recovered by simple centrifugation, has been tested in the addition of nitromethane to aromatic aldehydes, showing the same catalytic activity as the homogeneous ligand. Moreover, it was reused for two further recycling cycles without loss of efficiency. To the best of our knowledge, this is the first example of silver nanoclusters employed as a support for chiral ligands for heterogeneous phase asymmetric catalysis.

Preparation of a high-density vinyl silica gel to anchor cysteine via photo-click reaction and its applications in hydrophilic interaction chromatography.

Modification of surface silanols is a topic of interest in the preparation of organo-functionalized silica particles. Herein, two novel contributions, mainly focused on separation science, were presented: i) the horizontal polymerization on silica surface by using the vinyl-triacetoxy silane and ii) a preparation of cysteine-based stationary phase via photo-click thiol-ene coupling. In the first derivatization step, the vinyl-triacetoxy silane was employed instead of conventional trichloro vinyl one. The one-step synthetic procedure needed imidazole as an activating agent in addition to the silica hydration. Modified silica particles offer a high loading of vinyl fragments and an extensive passivation of silanols such as to not require a subsequent end-capping procedure. The structural morphology of media was deeper characterized by combining infrared spectroscopy, solid-state nuclear magnetic resonance, and elemental analysis. A first application, the photo-click cysteine-based material was prepared by photo-click reaction and the stationary phase was employed in the separation of some conventional targets by hydrophilic interaction chromatography.

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.

Fine-Tuning Synthesis of Fluorescent Silver Thiolate Nanoclusters.

Noble metal thiolate nanoclusters are a new class of nanomaterials with molecular-like properties such as high dispersibility and fluorescence in the visible and infrared spectral region, properties highly requested in biomedicine for imaging, sensing and drug delivery applications. We report on three new silver phenylethane thiolate nanoclusters, differing for slight modifications of the preparation, i.e., the reaction solvent and the thiolate quantity, producing changes in the nanocluster composition as well as in the fluorescence behavior. All samples, excited in the range 250-500 nm, emit around 400 and 700 nm differing in the emission maxima and behavior. The silver thiolate nanoclusters have been characterized by way of C, H, S elemental analyses and Thermal Gravimetric Analysis (TGA) to determine the nanocluster composition, Scanning Transmission Electron Microscopy (STEM) to investigate the nanocluster morphology and UV-Vis and fluorescence spectroscopy to study their optical properties.

Design of a fluorescent and clickable Ag38(SRN3)24 nanocluster platform: synthesis, modeling and self-assembling.

Fluorescent atomically precise Ag38(11-azido-2-ol-undecane-thiolate)24 nanoclusters are easily prepared using sodium ascorbate as a "green" reducer and are extensively characterized by way of elemental analyses, ATR-FTIR, XRD, SAXS, UV-vis, fluorescence spectroscopies, and theoretical modeling. The fluorescence and the atomically determined stoichiometry and structure, the facile and environmentally green synthesis, together with the novel presence of terminal azido groups in the ligands which opens the way to "click"-binding a wide set of molecular species, make Ag38(11-azido-2-ol-undecane-thiolate)24 nanoclusters uniquely appealing systems for biosensing, recognition and functionalization in biomedicine applications and in catalysis.

Preparation and Asymmetric Induction Evaluation of the First Ephedrine-Based Ligands Immobilized on Magnetic Nanoparticles.

Herein, the synthesis and catalytic activity of two ephedrine-based catalysts and two ephedrine-based magnetic nanoparticle-supported catalysts are reported. All catalysts developed were tested in the addition of diethylzinc to aromatic aldehydes and in the Henry reaction. The homogeneous catalysts showed moderate catalytic activity in the organozinc addition and good activity in the Henry reaction, whereas in the case of the nanocatalyst, it was not effective in the addition of diethylzinc to aldehydes and gave reasonable results in the Henry reaction. Moreover, the nanocatalyst remained unchanged over the course of up to three catalytic cycles. To the best of our knowledge, the proposed system is the first recyclable ephedrine-based magnetic nanocatalyst employed in an enantioselective reaction.

Antioxidant and Biological Activities of Hydroxytyrosol and Homovanillic Alcohol Obtained from Olive Mill Wastewaters of Extra-Virgin Olive Oil Production.

Some constituents of the Mediterranean diet, such as extra-virgin olive oil (EVOO) contain substances such as hydroxytyrosol (HT) and its metabolite homovanillic alcohol (HA). HT has aroused much interest due to its antioxidant activity as a radical scavenger, whereas only a few studies have been made on the HA molecule. Both chemical synthesis and extraction techniques have been developed to obtain these molecules, with each method having its advantages and drawbacks. In this study, we report the use of tyrosol from olive mill wastewaters as a starting molecule to synthesize HT and HA, using a sustainable procedure characterized by high efficiency and low cost. The effects of HT and HA were evaluated on two cell lines, THP-1 human leukemic monocytes and L-6 myoblasts from rat skeletal muscle, after treating the cells with a radical generator. Both HT and HA efficiently inhibited ROS production. In particular, HT inhibited the proliferation of the THP-1 leukemic monocytes, while HA protected L-6 myoblasts from cytotoxicity.

Stereocontrolled total synthesis of iminosugar 1,4-dideoxy-1,4-imino-D-iditol.

The first stereocontrolled total synthesis of iminosugar 1,4-dideoxy-1,4-imino-D-iditol is described. The key step in our approach was the double diastereoselection in the asymmetric dihydroxylation (AD) of suitable optically active olefin, the chiral vinyl azido alcohol 9. Performing the AD using the most common Cinchona alkaloids as ligands enabled us to identify the ligand of choice for the stereodivergent synthesis of 1,4-dideoxy-1,4-imino-D-iditol and 1,4-dideoxy-1,4-imino-D-galactitol. These type of iminosugars, both natural and unnatural, are intensively studied for their promising chemotherapeutic properties against viral infections, diabetes, cancer, and tuberculosis.

Linear ß-amino alcohol catalyst anchored on functionalized magnetite nanoparticles for enantioselective addition of dialkylzinc to aromatic aldehydes.

A linear ß-amino alcohol ligand, previously found to be a very efficient catalyst for enantioselective addition of dialkylzinc to aromatic aldehydes, has been anchored on differently functionalized superparamagnetic core-shell magnetite-silica nanoparticles (1a and 1b). Its catalytic activity in the addition of dialkylzinc to aldehydes has been evaluated, leading to promising results, especially in the case of 1b for which the recovery by simple magnetic decantation and reuse was successfully verified.

Role of Some Food-Grade Synthesized Flavonoids on the Control of Ochratoxin A in Aspergillus carbonarius.

Ochratoxin A (OTA) is a mycotoxin with a serious impact on human health. In Mediterranean countries, the black Aspergilli group, in particular Aspergillus carbonarius, causes the highest OTA contamination. Here we describe the synthesis of three polyphenolic flavonoids: 5-hydroxy-6,7-dimethoxy-flavone (MOS), 5,6-dihydroxy-7-methoxy-flavone (NEG), and 5,6 dihydroxy-flavone (DHF), as well as their effect on the prevention of OTA biosynthesis and lipoxygenase (LOX) activity in A. carbonarius cultured in a conducive liquid medium. The best control effect on OTA biosynthesis was achieved using NEG and DHF. In fungal cultures treated with these compounds at 5, 25, and 50 µg/mL, OTA biosynthesis significantly decreased throughout the 8-day experiment. NEG and DHF appear to have an inhibiting effect also on the activity of LOX, whereas MOS, which did not significantly inhibit OTA production, had no effect on LOX activity. The presence of free hydroxyls in catecholic position in the molecule appears to be a determining factor for significantly inhibiting OTA biosynthesis. However, the presence of a methoxy group in C-7 in NEG could slightly lower the molecule's reactivity increasing OTA inhibition by this molecule at 5 µg/mL. Polyphenolic flavonoids present in edible plants may be easily synthesized and used to control OTA biosynthesis.

Functionalized Magnetic Nanoparticles as Catalysts for Enantioselective Henry Reaction.

With the aim to easily recover and reuse the catalyst, an efficient amino alcohol catalyst previously tested in the asymmetric addition of diethylzinc to several aromatic aldehydes has been immobilized on proper functionalized superparamagnetic core-shell magnetite-silica nanoparticles and employed in the Henry reaction in the semi-homogeneous phase. The nanocatalyst exhibits a promising catalytic activity that remains unchanged in the three catalytic cycles performed. The results prove that highly efficient catalysts, by being immobilized on suitable magnetic nanosupports, can be easily recovered and reused, maintaining their catalytic behavior.

Validity and reliability of Italian version of the Non-Communicating Children's Pain Checklist: revised version.

BACKGROUND: The Non-Communicating Children Pain Check List-Revised (NCCPC-R) is a clinical assessment tool used to assess and measure pain in children aged 3 to 18 years, with mental and intellectual disabilities, incapable to speak. AIM: Aim of our study was to test the validity and reliability of the Italian version of the NCCPC-R in children with cognitive impairment, in order to obtain a valid tool for pain assessment in these children. DESIGN: Prospective observational study. SETTING: Pediatric Outpatient of Physical and Rehabilitative Medicine Department, and Pediatrics, Child Neurology and Psychiatry Department, Sapienza University, Rome. POPULATION: 55 non-communicating children, with severe intellectual disability, aged 3-18 years. METHODS: The guidelines for "translation, adaptation, and validation of instruments or scales for cross-cultural healthcare research" were used to translate the scale, which was administered by the parents/caregivers twice for 2 consecutive days, in association with NRS (Numerical Rating Scale). The reliability of the scale was evaluated using the intra and inter-class correlation coefficient (ICCs); Cronbach alpha coefficient was used to test the internal validity of the scale; "Receiver Operating Characteristic" (ROC) curves were used to compare pain-free scores with pain scores, determining threshold scores; Pearson correlation between NCCPC-R and NRS values was measured. RESULTS: The InterCC between the first and the second interviewer at T0 was 0,97, the IntraCC of the first interviewer at T0-T1 was 0,89, showing a high correlation; the Cronbach alpha coefficient at T0 was 0,97, showing a high scale's validity. Pearson correlation between NRS and NCCPC-R values at T0 was 0,54 showing a medium level of agreement (P<0,0001). AUC (area under the curve) obtained by ROC curve at T0 was 0,807 (P=0,001), with sensitivity 95,2 and specificity 55,6, while a T1 AUC was 0,814 (P<0,001), with sensitivity 86,49, specificity 78,57. CONCLUSIONS: The Italian version of NCCPC-R scale could be used to asses pain in non-communicating patients with mental and intellectual disabilities, showing a good correlation when compared to the NRS. CLINICAL REHABILITATION IMPACT: The use of NCCPC-R scale in daily life made parents/caregivers able to discriminate the presence/absence of pain in non-communicating children, based on the scores obtained with the questionnaire.