Structural and Size Effects on the Spectroscopic and Redox Properties of CdSe Nanocrystals in Solution: The Role of Defect States

Two series of CdSe quantum dots (QDs) with different diameters are prepared, according to frequently used protocols of the same synthetic procedure. For each sample the photophysical properties and the potentials for the first reduction and oxidation processes in organic solution are determined. The band gap obtained from electrochemical experiments is compared with that determined from the absorption and luminescence spectra. While the optical band gap decreases upon increasing the nanocrystal diameter, as expected on the basis of quantum confinement, the redox potentials and the electrochemical band gap are not monotonously related to the QD size. For both series, the smallest and largest QDs are both easier to oxidize and reduce than mid‐sized QDs. In fact, the latter samples exhibit very broad voltammetric profiles, which suggests that the heterogeneous electron‐transfer processes from/to the electrode are kinetically hindered. Conversely, the electrochemical band gap for the smallest and largest particles of each series is somewhat smaller than the optical band gap. These results indicate that, while the optical band gap depends on the actual electron–hole recombination within the nanocrystal, and therefore follows the size dependence expected from the particle‐in‐a‐box model, the electrochemical processes of these QDs are strongly affected by other factors, such as the presence of surface defects. The investigations suggest that the influence of these defects on the potential values is more important for the smallest and largest QDs of each series, as confirmed by the respective luminescence bands and quantum yields. An interpretation for the size‐dependent evolution of the surface defects in these nanocrystals is proposed based on the mechanism of their formation and growth.     

Quantification of L‐ergothioneine in human plasma and erythrocytes by liquid chromatography‐tandem mass spectrometry

A sensitive analytical method has been developed and validated for the quantification of L‐ergothioneine in human plasma and erythrocytes by liquid chromatography‐tandem mass spectrometry. A commercially available isotope‐labeled L‐ergothioneine‐d₉ is used as the internal standard. A simple protein precipitation with acetonitrile is utilized for bio‐sample preparation prior to analysis. Chromatographic separation of L‐ergothioneine is conducted using gradient elution on Alltime C18 (150 mm × 2.1 mm, 5 µ). The run time is 6 min at a constant flow rate of 0.45 ml/min. The mass spectrometer is operated under a positive electrospray ionization condition with multiple reaction monitoring mode. The mass transitions of L‐ergothioneine and L‐ergothioneine‐d₉ are m/z 230 > 127 and m/z 239 > 127, respectively. Excellent linearity [coefficient of determination (r²) ≥ 0.9998] can be achieved for L‐ergothioneine quantification at the ranges of 10 to 10 000 ng/ml, with the intra‐day and inter‐day precisions at 0.9–3.9% and 1.3–5.7%, respectively, and the accuracies for all quality control samples between 94.5 and 101.0%. This validated analytical method is suitable for pharmacokinetic monitoring of L‐ergothioneine in human and erythrocytes. Based on the determination of bio‐samples from five healthy subjects, the mean concentrations of L‐ergothioneine in plasma and erythrocytes are 107.4 ± 20.5 ng/ml and 1285.0 ± 1363.0 ng/ml, respectively. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of a New β-Galactosidase Inhibitor Displaying Pharmacological Chaperone Properties for GM1 Gangliosidosis

GM1 gangliosidosis is a rare lysosomal disease caused by the deficiency of the enzyme β-galactosidase (β-Gal; GLB1; E.C. 3.2.1.23), responsible for the hydrolysis of terminal β-galactosyl residues from GM1 ganglioside, glycoproteins, and glycosaminoglycans, such as keratan-sulfate. With the aim of identifying new pharmacological chaperones for GM1 gangliosidosis, the synthesis of five new trihydroxypiperidine iminosugars is reported in this work. The target compounds feature a pentyl alkyl chain in different positions of the piperidine ring and different absolute configurations of the alkyl chain at C-2 and the hydroxy group at C-3. The organometallic addition of a Grignard reagent onto a carbohydrate-derived nitrone in the presence or absence of a suitable Lewis Acid was exploited, providing structural diversity at C-2, followed by the ring-closure reductive amination step. An oxidation-reduction process allowed access to a different configuration at C-3. The N-pentyl trihydroxypiperidine iminosugar was also synthesized for the purpose of comparison. The biological evaluation of the newly synthesized compounds was performed on leucocyte extracts from healthy donors and identified two suitable β-Gal inhibitors, namely compounds 10 and 12. Among these, compound 12 showed chaperoning properties since it enhanced β-Gal activity by 40% when tested on GM1 patients bearing the p.Ile51Asn/p.Arg201His mutations.     

Derivatives of benzo[4,5]cyclohepta[1,2-b]thiophene. 4. Synthesis of 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines

Thirteen 1-(9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-4-yl)-3-alkylaminoazetidines 11 have been synthesized in three steps from 4-amino-9,10-dihydro-4H-benzo[4,5]cyclohepta[1,2-b]thiophene ( 6 ), which was obtained from the reduction of either 4-azido 4 or 4-hydroxyimino 5 derivatives. All the compounds have been evaluated as potential antidepressive agents.     

Molecular mechanics studies of the conformations of metal complexes of 1,4,7,10,13,16-hexaazacyclooctadecane: Calculations of macrocyclic cavity size

Molecular mechanics calculations are reported on metal complexes of 18-azacrown-6. Four possible conformations are considered which encapsulate the metal in different geometric environments, namely, chiral octahedral, meso octahedral, trigonal prismatic, and hexagonal bipyramidal. Crystal structures are available for all but the last geometry, and molecular mechanics calculations show an excellent fit to the experimental data. The strain energy of the macrocycle has been calculated for a range of M-N distances, and thus the hole size of the macrocycle has been obtained for various conformations. Two different methods were used to calculate the strain energy of the metal environment. We either used the conventional molecular mechanics term for angle bending,k _b — ₀)², and chose the ideal angles to fit the particular metal geometry, or we set the angle force constants to zero and introduced 1,3 van der Waals interactions between the ligand donor nitrogen atoms. Results from the two methods are compared.     

First-passage times and related moments for continuous-time birth–death chains

First-passage time problems for continuous-time birth–death chains are considered. Recursive formulas for the moments of the first-exit time and of the first-passage time in terms of the potential coefficients are explicitly obtained. Making use of the probability current, some functional relations between transition probabilities for unrestricted and restricted continuous-time birth–death chains are determined. Finally, two continuous-time birth–death chains with constant rates are taken in account; for them, closed form results on the first-exit time and on the first-passage time are explicitly obtained.

     

Impaired neurogenesis, learning and memory and low seizure threshold associated with loss of neural precursor cell survivin

Background

Survivin is a unique member of the inhibitor of apoptosis protein (IAP) family in that it exhibits antiapoptotic properties and also promotes the cell cycle and mediates mitosis as a chromosome passenger protein. Survivin is highly expressed in neural precursor cells in the brain, yet its function there has not been elucidated.

Results

To examine the role of neural precursor cell survivin, we first showed that survivin is normally expressed in periventricular neurogenic regions in the embryo, becoming restricted postnatally to proliferating and migrating NPCs in the key neurogenic sites, the subventricular zone (SVZ) and the subgranular zone (SGZ). We then used a conditional gene inactivation strategy to delete the survivin gene prenatally in those neurogenic regions. Lack of embryonic NPC survivin results in viable, fertile mice (Survivin ^Camcre ) with reduced numbers of SVZ NPCs, absent rostral migratory stream, and olfactory bulb hypoplasia. The phenotype can be partially rescued, as intracerebroventricular gene delivery of survivin during embryonic development increases olfactory bulb neurogenesis, detected postnatally. Survivin ^Camcre brains have fewer cortical inhibitory interneurons, contributing to enhanced sensitivity to seizures, and profound deficits in memory and learning.

Conclusions

The findings highlight the critical role that survivin plays during neural development, deficiencies of which dramatically impact on postnatal neural function.     

Targeting Innate Immunity with dsRNA‐Conjugated Mesoporous Silica Nanoparticles Promotes Antitumor Effects on Breast Cancer Cells

We describe herein a Toll‐like receptor 3 (TLR3) targeting delivery system based on mesoporous silica nanoparticles capped with the synthetic double stranded RNA polyinosinic–polycytidylic acid (poly(I:C)) for controlled cargo delivery in SK‐BR‐3 breast carcinoma cells. Our results show that poly(I:C)‐conjugated nanoparticles efficiently targeted breast cancer cells due to dsRNA–TLR3 interaction. Such interaction also triggered apoptotic pathways in SK‐BR‐3, significantly decreasing cells viability. Poly(I:C) cytotoxic effect in breast carcinoma cells was enhanced by loading nanoparticles′ mesopores with the anthracyclinic antibiotic doxorubicin, a commonly used chemotherapeutic agent.     

Plasma Catalytic Synthesis of Ammonia Using Functionalized-Carbon Coatings in an Atmospheric-Pressure Non-equilibrium Discharge

We investigate the synthesis of ammonia in a non-equilibrium atmospheric-pressure plasma using functionalized-nanodiamond and diamond-like-carbon coatings on α-Al₂O₃ spheres as catalysts. Oxygenated nanodiamonds were found to increase the production yield of ammonia, while hydrogenated nanodiamonds decreased the yield. Neither type of nanodiamond affected the plasma properties significantly. Using diffuse-reflectance FT-IR and XPS, the role of different functional groups on the catalyst surface was investigated. Evidence is presented that the carbonyl group is associated with an efficient surface adsorption and desorption of hydrogen in ammonia synthesis on the surface of the nanodiamonds, and an increased production of ammonia. Conformal diamond-like-carbon coatings, deposited by plasma-enhanced chemical vapour deposition, led to a plasma with a higher electron density, and increased the production of ammonia.