Distinct mechanisms for the oxidative addition of chloro-, bromo-, and iodoarenes to a bisphosphine palladium(0) complex with hindered ligands

We report an example of a bisphosphine palladium(0) complex with hindered ligands that undergoes oxidative addition of chloro-, bromo-, and iodoarenes in high yield. Addition of PhX (X = I, Br, Cl) to [Pd(Q-phos-tol)2] produced [Pd(Q-phos-tol)(Ph)(I)], [Pd(Q-phos-tol)(Ph)(Br)], and [Pd(Q-phos-tol)(Ph)(Cl)]2. To study the mechanisms of the oxidative addition of the three haloarenes to [Pd(Q-phos-tol)2], we determined the order of the reaction on the concentration of ligand and haloarene. The different haloarenes reacted through different mechanistic pathways. Addition of iodobenzene occurred by irreversible associative displacement of a phosphine. Addition of bromobenzene occurred by rate-limiting dissociation of phosphine. Addition of chlorobenzene occurred by reversible dissociation of phosphine, followed by rate-limiting oxidative addition. The mechanism of exchange of ligands from the Pd(0)L2 was also studied. The rate constant value for dissociation of ligand calculated from ligand exchange experiments is in agreement with the value calculated through experiments on oxidative addition.     

Unexpected reactivity of pyridinium salts toward alkynyl Fischer complexes to produce oxo‐heterocycles

The unprecedented reaction of ketone‐containing aromatic pyridinium salts 3a ‐ e and alkynyl Fischer complexes 1a ‐ f proceeds via a mild domino process to provide 4,6‐disubstituted pyran‐2‐ones 5a ‐ k and 2,3,5‐trisubstituted furans 6a ‐ h (45‐97%). According of the results of isotopic labeling experiments, a mechanism involving an initial Michael addition appears to be the key step, obtaining a mesomeric structure responsible for the formation of both products.     

An investigation of preservice teachers’ use of guess and check in solving a semi open-ended mathematics problem

Open-ended problems have been regarded as powerful tools for teaching mathematics. This study examined the problem solving of eight mathematics/science middle-school teachers. A semi-structured interview was conducted with (PTs) after completing an open-ended triangle task with four unique solutions. Of particular emphasis was how the PTs used a specific heuristic strategy. The results showed that the primary strategy PTs employed in attempting to solve the triangle problem task was guess and check; however, from the PTs’ reflections, we found there existed misapplications of guess and check as a systematic problem-solving strategy. In order to prepare prospective teachers to effectively teach, teacher educators should pay more attention to the mathematical proficiency of PTs, particularly their abilities to systematically and efficiently use guess and check while solving problems and explain their solutions and reasoning to middle-school students.     

Nanoparticles based on novel amphiphilic polyaspartamide copolymers

In this article, the synthesis of two amphiphilic polyaspartamide copolymers, useful to obtain polymeric nanoparticles without using surfactants or stabilizing agents, is described. These copolymers were obtained starting from α,β-poly-(N-2-hydroxyethyl)-dl-aspartamide (PHEA) by following a novel synthetic strategy. In particular, PHEA and its pegylated derivative (PHEA-PEG₂₀₀₀) were functionalized with poly(lactic acid) (PLA) through 1,1′-carbonyldiimidazole (CDI) activation to obtain PHEA–PLA and PHEA-PEG₂₀₀₀–PLA graft copolymers, respectively. These copolymers were properly purified and characterized by ¹H-NMR, FT-IR, and Size Exclusion Chromatography (SEC) analyses, which confirmed that derivatization reactions occurred. Nanoparticles were obtained from PHEA–PLA and PHEA-PEG₂₀₀₀–PLA graft copolymers by using the high pressure homogenization-solvent evaporation method, avoiding the use of surfactants or stabilizing agents. Polymeric nanoparticles were characterized by dimensional analysis, before and after freeze-drying process, and Scanning Electron Microscopy (SEM). Zeta potential measurements and X-ray Photoelectron Spectroscopy (XPS) analysis demonstrated the presence of PEG and/or PHEA onto the PHEA-PEG₂₀₀₀–PLA and PHEA–PLA nanoparticle surface, respectively.     

Polyaspartamide–Polylactide Graft Copolymers with Tunable Properties for the Realization of Fluorescent Nanoparticles for Imaging

Here, the synthesis and the characterization of novel amphiphilic graft copolymers with tunable properties, useful in obtaining polymeric fluorescent nanoparticles for application in imaging, are described. These copolymers are obtained by chemical conjugation of rhodamine B (RhB) moieties, polylactic acid (PLA), and O‐(2‐aminoethyl)‐O′‐methyl poly(ethylene glycol) (PEG) on α,β‐poly(N‐2‐hydroxyethyl)‐d,l ‐aspartamide (PHEA). In particular, PHEA is first functionalized with RhB to obtain PHEA–RhB with a derivatization degree in RhB (DD_RhB) equal to 0.55 mol%. By varying the reaction conditions, different amounts of PLA are grafted on PHEA–RhB to obtain PHEA‐RhB‐PLA with DD_PLA equal to 1.9, 4.0, and 6.2 mol%. Then, PEG chains are grafted on PHEA‐RhB‐PLA derivatives to obtain PHEA‐RhB‐PLA‐PEG graft copolymers. The preparation of polymeric fluorescent nanoparticles with tunable properties and spherical shape is described by using PHEA‐RhB‐PLA‐PEG with DD in PLA and PEG equal to 4.0 and 4.9 mol%, by following easily scaling up processes, such as emulsion‐solvent evaporation and high pressure homogenization (HPH)‐solvent evaporation techniques.

     

Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy

Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin.     

Profiling of grape monoterpene glycosides (aroma precursors) by ultra‐high performance‐liquid chromatography‐high resolution mass spectrometry (UHPLC/QTOF)

A ‘suspect screening analysis’ method for grape metabolomics by ultra‐high performance‐liquid chromatography (UHPLC) and high‐resolution quadrupole‐time of flight (QTOF) mass spectrometry was recently developed. This method was applied to study grape monoterpene glycosides, the main grape aroma precursors. Since standard compounds were not available, they were tentatively identified by overlapping various analytical approaches, in agreement with the indications recommended in mass spectrometry (MS)‐based metabolomics. Accurate mass and isotopic pattern, MS/MS fragmentation, correlation between fragments observed and putative structures and between liquid chromatography coupled with mass spectrometry (LC/MS) and gas chromatography/mass spectrometry signals were studied. Seventeen monoterpene glycosides were identified without performing the hydrolytic artifacts commonly used to study these compounds which may affect sample profile. This is the first time that a detailed study of these aroma precursors has been carried out by direct LC/MS analysis. Copyright © 2014 John Wiley & Sons, Ltd.     

Amorphous Aggregation of Amyloid Beta 1‐40 Peptide in Confined Space

The amorphous aggregation of Aβ1‐40 peptide is addressed by using micromolding in capillaries. Both the morphology and the size of the aggregates are modulated by changing the contact angle of the sub‐micrometric channel walls. Upon decreasing the hydrophilicity of the channels, the aggregates change their morphology from small aligned drops to discontinuous lines, thereby keeping their amorphous structure. Aβ1‐40 fibrils are observed at high contact angles.     

Backward production of the B meson in K−p interactions at 4.2 GeVc

The backward production of the B(1235) meson is studied in the reaction K^?p→Σ^?π⁺ω. This reaction is observed in the final state Σ^?π⁺π⁺π^?π⁰. A π⁺ω mass enhancement is visible in the region of the B meson for events with small |u|K^? →Σ^?) squared four-momentum transfer. The properties of the enhancement agree with those of the B meson. The cross section for K^?p→Σ^?B⁺ at $\text{4.15}\text{GeV}\text{c}$ incident K^? momentum is (3.2 ± 0.5) μb. The backward production of the B meson is compared with similar baryon exchange productions of the A₁ and C(Q₁) axial vector mesons observed in the same experiment.     

Ω− produced in K−p reactions at 4.2 GeV/c

Forty $\text{Ω}{}^{\mathrm{?}}$ events have been observed in a large (133 events/βb) experiment at 4.2 GeV/c incident K^? momentum. Thirty nine of the events come from the three-body reaction $\text{K}{}^{\mathrm{?}}\text{p}\text{→Ω}{}^{\mathrm{?}}\text{K}{}^{\mathrm{+}}\text{K}{}^0$. The $\text{Ω}{}^{\mathrm{?}}$ is mainly produced in the forward hemisphere (direction of the incident K^?). The lifetime is measured to be τ = (0.75 _+0.14?0.11 × 10^?10 sec substantially less than the Particle Data Group value of (1.3 _?0.3^+0.2) × 10^?10 sec. The mass is determined to be 1671.7 ± 0.6 MeV, in good agreement with other determinations. The decay asymmetry parameter α (for the decay mode $\text{Ω}{}^{\mathrm{?}}\text{→ Λ}\text{K}{}^{\mathrm{?}}$) is found to be ?0.2 ± 0.4.