Tandem reactions of 1,2,4-oxadiazoles with allylamines

A reaction of 3-chloro-1,2,4-oxadiazoles with allylamine and diallylamine has been investigated. 3,3a,4,5-Tetrahydroisoxazolo[3,4-d]pyrimidines are produced through a tandem ANRORC/[3 + 2]cycloaddition pathway consisting of the addition of allylamine to the 1,2,4-oxadiazole, followed by ring opening, nitrone formation, and finally cycloaddition. 3-N-Allylamino-1,2,4-oxadiazoles were also obtained as minor products through a classical SNAr. Conversely, a reaction with diallylamine produces 3-N,N-diallylamino-1,2,4-oxadiazole and imidazoline through tandem SNAr/aziridination and nucleophilic ring opening.     

Effect of SiO2 on the dynamics of proton conducting [Nafion/(SiO2)X] composite membranes: a solid-state 19F NMR study

Composite membranes, consisting of Nafion and inorganic oxide additives, are frequently discussed alternative materials to overcome the known low conductivity of pure Nafion at temperatures above 100 °C and at low relative humidity. It has been reported that under dry conditions, these membranes show enhanced water uptake and diffusion as compared to filler-free Nafion. This work focuses on the polymer mobility in Nafion/SiO(2) composites and on the impact of the silica particles on the polymer dynamics. [Nafion/(SiO(2))(X)] composite membranes (with X ranging from 0 to 15 wt%) in the dry and wet states were investigated by variable temperature solid-state (19)F NMR spectroscopy. (19)F T(1) and T(1ρ) relaxation times, and NMR lineshapes (linewidths and spinning sideband intensities) were analyzed to get information about the polymer mobility. It is found that Nafion composite membranes, in general, possess a higher mobility as compared to recast Nafion which is in agreement with previous results from conductivity studies. These findings are attributed to the ability of the SiO(2) particles to keep more water inside the composite membranes which also leads to a higher mobility of the polymer component. The results are further supported by the experimental (19)F{(1)H} CP/MAS NMR spectra. It is also shown that the structure of the composite membranes is more stable after dehydration, and possible condensation reactions are diminished in these membranes. In addition, the decrease in ionic exchange capacity after dehydration is less pronounced for the composite membranes as compared to filler-free Nafion.     

A molecular modeling study of complex formation and self-aggregation behavior of a porphyrin–β-cyclodextrin conjugate

This paper reports a molecular modeling study of complex formation and aggregation behavior of a supramolecular system comprising three different moieties forming two distinct molecules. One molecule is a phenol derivative of porphyrin conjugated to a macrocyclic oligosaccharide, β-cyclodextrin (β-CD), and the other is 1-adamantanol (ADM). The inclusion complex of the latter molecule with the porphyrin–β-cyclodextrin (β-CD) conjugate, and the dimeric aggregates of the conjugate both in the presence and in the absence of the guest are investigated through molecular mechanics and molecular dynamics methods in vacuo, since the systems are scarcely soluble in polar solvents. In this way, we can find the most likely geometry of the complexes or aggregates and characterize the competitive inclusion behavior of ADM and of a porphyrin phenol within the β-CD cavity in terms of the various energy contributions stabilizing the resulting aggregates and/or inclusion complexes.     

Photosensitization Reactions of Fluoroquinolones and Their Biological Consequences

This review focuses on damage photosensitized by the fluoroquinolone (FQ) antibacterial drugs. Different models are employed to study biosubstrate photodamage mediated by FQs (organisms, cells, isolated biomolecules and super molecules). Being that the effect of environment (polarity of the medium, ions, pH, binding with bio‐molecules, etc.) is crucial in FQ photochemistry, photobiological reactions can be consequently dramatically influenced. Thus, the photosensitization processes induced by FQs are here discussed taking into account that such extensive and cross‐targeted pathological implications request an excursus covering photosensitization in systems of increasing molecular complexity. In vivo and in vitro evidences for photoallergy, phototoxicity, photomutagenesis and photocarcinogenesis mediated by FQs are discussed.     

Structural investigation and biological activity of the lipooligosaccharide from the psychrophilic bacterium Pseudoalteromonas haloplanktis TAB 23

Pseudoalteromonas haloplanktis TAB 23 is a Gram-negative psychrophilic bacterium isolated from the Antarctic coastal sea. To survive in these conditions psychrophilic bacteria have evolved typical membrane lipids and "antifreeze" proteins to protect the inner side of the microorganism. As for Gram-negative bacteria, the outer membrane is mainly constituted by lipopoly- or lipooligosaccharides (LPS or LOS, respectively), which lean towards the external environment. Despite this, very little is known about the peculiarity of LPS from Gram-negative psychrophilic bacteria and what their role is in adaptation to cold temperature. Here we report the complete structure of the LOS from P. haloplanktis TAB 23. The lipid A was characterized by MALDI-TOF MS analysis and was tested in vitro showing a significant inhibitory effect on the LPS-induced pro-inflammatory cytokine production when added in culture with LPS from Escherichia coli. The product obtained after de-O-acylation of the LPS was analyzed by MALDI-TOF MS revealing the presence of several molecular species, differing in phosphorylation degree and oligosaccharide length. The oligosaccharide portion released after strong alkaline hydrolysis was purified by anion-exchange chromatography-pulsed amperometric detection (HPAEC-PAD) to give three main fractions, characterized by means of 2D NMR spectroscopy, which showed a very short highly phosphorylated saccharidic chain with the following general structure. α-Hepp3R,6R,4R'-(1→5)-α-Kdop4P-(2→6)-β-GlcpN4R-(1→6)-α-GlcpN1P (R=-H(2)PO(3) or -H; R'=α-Galp-(1→4)-β-Galp-(1→ or H-).     

Conjugated zwitterionic polyelectrolyte as the charge injection layer for high-performance polymer light-emitting diodes

A new zwitterionic conjugated polyelectrolyte without free counterions has been used as an electron injection material in polymer light-emitting diodes. Both the efficiency and maximum brightness were considerably improved in comparison with standard Ca cathode devices. The devices showed very fast response times, indicating that the improved performance is, in addition to hole blocking, due to dipoles at the cathode interface, which facilitate electron injection.     

CORAL: QSPR models for solubility of [C60] and [C70] fullerene derivatives

Quantitative structure–property relationships (QSPRs) between the molecular structure of [C₆₀] and [C₇₀] fullerene derivatives and their solubility in chlorobenzene (mg/mL) have been established by means of CORAL (CORrelations And Logic) freeware. The CORAL models are based on representation of the molecular structure by simplified molecular input line entry system (SMILES). Three random splits into the training and the external validation sets have been examined. The ranges of statistical characteristics of these models are as follows: n = 18, r ² = 0.748–0.815, s = 15.1 –17.5 (mg/mL), F = 47–71 (training set); n = 9, r ² = 0.806–0.936, s = 12.5–17.5 (mg/mL), F = 29–103 (validation set).     

Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects

The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2,3-dihydro-1H-cyclopenta[b]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out. Cytotoxicity, cytofluorimetry, and protein expression assays on prodrugs were also performed to assess their potential as antiproliferative agents that could help hypothesize an effective use as anticancer therapeutics. Encouraging results suggest that the studied compounds could act not only as precursors of the anti-inflammatory metabolite, but also as direct antiproliferative agents.     

Photoluminescent decoration of iron oxide magnetic nanoparticles for dual-imaging applications

A selective functionalization of dopamine amino group with the photoluminescent 7-nitroben-zofurazan was achieved through a one-pot protection-functionalization-deprotection sequence. The resulting fluorescent catecholic ligand was used as a capping agent for iron oxide nanoparticles thus obtaining photoluminescent magnetic nanoparticles (PL-MNPs). The PL-MNPs were then embedded into PLGA-b-PEG polymeric nanocarriers which quenched the emission of the capping agent. Full recovery of fluorescence was observed after disassembling the polymeric layer of the nanoparticle, thus supporting the use of PL-MNPs as a multifunctional system for targeted drug delivery.