Chemical promenades: Exploring potential-energy surfaces with immersive virtual reality

The virtual-reality framework AVATAR (Advanced Virtual Approach to Topological Analysis of Reactivity) for the immersive exploration of potential-energy landscapes is presented. AVATAR is based on modern consumer-grade virtual-reality technology and builds on two key concepts: (a) the reduction of the dimensionality of the potential-energy surface to two process-tailored, physically meaningful generalized coordinates, and (b) the analogy between the evolution of a chemical process and a pathway through valleys (potential wells) and mountain passes (saddle points) of the associated potential energy landscape. Examples including the discovery of competitive reaction paths in simple A + BC collisional systems and the interconversion between conformers in ring-puckering motions of flexible rings highlight the innovation potential that augmented and virtual reality convey for teaching, training, and supporting research in chemistry.     

Laquinimod Modulates Human Astrocyte Function and Dampens Astrocyte-Induced Neurotoxicity during Inflammation

Astrocytes greatly participate to inflammatory and neurotoxic reactions occurring in neurodegenerative diseases and are valuable pharmacological targets to support neuroprotection. Here we used human astrocytes generated from reprogrammed fibroblasts as a cellular model to study the effect of the compound Laquinimod and its active metabolite de-Laquinimod on astrocyte functions and the astrocyte–neuron interaction. We show that human iAstrocytes expressed the receptor for the inflammatory mediator IL1 and responded to it via nuclear translocation of NFκB, an event that did not occur if cells were treated with Laquinimod, indicating a direct anti-inflammatory activity of the drug on the human astrocyte. Similarly, while exposure to IL1 downregulated glial glutamate transporters GLAST and GLT1, treatment with Laquinimod supported maintenance of physiological levels of these proteins despite the inflammatory milieu. Laquinimod also induced nuclear translocation of the aryl hydrocarbon receptor (AHR), suggesting that drug action was mediated by activation of the AHR pathway. However, the drug was effective despite AHR inhibition via CH223191, indicating that AHR signaling in the astrocyte is dispensable for drug responses. Finally, in vitro experiments with rat spinal neurons showed that laquinimod did not exert neuroprotection directly on the neuron but dampened astrocyte-induced neurodegeneration. Our findings indicate that fibroblast-derived human astrocytes represent a suitable model to study astrocyte–neuron crosstalk and demonstrate indirect, partial neuroprotective efficacy for laquinimod.     

Enhancement of temozolomide stability by loading in chitosan-carboxylated polylactide-based nanoparticles

In the presented work, amphiphilic nanoparticles based on chitosan and carboxy-enriched polylactic acid have been prepared to improve the stability of the pro-drug temozolomide in physiological media by encapsulation. The carrier, with a diameter in the range of 150–180 nm, was able to accommodate up to 800 μg of temozolomide per mg of polymer. The obtained formulation showed good stability in physiological condition and preparation media up to 1 month. Temozolomide loaded inside the carrier exhibited greater stability than the free drug, in particular in simulated physiological solution at pH 7.4 where the hydrolysis in the inactive metabolite was clearly delayed. CS-SPLA nanoparticles demonstrated a pH-dependent TMZ release kinetics with the opportunity to increase or decrease the rate. Mass spectroscopy, UV-Vis analysis, and in vitro cell tests confirmed the improvement in temozolomide stability and effectiveness when loaded into the polymeric carrier, in comparison with the free drug.     

Absolute configuration of 1,n-diols by NMR: the importance of the combined anisotropic effects in bis-arylmethoxyacetates

The absolute configuration of a 1,n-diol can be assigned from the (1)H NMR spectra of its (R)- and (S)-AMAA diesters if the chemical shifts are interpreted as the result of the joint action of the two chiral auxiliaries.     

Method for intracellular magnetic labeling of human mononuclear cells using approved iron contrast agents

A method for intracellular iron labeling of human mononuclear cells (lymphocytes and monocytes) for magnetic resonance imaging (MRI) using simple incubation of cells with approved MRI iron contrast agents is presented. Labeled cells can be detected by MRI in vitro, and this suggests the possibility that the technique could become a marker for in vivo lymphocyte and monocyte trafficking studies in acute inflammatory lesions such as those in Multiple Sclerosis.     

Homogeneous Ziegler–Natta catalysis. II. Ethylene polymerization by IVB transition metal complexes/methyl aluminoxane catalyst systems

Homogeneous Ziegler-Natta systems for the ethylene polymerization, deriving from R₂R_2′M complexes (R = cyclopentadienyl; R′ = alkyl, aryl; M = Ti, Zr, Hf) and oligomeric oxoalane compounds, were studied. Further results concerning the methyl aluminoxane synthesis and the related chemistry are reported. On the basis of spectroscopic data a delocalized electronic structure could be inferred for these compounds. Results from polymerization experiments showed that the highest productivities are obtained only by oxoalane cocatalysts having a high degree of oligomerization. The catalytic activity of the systems under investigation was strongly affected also by changing both the σ-alkyl and the π-cyclo-pentadienyl ligands. Furthermore, it was found that in the presence of methyl aluminoxane, the homoleptic σ-alkyl derivatives of IVB transition metals, such as Zr(CH₂C₆H₅)₄, are also able to polymerize ethylene with a fairly high productivity. Active species containing Zr? O? Al bonds have been postulated.     

Oxygenation of calixarene phenol rings

[structure: see text] The first examples of epoxy-p-quinol and diepoxy-p-quinol calixarene derivatives have been obtained by base-promoted direct addition of O(2)(oxygenation) to calixarene phenol rings. The regio- and stereochemistry of these derivatives was determined by 2D NMR studies, in conjunction with MM3 calculations, and X-ray crystallography. Both the oxygenation and the subsequent carbonyl reduction occur with a preferential attack to the less hindered exo face of the calixarene rings.     

Optimized Mueller polarimeter with liquid crystals

We demonstrate a Mueller polarimeter in which the polarization-state generator and analyzer are both composed of a linear polarizer and two liquid-crystal variable retarders. The polarimeter is designed to optimize the accuracy of the final results by minimization of the condition numbers of the modulation and analysis matrices. The polarimeter calibration, a difficult task by conventional procedures, is achieved easily by use of the eigenvalue method of Compain et al. [Appl. Opt. 38, 3490 (1999)]. The overall polarimeter performance is tested with a linear polarizer at various angles and a compensator at various retardations.     

Singular Perturbations of Nonlinear Degenerate Parabolic PDEs: a General Convergence Result

The main result of the paper is a general convergence theorem for the viscosity solutions of singular perturbation problems for fully nonlinear degenerate parabolic PDEs (partial differential equations) with highly oscillating initial data. It substantially generalizes some results obtained previously in [2]. Under the only assumptions that the Hamiltonian is ergodic and stabilizing in a suitable sense, the solutions are proved to converge in a relaxed sense to the solution of a limit Cauchy problem with appropriate effective Hamiltonian and initial data. In its formulation, our convergence result is analogous to the stability property of Barles and Perthame. It should thus reveal a useful tool for studying general singular perturbation problems by viscosity solutions techniques. A detailed exposition of ergodicity and stabilization is given, with many examples. Applications to homogenization and averaging are also discussed.