Potential Roles of Extracellular Vesicles as Biomarkers and a Novel Treatment Approach in Multiple Sclerosis.

Extracellular vesicles (EVs) are a heterogeneous group of bilayer membrane-wrapped molecules that play an important role in cell-to-cell communication, participating in many physiological processes and in the pathogenesis of several diseases, including multiple sclerosis (MS). In recent years, many studies have focused on EVs, with promising results indicating their potential role as biomarkers in MS and helping us better understand the pathogenesis of the disease. Recent evidence suggests that there are novel subpopulations of EVs according to cell origin, with those derived from cells belonging to the nervous and immune systems providing information regarding inflammation, demyelination, axonal damage, astrocyte and microglia reaction, blood-brain barrier permeability, leukocyte transendothelial migration, and ultimately synaptic loss and neuronal death in MS.

Modeling the Interaction of Carbon Monoxide with Flexible Graphene: From Coupled Cluster Calculations to Molecular-Dynamics Simulations.

The interaction of CO with graphene was studied at different theoretical levels. Quantum-mechanical calculations on finite graphene models with the use of coronene for coupled cluster calculations and circumcoronene for B97D calculations showed that there was no preferential site for adsorption and that the most important factor was the orientation of CO relative to graphene. The parallel orientation was preferred, with binding energies around 9 kJ mol at the CCSD(T) and B97D levels, which was in good agreement with experimental findings.

π-Ring currents in doped coronenes with nitrogen and boron: diatropic-paratropic duality.

The change in the electronic structure of coronene upon doping with nitrogen or boron has been theoretically studied by means of its magnetic properties and magnetic field induced current density maps. The addition of two atoms of nitrogen or boron to the central ring of coronene causes a drastic variation in the delocalization of π-electrons, which does not depend on its nature but instead on its position. Then, doping in the para position makes coronene more aromatic while doping in the meta position makes it to become antiaromatic.

CCSD-CTOCD static dipole shielding polarizability for quantification of the chiral NMR effects in oxaziridine derivatives.

Chiral discrimination by nuclear magnetic resonance (NMR) spectroscopy might be achieved through the pseudo-scalar derived from the dipole shielding polarizability tensor. Coupled Cluster Singles and Doubles-Quadratic Response (CCSD-QR) calculations inside the continuous translation of the origin of the current density formalism have been carried out to determine the effects of basis set, electron correlation, and gauge translation on the determination of this magnitude in oxaziridine derivatives. Inclusion of electronic correlation is needed for adequately describing the pseudo-scalar for the heavier nuclei, making CCSD a rigorous and affordable method to compute these high order properties in medium-sized molecules.

Energy interactions in amyloid-like fibrils from NNQQNY.

We use large-scale MP2 calculations to analyze the interactions appearing in amyloid fibers, which are difficult to determine experimentally. To this end, dimers and trimers of the hexapeptide NNQQNY from the yeast prion-like protein Sup35 were considered as model systems. We studied the energy interactions present in the three levels of organization in which the formation of amyloid fibrils is structured.

Parity-violation energy of biomolecules-IV: protein secondary structure.

The parity-violation energy difference between enantiomeric forms of the same amino acid sequence, from the amyloid β-peptide involved in Alzheimer's disease, in both α-helix and β-sheet configurations, is investigated with ab-initio techniques. To this end, we develop an extension of the N2 computational scheme that selectively includes neighboring amino acids to preserve the relevant H-bonds. In agreement with previous speculations, it is found that the helical α structure is associated with larger parity-violation energy differences than the corresponding β form.

Cholesky decomposition-based definition of atomic subsystems in electronic structure calculations.

Decomposing the Hartree-Fock one-electron density matrix and a virtual pseudodensity matrix, we obtain an orthogonal set of normalized molecular orbitals with local character to be used in post-Hartree-Fock calculations. The applicability of the procedure is illustrated by calculating CCSD(T) energies and CCSD molecular properties in reduced active spaces.

Aromaticity of α-Oligothiophenes and Equivalent Oligothienoacenes.

The aromaticity and the degree of π-electronic delocalization have been theoretically investigated for α,α'-linked oligothiophenes containing three and five rings and for their fused analogs oligothienoacenes. By computing magnetic susceptibilities and (1)H NMR shieldings as well as current density maps, it is found that the fused oligomers are more aromatic than the corresponding nonfused partners. The increase of aromaticity with the size of the oligomer-even in the case of quinoidal forms-is also proven.

Understanding the ring current effects on magnetic shielding of hydrogen and carbon nuclei in naphthalene and anthracene.

The local response to an external magnetic field normal to the molecular plane of naphthalene and anthracene was investigated via current density and magnetic shielding density maps. The Biot-Savart law shows that the deshielding caused by pi-ring currents in naphthalene is stronger for alpha- than for beta-protons due to geometrical factors. The shielding tensor of the carbon nuclei in both molecules is strongly anisotropic and its out-of-plane component determines the up-field chemical shift of (13)C in nuclear magnetic resonance spectra.

Theoretical study on the structures and electronic spectra of TCNE2-.

Investigations into the charge-separated states and electron-transfer transitions in tetracyanoethylene (TCNE) complexes have recently generated much interest. In this work we present theoretical calculations showing that the most stable structure of the dianion TCNE2- has D2d symmetry in vacuum as well as in the solvents dichloromethane and acetonitrile. By means of the coupled cluster linear response, we compute the vertical electronic spectrum in both the gas phase and solution.

Structure, magnetizability, and nuclear magnetic shielding tensors of bis-heteropentalenes. IV. Dihydrophospholophosphole isomers.

The geometry of the heteropentalenes formed by two phosphole units has been determined at the DFT level. The magnetic susceptibility and the nuclear magnetic shielding at the nuclei of these systems have also been calculated using gauge-including atomic orbitals and a large Gaussian basis set to achieve near Hartree-Fock estimates. A comparative study of the various isomers, of their flattened analogs, and of the parent phosphole molecule, shows that the [3,4-c] isomer is the most aromatic system in the set considered, assuming diatropicity and degree of planarity as indicators, even if it is the less stable in terms of total molecular energy.