Multiadducts of C60 Modulate Amyloid-ß Fibrillation with Dual Acetylcholinesterase Inhibition and Antioxidant Properties: In Vitro and In Silico Studies.

BACKGROUND: Amyloid-ß (Aß) fibrils induce cognitive impairment and neuronal loss, leading to onset of Alzheimer's disease (AD). The inhibition of Aß aggregation has been proposed as a therapeutic strategy for AD. Pristine C60 has shown the capacity to interact with the Aß peptide and interfere with fibril formation but induces significant toxic effects in vitro and in vivo. OBJECTIVE: To evaluate the potential of a series of C60 multiadducts to inhibit the Aß fibrillization. METHODS: A series of C60 multiadducts with four to six diethyl malonyl and their corresponding disodium-malonyl substituents were synthesized as individual isomers. Their potential on Aß fibrillization inhibition was evaluated in vitro, in cellulo, and silico. Antioxidant activity, acetylcholinesterase inhibition capacity, and toxicity were assessed in vitro. RESULTS: The multiadducts modulate Aß fibrils formation without inducing cell toxicity, and that the number and polarity of the substituents play a significant role in the adducts efficacy to modulate Aß aggregation. The molecular mechanism of fullerene-Aß interaction and modulation was identified. Furthermore, the fullerene derivatives exhibited antioxidant capacity and reduction of acetylcholinesterase activity. CONCLUSION: Multiadducts of C60 are novel multi-target-directed ligand molecules that could hold considerable promise as the starting point for the development of AD therapies.

Determination of liquid-vapor equilibrium and critical properties of fatty acids for biodiesel production through molecular dynamics.

In recent years, biodiesel production has emerged as an option for renewable and green fuel generation due to the constant reduction of fossil fuel reservoirs. Biofuels as biodiesel also show valuable attributes, environmentally speaking, due to their low environmental impact, contributing to the achievement of sustainability. However, costs are not allowable for large-scale production. Thereby, several novel processes have been proposed (e.g., reactive distillation) to solve this issue. An inconvenience for the development of these processes is the little information in the literature about the critical properties of fatty acids, which are precursors of biodiesel. Determination of critical properties for fatty acids through experimentation is difficult. The reason is that fatty acids tend to self-associate (to dimerize) due to carboxylic groups presence through hydrogen bonds, and consequently, have higher boiling points than other compounds of similar molecular mass (e.g., hydrocarbons, esters). Therefore, alternative methods for this determination are required. One choice is the group-contribution method, which is based on the structure of the molecule; however, results can significantly vary among different group-contribution approaches. Another alternative (and the focus of this research) for the determination of these properties is molecular simulation techniques. In this work, the liquid-vapor equilibrium as a function of temperature and the surface tension of three pure fatty acids of long chain (linoleic, oleic, and palmitic acid) have been calculated. Simulations have been performed by molecular dynamics using the method of direct determination of phase coexistence with the software GROMACS; in which the transferable potentials for phase equilibria united atom forcefield (TraPPE-UA) have been implemented for these specific molecules. Orthobaric densities and surface tension values have been reported at temperatures near the critical point (from 650 K to 800 K). Critical properties (temperature, pressure, density) have been extrapolated from trajectories obtained in these simulations using scaling law relations. Critical properties for these compounds are not available experimentally, therefore, group contribution calculations from the literature were used as a reference. In this comparison, the palmitic acid properties calculated in this work, show the best agreement among the three substances investigated.

Gelatin as a Photosensitive Material.

Because this issue journal is dedicated to Gelatin, here we present a few applications of gelatin in the field of optics. Optics is the science that studies the production, propagation, interaction and detection of light. Various materials sensitive to light (photosensitive) are used for detection of light, such as photomultipliers, CCDs, crystals, two dimensional (2D) materials and more. Among the 2D materials, the most popular for several centuries has been gelatin based photographic emulsion, which records spatial distributions of light. More recently (1970), films made of Gelatin with Dichromate (DCG) and dyes have been used. We describe some characteristics and applications of these two photosensitive materials. We also describe examples where gelatin is used as a Relative Humidity (RH) sensor and in the fabrication of optical elements based on gelatin. This article is intended for researchers outside the optics community.

Colloid-polymer mixtures under slit confinement.

We report a NVT molecular dynamic study of colloid-polymer mixtures under slit confinement. For this purpose, we are employing the Asakura-Oosawa model for studying colloidal particles, polymer coils, and hard walls as the external confining field. The colloid-polymer size ratio, q, is varied in the range 1⩾q⩾0.4 and the confinement distance, H, in 10σc⩾H⩾3σc, σc being the colloidal diameter. Vapor-liquid coexistence properties are assessed, from which phase diagrams are built. The obtained data fulfill the corresponding states law for a constant H when q is varied. The shift of the polymer and colloidal chemical potentials of coexistence follows a linear relationship with (H-σc)-1 for H≳4σc. The confined vapor-liquid interfaces can be fitted with a semicircular line of curvature (H-σc)-1, from which the contact angle can be obtained. We observe complete wetting of the confining walls for reservoir polymer concentrations above and close to the critical value, and partial wetting for reservoir polymer concentrations above and far from it.

A Wavefront Division Polarimeter for the Measurements of Solute Concentrations in Solutions.

Polarimeters are useful instruments that measure concentrations of optically active substances in a given solution. The conventional polarimetric principle consists of measuring the rotation angle of linearly polarized light. Here, we present a novel polarimeter based on the study of interference patterns. A Mach-Zehnder interferometer with linearly polarized light at the input is used. One beam passes through the liquid sample and the other is a reference beam. As the linearly polarized sample beam propagates through the optically active solution the vibration plane of the electric field will rotate. As a result, the visibility of the interference pattern at the interferometer output will decrease. Fringe contrast will be maximum when both beams present a polarization perpendicular to the plane of incidence. However, minimum visibility is obtained when, after propagation through the sample the polarization of the sample beam is oriented parallel to the plane of incidence. By using different solute concentrations, a calibration plot is obtained showing the behavior of visibility.

Storage of hydrogen as a guest of a nanoporous polymeric crystalline phase.

A mechanism of H(2) uptake, based on adsorption in the ordered cavities of nanoporous polymeric crystalline phases rather than on disordered amorphous polymeric surfaces, has been clearly established, for aerogels of syndiotactic polystyrene (s-PS) exhibiting the nanoporous δ phase. An ordered arrangement of the H(2) molecules is proven by FTIR spectra while the inclusion of H(2) is assessed by gravimetric measurements and molecular simulations.

A molecular model for H(2) interactions in aliphatic and aromatic hydrocarbons.

A model for molecular hydrogen interacting with aliphatic and aromatic hydrocarbons is presented. The model has been derived using ab initio techniques and molecular dynamics simulations. In particular, quadrupole moments of hydrogen, and variation on energy with intermolecular distance of different conformations for the hydrogen-benzene couple were calculated using the Møller-Plesset method. Hydrogen was modelled using a two-centre Lennard-Jones potential plus electrostatic interactions. Lennard-Jones parameters were optimized on the basis of a correct reproduction of experimental data of hydrogen solubility in benzene and cyclohexane, calculated using the test particle insertion method. Different sets of parameters for specific interactions (hydrogen-aliphatic and hydrogen-aromatic systems) were considered avoiding the simple use of Lorentz-Berthelot combining rules. Additionally, structural and thermodynamic properties of hydrogen-benzene, hydrogen-cyclohexane and hydrogen in an equimolar mixture of benzene-cyclohexane at different low concentrations of hydrogen were investigated by means of molecular dynamics simulations. Electrostatic charges were taken from ab initio quantum mechanical calculations but after careful analysis of the calculated properties, their irrelevance was evidenced. Moreover, Coulombic interactions make simulations more expensive and, therefore, we do not recommend their inclusion in the modelling of hydrogen-aliphatic and aromatic interactions.