Adsorption of Capsaicin into the Nanoconfined Interlayer Space of Montmorillonite by DFT Calculations.

Capsaicin is the main compound responsible of the hot sense of the chili fruits. This compound has interesting therapeutic properties including anticancer, anti-inflammatory effects, and analgesic. However, its use has several secondary effects, such as skin irritation and allergies. Then, new therapeutic strategies are searched in order to overcome these problems. Montmorillonite has proved to be an excellent excipient for the release of pharmaceutical drugs. In this work, the molecular structure and crystal structure of capsaicin, and the adsorption of this molecule into the interlayer space of montmorillonite have been studied using quantum mechanical calculations based on Density Functional Theory (DFT) level of theory and molecular dynamics simulations. The crystal structure has been predicted with these calculations and the intermolecular interactions have been determined with a higher resolution than the previous experimental data. The adsorption of capsaicin into the confined interlayer space of montmorillonite is energetically favourable with low and high octahedral charge. This adsorption can be monitored by IR spectroscopy observing frequency shifts in some bands during the adsorption. This enhances the use of these clay minerals for capsaicin therapeutic formulations.

Experimental and Theoretical Studies on the Intercalation of Naproxen into the Mg2Al and Zn2Al Layered Double Hydroxides by Ion Exchange Reaction.

In this work, Layered Double Hydroxide (LDH) materials carrying the worldwide administered non-steroidal anti-inflammatory drug naproxen (NAP), and the sodium naproxenate salt (NaNAP) for comparison, were studied by computational approaches aiming to model the structure of hybrid LDH-drug and shed light on NAP intercalation process. Atomic modeling calculations were performed at the quantum mechanical level based on Density Functional Theory and classical force fields based on empirical interatomic potentials. LDHNAP materials were prepared by ion exchange reaction from Mg2Al(OH)6Cl and Zn2Al(OH)6Cl pristine phases. The characterization of the materials confirmed NAP intercalation and also the permanence of the pristine phases in the isolated materials after ion exchange. Crystallographic lattice parameters, elemental analysis, and TGA experimental results were then employed in the calculations, which revealed that NAP anions can completely neutralize the positive charge of the LDH layers: both Mg2Al and Zn2Al LDH structures could be optimized with all Cl- anions substituted by NAP. The drug assumed different dispositions in the NaNAP crystal or when intercalated into LDH. Additionally, infrared wavenumbers calculations agreed with the experimental results and showed useful to support LDHNAP bands assignment. The employed theoretical models to represent the structure of LDHNAP systems are expected to assist the interpretation of future experimental results and to be used as auxiliary tools to tune properties of LDH-drug pharmaceutical formulations.

Force Field Parametrization from the Hirshfeld Molecular Electronic Density.

The Hirshfeld charges are linearly increased to reproduce the experimental dielectric constant of 10 polar solvents having values between 13 (pyridine) and 182 ( N-methylformamide). The OPLS/AA force field is used to obtain the new parameters. The surface tension and liquid density are also target properties to determine the new nonbonding parameters. The charge scaling factor is between 1.2 and 1.3. In addition, properties that were not used in the parametrization procedure, such as the heat of vaporization, self-diffusion coefficient, shear viscosity, isothermal compressibility, and volumetric expansion coefficient are obtained. Binary mixtures of amide/water and amide/amide are also studied. The original parameters of OPLS/AA, CGenFF, and GAFF force fields are evaluated. The TIP4P/ε force field is used to simulate water. The results from this work with the new parameters, for both pure components and binary mixtures, are in better agreement with experimental data than those obtained with the original values for most of the calculated properties. The maximum density of N-methylformamide in aqueous solutions is correctly predicted only with the new parameters. The high value of the dielectric constant of acetamide, formamide, and N-methylformamide is discussed in terms of the chain formation from the hydrogen bond interactions.

Force Field Benchmark of the TraPPE_UA for Polar Liquids: Density, Heat of Vaporization, Dielectric Constant, Surface Tension, Volumetric Expansion Coefficient, and Isothermal Compressibility.

The transferable potential for a phase equilibria force field in its united-atom version, TraPPE_UA, is evaluated for 41 polar liquids that include alcohols, thiols, ethers, sulfides, aldehydes, ketones, and esters to determine its ability to reproduce experimental properties that were not included in the parametrization procedure. The intermolecular force field parameters for pure components were fit to reproduce experimental boiling temperature, vapor-liquid coexisting densities, and critical point (temperature, density, and pressure) using Monte Carlo simulations in different ensembles. The properties calculated in this work are liquid density, heat of vaporization, dielectric constant, surface tension, volumetric expansion coefficient, and isothermal compressibility. Molecular dynamics simulations were performed in the gas and liquid phases, and also at the liquid-vapor interface. We found that relative error between calculated and experimental data is 1.2% for density, 6% for heat of vaporization, and 6.2% for surface tension, in good agreement with the experimental data. The dielectric constant is systematically underestimated, and the relative error is 37%. Evaluating the performance of the force field to reproduce the volumetric expansion coefficient and isothermal compressibility requires more experimental data.