Tuning molecular dynamics by hydration and confinement: antiplasticizing effect of water in hydrated prilocaine nanoclusters.

In glass-forming substances, the addition of water tends to produce the effect of lowering the glass transition temperature, Tg. In a previous work by some of us (Ruiz et al., Sci. Rep., 2017, 7, 7470) we reported on a rare anti-plasticizing effect of water on the molecular dynamics of a simple molecular system, the pharmaceutically active prilocaine molecule, for which the addition of water leads to an increase of Tg. In the present work, we study pure and hydrated prilocaine confined in 0.5 nm and 1 nm pore size molecular sieves, and carry out a comparison with the bulk compounds in order to gain a better understanding of the microscopic mechanisms that result in this rare effect. We find that the Tg of the drug under nanometric confinement can be lower than the bulk value by as much as 17 K. Through the concurrent use of differential scanning calorimetry and broadband dielectric spectroscopy we are able to observe the antiplasticizing effect of water in prilocaine also under nanometric confinement, finding an increase of Tg of up to almost 6 K upon hydration. The extension of our analysis to nanoconfined systems provides a plausible explanation for the very uncommon antiplasticizing effect, based on the formation of water-prilocaine molecular complexes. Moreover, this study deepens the understanding of the behavior of drugs under confinement, which is of relevance not only from a fundamental point of view, but also for practical applications such as drug delivery.

Orientational relaxations in solid (1,1,2,2)tetrachloroethane.

We employ dielectric spectroscopy and molecular dynamic simulations to investigate the dipolar dynamics in the orientationally disordered solid phase of (1,1,2,2)tetrachloroethane. Three distinct orientational dynamics are observed as separate dielectric loss features, all characterized by a simply activated temperature dependence. The slower process, associated to a glassy transition at 156 ± 1 K, corresponds to a cooperative motion by which each molecule rotates by 180° around the molecular symmetry axis through an intermediate state in which the symmetry axis is oriented roughly orthogonally to the initial and final states. Of the other two dipolar relaxations, the intermediate one is the Johari-Goldstein precursor relaxation of the cooperative dynamics, while the fastest process corresponds to an orientational fluctuation of single molecules into a higher-energy orientation. The Kirkwood correlation factor of the cooperative relaxation is of the order of one tenth, indicating that the molecular dipoles maintain on average a strong antiparallel alignment during their collective motion. These findings show that the combination of dielectric spectroscopy and molecular simulations allows studying in great detail the orientational dynamics in molecular solids.

Structure and reorientational dynamics of 1-F-adamantane.

The polymorphism and the dynamics of a simple rigid molecule (1-fluoro-adamantane) have been studied by means of X-ray powder diffraction and broadband dielectric spectroscopy. At temperatures below the melting point, the molecule forms an orientationally disordered Phase I with a cubic-centered structure (Phase I, Fm3¯m, Z = 4). This phase possesses eight equilibrium positions for the fluorine atom, with equal occupancy factors of 1/8. A solid-solid phase transition to a low-temperature tetragonal phase (Phase II, P4¯2(1)c, Z = 2) reduces the statistical disorder to only four possible equivalent sites for the fluorine atom, with fractional occupancies of 1/4. The dynamics has been rationalized under the constraints imposed by the space group of the crystal structure determined by powder X-ray diffraction. The dielectric spectroscopy study reveals that the statistical disorder in Phase II is dynamic in character and is associated with reorientational jumps along the two- and three-fold axes. In the dielectric loss spectra, the cooperative (α) relaxation exhibits a shoulder on the high-frequency side. This remarkable finding clearly reveals the existence of two intrinsic reorientational processes associated with the exchange of the F atom along the four sites. In addition to such "bimodal" relaxation, a secondary Johari-Goldstein relaxation is detected at lower temperatures.

Molecular diffusion and dc conductivity perfectly correlated with molecular rotational dynamics in a plastic crystalline electrolyte.

We probe the ionic conduction and the molecular dynamics in a pure and lithium-salt doped dinitrile molecular plastic crystal. While the diffusion of the Li(+) ions is decoupled from the molecular reorientational dynamics, in the undoped plastic crystal the temperature dependence of the mobility of dinitrile ions and thus of the conductivity is virtually identical to that of on-site molecular rotations. The undoped material is found to obey the Walden and Stokes-Einstein rules typical of ideal liquid electrolytes, implying that an effective viscosity against diffusion can be defined even for a plastic crystalline phase. These surprising results, never reported before in a translationally ordered solid, indicate that in this dinitrile plastic crystalline material the timescale of translational diffusion is perfectly correlated with that of the purely reorientational on-site dynamics.