On the microscopic origin of the cryoprotective effect in lysine solutions.

The amino acid lysine has been shown to prevent water crystallization at low temperatures in saturated aqueous solutions [S. Cerveny and J. Swenson, Phys. Chem. Chem. Phys., 2014, 16, 22382-22390]. Here, we investigate two ratios of water and lysine (5.4 water molecules per lysine (saturated) and 11 water molecules per lysine) by means of the complementary use of computer simulations and neutron diffraction. By performing a detailed structural analysis we have been able to explain the anti-freeze properties of lysine by the strong hydrogen bond interactions of interstitial water molecules with lysine that prevent them from forming crystalline seeds. Additional water molecules beyond the 1 : 5.4 proportion are no longer tightly bonded to lysine and therefore are free to form crystals.

Calorimetric study of water's two glass transitions in the presence of LiCl.

A DSC study of dilute glassy LiCl aqueous solutions in the water-dominated regime provides direct evidence of a glass-to-liquid transition in expanded high density amorphous (eHDA)-type solutions. Similarly, low density amorphous ice (LDA) exhibits a glass transition prior to crystallization to ice Ic. Both glass transition temperatures are independent of the salt concentration, whereas the magnitude of the heat capacity increase differs. By contrast to pure water, the glass transition endpoint for LDA can be accessed in LiCl aqueous solutions above 0.01 mole fraction. Furthermore, we also reveal the endpoint for HDA's glass transition, solving the question on the width of both glass transitions. This suggests that both equilibrated HDL and LDL can be accessed in dilute LiCl solutions, supporting the liquid-liquid transition scenario to understand water's anomalies.

Relaxation Dynamics vs Crystallization Kinetics in the Amorphous State: The Case of Stiripentol.

With the aim of finding a correlation between the crystallization kinetics and the molecular dynamics of a substance that would allow prediction of its crystallization time as a function of temperature for a given α relaxation time, we have studied stiripentol, an anticonvulsant drug. Stiripentol has been characterized in its supercooled liquid, amorphous (glass), and crystalline states by the concurrent use of broadband dielectric spectroscopy (BDS), differential scanning calorimetry, X-ray diffraction, and optical microscopy. BDS was employed to study both the dipolar molecular dynamics and the kinetics of crystallization from the melt. Three different molecular relaxation dynamics were identified: an α relaxation corresponding to the collective reorientation of the molecules and associated with the glass transition (Tg = 246.2 ± 0.5 K), a Johari Goldstein ß relaxation that can be associated with the single-molecule precursor of the α process, and a γ relaxation arising from intramolecular motions. Isothermal crystallization of Stiripentol was studied by means of BDS well above the glass transition (between 273 and 293 K), and it was observed under optical microscope at ambient conditions. Stiripentol did not exhibit any sign of polymorphism at ambient pressure, and it recrystallized from the melt into its stable crystalline form. The crystallization kinetics did not obey the Avrami law. Stiripentol displayed a very low nucleation rate, and drops of liquid stiripentol were observed to crystallize completely from a single nucleus before the appearance of new nuclei, so that the crystallite grew according to the morphology of the liquid domains, a fact that might explain the lack of validity of the Avrami law. Possible correlations between the crystallization kinetics and the molecular dynamics have been analyzed, finding that the crystallization time has a sublinear dependence on the cooperative relaxation time, as is the case in other substances reported in the scientific literature. This could suggest a general correlation of these parameters, at least at temperatures above Tg. The low nucleation rate is an interesting feature in the quest of possible mechanisms that allow enhancing the physical stability of amorphous drugs.

Genuine antiplasticizing effect of water on a glass-former drug.

Water is the most important plasticizer of biological and organic hydrophilic materials, which generally exhibit enhanced mechanical softness and molecular mobility upon hydration. The enhancement of the molecular dynamics upon mixing with water, which in glass-forming systems implies a lower glass transition temperature (T g ), is considered a universal result of hydration. In fact, even in the cases where hydration or humidification of an organic glass-forming sample result in stiffer mechanical properties, the molecular mobility of the sample almost always increases with increasing water content, and its T g decreases correspondingly. Here, we present an experimental report of a genuine antiplasticizing effect of water on the molecular dynamics of a small-molecule glass former. In detail, we show that addition of water to prilocaine, an active pharmaceutical ingredient, has the same effect as that of an applied pressure, namely, a decrease in mobility and an increase of T g . We assign the antiplasticizing effect to the formation of prilocaine-H 2 O dimers or complexes with enhanced hydrogen bonding interactions.

On the structure of prilocaine in aqueous and amphiphilic solutions.

The solvation of prilocaine has been investigated in pure water and in an amphiphilic methanol/water solution using a combination of neutron diffraction with isotopic substitution augmented by Empirical Potential Structure Refinement (EPSR) simulations. This combination of techniques allows for details of the solvation structure on the atomic scale to be unravelled. The hydration of prilocaine is significantly altered relative to when this molecule is in pure water (as a hydrochloride salt) or in an amphiphilic environment (as a freebase compound). Interestingly, there is not a significant change in hydration around the amine group on prilocaine hydrochloride compared with prilocaine as a freebase. Despite this group being an ammonium group in water and an amine group in methanol/water solutions, the hydration of this motif remains largely intact. The changes in hydration between prilocaine as a free base and prilocaine·HCl instead appears to arise from a change in hydration around the aromatic ring and the amide group in the prilocaine molecule.