Role of Anisotropy in Understanding the Molecular Grounds for Density Scaling in Dynamics of Glass-Forming Liquids.

Molecular Dynamics MD simulations of glass-forming liquids play a pivotal role in uncovering the molecular nature of the liquid vitrification process. In particular, much focus was given to elucidating the interplay between the character of intermolecular potential and molecular dynamics behavior. This has been tried to achieve by simulating the spherical particles interacting via isotropic potential. However, when simulation and experimental data are analysed in the same way by using the density scaling approach, serious discrepancies are revealed between them. Similar scaling exponent values are determined by analysing the relaxation times and pVT data obtained from computer simulations. In contrast, these values differ significantly when the same analysis is carried out in the case of experimental data. As discussed thoroughly herein, the coherence between these results can be achieved if anisotropy of intermolecular interactions is introduced to MD simulations. In practice, it has been realized in two different ways: (1) by using the anisotropic potential of the Gay-Berne type or (2) by replacing the spherical particles with quasi-real polyatomic anisotropic molecules interacting through isotropic Lenar-Jones potential. In particular, the last strategy has the potential to be used to explore the relationship between molecular architecture and molecular dynamics behavior. Finally, we hope that the results presented in this review will also encourage others to explore how "anisotropy" affects remaining aspects related to liquid-glass transition, like heterogeneity, glass transition temperature, glass forming ability, etc. .

Tuning the Physical State of Aripiprazole by Mesoporous Silica.

The main purpose of our studies is to demonstrate that commercially available mesoporous silica (MS) can be used to control the physical state of aripiprazole (ARP). The investigations performed utilizing differential scanning calorimetry and broadband dielectric spectroscopy reveal that silica can play different roles depending on its concentration in the system with amorphous ARP. At low MS content, it activates recrystallization of the active pharmaceutical ingredient and supports forming the III polymorphic form of ARP. At intermediate MS content (between ca. 27 and 65 wt %), MS works as a recrystallization inhibitor of ARP. At these concentrations, the formation of III polymorphic form is no longer favorable; therefore, it is possible to use this additive to obtain ARP in either IV or X polymorphic form. At the same time, employing MS in concentrations >65 wt % amorphous form of ARP with high physical stability can be obtained. Finally, regardless of the polymorphic form it crystallizes into, each composite is characterized by the same temperature dependence of relaxation times in the supercooled and glassy states.

Dynamics of Water Clusters Confined in Ionic Liquid at an Elevated Pressure.

Over the years, numerous experimental and theoretical efforts have been dedicated to investigating the mysteries of water and determining its new unexplored physical properties. Despite this, high-pressure studies of water and aqueous mixtures close to the glass transition still represent an unknown area of research. Herein, we address a fundamental issue: the validity of the density scaling concept for fast water dynamics. For this purpose, we performed ambient and high-pressure dielectric measurements of a supercooled equimolar aqueous mixture of an acidic ionic liquid. All isothermal and isobaric relaxation data describing the time scale of charge transport (τσ) and fast dynamics within the water clusters (τν) reveal visual evidence of a liquid-glass transition. Furthermore, both relaxation processes satisfy the ργ/T scaling concept with a single exponent γ = 0.58. Thus, the scaling exponent is a state-point-independent parameter for the dynamics of water clusters confined in ionic liquid investigated in the pressure range up to 300 MPa.

The existence of a strongly bonded layer in associating liquids within silica pores - a spectral and molecular dynamics study.

The properties of confined materials are assumed to be governed by the phenomena occurring at the interface, especially the formation of an irreversible adsorption layer (IAL), which has been widely discussed and detected in the case of thin polymer films and silica nanoparticles. In this paper, we present a novel experimental approach allowing us to reveal the formation of an IAL in two phenyl alcohols infiltrated into various mesoporous silica templates. The proposed methodology (based on evaporation) allowed us to detect the alterations in the OH and aromatic CH stretching vibration bands in infrared spectra, which were considered as evidence of the existence of IAL in constrained systems. Such interpretation was also confirmed by complementary molecular dynamics (MD) simulations that indicated the creation of much stronger hydrogen bonds between alcohols and silanol units than between alcohols themselves. Moreover, computation allowed us to identify additional enormously strong π-stacking interactions between phenyl rings stabilizing the interfacial layer. MD simulations also shed new light on the clustering process of both alcohols under confinement. Simulation and experimental data presented in this paper allowed a much deeper understanding of the processes occurring at the interface-formation of IAL and the association phenomenon at the nanoscale level.

Fragility and Tendency to Crystallization for Structurally Related Compounds.

The present study was designed to investigate the physical stability of three organic materials with similar chemical structures. The examined compounds revealed completely different crystallization tendencies in their supercooled liquid states and were classified into three distinct classes based on their tendency to crystallize. (S)-4-Benzyl-2-oxazolidinone easily crystallizes during cooling from the melt; (S)-4-Benzylthiazolidine-2-thione does not crystallize during cooling from the melt, but crystallizes easily during subsequent reheating above Tg; and (S)-4-Benzyloxazolidine-2-thione does not crystallize either during cooling from the melt or during reheating. Such different tendencies to crystallize are observed despite the very similar chemical structures of the compounds, which only differ in oxide or sulfur atoms in one of their rings. We also studied the isothermal crystallization kinetics of the materials that were shown to transform into a crystalline state. Molecular dynamics and thermal properties were thoroughly investigated using broadband dielectric spectroscopy, as well as conventional and temperature-modulated differential scanning calorimetry in the wide temperature range. It was found that all three glass formers have the same dynamic fragility (m = 93), calculated directly from dielectric structural relaxation times. This result verifies that dynamic fragility is not related to the tendency to crystallize. In addition, thermodynamic fragility predictions were also made using calorimetric data. It was found that the thermodynamic fragility evaluated based on the width of the glass transition, observed in the temperature dependence of heat capacity, correlates best with the tendency to crystallize.

Internal Secondary Relaxation as a Dielectric Probe of Molecular Surroundings.

We investigated the secondary relaxation behavior in rotor molecules in a glassy and crystalline state by using the dielectric method. Without changing the molecular source of secondary relaxation, only by modifying the environment around the rotating unit we observed notable variations in spectral parameters. Our results show that internal rotation, like a probe, can sample the immediate surroundings with high sensitivity to molecular-level changes that impact the rotation parameters. Our research offers a new perspective on the dielectric behavior of internal secondary relaxations and challenges the paradigm of their irrelevant nature.

The influence of molecular shape on reorientation dynamics of sizable glass-forming isomers at ambient and elevated pressure.

We used dielectric spectroscopy to access the molecular dynamics of three isomers with a structure based on a sizable, partially rigid, and non-polar core connected to a polar phenylene unit differing in the position of the polar group, and, consequently, the direction and magnitude of the dipole moment to address the question how unique molecular properties, in particular large size and elongated shape, affect the dynamics. The position of the polar group differentiates the molecular shape and isomer's anisotropy and leads to different thermal and dynamic properties of the isomers. The shape of permittivity loss spectra was governed by magnitudes of the longitudinal and transverse components of dipole moment to a large extent. For para isomer with negligible traverse component of dipole moment, the narrowest loss peak was found while for meta isomer, the bimodal loss peak was observed at high temperatures. Its shape evolved on cooling limiting the possibility of individual mode separation near glass transition where the dynamics were more cooperative. High-pressure dielectric studies showed that sizable isomers were characterized by the pronounced sensitivity of glass transition temperature, Tg, to compression. Observed high activation volumes, such as 735 cm3/mol at Tg for para isomer, were found to correlate with the length scale of dynamic cooperativity. The number of dynamically correlated molecules depended on molecular shape and varied among isomers while the determined values were much smaller than that reported for other glass-forming liquids. We discussed here the obtained results in the context of the specific properties of the systems studied showing the overriding role of anisotropy.

Pressure-Induced Aggregation of Associating Liquids as a Driving Force Enhancing Hydrogen Bond Cooperativity.

The behavior of hydrogen bonds under extreme pressure is still not well understood. Until now, the shift of the stretching vibration band of the X-H group (X = the donor atom) in infrared spectra has been attributed to the variation in the length of the covalent X-H bond. Herein, we combined infrared spectroscopy and X-ray diffraction experimental studies of two H-bonded liquid hexane derivatives, i.e., 2-ethyl-1-hexanol and 2-ethyl-1-hexylamine, in diamond anvil cells at pressures up to the GPa level, with molecular dynamics simulations covering similar thermodynamic conditions. Our findings revealed that the observed changes in the X-H stretching vibration bands under compression are not primarily due to H-bond shortening resulting from increased density but mainly due to cooperative enhancement of H-bonds caused by intensified molecular clustering. This sheds new light on the nature of H-bond interactions and the structure of liquid molecular systems under compression.

Visible-light-induced ATRP under high-pressure: synthesis of ultra-high-molecular-weight polymers.

In this study, a high-pressure-assisted photoinduced atom transfer radical polymerization (p ≤ 250 MPa) enabled the synthesis of ultra-high-molecular-weight polymers (UHMWPs) of up to 9 350 000 and low/moderate dispersity (1.10 < D < 1.46) in a co-solvent system (water/DMSO), without reaction mixture deoxygenation.

Predicting the Density-Scaling Exponent of a Glass-Forming Liquid from Complex Dielectric Permittivity Measurements.

One of the challenging problems related to the liquid-glass transition phenomenon is establishing a link between the character of intermolecular interactions and the behavior of molecular dynamics. Introducing the density scaling concept, according to which dynamic quantities, e.g., viscosity or structural relaxation time (τ_{α}) measured at different thermodynamic conditions are expressed as a single universal curve if plotted against ρ^{γ}/T, led to significant progress in solving this problem since the scaling exponent γ defines the steepness of the repulsive part of the intermolecular potential. Herein, we found that relaxation dynamics of van der Waals and H-bonding glass formers, for which the Kirkwood factor (g_{K}) is an isomorph-invariant quantity, satisfy an alternative scaling, logτ_{α} vs T(Δϵ_{s}T)^{-γ}. As a result, the exponent γ is determined from the temperature and pressure evolutions of τ_{α} and dielectric relaxation strength Δϵ-both obtained in a single dielectric experiment, which makes the γ coefficient to be accessed in the future for an extensive database of glass-forming liquids.

Self-Assembled Nanostructures in Aprotic Ionic Liquids Facilitate Charge Transport at Elevated Pressure.

Ionic liquids (ILs), revealing a tendency to form self-assembled nanostructures, have emerged as promising materials in various applications, especially in energy storage and conversion. Despite multiple reports discussing the effect of structural factors and external thermodynamic variables on ion organization in a liquid state, little is known about the charge-transport mechanism through the self-assembled nanostructures and how it changes at elevated pressure. To address these issues, we chose three amphiphilic ionic liquids containing the same tetra(alkyl)phosphonium cation and anions differing in size and shape, i.e., thiocyanate [SCN]-, dicyanamide [DCA]-, and tricyanomethanide [TCM]-. From ambient pressure dielectric and mechanical experiments, we found that charge transport of all three examined ILs is viscosity-controlled at high temperatures. On the other hand, ion diffusion is much faster than structural dynamics in a nanostructured supercooled liquid (at T < 210 ± 3 K), which constitutes the first example of conductivity independent from viscosity in neat aprotic ILs. High-pressure measurements and MD simulations reveal that the created nanostructures depend on the anion size and can be modified by compression. For small anions, increasing pressure shapes immobile alkyl chains into lamellar-type phases, leading to increased anisotropic diffusivity of anions through channels. Bulky anions drive the formation of interconnected phases with continuous 3D curvature, which render ion transport independent of pressure. This work offers insight into the design of high-density electrolytes with percolating conductive phases providing efficient ion flow.

Nature of Dielectric Response of Phenyl Alcohols.

Phenyl alcohols (PhAs) are an interesting class of materials, for which the dielectric response reveals only the presence of single prominent Debye-like (D) relaxation, interpreted as a genuine structural (α) process. Herein, we have performed dielectric and mechanical measurements on a series of PhAs characterized by the varying length of the alkyl chain and found that this interpretation is not valid. Analysis of the derivative of the real part of the complex permittivity together with the mechanical and light scattering data clearly indicated that the prominent dielectric D-like peak is actually a superposition of both cross-correlation between dipole-dipole (D-mode) and self-dipole correlation (α-process) and that the distinguished α-mode exhibits a similar ("generic") shape of PhAs independently to their molecular weight and applied experimental technique. Therefore, the data presented herein contribute to the whole discussion focused on the dielectric response function and universality (or diversity) of the spectral shape of the α-mode of polar liquids.

On the relationship between the Debye process in dielectric response and a dissociation-association phenomenon in phenyl alcohols.

In this paper, we have examined a series of phenyl-substituted primary monohydroxy alcohols (phenyl alcohols, PhAs), from ethanol to hexanol by means of dielectric and Fourier transform infrared (FTIR) spectroscopies supported by the mechanical investigations. The combination of both dielectric and mechanical data allows calculation of the energy barrier, Ea, for dissociation by the Rubinstein approach developed to describe the dynamical properties of self-assembling macromolecules. It was observed that the determined activation energy remains constant, |Ea,RM| ∼ 12.9-14.2 kJ mol-1, regardless of the molecular weight of the examined material. Surprisingly, the obtained values agree very well with Ea of the dissociation process determined from the FTIR data analysed within the van't Hoff relationship, where Ea,vH ∼ 9.13-13.64 kJ mol-1. Thus, the observed agreement between Ea determined by both applied approaches clearly implies that in the case of the examined series of PhAs, the dielectric Debye-like process is governed by the association-dissociation phenomenon as proposed by the transient chain model.

Entropy Scaling of Molecular Dynamics in a Prototypical Anisotropic Model near the Glass Transition.

Dynamics and thermodynamics of molecular systems in the vicinity of the boundary between thermodynamically nonequilibrium glassy and metastable supercooled liquid states are still incompletely explored and their theoretical and simulation models are imperfect despite many previous efforts. Among them, the role of total system entropy, configurational entropy, and excess entropy in the temperature-pressure or temperature-density dependence of global molecular dynamics (MD) timescale relevant to the glass transition is an essential topic intensively studied for over half of a century. By exploiting a well-known simple ellipsoidal model recently successfully applied to simulate the supercooled liquid state and the glass transition, we gain a new insight into the different views on the relationship between entropy and relaxation dynamics of glass formers, showing the molecular grounds for the entropy scaling of global MD timescale. Our simulations in the anisotropic model of supercooled liquid, which involves only translational and rotational degrees of freedom, give evidence that the total system entropy is sufficient to scale global MD timescale. It complies with the scaling effect on relaxation dynamics exerted by the configurational entropy defined as the total entropy diminished by vibrational contributions, which was earlier discovered for measurement data collected near the glass transition. Moreover, we argue that such a scaling behavior is not possible to achieve by using the excess entropy that is in excess of the ideal gas entropy, which is contrary to the results earlier suggested within the framework of simple isotropic models of supercooled liquids. Thus, our findings also warn against an excessive reliance on isotropic models in theoretical interpretations of molecular phenomena, despite their simplicity and popularity, because they may reflect improperly various physicochemical properties of glass formers.

Hot Melt Extruded Posaconazole-Based Amorphous Solid Dispersions-The Effect of Different Types of Polymers.

Four model polymers, representing (i) amorphous homopolymers (Kollidon K30, K30), (ii) amorphous heteropolymers (Kollidon VA64, KVA), (iii) semi-crystalline homopolymers (Parteck MXP, PXP), and (iv) semi-crystalline heteropolymers (Kollicoat IR, KIR), were examined for their effectiveness in creating posaconazole-based amorphous solid dispersions (ASDs). Posaconazole (POS) is a triazole antifungal drug that has activity against Candida and Aspergillus species, belonging to class II of the biopharmaceutics classification system (BCS). This means that this active pharmaceutical ingredient (API) is characterized by solubility-limited bioavailability. Thus, one of the aims of its formulation as an ASD was to improve its aqueous solubility. Investigations were performed into how polymers affected the following characteristics: melting point depression of the API, miscibility and homogeneity with POS, improvement of the amorphous API's physical stability, melt viscosity (and associated with it, drug loading), extrudability, API content in the extrudate, long term physical stability of the amorphous POS in the binary drug-polymer system (in the form of the extrudate), solubility, and dissolution rate of hot melt extrusion (HME) systems. The obtained results led us to conclude that the physical stability of the POS-based system increases with the increasing amorphousness of the employed excipient. Copolymers, compared to homopolymers, display greater homogeneity of the investigated composition. However, the enhancement in aqueous solubility was significantly higher after utilizing the homopolymeric, compared to the copolymeric, excipients. Considering all of the investigated parameters, the most effective additive in the formation of a POS-based ASD is an amorphous homopolymer-K30.

Tailoring Phosphonium Ionic Liquids for a Liquid-Liquid Phase Transition.

The existence of more than one liquid state in a single-component system remains the most intriguing physical phenomenon. Herein, we explore the effect of cation self-assembly on ion dynamics in the vicinity of liquid-liquid and liquid-glass transition of tetraalkyl phosphonium ([Pmmm,n]+, m = 4, 6; n = 2-14) ionic liquids. We found that nonpolar local domains formed by 14-carbon alkyl chains are crucial in obtaining two supercooled states of different dynamics within a single ionic liquid. Although the nano-ordering, confirmed by Raman spectroscopy, still occurs for shorter alkyl chains (m = 6, n < 14), it does not bring calorimetric evidence of LLT. Instead, it results in peculiar behavior of ion dynamics near the liquid-glass transition and 20-times smaller size of the dynamic heterogeneity compared to imidazolium ionic liquids. These results represent a crucial step toward understanding the nature of the LLT phenomenon and offer insight into the design of efficient electrolytes based on ionic liquids revealing self-assembly behavior.

Effect of Shear Strain on the Supercooled Itraconazole.

This article investigated the effect of shear strain on the nematic itraconazole (ITR) from both elastic and plastic deformation regions. The rheo-dielectric technique was used for this purpose. It has been demonstrated that shear strain can change the sample color, liquid crystal alignment as well as its dielectric and thermal properties. The observed modifications depend on the shear strain value. One can distinguish four regions regarding the slope of ITR stress-strain dependence and caused changes. Proper alignment changes (obtained after the shearing procedure) can additionally affect the further recrystallization of ITR to other than the initial, i.e., second polymorphic form.

Preparation and advanced characterization of highly drug-loaded, 3D printed orodispersible tablets containing fluconazole.

Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.

New Insights from Nonequilibrium Kinetics Studies on Highly Polar S-Methoxy-PC Infiltrated into Pores.

Herein, the annealing of highly polar (S)-(-)-4-methoxymethyl-1,3-dioxolan-2-one (S-methoxy-PC) within alumina and silica porous membranes characterized by different pore diameters was studied by means of dielectric spectroscopy. We found a significant slowing down of the structural dynamics of confined S-methoxy-PC with annealing time below and, surprisingly, also above the glass transition temperatures of the interfacial layer, Tg,interfacial. Furthermore, unexpectedly, a change in the slope of temperature dependencies of the characteristic time scale of this process τanneal, at Tg,interfacial for all confined samples, was reported. By modeling τanneal(T), we noted that the observed enormous variation of τanneal results from a decrease of the pore radius due to the vitrification of the interfacial molecules. This indicates that the enhanced dynamics of confined materials upon cooling is mainly controlled by the interfacial molecules.

The unique role of pore wall nanostructurization in the intrachannel photo-ATRP for fine-tuning PMMA tacticity.

In this paper, efficient MMA photo O-ATRP protocols conducted inside nanoreactors varying in nanostructured interfaces are reported for the first time. We showed that the microstructure of recovered polymers could be easily tuned just by implementing a given type of nanochannel (d = 10, 19-28, 35, 160 nm).