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In this paper, the molecular dynamics at different thermodynamic conditions of hydrogen-bonded (H-bonded) active pharmaceutical ingredient—ticagrelor (TICA) have been investigated. Extensive high-pressure (HP) dielectric studies revealed surprising high sensitivity of the structural (α)-relaxation to compression. They also showed that unexpectedly the shape of the α-peak remains invariable at various temperature (T) and pressure (p) conditions at constant α-relaxation time. Further infrared measurements on the ordinary and pressure densified glasses of the examined compound indicated that the hydrogen-bonding pattern in TICA is unchanged by the applied experimental conditions. Such behavior was in contrast to that observed recently for ritonavir (where the organization of hydrogen bonds varied at high p) and explained the lack of changes in the width of α-dispersion with compression. Moreover, HP dielectric measurements performed in the glassy state of TICA revealed the high sensitivity of the slow secondary (β)-relaxation (Johari–Goldstein type) to pressure and fulfillment of the isochronal superpositioning of α- and JG-β-relaxation times. Additionally, it was found that the activation entropy for the β-process, estimated from the Eyring equation (a high positive value at 0.1 MPa) slightly increases with compression. We suggested that the reason for that are probably small conformational variations of TICA molecules at elevated p. [ABSTRACT FROM AUTHOR]

In this paper, broadband dielectric spectroscopy was applied to investigate molecular dynamics of 1,2,3,4,6-penta-O-(trimethylsilyl)-D-glucopyranose (S-GLU) at ambient and elevated pressures. Our studies showed that apart from the structural relaxation, one well resolved asymmetric secondary process (initially labeled as β) is observed in the spectra measured at p = 0.1 MPa. Analysis with the use of the coupling model and criterion proposed by Ngai and Capaccioli indicated that the β-process in S-GLU is probably a Johari-Goldstein relaxation of intermolecular origin. Further high pressure experiments demonstrated that there are in fact two secondary processes contributing to the β-relaxation. Therefore, one can postulate that the coupling model is a necessary, but not sufficient criterion to identify the true nature of the given secondary relaxation process. The role of pressure experiments in better understanding of the molecular origin of local mobility seems to be much more important. Interestingly, our research also revealed that the structural relaxation in S-GLU is very sensitive to compression. It was reflected in an extremely high pressure coefficient of the glass transition temperature (dTg/dp = 412 K/GPa). According to the literature data, such a high value of dTg/dp has not been obtained so far for any H-bonded, van der Waals, or polymeric glassformers. [ABSTRACT FROM AUTHOR]

[Display omitted] • The unique high-pressure infrared, dielectric, and volumetric data were analyzed. • T and p dependence of H-bonding energy along various isolines was studied. • A phase diagram of 2E1H, identifying isolines in the T - p plane, was constructed. • T controls the intramolecular dynamics of O H units in 2E1H. • The impact of density fluctuation grows with increasing T and weakening of HBs. The nature of H-bonding interactions is still far from being understood despite intense experimental and theoretical studies on this subject carried out by the leading research centers. In this paper, by a combination of unique high-pressure infrared, dielectric and volumetric data, the intramolecular dynamics of hydroxyl moieties (which provides direct information about H-bonds) was studied along various isolines, i.e., isotherms, isobars, isochrones, and isochores, in a simple monohydroxy alcohol (2-ethyl-1-hexanol). This allowed us to discover that the temperature controls the intermolecular hydrogen bonds, which then affect the intramolecular dynamics of O H units. Although the role of density fluctuations gets stronger as temperature rises. We also demonstrated a clear connection between the intra- and intermolecular dynamics of the associating liquid at high pressure. The data reported herein open a new perspective to explore this important aspect of the glass transition phenomenon and understand H-bonding interactions at varying thermodynamic conditions. [ABSTRACT FROM AUTHOR]

In this work, broadband dielectric spectroscopy (BDS) has been applied to investigate the aging kinetics in a low-molecular weight pharmaceutical - probucol (PRO) at various pressure (p) conditions. Unexpectedly, we found that isostructural relaxation times (τ i so , i.e., τ α in the glass), as well as the stretch exponent (β ag) calculated using the Casalini and Roland (CR) approach at 115 and 160 MPa, vary from the respective τ i so and β ag determined at 0.1 MPa. These results were different in regard to the data reported earlier for polymethylmethacrylate (PMMA). Further Fourier transform infrared (FTIR) measurements on the glass recovered from high- p experiments (pressure densified glass, PDG) allowed us to certify that most likely the change in the specific intermolecular interactions, namely the formation of weak, rarely observed O H⋯S hydrogen bonds might be responsible for that. Moreover, taking into account the values of β ag (free parameter) obtained from the analysis of aging data using the CR approach, we estimated primitive relaxation times (τ 0) from the Coupling Model, which were close to experimental Johari-Goldstein (JG) β -relaxation times (τ JG-β). Findings reported herein may contribute to a better understanding of the aging phenomenon occurring in the pressurized H-bonded systems. Unlabelled Image • τ i so calculated using the CR model at elevated p vary from those obtained at 0.1 MPa. • The observed behavior is different than that reported for polymethylmethacrylate. • Weak O H∙∙S hydrogen bonds are formed in probucol at high compression. • Our results enable a better understanding of the aging process in pressurized systems. [ABSTRACT FROM AUTHOR]

In this article, we have addressed fundamental relationships between the chemical structure, intermolecular order, degree of the association and the dynamical properties, including the nature of dielectric response function, the variation of the glass transition temperature and the Kirkwood factor in three homologues phenyl derivatives of monohydroxy alcohols: 1-phenyl-2-butanol, 4-phenyl-1-butanol, and 4-phenyl-2-butanol. Dielectric data supported by infrared and diffraction investigations allowed us to certify that the Debye relaxation can be detected not only in aliphatic but also aromatic monohydroxy alcohols, suggesting its universal character, irrespectively of the chemical structure and steric hindrance. Moreover, we discovered that besides water, 4-phenyl-1-butanol is a next H-bonded system that exhibits the Debye-like relaxation process and no sign of the diffraction pre-peak being a fingerprint of the medium-range intermolecular order. This finding alters our understanding of the molecular origin of the scattering pre-peak and Debye-type process in diffractograms and dielectric loss spectra, respectively. Finally, we revealed that the activation volume, which is a measure of the volume required for reorientational motions of molecules to occur, is the greatest for the system with the highest Kirkwood factor at the glass transition temperature. It means that except the static parameters characterising the size of the supramolecular associates, their morphology, and the degree of intermolecular order, also dynamical quantity related to the volume of relaxing supramolecular structures is required to understand the fluctuations in the Kirkwood factor, and generally, the behaviour of associating liquids at varying thermodynamic conditions. • Phenyl alcohols forming strong hydrogen bonds. • Main contribution to dielectric loss peak in phenyl alcohols due to Debye relaxation. • Debye relaxation universal in aliphatic and aromatic monohydroxy alcohols. • Debye mode in associating, hydrogen-bonded liquids with no diffraction pre-peak. • Static and dynamic parameters determining the molecular dynamics. [ABSTRACT FROM AUTHOR]