Fragile Glass Formers Research Articles

Crystallization kinetics and molecular mobility of an amorphous active pharmaceutical ingredient: A case study with Biclotymol

The present case study focuses on the crystallization kinetics and molecular mobility of an amorphous mouth and throat drug namely Biclotymol, through differential scanning calorimetry (DSC), temperature resolved X-ray powder diffraction (TR-XRPD) and hot stage microscopy (HSM). Kinetics of crystallization above the glass transition through isothermal and non-isothermal cold crystallization were considered. Avrami model was used for isothermal crystallization process. Non-isothermal cold crystallization was investigated through Augis and Bennett model. Differences between crystallization processes have been ascribed to a site-saturated nucleation mechanism of the metastable form, confirmed by optical microscopy images. Regarding molecular mobility, a feature of molecular dynamics in glass-forming liquids as thermodynamic fragility index m was determined through calorimetric measurements. It turned out to be around m=100, describing Biclotymol as a fragile glass-former for Angell’s classification. Relatively long-term stability of amorphous Biclotymol above Tg was analyzed indirectly by calorimetric monitoring to evaluate thermodynamic parameters and crystallization behavior of glassy Biclotymol. Within eight months of storage above Tg (T=Tg+2°C), amorphous Biclotymol does not show a strong inclination to crystallize and forms a relatively stable glass. This case study, involving a multidisciplinary approach, points out the importance of continuing looking for stability predictors.

Vapor-deposited non-crystalline phase vs ordinary glasses and supercooled liquids: Subtle thermodynamic and kinetic differences.

Vapor deposition of molecules on a substrate often results in glassy materials of high kinetic stability and low enthalpy. The extraordinary properties of such glasses are attributed to high rates of surface diffusion during sample deposition, which makes it possible for constituents to find a configuration of much lower energy on a typical laboratory time scale. However, the exact nature of the resulting phase and the mechanism of its formation are not completely understood. Using fast scanning calorimetry technique, we show that out-of-equilibrium relaxation kinetics and possibly the enthalpy of vapor-deposited films of toluene and ethylbenzene, archetypical fragile glass formers, are distinct from those of ordinary supercooled phase even when the deposition takes place at temperatures above the ordinary glass softening transition temperatures. These observations along with the absolute enthalpy dependences on deposition temperatures support the conjecture that the vapor-deposition may result in formation of non-crystalline phase of unique structural, thermodynamic, and kinetic properties.

Rigidity and soft percolation in the glass transition of an atomistic model of ionic liquid, 1-ethyl-3-methyl imidazolium nitrate, from molecular dynamics simulations--Existence of infinite overlapping networks in a fragile ionic liquid.

The typical ionic liquid, 1-ethyl-3-methyl imidazolium nitrate (EMIM-NO3), was examined by molecular dynamics simulations of an all-atomistic model to show the characteristics of networks of cages and/or bonds in the course of vitrification of this fragile glass-former. The system shows changes of dynamics at two characteristic temperatures, TB (or Tc) and the glass transition temperature Tg, found in other fragile glass forming liquids [K. L. Ngai and J. Habasaki, J. Chem. Phys. 141, 114502 (2014)]. On decreasing temperature, the number of neighboring cation-anion pairs, NB, within the first minimum of the pair correlation function, g(r)min, increases. On crossing TB (>Tg), the system volume and diffusion coefficient both show changes in temperature dependence, and as usual at Tg. The glass transition temperature, Tg, is characterized by the saturation of the total number of "bonds," NB and the corresponding decrease in degree of freedom, F = [(3N - 6) - NB], of the system consisting of N particles. Similar behavior holds for the other ion-ion pairs. Therefore, as an alternative, the dynamics of glass transition can be interpreted conceptually by rigidity percolation. Before saturation occurring at Tg, the number of bonds shows a remarkable change at around TB. This temperature is associated with the disappearance of the loosely packed coordination polyhedra of anions around cation (or vice versa), related to the loss of geometrical freedom of the polyhedra, fg, of each coordination polyhedron, which can be defined by fg = [(3NV - 6) - Nb]. Here, 3Nv is the degree of freedom of NV vertices of the polyhedron, and Nb is number of fictive bonds. The packing of polyhedra is characterized by the soft percolation of cages, which allows further changes with decreasing temperature. The power spectrum of displacement of the central ion in the cage is found to be correlated with the fluctuation of Nb of cation-cation (or anion-anion) pairs in the polyhedron, although the effect from the coordination shells beyond the neighboring ions is not negligible.

Quantitative relations between cooperative motion, emergent elasticity, and free volume in model glass-forming polymer materials

The study of glass formation is largely framed by semiempirical models that emphasize the importance of progressively growing cooperative motion accompanying the drop in fluid configurational entropy, emergent elasticity, or the vanishing of accessible free volume available for molecular motion in cooled liquids. We investigate the extent to which these descriptions are related through computations on a model coarse-grained polymer melt, with and without nanoparticle additives, and for supported polymer films with smooth or rough surfaces, allowing for substantial variation of the glass transition temperature and the fragility of glass formation. We find quantitative relations between emergent elasticity, the average local volume accessible for particle motion, and the growth of collective motion in cooled liquids. Surprisingly, we find that each of these models of glass formation can equally well describe the relaxation data for all of the systems that we simulate. In this way, we uncover some unity in our understanding of glass-forming materials from perspectives formerly considered as distinct.

Nonlinear acoustics at GHz frequencies in a viscoelastic fragile glass former.

Using a picosecond pump-probe ultrasonic technique, we study the propagation of high-amplitude, laser-generated longitudinal coherent acoustic pulses in the viscoelastic fragile glass former DC704. We observe an increase of almost 10% in acoustic pulse propagation speed at the highest optical pump fluence which is a result of the supersonic nature of nonlinear propagation in the viscous medium. From our measurement, we deduce the nonlinear acoustic parameter of the glass former in the gigahertz frequency range across the glass transition temperature.

How much time is needed to form a kinetically stable glass? AC calorimetric study of vapor-deposited glasses of ethylcyclohexane.

Glasses of ethylcyclohexane produced by physical vapor deposition have been characterized by in situ alternating current chip nanocalorimetry. Consistent with previous work on other organic molecules, we observe that glasses of high kinetic stability are formed at substrate temperatures around 0.85 Tg, where Tg is the conventional glass transition temperature. Ethylcyclohexane is the least fragile organic glass-former for which stable glass formation has been established. The isothermal transformation of the vapor-deposited glasses into the supercooled liquid state was also measured. At seven substrate temperatures, the transformation time was measured for glasses prepared with deposition rates across a range of four orders of magnitude. At low substrate temperatures, the transformation time is strongly dependent upon deposition rate, while the dependence weakens as Tg is approached from below. These data provide an estimate for the surface equilibration time required to maximize kinetic stability at each substrate temperature. This surface equilibration time is much smaller than the bulk α-relaxation time and within two orders of magnitude of the β-relaxation time of the ordinary glass. Kinetically stable glasses are formed even for substrate temperatures below the Vogel and the Kauzmann temperatures. Surprisingly, glasses formed in the limit of slow deposition at the lowest substrate temperatures are not as kinetically stable as those formed near 0.85 Tg.

Glass formers display universal non-equilibrium dynamics on the level of single-particle jumps

Glasses are inherently out-of-equilibrium systems evolving slowly toward their equilibrium state in a process called physical aging. During aging, dynamic observables depend on the history of the system, hampering comparative studies of dynamics in different glass formers. Here, we demonstrate how glass formers can be directly compared on the level of single-particle jumps, i.e. the structural relaxation events underlying the α-process. Describing the dynamics in terms of a continuous-time random walk, an analytic prediction for the jump rate is derived. The result is subsequently compared to molecular-dynamics simulations of amorphous silica and a polymer melt as two generic representatives of strong and fragile glass formers, and good agreement is found.

An alternative explanation of the change in T-dependence of the effective Debye-Waller factor at T(c) or T(B).

The cusp-like temperature dependence of the Debye-Waller factor or non-ergodicity parameter f(Q)(T) at some temperature T(c) above T(g) found by experiments in several fragile glassformers has been considered as critical evidence for validity of the ideal Mode Coupling Theory (MCT). A comprehensive review of experimental data of f(Q)(T) and beyond brings out various problems of the MCT predictions. For example, the molten salt, 0.4Ca(NO3)2-0.6KNO3 (CKN), was the first glassformer measured by neutron scattering to verify the cusp-like behavior of f(Q)(T) at T(c) predicted by ideal MCT. While the fits of the other scaling laws of MCT to viscosity, light scattering, and dielectric relaxation data all give T(c) in the range from 368 to 375 K, there is no evidence of cusp-like behavior of f(Q)(T) at T(c) from more accurate neutron scattering data obtained later on by Mezei and Russina [J. Phys.: Condens. Matter 11, A341 (1999)] at temperatures below 400 K. In several molecular glass-formers, experiments have found at temperatures below T(c) that [1-f(Q)(T)] is manifested as nearly constant loss (NCL) in the frequency dependent susceptibility. The NCL persists down to below T(g) and is not predicted by the ideal MCT. No clear evidence of the change of T-dependence of f(Q)(T) at any T(c) was found in intermediate and strong glassformers, although ideal MCT does not distinguish fragile and strong glassformers in predicting the critical behavior of f(Q)(T) a priori. Experiments found f(Q)(T) changes T-dependence not only at T(c) but also at the glass transition temperature T(g). The changes of T-dependence of f(Q)(T) at T(c) and T(g) are accompanied by corresponding changes of dynamic variables and thermodynamic quantities at T(B) ≈ T(c) and at T(g). The dynamic variables include the relaxation time τ(α)(T), the non-exponentiality parameter n(T), and the generalized fragility m(T) of the structural α-relaxation. The thermodynamic quantities are the free volume deduced from positron annihilation spectroscopy, and the configurational entropy obtained from adiabatic calorimetry measurements. These changes of dynamic variables and thermodynamic quantities in temperature dependence at T(B) ≈ T(c) occur concurrently with the change of f(Q)(T) and suggest the effects are related, and have to be explained altogether. Since this task cannot be carried out by the ideal MCT, we have provided a different interpretation of f(Q)(T) and an alternative explanation of the change in its T-dependence of f(Q)(T) at T(B) ≈ T(c) as well as the other dynamic variables. We show f(Q)(T) originates from the dissipation of the molecules while caged by the anharmonic intermolecular potential, and manifested as the NCL at lower temperatures. The cusp-like change of T-dependence of f(Q)(T) at T(c) originates from the corresponding change of free volume and configurational entropy at T(B) ≈ T(c), which also explains the simultaneous changes of the T-dependencies of the other dynamic variables. The alternative explanation is able to resolve the conundrum in CKN because T(B) is ≥400 K, and hence the change of T-dependence of f(Q)(T) at T(c) ≈ T(B) was not observed in data taken at temperatures lower than 400 K by Mezei and Russina. The alternative explanation also can rationalize the difference between fragile and non-fragile glassformers in the strength of the observed changes of f(Q)(T) at T(c) and T(g) as well as the other dynamic quantities at T(B) ≈ T(c) and T(g).

Molecular dynamics of amorphous pharmaceutical fenofibrate studied by broadband dielectric spectroscopy

Fenofibrate is mainly used to reduce cholesterol level in patients at risk of cardiovascular disease. Thermal transition study with the help of differential scanning calorimetry (DSC) shows that the aforesaid active pharmaceutical ingredient (API) is a good glass former. Based on our DSC study, the molecular dynamics of this API has been carried out by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency ranges. Dielectric measurements of amorphous fenofibrate were performed after its vitrification by fast cooling from a few degrees above the melting point (Tm=354.11K) to deep glassy state. The sample does not show any crystallization tendency during cooling and reaches the glassy state. The temperature dependence of the structural relaxation has been fitted by single Vogel–Fulcher–Tamman (VFT) equation. From VFT fit, glass transition temperature (Tg) was estimated as 250.56K and fragility (m) was determined as 94.02. This drug is classified as a fragile glass former. Deviations of experimental data from Kohlrausch–Williams–Watts (KWW) fits on high-frequency flank of α-peak indicate the presence of an excess wing in fenofibrate. Based on Ngai׳s coupling model, we identified the excess wing as true Johari–Goldstein (JG) process. Below the glass transition temperature one can clearly see a secondary relaxation (γ) with an activation energy of 32.67kJ/mol.

Role of fragility in the formation of highly stable organic glasses.

In situ dielectric spectroscopy has been used to characterize vapor-deposited glasses of methyl-m-toluate (MMT), an organic glass former with low fragility (m = 60). Deposition near 0.84T(g) produces glasses of very high kinetic stability; these materials are comparable in stability to the most stable glasses produced from more fragile glass formers. Highly stable glasses of MMT, when annealed above T(g), transform into the supercooled liquid by a heterogeneous mechanism. A constant velocity propagating front is initiated at the free surface and controls the transformation of thin films. The transition to a bulk-dominated transformation process occurs at 5 μm, the largest length scale reported for any glass. Contrary to recent conclusions, we find that physical vapor deposition can form highly stable organic glasses across the entire range of liquid fragilities.

Dynamics in a tetrahedral network glassformer: vibrations, network rearrangements, and diffusion.

We perform molecular dynamics simulation on a tetrahedral network glassformer using a model for viscous SiO2 by Coslovich and Pastore [J. Phys.: Condens. Matter 21, 285107 (2009)]. In this system, Si and O particles form a random network at low temperature T. We attach an ellipsoid to each particle to represent its time-averaged vibration tensor. We then examine the anisotropic vibrations of Si and O, where the ellipsoid orientations are correlated with the network. The ellipsoids exhibit marked vibrational heterogeneity. The configuration changes occur as breakage and reorganization of the network, where only one or two particles undergo large jumps at each rearrangement leading to diffusion. To the time-correlation functions, however, the particles surrounding these largely displaced ones yield significantly T-dependent contributions, resulting in a weak violation of the Stokes-Einstein relation. This crossover is mild in silica due to the small Si-O bond numbers per particle, while it is strong in fragile glassformers with large coordination numbers. On long timescales, jump events tend to occur in the same regions forming marked dynamic heterogeneity. We also calculate the diffusion constants and the viscosity. The diffusion obeys activation dynamics and may be studied by short-time analysis of irreversible jumps.

Polymer brushes: a controllable system with adjustable glass transition temperature of fragile glass formers.

We present results of molecular dynamics simulations for coarse-grained polymer brushes in a wide temperature range to investigate the factors that affect the glass transition in these systems. We focus on the influences of free surface, polymer-substrate interaction strength, grafting density, and chain length not only on the change of glass transition temperature Tg, but also the fragility D of the glass former. It is found that the confinement can enhance the dependence of the Tg on the cooling rate as compared to the bulk melt. Our layer-resolved analysis demonstrates that it is possible to control the glass transition temperature Tg of polymer brushes by tuning the polymer-substrate interaction strength, the grafting density, and the chain length. Moreover, we find quantitative differences in the influence range of the substrate and the free surface on the density and dynamics. This stresses the importance of long range cooperative motion in glass formers near the glass transition temperature. Furthermore, the string-like cooperative motion analysis demonstrates that there exists a close relation among glass transition temperature Tg, fragility D, and string length ⟨S⟩. The polymer brushes that possess larger string length ⟨S⟩ tend to have relatively higher Tg and smaller D. Our results suggest that confining a fragile glass former through forming polymer brushes changes not only the glass transition temperature Tg, but also the very nature of relaxation process.

Molecular Mobility of Amorphous S-Flurbiprofen: A Dielectric Relaxation Spectroscopy Approach

Amorphous S-flurbiprofen was obtained by the melt quench/cooling method. Dielectric measurements performed in the isochronal mode, conventional and temperature modulated differential scanning calorimetry (TMDSC) studies showed a glass transition, recrystallization, and melting. The different parameters characterizing the complex molecular dynamics of amorphous S-flurbiprofen that can have influence on crystallization and stability were comprehensively characterized by dielectric relaxation spectroscopy experiments (isothermal mode) covering a wide temperature (183 to 408 K) and frequency range (10(-1) to 10(6) Hz): width of the α-relaxation (βKWW), temperature dependence of α-relaxation times (τα), fragility index (m), relation of the α-relaxation with the β-secondary relaxation, and the breakdown of the Debye-Stokes-Einstein (DSE) relationship between the structural relaxation time and dc-conductivity (σdc) at deep undercooling close to Tg. The β-relaxation, observed in the glassy as well as in the supercooled state was identified as the genuine Johari-Goldstein process, attributed to localized motions and regarded as the precursor of the α-relaxation as suggested in the coupling model. A separation of about 6 decades between the α- and β-relaxation was observed at Tg; this decoupling decreased on increasing temperature, and both processes merged at Tαβ = 295 K. The temperature dependence of the α-relaxation time, τα, was described by two Vogel-Fulcher-Tammann-Hesse equations, which intercept at a crossover temperature, TB = 290 K, close to the splitting temperature between the α- and β-relaxation. From the low temperature VFTH equation, a Tg(DRS) = 265.2 was estimated (at τα =100 s) in good agreement with the calorimetric value (Tg,onset,TMDSC = 265.6 K), and a fragility or steepness index m = 113 was calculated allowing to classify S-flurbiprofen as a fragile glass former. The α-relaxation spectra were found to be characterized by a relatively large degree of nonexponentiality (βKWW = 0.52). A breakdown of the DSE log10 σdc - log10 τ relation was observed revealing an enhancement of translational ionic motions in comparison with the orientational molecular motions as the glass transition temperature Tg is approached from above.

Cooperativity length scale in nanocomposites: Interfacial and confinement effects

Interfacial and confinement effects on the evolution of cooperativity on approaching the glass transition have been studied in poly(propylenecoethylene) functionalized with diethylmaleate, polyethylene 1,4-cyclohexylenedimethylene terephthalate glycol and their nanocomposites with montmorillonite. A small increase of the structural dynamic cooperativity, a weak alteration of the temperature dependence of the characteristic relaxation frequency, and no changes in the glass transition temperature observed in poly(propylenecoethylene)-based samples can be rationalized in terms of interfacial interactions between polymer and exfoliated clay. On the other hand, confinement of polymer chains in the galleries of clay (intercalated nanocomposite) produces a strong reduction of cooperativity, of the temperature dependence of the characteristic relaxation frequency, and of the glass transition temperature in polyethylene 1,4-cyclohexylenedimethylene terephthalate glycol samples. Finally, by investigating the temperature dependence of a generalized fragility and of cooperativity, we evidenced that fragility of glass formers is determined not only by cooperativity.

Inelastic Neutron Scattering from Glass Formers

Neutron spectra below and above the glass transition temperature show a pronounced difference between strong and fragile glass formers in Angell's fragility scheme. The strong anharmonic increase of the inelastic scattering with increasing temperature in fragile substances is absent in the strongest glass former SiO2. That difference is reflected in the temperature dependence of Brillouin sound velocities above the glass transition. Coherent inelastic neutron scattering data indicate a mixture of sound waves and local modes at the low frequency boson peak. A relation between the fragility and the temperature dependence of the transverse hypersound velocity at the glass temperature is derived.

Molecular dynamics in liquid and glassy states of non-steroidal anti-inflammatory drug: Ketoprofen

Ketoprofen is a well known nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body’s production of prostaglandin. The molecular mobility of amorphous ketoprofen has been investigated by broadband dielectric spectroscopy (BDS) covering wide temperature and frequency range. Multiple relaxation processes were observed. Besides the primary α-relaxation, one secondary relaxation, γ-have been identified. The γ-process visible in the dielectric spectra at very low temperature is non-JG relaxation, and has an activation energy E=37.91kJ/mol typical for local mobility. Based on Ngai’s coupling model smaller n or a larger Kohlrausch exponent (1−n) of the α-relaxation associated with larger τβ (Tg). In the case of ketoprofen we conclude that the secondary relaxation (β) emerging from intermolecular motions, is hidden under the dominant α-peak. The temperature dependence of the relaxation time of the α-process can be described over the entire measured range by a single Vogel–Fulcher–Tammann (VFT) equation. From VFT fits, the glass transition temperature (Tg) was estimated as 267.07K, and a fragility or steepness index m=86.57 was calculated, showing that ketoprofen is a fragile glass former. Our differential scanning calorimetry (DSC) study shows that ketoprofen is a non-crystallizing compound. To confirm the hydrogen bond patterns of ketoprofen FTIR spectroscopy was applied in both crystalline and amorphous phases. Solubility test performed at 37°C proved that amorphous phase is more soluble than the crystalline phase.

Breakdown of the Stokes-Einstein relation in two, three, and four dimensions

The breakdown of the Stokes-Einstein (SE) relation between diffusivity and viscosity at low temperatures is considered to be one of the hallmarks of glassy dynamics in liquids. Theoretical analyses relate this breakdown with the presence of heterogeneous dynamics, and by extension, with the fragility of glass formers. We perform an investigation of the breakdown of the SE relation in 2, 3, and 4 dimensions in order to understand these interrelations. Results from simulations of model glass formers show that the degree of the breakdown of the SE relation decreases with increasing spatial dimensionality. The breakdown itself can be rationalized via the difference between the activation free energies for diffusivity and viscosity (or relaxation times) in the Adam-Gibbs relation in three and four dimensions. The behavior in two dimensions also can be understood in terms of a generalized Adam-Gibbs relation that is observed in previous work. We calculate various measures of heterogeneity of dynamics and find that the degree of the SE breakdown and measures of heterogeneity of dynamics are generally well correlated but with some exceptions. The two-dimensional systems we study show deviations from the pattern of behavior of the three- and four-dimensional systems both at high and low temperatures. The fragility of the studied liquids is found to increase with spatial dimensionality, contrary to the expectation based on the association of fragility with heterogeneous dynamics.

Microscopic Picture of Aging inSiO2

We investigate the aging dynamics of amorphous SiO(2) via molecular dynamics simulations of a quench from a high temperature T(i) to a lower temperature T(f). We obtain a microscopic picture of aging dynamics by analyzing single particle trajectories, identifying jump events when a particle escapes the cage formed by its neighbors, and determining how these jumps depend on the waiting time t(w), the time elapsed since the temperature quench to T(f). We find that the only t(w)-dependent microscopic quantity is the number of jumping particles per unit time, which decreases with age. Similar to previous studies for fragile glass formers, we show here for the strong glass former SiO(2) that neither the distribution of jump lengths nor the distribution of times spent in the cage are t(w) dependent. We conclude that the microscopic aging dynamics is surprisingly similar for fragile and strong glass formers.

Ultrafast spherulitic crystal growth as a stress-induced phenomenon specific of fragile glass-formers

We propose a model for the abrupt emergence, below temperatures close to the glass transition, of the ultrafast (glass-to-crystal) steady mode of spherulitic crystal growth in deeply undercooled liquids. We interpret this phenomenon as controlled by the interplay between the generation of stresses by crystallization and their partial release by flow in the surrounding amorphous visco-elastic matrix. Our model is consistent with both the observed ratios (∼10(4)) of fast-to-slow velocities and the fact that fast growth emerges close to the glass transition. It leads us to conclude that the existence of a fast growth regime requires both (i) a high fragility of the glassformer; (ii) the fine sub-structure specific of spherulites. It finally predicts that the transition is hysteretic, thus allowing for an independent experimental test.

Glassy dynamics in a confined monatomic fluid

Molecular dynamic simulations of a strongly inhomogeneous system reveals that a single-component soft-sphere fluid can behave as a fragile glass former due to confinement. The self-intermediate scattering function, F(s)(k,t), of a Lennard-Jones fluid confined in slit-shaped pores, which can accommodate two to four fluid layers, exhibits a two-step relaxation at moderate temperatures. The mean-squared displacement data are found to follow time-temperature superposition and both the self-diffusivity and late α relaxation times exhibit power-law divergences as the fluid is cooled. The system possesses a crossover temperature and follows the scalings of mode coupling theory for the glass transition. The temperature dependence of the self-diffusivity can be expressed using the Vogel-Fulcher-Tammann equation, and estimates of the fragility index of the system indicates a fragile glass former. At lower temperatures, signatures of additional relaxation processes are observed in the various dynamical quantities with a three-step relaxation observed in the F(s)(k,t).