Is Ortho-Terphenyl a Rigid Glass Former?

Ortho-terphenyl (OTP) has long been used as a model system to study the glass transition due to its apparent simplicity and a widespread assumption that it is a rigid molecule. Here, we employ terahertz time-domain spectroscopy and low-frequency Raman spectroscopy to investigate the rigidity of OTP by direct observation of the low-frequency vibrational dynamics. These terahertz phonons involve complex large-amplitude atomic motions where intramolecular and intermolecular displacements are often mixed. Comparison of experimental results with density functional theory and ab initio molecular dynamics simulations shows that the assumption of rigidity neglects important implications for the glass transition and must be revisited. These results highlight the significance of terahertz modes on elasticity, which will be even more critical in more complex systems such as biomolecules.

Terahertz Signatures of the Methane Replacement Reaction in Hydroquinone Clathrates.

We report a comprehensive experimental and computational study into low-frequency vibrational dynamics of hydroquinone clathrate during in situ gas loading, in order to monitor replacement of carbon dioxide with methane in its atomic-level pores. We used terahertz time-domain spectroscopy, because terahertz modes are highly sensitive to the identity and structure of enclathrated guest molecules. Through ab initio simulations, we determined that the replacement reaction is not completed. Instead we observed the formation of a heterogeneous material, with methane molecules occupying approximately one-third of available adsorption sites. While the structure of the methane-hydroquinone clathrate system has been previously determined, our observations suggest the reported symmetry is incorrect due to methane molecules weakly interacting with the framework, resulting in dynamic (as opposed to positional) disorder of guests, unlike the related fully ordered carbon dioxide clathrate. This work puts us on the path to quantitatively tracking gas loading in porous materials using terahertz spectroscopy.

Terahertz Spectroscopy Unambiguously Determines the Orientation of Guest Water Molecules in a Structurally Elusive Metal-Organic Framework.

Porous materials, particularly metal-organic frameworks (MOFs), hold great promise for advanced applications. MIL-53(Al) is an exceptionally well-studied MOF that exhibits a phase transition upon guest capture─in this case, water─resulting in a dramatic change in the pore volume. Despite extensive studies, the structure of the water-loaded narrow-pore phase, MIL-53(Al)-np, remains controversial, particularly with respect to the positions of the adsorbed water molecules. We use terahertz spectroscopy, coupled with powder X-ray diffraction and density functional theory simulations, to unambiguously resolve this controversy. We show that the low-frequency (<100 cm-1) vibrational spectrum depends on weak long-range forces that are extremely sensitive to the orientation of the adsorbed water molecules. This enables definitively determining the correct structure of MIL-53(Al)-np while highlighting the extreme sensitivity of terahertz spectroscopy to bulk structure, suggesting its potential as a robust complement to X-ray diffraction for precise characterization of host-guest complexes.

Dynamical Transition in Dehydrated Proteins.

Terahertz time-domain spectroscopy and differential scanning calorimetry were used to study the role of the dynamics of biomolecules decoupled from solvent effects. Lyophilized sucrose exhibited steadily increasing absorption with temperature as anharmonic excitations commenced as the system emerged from a deep minimum of the potential energy landscape where harmonic vibrations dominate. The polypeptide bacitracin and two globular proteins, lysozyme and human serum albumin, showed a more complex temperature dependence. Further analysis focused on the spectral signature below and above the boson peak. We found evidence of the onset of anharmonic motions that are characteristic for partial unfolding and molecular jamming in the dry biomolecules. The activation of modes of the protein molecules at temperatures comparable to the protein dynamical transition temperature was observed in the absence of hydration. No evidence of Fröhlich coherence, postulated to facilitate biological function, was found in our experiments.

Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation.

The solvation shell is essential for the folding and function of proteins, but how it contributes to protein misfolding and aggregation has still to be elucidated. We show that the mobility of solvation shell H2 O molecules influences the aggregation rate of the amyloid protein α-synuclein (αSyn), a protein associated with Parkinson's disease. When the mobility of H2 O within the solvation shell is reduced by the presence of NaCl, αSyn aggregation rate increases. Conversely, in the presence CsI the mobility of the solvation shell is increased and αSyn aggregation is reduced. Changing the solvent from H2 O to D2 O leads to increased aggregation rates, indicating a solvent driven effect. We show the increased aggregation rate is not directly due to a change in the structural conformations of αSyn, it is also influenced by a reduction in both the H2 O mobility and αSyn mobility. We propose that reduced mobility of αSyn contributes to increased aggregation by promoting intermolecular interactions.

Decreased Water Mobility Contributes To Increased α-Synuclein Aggregation.

The solvation shell is essential for the folding and function of proteins, but how it contributes to protein misfolding and aggregation has still to be elucidated. We show that the mobility of solvation shell H2O molecules influences the aggregation rate of the amyloid protein α-synuclein (αSyn), a protein associated with Parkinson's disease. When the mobility of H2O within the solvation shell is reduced by the presence of NaCl, αSyn aggregation rate increases. Conversely, in the presence CsI the mobility of the solvation shell is increased and αSyn aggregation is reduced. Changing the solvent from H2O to D2O leads to increased aggregation rates, indicating a solvent driven effect. We show the increased aggregation rate is not directly due to a change in the structural conformations of αSyn, it is also influenced by a reduction in both the H2O mobility and αSyn mobility. We propose that reduced mobility of αSyn contributes to increased aggregation by promoting intermolecular interactions.

In Situ Observation of the Structure of Crystallizing Magnesium Sulfate Heptahydrate Solutions with Terahertz Transmission Spectroscopy.

Terahertz time-domain spectroscopy in a transmission geometry combined with visual analysis was used to investigate the crystallization process of MgSO4 solution. Careful spectral analysis of both a feature at 1.6 THz and the overall magnitude of absorption allowed the extraction of information about the liquid phase before and during crystallization, aiding the investigation of solvation dynamics and the behavior of molecular species at phase boundaries. The method was reproducibly applied to a number of measurements on a series of solutions of three chosen concentrations at different temperatures. When increasing temperature at the end of the measurement, the dissolution of crystals was observed as well. The temperature-dependent absorption data of the semicrystalline systems were converted to the solvent concentrations using a recently developed method. Solutions of a series of concentrations were also investigated in the temperature range of 4-25 °C. The results were compared to the theoretical calculated values, and the consistent differences proved the existence of a hydration shell around the salt ions whose behavior is different from bulk water. Future work will focus on triggering nucleation at specific positions in order to study the very beginning of the crystallization process. MgSO4 heptahydrate is used as a model system in this study, while the concept and the setup can be applied to other systems.

Measuring Solute Concentration with Terahertz Time-Domain Spectroscopy in Single and Multiphase Systems.

A versatile setup based on a microfluidic platform allows investigation of liquid samples at various temperatures with terahertz time-domain spectroscopy. The setup is applied to develop a novel method that performs temperature and concentration calibrations of liquid samples at terahertz frequencies. Other than measuring the concentration of pure liquid phase solutions, it enables the studies of local concentration of semicrystalline systems. An equivalent solute concentration during crystallization can be calculated from the extracted absorption at low frequencies. The MgSO4-water system is discussed as an example to illustrate the idea of this method.

Predicting the structures and associated phase transition mechanisms in disordered crystals via a combination of experimental and theoretical methods.

Disordered materials make up a large proportion of condensed phase systems, but the difficulties in describing their structures and molecular dynamics limit their potential applications. Disordered crystalline systems, also known as plastic crystals, offer a unique perspective into these factors because the systems retain a degree of crystallinity, reducing the degrees of freedom that must be explored when interpreting the results. However, while disordered crystals do diffract X-rays, it is difficult to fully resolve meaningful crystalline structures, with the best scenario resulting in lattice parameters. In this study, we use a combination of experimental terahertz time-domain spectroscopy, and theoretical solid-state ab initio density functional theory and molecular dynamics simulations to fully elucidate the structures and associated dynamics of organic molecular solids. The results highlight that this combination provides a complete description of the energetic and mechanistic pathways involved in the formation of disordered crystals, and highlights the importance of low-frequency dynamics in their properties. Finally, with structures fully determined and validated by the experimental results, recent progress into anharmonic calculations, namely the quasi-harmonic approximation method, enables full temperature and pressure-dependent properties to be understood within the framework of the potential energy hyper-surface structure.