Role of Exchange Cations and Layer Charge on the Dynamics of Confined Water.

Describing the dynamic behavior of water confined in clay minerals is a fascinating challenge and crucial in many research areas, ranging from materials science and geotechnical engineering to environmental sustainability. Water is the most abundant resource on Earth, and the high reactivity of naturally occurring hydrous clay minerals used since prehistoric times for a variety of applications means that water-clay interaction is a ubiquitous phenomenon in nature. We have attempted to experimentally distinguish the rotational dynamics and translational diffusion of two distinct populations of interlayer water, confined and ultraconfined, in the sodium (Na) forms of two smectite clay minerals, montmorillonite (Mt) and hectorite (Ht). Samples hydrated at a pseudo one-layer hydration (1LH) state under ambient conditions were studied with quasi-elastic neutron scattering (QENS) between 150 and 300 K. Using a simplified revised jump-diffusion and rotation-diffusion model (srJRM), we observed that while interlayer water near the ditrigonal cavity in Ht forms strong H-bonds to both adjacent surface O and structural OH, H-bonding of other more prevalent interlayer water with the surface O is weaker compared to Mt, inducing a higher temperature for dynamical changes of confined water. Given the lower layer charge and faster dynamics observed for Ht compared to Mt, we consider this strong evidence confirming the influence of the interlayer cation and surfaces on confined water dynamics.

Control of H-Related Defects in γ-MnO2 in a Hydrothermal Synthesis.

Manganese dioxide is a good candidate for effective energy storage and conversion as it possesses rich electrochemistry. The compound also shows a wide polymorphism. The γ-variety, an intergrowth of ß- and R-MnO2, has been extensively studied in several types of batteries (e.g., Zn/MnO2, Li-ion) and is a common electrode material for commercial batteries. It is well known that the insertion of protons thermodynamically stabilizes γ-MnO2 with respect to ß-MnO2. Protons can enter the structure either by forming groups of 4 hydroxyls around a Mn4+ vacancy, called a Ruetschi defect, or by forming a hydroxyl group near a Mn3+ ion, called a Coleman defect. These defects differently affect the electrochemistry of manganese oxide, and tailoring their amount in the structure can be used to tune the material properties. Previous studies have addressed the proton insertion process, but the role of the synthesis pathway on the amount of defects created is not well understood. We here investigate how the parameters in a hydrothermal synthesis of γ-MnO2 nanoparticles influence the amount and type of H-related defects. Structural investigations are carried out using Pair Distribution Function analysis, X-ray absorption spectroscopy, thermogravimetric analysis, and inelastic neutron scattering. We demonstrate the possibility to control the amount and type of defects introduced during the synthesis. While the amount of Ruetschi defects increases with synthesis temperature, it decreases with extended synthesis time, along with the amount of Coleman defects. Moreover, we discuss the arrangement of the defects in the γ-MnO2 nanoparticles.

Water Dynamics in Cancer Cells: Lessons from Quasielastic Neutron Scattering.

The severity of the cancer statistics around the globe and the complexity involving the behavior of cancer cells inevitably calls for contributions from multidisciplinary areas of research. As such, materials science became a powerful asset to support biological research in comprehending the macro and microscopic behavior of cancer cells and untangling factors that may contribute to their progression or remission. The contributions of cellular water dynamics in this process have always been debated and, in recent years, experimental works performed with Quasielastic neutron scattering (QENS) brought new perspectives to these discussions. In this review, we address these works and highlight the value of QENS in comprehending the role played by water molecules in tumor cells and their response to external agents, particularly chemotherapy drugs. In addition, this paper provides an overview of QENS intended for scientists with different backgrounds and comments on the possibilities to be explored with the next-generation spectrometers under construction.

Hydrogen bond dynamics and conformational flexibility in antipsychotics.

Effective treatment of disorders of the central nervous system can often be achieved using bioactive molecules of similar moieties to those known to be tolerable. A better understanding of the solid-state characteristics of such molecules could thereby create new opportunities for research on pharmaceutical preparations and drug prescriptions, while information about their rich intramolecular dynamics may well add an important aspect in the field of in silico drug discovery. We have therefore investigated three different antipsychotic drugs: haloperidol (C21H23ClFNO2, HAL), aripiprazole (C23H27Cl2N3O2, APZ) and quetiapine hemifumarate (C21H25N3O2S·0.5C4H4O4, QTP) based on similarities either in their structures, hydrophobic and hydrophilic moieties, or in their modes of action, typical or atypical. Our aim was to test the structural and molecular stability of these three different antipsychotics. To this end, we compared the molecular vibrations observed by inelastic neutron spectroscopy of these systems with those from theoretical periodic calculations of the crystalline antipsychotics using the Vienna ab initio simulation package (VASP). While most of the observed features in the lattice region were reasonably well represented by the calculations, the overall spectra were relatively complex, and hence traditional assignment procedures for the approximately 600 normal modes in the unit cell were not possible. These results indicate that in the search for new drug candidates, not only analysis of the flexibility of the receptor, but also the dynamics of the active molecules play a role in improving the prediction of binding affinities.

Sample cell for studying liquid interfaces with an in situ electric field using X-ray reflectivity and application to clay particles at oil-oil interfaces.

Commissioning results of a liquid sample cell for X-ray reflectivity studies with an in situ applied electrical field are presented. The cell consists of a Plexiglas container with lateral Kapton windows for air-liquid and liquid-liquid interface studies, and was constructed with grooves to accept plate electrodes on the walls parallel to the direction of the beam. Both copper and ITO plate electrodes have been used, the latter being useful for simultaneous optical studies. Commissioning tests were made at the I07 beamline of the Diamond Light Source.

Polymorphism of paracetamol: a new understanding of molecular flexibility through local methyl dynamics.

This study focuses on the interplay of molecular flexibility and hydrogen bonding manifested in the monoclinic (form I) and orthorhombic (form II) polymorphs of paracetamol. By means of incoherent inelastic neutron scattering and density functional theory calculations, the relaxation processes related to the methyl side-group reorientation were analyzed in detail. Our computational study demonstrates the importance of considering quantum effects to explain how methyl reorientations and subtle conformational changes of the molecule are intertwined. Indeed, by analyzing the quasi elastic signal of the neutron data, we were able to show a unique and complex motional flexibility in form II, reflected by a coupling between the methyl and the phenyl reorientation. This is associated with a higher energy barrier of the methyl rotation and a lower Gibbs free energy when compared to form I. We put forward the idea that correlating solubility and molecular flexibility, through the relation between pKa and methyl rotation activation energy, might bring new insights to understanding and predicting drug bioavailability.

Physics-Based Protein Networks Might Recover Effectful Mutations─a Case Study on Cathepsin G.

Molecular dynamics simulations have been remarkably effective for observing and analyzing structures and dynamics of proteins, with longer trajectories being computed every day. Still, often, relevant time scales are not observed. Adequately analyzing the generated trajectories can highlight the interesting areas within a protein such as mutation sites or allosteric hotspots, which might foreshadow dynamics untouched by the simulations. We employ a physics-based protein network and propose that such a network can adequately analyze the protein dynamics. The analysis is conducted on simulations of cathepsin G and neutrophil elastase, which are remarkably similar but with different specificities. However, a single mutation in cathepsin G recovers the specificity of neutrophil elastase. The physics-based network built on the interactions between residues instead of the distances can pinpoint the active triad in the proteins studied. Overall, the network seems to capture the structural behavior better than purely distance-based networks.

Single-voxel delay map from long-axial field-of-view PET scans.

Objective: We present an algorithm to estimate the delay between a tissue time-activity curve and a blood input curve at a single-voxel level tested on whole-body data from a long-axial field-of-view scanner with tracers of different noise characteristics. Methods: Whole-body scans of 15 patients divided equally among three tracers, namely [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, which were used in development and testing of the algorithm. Delay times were estimated by fitting the cumulatively summed input function and tissue time-activity curve with special considerations for noise. To evaluate the performance of the algorithm, it was compared against two other algorithms also commonly applied in delay estimation: name cross-correlation and a one-tissue compartment model with incorporated delay. All algorithms were tested on both synthetic time-activity curves produced with the one-tissue compartment model with increasing levels of noise and delays between the tissue activity curve and the blood input curve. Whole-body delay maps were also calculated for each of the three tracers with data acquired on a long-axial field-of-view scanner with high time resolution. Results: Our proposed model performs better for low signal-to-noise ratio time-activity curves compared to both cross-correlation and the one-tissue compartment models for non-[15O]H2O tracers. Testing on synthetically produced time-activity curves showed only a small and even residual delay, while the one-tissue compartment model with included delay showed varying residual delays. Conclusion: The algorithm is robust to noise and proves applicable on a range of tracers as tested on [15O]H2O, [18F]FDG and [64Cu]Cu-DOTATATE, and hence is a viable option offering the ability for delay correction across various organs and tracers in use with kinetic modeling.

Simulating selected magnetic properties of TbxPr1-xAl2, a magnetocaloric compound.

TbxPr1-xAl2are ferrimagnetic materials exhibiting magnetocaloric effect that have gained considerable attention due to their potential use as an alternative in refrigeration, magnetic sensors and in information storage technology. Here using the mean field approach numerical simulations were conducted forx= 0.1, 0.2, 0.3, 0.4, 0.5, and 0.75, to analyze selected physical properties, such as x-ray and neutron powder diffraction, magnetization and heat capacity. The simulations successfully reproduced the experimental data providing a comprehensive characterization and improved understanding of this family of compound.

Molecular spectroscopy, solvent effect, and DFT studies of azithromycin solvate.

Azithromycin ethanol solvate monohydrate [C38H72N2O120.5(C2H6O)H2O], abbreviated by AZM-MH-EtOH, was synthesized by slow evaporation method and investigated by powder X-ray diffraction, Raman and infrared (IR) spectroscopy combined with density functional theory (DFT) studies. Electronic and vibrational properties were properly investigated based on a theoretical study of solvation effects, using implicit solvation and solute electron density models. The electronic and vibrational studies were evaluated under aqueous, ethanolic, and vacuum conditions. The electronic structure calculations indicated that the AZM-MH-EtOH is chemically more stable in solvents compared to vacuum condition. Ultraviolet-visible (UV-vis) measurements confirmed the stability of the material in ethanolic medium, due to higher absorbance values compared to the aqueous medium. Vibrational changes were observed in the Raman and IR bands, which have connection with hydrogen bonds. The experimental vibration modes showed better accordance with the predicted modes' values under solvation effects, but a slight divergence is noticed when we compared to vibration modes obtained in vacuum. Furthermore, the results have revealed a greater affinity profile of AZM-MH-EtOH for water and ethanol solvents compared to theoretical data under vacuum condition.

Solitonic lattice and Yukawa forces in the rare-earth orthoferrite TbFeO3.

The random fluctuations of spins give rise to many interesting physical phenomena, such as the 'order-from-disorder' arising in frustrated magnets and unconventional Cooper pairing in magnetic superconductors. Here we show that the exchange of spin waves between extended topological defects, such as domain walls, can result in novel magnetic states. We report the discovery of an unusual incommensurate phase in the orthoferrite TbFeO(3) using neutron diffraction under an applied magnetic field. The magnetic modulation has a very long period of 340 Å at 3 K and exhibits an anomalously large number of higher-order harmonics. These domain walls are formed by Ising-like Tb spins. They interact by exchanging magnons propagating through the Fe magnetic sublattice. The resulting force between the domain walls has a rather long range that determines the period of the incommensurate state and is analogous to the pion-mediated Yukawa interaction between protons and neutrons in nuclei.

Colorimetric pH indicators based on well-defined amylose and amylopectin matrices enriched with anthocyanins from red cabbage.

This study aimed to prepare a novel colorimetric indicator film from virtually pure (99 %) amylose (AM) and anthocyanins extracted from red cabbage (RCA). The AM used was a unique engineered bulk material extracted from transgenic barley grains. Films produced by solution casting were compared to normal barely starch (NB) and pure barley amylopectin (AP), with amylose contents of 30 % and 0 %, respectively. The pH-indicator films were produced by incorporation of RCA into the different starch support matrices with different amylose contents. Barrier, thermal, and mechanical properties, photo degradation stability, and release behavior data revealed that RCA interact differently through the glucan matrices. Microstructural observations showed that RCA were evenly dispersed in the glucan matrix, and AM+RCA indicator films showed high UV-barrier and mechanical performance over normal starch. FTIR revealed that RCA was properly affected by the AM matrix. Moreover, the AM+RCA films showed sensitive color changes in the pH range (2-11) and a predominant Fickian diffusion release mechanism for RCA. This study provides for the first time data regarding AM films with RCA and their promising potential for application as support matrices in responsive food and other industrial biodegradable packaging materials.

Application of incoherent inelastic neutron scattering in pharmaceutical analysis: relaxation dynamics in phenacetin.

This study centers on the use of inelastic neutron scattering as an alternative tool for physical characterization of solid pharmaceutical drugs. On the basis of such approach, relaxation processes in the pharmaceutical compound phenacetin (p-ethoxyacetanilide, C(10)H(13)NO(2)) were evidenced on heating between 2 and 300 K. By evaluating the mean-square displacement obtained from the elastic fixed window approach, using the neutron backscattering technique, a crossover of the molecular fluctuations between harmonic and nonharmonic dynamical regimes around 75 K was observed. From the temperature dependence of the quasi-elastic line-width, summed over the total Q range explored by the time-of-flight technique, it was possible to attribute the onset of this anharmonicity to methyl group rotations. Finally, using density functional theory-based methods, we were able to calculate the lattice vibrations in the harmonic approximation. The overall spectral profile of the calculated partial contributions to the generalized density of states compares satisfactorily to the experimental spectra in the region of the lattice modes where the intermolecular interactions are expected to play an important role. This study contributes to understanding the relationships between intermolecular hydrogen bonds, intramolecular dynamics, and conformational flexibility in pharmaceuticals on a molecular level, which can help in evaluating phase stability with respect to temperature variations on processing or on storage, and is related to control of polymorphism and pseudopolymorphism.

Neither too little nor too much: Finding the ideal proportion of excipients using confocal Raman and chemometrics.

The applications of Raman imaging in pharmaceutical field are ever-increasing due its ability to obtain spatial and spectral information simultaneously, once it allows determine the chemical distribution of compounds. In this sense, it is used to study homogeneity, of paramount importance during the development of pharmaceutical formulations due to its relation to stability, safety and efficacy. Commonly, just surface is analyzed, but confocal Raman spectroscopy can also characterize the inner part of samples, allowing to determine phase separation in the early stages. In this sense, confocal 3D Raman microscopy was crucial to obtain the optimal proportion of Apifil®, Capryol® 90 and Transcutol® to promote controlled release of the local anesthetic butamben (BTB). 3D chemical maps were obtained by classical least squares (CLS) using pure compound spectra as S matrix, showing that chemical distribution throughout the material was different. Knowing that the composition of samples affects the homogeneity parameter, standard deviation and distributional homogeneity index (DHI) were used in mixture experimental design (DoE). From this analysis, it was revealed that a correct amount of Capryol® 90 enhances both miscibility and solubility. Furthermore, suitable miscibility was observed in two ratio proportions of excipients with a desirability of 0.783 and 0.742. These results unequivocally demonstrated that confocal Raman microscopy combined to DoE can bring pharmaceutical development to a higher level.

Structure-property relations in crystalline L-leucine obtained from calorimetry, X-rays, neutron and Raman scattering.

We have studied the amino acid L-leucine (LEU) using inelastic neutron scattering, X-rays and neutron diffraction, calorimetry and Raman scattering as a function of temperature, focusing on the relationship between the local dynamics of the NH(3), CH(3), CH(2) and CO(2) moieties and the molecular structure of LEU. Calorimetric and diffraction data evidenced two novel phase transitions at about 150 K (T(1)) and 275 K (T(2)). The dynamical susceptibility function, obtained from the inelastic neutron scattering results, shows a re-distribution of the intensity of the vibrational bands that can be directly correlated with the phase transitions observed at T(1) and T(2), as well as with the already reported phase transition at T(3) = 353 K. Through the analysis of the Raman modes, the new structural arrangement observed below T(1) was related to conformational modifications of the CH and CH(3) groups, while the behavior of the N-H stretching vibration, ν(NH(3)), gave insight into the intermolecular N-H…O interactions. The observation of changes in the translational symmetry in the crystalline lattice, as well as anharmonic dynamics, allows for localized motions in LEU.

Is artificial intelligence magic dust for big-science facilities?

AI is no magic dust: for it to become a true discovery accelerator, much work is needed to make it transparent and robust.

Dynamical Accuracy of Water Models on Supercooling.

Molecular dynamics (MD) simulations are commonly used to explore the structural and dynamical properties of supercooled bulk water in the so-called "no man's land" (NML) (150-227 K), where crystallization occurs almost instantaneously. This approach has provided significant insight into experimentally inaccessible phenomena. In this paper, we compare the dynamics of simulations using one-, three-, and four-body water models to experimentally measured quasielastic neutron scattering spectra. We show that the agreement between simulated and experimental data becomes substantially worse with a decrease in temperature toward the deeply supercooled regime. It was found that it is mainly the nature of the local dynamics that is poorly reproduced, as opposed to the macroscopic properties such as the diffusion coefficient. This strongly implies that the molecular mechanism describing the water dynamics is poorly captured in the MD models, and simulated structural and dynamical properties of supercooled water in NML must be interpreted with care.

Effect of Paclitaxel in the Water Dynamics of MCF-7 Breast Cancer Cells Revealed by Dielectric Spectroscopy.

Using dielectric spectroscopy experiments performed at multiple temperatures and frequency ranges, we demonstrate how the chemotherapy drug paclitaxel changes the dynamic properties of water in a breast cancer cell line (MCF-7). From the measured data, we present evidence that treatment with paclitaxel leads to a slight increase in activation energy in a relaxation related to bulk-like water. More importantly, we also observe that paclitaxel changes the constraining imposed by the biological interfaces on hydration water, whose single-particle dynamics becomes slower and with higher activation energy. These variations are only observable after freezing the dynamics from other cellular components, such as proteins and DNAs, regardless of the state of the cells, that is, treated or not treated or even if the cells are no longer viable. Therefore, changes in water dynamics could be detected prior to those related to the global dynamics within the cellular environment.

Mutations in a Single Signaling Pathway Allow Cell Growth in Heavy Water.

Life is completely dependent on water. To analyze the role of water as a solvent in biology, we replaced water with heavy water (D2O) and investigated the biological effects by a wide range of techniques, using Schizosaccharomyces pombe as model organism. We show that high concentrations of D2O lead to altered glucose metabolism and growth retardation. After prolonged incubation in D2O, cells displayed gross morphological changes, thickened cell walls, and aberrant cytoskeletal organization. By transcriptomics and genetic screens, we show that the solvent replacement activates two signaling pathways: (1) the heat-shock response pathway and (2) the cell integrity pathway. Although the heat-shock response system upregulates various chaperones and other stress-relieving enzymes, we find that the activation of this pathway does not offer any fitness advantage to the cells under the solvent-replaced conditions. However, limiting the D2O-triggered activation of the cell integrity pathway allows cell growth when H2O is completely replaced with D2O. The isolated D2O-tolerant strains may aid biological production of deuterated biomolecules.

Ammonia Storage in Hydrogen Bond-Rich Microporous Polymers.

The fascinating structural flexibility of porous polymers is highly attractive because it can result in optimized materials with specific host-guest interactions. Nevertheless, the fundamental mechanisms responsible for controlling the weak interactions of these hydrogen bond-rich networks-essential for developing smart task-specific materials used in recognition, capture, and sequestration processes-remain unexplored. Herein, by systematically comparing performance changes between poly(amic acid) (PAA)- and polycyclic imide (PI)-based porous polymers before and after NH3 adsorption, the role of hydrogen bonds in conformational lability and responsiveness toward guest molecules is highlighted. By combining thermal gravimetric analysis with neutron spectroscopy supported by DFT calculations, we demonstrate that PAA's chemical and physical stability is enhanced by the presence of stronger host-guest interactions. This observation also emphasizes the idea that efficient adsorption relies on having a high number of sites, upon which gas molecules can adsorb with greater affinity via strong hydrogen bonding interactions.