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.

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.

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.

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.

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.

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.

The development of new oral vaccines using porous silica

Ordered mesoporous silica was proved to be an efficient oral adjuvant capable to deliver a wide in size variety of different antigens, promoting efficient immunogenicity. This material can be used in single or polivalent vaccines, which have been developed by a group of Brazilian scientists. The experiments performed with the model protein Bovine Serum Albumin (BSA) gave the first promissing results, that were also achieved by testing the virus like particle surface antigen of hepatitis B (HBsAg) and diphtheria anatoxin (dANA). Nanostructured ordered mesoporous silica, SBA-15 type, with bi-dimensional hexagonal porous symmetry was used to encapsulate the antigens either in the mesoporous (pore diameter ~10 nm) or macroporous ( pore diameter > 50 nm) regions. This silica vehicle proved to be capable to create an inflammatory response, did not exhibit toxicity, being effective to induce immunity in high and low responder mice towards antibody production. The silica particles are in the range of micrometer size, leaving no trace in mice organs due to its easy expulsion by faeces. The methods of Physics, usually employed to characterize the structure, composition and morphology of materials are of fundamental importance to develop proper oral vaccines in order to state the ideal antigen load to avoid clustering and to determine the rate of antigen release in different media mimicking body fluids.

Assessing the efficiency of SBA-15 as a nanocarrier for diphtheria anatoxin

SBA-15 ordered mesoporous silica can be considered a promising inorganic nanocarrier with emerging potential as an oral vaccine adjuvant. In this study, we investigated its application in the encapsulation of the diphtheria anatoxin (dANA). We observed a considerable preservation of dANA secondary and tertiary structures, even after the drying process by means of Circular Dichroism (CD) and fluorescence spectroscopies. Antigen loading was assessed at a number of different ratios of adjuvant-to-antigen using a combination of nitrogen adsorption porosimetry and Small Angle X-ray Scattering (SAXS). Our data showed that the mass ratio of 1:10 (dANA:SBA-15) is recommended for total encapsulation of dANA in the mesopores, considering that at this relative mass concentration antigen clustering was avoided, which is deleterious effect for immunization purposes. dANA release in mimetic intestine fluid, at a pH equal to 6.8, was followed by in-situ SAXS measurements and shown to be slow, being more pronounced after 6 h and continuous up to 35 h. Finally, the immunogenic complex was tested in isogenic Balb C mice by oral and subcutaneous immunization routes, including a comparison with the only permitted adjuvant for human use, aluminum hydroxide. A higher antibody titer was obtained by subcutaneous and oral administration routes using SBA-15 as the vehicle of dANA, compared with the conventional aluminum hydroxide, demonstrating the viability to use this ordered mesoporous silica in the formulation of oral vaccines, as already proved for the Virus Like Particles (VLP) Hepatitis B (HBsAg) case.

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.

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.

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.

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.

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.

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.

Water dynamics in MCF-7 breast cancer cells: a neutron scattering descriptive study.

Water mobility in cancer cells could be a powerful parameter to predict the progression or remission of tumors. In the present descriptive work, new insight into this concept was achieved by combining neutron scattering and thermal analyses. The results provide the first step to untangle the role played by water dynamics in breast cancer cells (MCF-7) after treatment with a chemotherapy drug. By thermal analyses, the cells were probed as micrometric reservoirs of bulk-like and confined water populations. Under this perspective we showed that the drug clearly alters the properties of the confined water. We have independently validated this idea by accessing the cellular water dynamics using inelastic neutron scattering. Finally, analysis of the quasi-elastic neutron scattering data allows us to hypothesize that, in this particular cell line, diffusion increases in the intracellular water in response to the action of the drug on the nanosecond timescale.

3D visualisation of hepatitis B vaccine in the oral delivery vehicle SBA-15.

Developing a technology that enables oral vaccines to work efficiently remains a considerable effort since a number of difficulties must be addressed. The key objective being to ensure the safe passage through the harsh conditions within the gastrointestinal tract, promoting delivery that induces enhanced immune response. In the particular case of hepatitis B, the oral formulation in the nanostructured silica SBA-15 is a viable approach. As a result of its porous structure, low toxicity and structural stability, SBA-15 is capable to protect and release the hepatitis B surface antigen (HBsAg), used in the vaccination scheme, at the desired destination. Furthermore, when compared to the currently used injection based delivery method, better or similar antibody response has been observed. However, information about the organisation of the antigen protein remains unknown. For instance, HBsAg is too large to enter the 10 nm ordered mesopores of SBA-15 and has a tendency to agglomerate when protected by the delivery system. Here we report on the pH dependence of HBsAg aggregation in saline solution investigated using small angle X-rays scattering that resulted in an optimisation of the encapsulation conditions. Additionally, X-ray microscopy combined with neutron and X-ray tomography provided full 3D information of the HBsAg clustering (i.e. agglomeration) inside the SBA-15 macropores. This method enables the visualisation of the organisation of the antigen in the interior of the delivery system, where agglomerated HBsAg coexists with its immunological effective uniformly distributed counterpart. This new approach, to be taken into account while preparing the formulation, can greatly help in the understanding of clinical studies and advance new formulations.

3D visualisation of hepatitis B vaccine in the oral delivery vehicle SBA-15

Developing a technology that enables oral vaccines to work efficiently remains a considerable effort since a number of difficulties must be addressed. The key objective being to ensure the safe passage through the harsh conditions within the gastrointestinal tract, promoting delivery that induces enhanced immune response. In the particular case of hepatitis B, the oral formulation in the nanostructured silica SBA-15 is a viable approach. As a result of its porous structure, low toxicity and structural stability, SBA-15 is capable to protect and release the hepatitis B surface antigen (HBsAg), used in the vaccination scheme, at the desired destination. Furthermore, when compared to the currently used injection based delivery method, better or similar antibody response has been observed. However, information about the organisation of the antigen protein remains unknown. For instance, HBsAg is too large to enter the 10?nm ordered mesopores of SBA-15 and has a tendency to agglomerate when protected by the delivery system. Here we report on the pH dependence of HBsAg aggregation in saline solution investigated using small angle X-rays scattering that resulted in an optimisation of the encapsulation conditions. Additionally, X-ray microscopy combined with neutron and X-ray tomography provided full 3D information of the HBsAg clustering (i.e. agglomeration) inside the SBA-15 macropores. This method enables the visualisation of the organisation of the antigen in the interior of the delivery system, where agglomerated HBsAg coexists with its immunological effective uniformly distributed counterpart. This new approach, to be taken into account while preparing the formulation, can greatly help in the understanding of clinical studies and advance new formulations.

Dynamics of encapsulated hepatitis B surface antigen: a combined neutron spectroscopy and thermo-analysis study

As a consequence of its ordered pore architecture, mesoporous SBA-15 offers new possibilities for incorporating biological agents. Considering its applicability in oral vaccination, which shows more beneficial features when compared with parenteral vaccines, SBA-15 is also seen as a very promising adjuvant to carry, protect, and deliver entrapped antigens. Recent studies have shown several remarkable features in the immunization of hepatitis B, a viral disease transmitted mainly through blood or serum transfer. However, the surface antigen of the hepatitis B virus, HBsAg, is too large to fit inside the SBA-15 matrix with mean pore diameter around 10 nm, thus raising the question of how SBA-15 can protect the antigen. In this work, thermal analysis combined with neutron spectroscopy allowed us to shed light on the interactions between HBsAg and SBA-15 as well as on the role that these interactions play in the efficiency of this promising oral vaccination method. This information was obtained by verifying how the dynamic behaviour of the antigen is modified under confinement in SBA-15, thus also establishing an experimental method for verifying molecular dynamics simulations.

3D visualisation of hepatitis B vaccine in the oral delivery vehicle SBA-15

Developing a technology that enables oral vaccines to work efficiently remains a considerable effort since a number of difficulties must be addressed. The key objective being to ensure the safe passage through the harsh conditions within the gastrointestinal tract, promoting delivery that induces enhanced immune response. In the particular case of hepatitis B, the oral formulation in the nanostructured silica SBA-15 is a viable approach. As a result of its porous structure, low toxicity and structural stability, SBA-15 is capable to protect and release the hepatitis B surface antigen (HBsAg), used in the vaccination scheme, at the desired destination. Furthermore, when compared to the currently used injection based delivery method, better or similar antibody response has been observed. However, information about the organisation of the antigen protein remains unknown. For instance, HBsAg is too large to enter the 10?nm ordered mesopores of SBA-15 and has a tendency to agglomerate when protected by the delivery system. Here we report on the pH dependence of HBsAg aggregation in saline solution investigated using small angle X-rays scattering that resulted in an optimisation of the encapsulation conditions. Additionally, X-ray microscopy combined with neutron and X-ray tomography provided full 3D information of the HBsAg clustering (i.e. agglomeration) inside the SBA-15 macropores. This method enables the visualisation of the organisation of the antigen in the interior of the delivery system, where agglomerated HBsAg coexists with its immunological effective uniformly distributed counterpart. This new approach, to be taken into account while preparing the formulation, can greatly help in the understanding of clinical studies and advance new formulations.

Dynamics of encapsulated hepatitis B surface antigen: a combined neutron spectroscopy and thermo-analysis study

As a consequence of its ordered pore architecture, mesoporous SBA-15 offers new possibilities for incorporating biological agents. Considering its applicability in oral vaccination, which shows more beneficial features when compared with parenteral vaccines, SBA-15 is also seen as a very promising adjuvant to carry, protect, and deliver entrapped antigens. Recent studies have shown several remarkable features in the immunization of hepatitis B, a viral disease transmitted mainly through blood or serum transfer. However, the surface antigen of the hepatitis B virus, HBsAg, is too large to fit inside the SBA-15 matrix with mean pore diameter around 10 nm, thus raising the question of how SBA-15 can protect the antigen. In this work, thermal analysis combined with neutron spectroscopy allowed us to shed light on the interactions between HBsAg and SBA-15 as well as on the role that these interactions play in the efficiency of this promising oral vaccination method. This information was obtained by verifying how the dynamic behaviour of the antigen is modified under confinement in SBA-15, thus also establishing an experimental method for verifying molecular dynamics simulations.