Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of high pressure. At the molecular level both TMAO and pressure perturb water structure but it is not understood how they act in combination. Here, we use neutron scattering coupled with computational modelling to provide atomistic insight into the structure of water under pressure at 4 kbar in the presence and absence of TMAO. The data reveal that TMAO resists pressure-induced perturbation to water structure, particularly in retaining a clear second solvation shell, enhanced hydrogen bonding between water molecules and strong TMAO - water hydrogen bonds. We calculate an 'osmolyte protection' ratio at which pressure and TMAO-induced energy changes effectively cancel out. Remarkably this ratio translates across scales to the organism level, matching the observed concentration dependence of TMAO in the muscle tissue of organisms as a function of depth. Osmolyte protection may therefore offer a molecular mechanism for the macroscale survival of life in extreme environments.

The microscopic structure of nitric oxide is investigated using neutron scattering experiments. The measurements are performed at various temperatures between 120 and 144 K and at pressures between 1.1 and 9 bar. Using the technique of empirical potential structure refinement (EPSR), our results show that the dimer is the main form, around 80%, of nitric oxide in the liquid phase at 120 K, but the degree of dissociation to monomers increases with increasing temperature. The reported degree of dissociation of dimers, and its trend with increasing temperature, is consistent with earlier measurements and studies. It is also shown that nonplanar dimers are not inconsistent with the diffraction data and that the possibility of nitric oxide molecules forming longer oligomers, consisting of bonded nitrogen atoms along the backbone, cannot be ruled out in the liquid. A molecular dynamics simulation is used to compare the present EPSR simulations with an earlier proposed intermolecular potential for the liquid.

Understanding the underlying processes of biomineralization is crucial to a range of disciplines allowing us to quantify the effects of climate change on marine organisms, decipher the details of paleoclimate records and advance the development of biomimetic materials. Many biological minerals form via intermediate amorphous phases, which are hard to characterize due to their transient nature and a lack of long-range order. Here, using Monte Carlo simulations constrained by X-ray and neutron scattering data together with model building, we demonstrate a method for determining the structure of these intermediates with a study of amorphous calcium carbonate (ACC) which is a precursor in the bio-formation of crystalline calcium carbonates. We find that ACC consists of highly ordered anhydrous nano-domains of approx. 2 nm that can be described as nanocrystalline. These nano-domains are held together by an interstitial net-like matrix of water molecules which generate, on the mesoscale, a heterogeneous and gel-like structure of ACC. We probed the structural stability and dynamics of our model on the nanosecond timescale by molecular dynamics simulations. These simulations revealed a gel-like and glassy nature of ACC due to the water molecules and carbonate ions in the interstitial matrix featuring pronounced orientational and translational flexibility. This allows for viscous mobility with diffusion constants four to five orders of magnitude lower than those observed in solutions. Small and ultra-small angle neutron scattering indicates a hierarchically-ordered organization of ACC across length scales that allow us, based on our nano-domain model, to build a comprehensive picture of ACC formation by cluster assembly from solution. This contribution provides a new atomic-scale understanding of ACC and provides a framework for the general exploration of biomineralization and biomimetic processes.

Aqueous salt systems are ubiquitous in all areas of life. The ions in these solutions impose important structural and dynamic perturbations to water. In this study, we employ a combined neutron scattering, nuclear magnetic resonance, and computational modeling approach to deconstruct ion-specific perturbations to water structure and dynamics and shed light on the molecular origins of bulk thermodynamic properties of the solutions. Our approach uses the atomistic scale resolution offered to us by neutron scattering and computational modeling to investigate how the properties of particular short-ranged microenvironments within aqueous systems can be related to bulk properties of the system. We find that by considering only the water molecules in the first hydration shell of the ions that the enthalpy of hydration can be determined. We also quantify the range over which ions perturb water structure by calculating the average enthalpic interaction between a central halide anion and the surrounding water molecules as a function of distance and find that the favorable anion-water enthalpic interactions only extend to ∼4 Å. We further validate this by showing that ions induce structure in their solvating water molecules by examining the distribution of dipole angles in the first hydration shell of the ions but that this perturbation does not extend into the bulk water. We then use these structural findings to justify mathematical models that allow us to examine perturbations to rotational and diffusive dynamics in the first hydration shell around the potassium halide ions from NMR measurements. This shows that as one moves down the halide series from fluorine to iodine, and ionic charge density is therefore reduced, that the enthalpy of hydration becomes less negative. The first hydration shell also becomes less well structured, and rotational and diffusive motions of the hydrating water molecules are increased. This reduction in structure and increase in dynamics are likely the origin of the previously observed increased entropy of hydration as one moves down the halide series. These results also suggest that simple monovalent potassium halide ions induce mostly local perturbations to water structure and dynamics.

The porous glass MCM-41 is an important adsorbent to study the process of adsorption of gases onto a cylindrical surface. In this work, we study the adsorption of oxygen, nitrogen, deuterium, and deuteriated methane gases into MCM-41 using a combination of neutron diffraction analysis and atomistic computer modeling to interpret the measured data. Adsorption is achieved by immersing a sample of MCM-41 in a bath of the relevant gas, keeping the gas pressure constant (0.1 MPa), and lowering the temperature in steps toward the corresponding bulk liquid boiling point. All four gases have closely analogous behaviors, with an initial layering of liquid on the inside surface of the pores, followed by a relatively sharp capillary condensation (CC) when the pore becomes filled with dense fluid, signaled by a sharp decrease in the intensity of (100) Bragg diffraction reflection. At the temperature of CC, there is a marked distortion of the hexagonal lattice of pores, as others have seen, which relaxes close to the original structure after CC, and this appears to be accompanied by notable excess heterogeneity along the pore compared to when CC is complete. In none of the four gases studied does the final density of fluid in the pore fully attain the value of the bulk liquid at its boiling point at this pressure, although it does approach that limit closely near the center of the pore, and in all cases, the pronounced layering near the silica interface seen in previous studies is observed here as well.

Here, we approach the issue of ACC ultrastructure by applying a method for determining atomically resolved structures of amorphous materials using Monte Carlo simulations constrained by both X-ray and neutron scattering data. This structural analysis approach allows us to develop a detailed model for ACC at the atomic level. Our findings reveal that synthetic ACC, rapidly precipitated at high pH, consists of two-nanometer sized units containing a high degree of near range order similar to partially disordered nano-crystals. Small-angle scattering analyses show a multi-scale hierarchical organisation of the structure, supportive of a multi-step colloid self-assembly process. Computer simulations and high-resolution transmission electron microscopy show that the mesostructure of ACC resembles that of a glassy gel with crystalline material in domains. Our findings support the formation of ACC by a nanoparticle aggregation process that likely starts from prenucleation clusters in solution.

Liquid water is known as the "universal" solvent, capable of dissolving a wide variety of different solutes. While much is now understood about the impact of solutes on the water structure in binary solutions, it is much more challenging to deconvolute the potentially competing effects of more complex solutions. Here, we present a correlative NMR and neutron diffraction study to examine the solute induced perturbation of water structure and dynamics in a tertiary solution containing the naturally occurring osmolyte trimethylamine N-oxide (TMAO) and magnesium perchlorate (Mg(ClO4)2). We show that while TMAO and Mg(ClO4)2 perturb the water structure in an opposing manner, the two solutes slow water dynamics in an additive manner. We quantify the relative ability of each solute to perturb water by introducing a weighting parameter and show that TMAO is 1.54 times more effective at perturbing water structure and dynamics than Mg(ClO4)2. The combination of NMR, neutron diffraction, and computational modelling offers unprecedented access to the structure and dynamics of more complex aqueous solutions, permitting the deconvolution of solute specific perturbation of water. Such insight provides a new route to understand this universal solvent in the context of important and relevant aqueous environments.

Physics of supercritical state is understood to a much lesser degree compared to subcritical liquids. Carbon dioxide in particular has been intensely studied, yet little is known about the supercritical part of its phase diagram. Here, we combine neutron scattering experiments and molecular dynamics simulations and demonstrate the structural crossover at the Frenkel line. The crossover is seen at pressures as high as 14 times the critical pressure and is evidenced by changes of the main features of the structure factor and pair distribution functions.

The presence of magnesium perchlorate (Mg(ClO4)(2)) as the dominant ionic compound in the Martian regolith and the recent discovery of a subsurface lake on Mars suggests that beneath the Martian surface may lie an aqueous environment suitable for life, rich in chaotropic ions. Closer to Earth, terrestrial organisms use osmolytes, such as trimethylamine N-oxide (TMAO), to overcome the biologically damaging effects of pressure. While previous studies have revealed that Mg(ClO4)(2) acts to modify water structure as if it has been pressurized, little is known about the competing effects of chaotropes and kosmotropes. Here we ask whether TMAO can help to preserve the hydrogen bond network of water against the pressurising effect of Mg(ClO4)(2)? We address this question using neutron scattering, computational modelling using Empirical Potential Structure Refinement (EPSR) analysis, and a new approach to quantifying hydrogen bond conformations and energies. We find that the addition of 1.0 M TMAO to 0.2 M Mg(ClO4)(2) or to 2.7 M Mg(ClO4)(2) is capable of partially restoring the hydrogen bond network of water, and the fraction of water molecules in energetically unfavourable conformations. This suggests that terrestrial protecting osmolytes could provide a protective mechanism to the extremes found in Martian environments for biological systems.

The microscopic structure of Ar-N-2 supercritical mixtures was obtained using neutron scattering experiments at temperatures between 128.4 and 154.1 K, pressures between 48.7 and 97.8 bar and various mole fractions. Molecular Dynamics simulations (MD) were used to study the thermodynamics, microscopic structure and single molecule dynamics at the same conditions. The agreement between experimental and theoretical results on the intermolecular structure was very good. Furthermore, a new explicitly-correlated coupled cluster potential energy surface was obtained for the Ar-N-2 van der Waals complex. The ab initio potential energy surface (PES) was found to be in agreement with the MD interaction potential. The global minimum of the ab initio PES D-e = 98.66 cm(-1) was located at the T-shaped geometry and at the intermolecular equilibrium distance of R-e = 7.00a(0). The dissociation energy of the complex was determined to be D-0 = 76.86 cm(-1). Quantum mechanical (QM) calculations on the newly obtained PES were used to provide the bound levels of the complex. Finally, integral and differential QM cross sections in Ar + N-2 collisions were calculated at collision energy corresponding to the average temperature of the experiments and at room temperature. (C) 2019 Elsevier B.V. All rights reserved.

Molecular mobility has been traditionally invoked to explain physical and chemical stability of diverse pharmaceutical systems. Although the molecular mobility concept has been credited with creating a scientific basis for stabilization of amorphous pharmaceuticals and biopharmaceuticals, it has become increasingly clear that this approach represents only a partial description of the underlying fundamental principles. An additional mechanism is proposed herein to address 2 key questions: (1) the existence of unfrozen water (i.e., partial or complete freezing inhibition) in aqueous solutions at subzero temperatures and (2) the role of water in the chemical stability of amorphous pharmaceuticals. These apparently distant phenomena are linked via the concept of water clusters. In particular, freezing inhibition is associated with the confinement of water clusters in a solidified matrix of an amorphous solute, with nanoscaled water clusters being observed in aqueous glasses using wide-angle neutron scattering. The chemical instability is suggested to be directly related to the catalysis of proton transfer by water clusters, considering that proton transfer is the key elementary reaction in many chemical processes, including such common reactions as hydrolysis and deamidation.

The recent discovery of subsurface water on Mars has challenged our understanding of the natural limits of life. The presence of magnesium perchlorate (Mg(ClO4)2) on the Martian surface raises the possibility that it may also be present in this subsurface lake. Given that the subsurface lakes on Earth, such as Lake Vostok and Lake Whillans, are capable of harbouring surprising amounts of life, these new findings raise interesting possibilities for how biomolecules might self-assemble in this environment on Mars. Here we investigate the self-association and hydration of the amino acid glycine in aqueous Mg(ClO4)2 at 25°C and −20°C using neutron diffraction with hydrogen isotope substitution and subsequent analysis with empirical potential structure refinement to yield a simulated box of atoms consistent with the scattering data. We find that although the highly chaotropic properties of Mg(ClO4)2 disrupt the hydration and hydrogen bonding ability of the amino acid, as well as the bulk water structure, glycine molecules are nonetheless still able to self-associate. This occurs more readily at lower temperature, where clusters of up to three molecules are observed, allowing us to speculate that the formation of biological molecules is possible in the Martian environment. GRAPHICAL ABSTRACT

One of the greatest achievements of the human intellect is the ability to project, away from the world we are familiar with, to situations which are totally beyond our experience. People like Isaac...

Cononsolvency is a phenomenon for which the solubility of a macromolecule decreases or even vanishes in the mixture of two good solvents. Although it has been widely applied in the physicochemical, green chemical, and pharmaceutical industries, its origin is still under active debate. Here, by using combined neutron total scattering, deuterium-labeling, and all-atom molecular dynamic simulations, we demonstrated that it is the strong water/cosolvent attraction that leads to the cononsolvency, both competitive hydrogen bonding and water/cosolvent complexation are its results. The combined approach presented here has opened a new route for investigating the most probable all-atom structure in macromolecular solutions.

We investigate the state of water confined in the cylindrical pores of MCM-41 type mesoporous silica, with pore diameters of 2.8 nm and 4.5 nm, over the temperature range 160–290 K by combining small angle neutron scattering and wide angle diffraction.

The idea that water is a mixture of two distinct states is analyzed in some detail. It is shown that the known compressibility of water is in fact sufficiently small that for a volume of water of size 1 nm3, the density fluctuations are of order 4% of the average density. This is much smaller than the ≈25% density fluctuations that would be required for significant regions of high and low density water to occur on this volume scale. It is also pointed out that the density fluctuations in water are, if anything, smaller than those that occur in other common liquids which do not have the anomalous properties of water. It is shown that if the distribution of density fluctuations is unimodal, the system is in the one-phase region, and if bimodal, it is in the two-phase region. None of the liquid or amorphous phases of water explored in this work give any sign of being in the two-phase region. Existing neutron and X-ray scattering data on water in the amorphous phases, and in the stable liquid phases as a function pressure and temperature, are subject to a new set of empirical potential structure refinement simulations. These simulations are interrogated for their configurational entropy, using a spherical harmonic reconstruction of the full orientational pair correlation function. It is shown that the excess pair entropy derived from this function, plus the known perfect gas contributions, give a reasonable account of the total entropy of water, within the likely errors. This estimated entropy follows the expected declining trend with decreasing temperature. Evidence that higher density water will have higher entropy than lower density water emerges, in accordance with what is expected from the negative thermal expansion coefficient of water at low temperatures. However, this entropy increase is not large and goes through a maximum before declining at yet higher densities and pressures, in a manner reminiscent of what has been previously observed in the diffusion coefficient as a function of pressure. There is no evidence that ambient water can be regarded as patches of high density, high entropy and low density, low entropy liquid, as some have claimed, since high density water has a similar entropy to low density water. There is some evidence that the distinction between these two states will become more pronounced as the temperature is lowered. Extensive discussion of the use of order parameters to describe water structure is given, and it is pointed out that these indices generally cannot be used to infer two-state behavior.

Trehalose, commonly found in living organisms, is believed to help them survive severe environmental conditions, such as drought or extreme temperatures. With the aim of trying to understand these properties, two recent neutron scattering studies investigate the structure of trehalose water solutions but come to seemingly opposite conclusions. In the first study, which looks at two concentrations of trehalose-water mole ratios of 1:100 and 1:25, the conclusion is that trehalose hydrogen-bonds to water rather weakly and has a relatively minor impact on the structure of water in solution compared to bulk water. On the other hand, for the other, using a mole ratio of 1:38, the conclusion is that the water structure is rather substantially modified by the presence of trehalose and that the hydrogen bonding between water and trehalose hydroxyl groups is significant. In an attempt to try to understand the origin of these divergent views, which arise from similar but independent analyses of different neutron diffraction data, we have performed additional X-ray scattering experiments, which are highly sensitive to water structure, at the same trehalose-water concentrations used in the first study, and combined these with empirical potential structure refinement on the previously collected neutron data. The new analysis unequivocally confirms that trehalose does indeed have only a minor impact on the structure of water, at all three concentrations, and forms relatively weak hydrogen bonds with water. Far from being discrepant with the existing literature, our new analysis of the different datasets suggests a natural explanation for the increased glass-transition temperature of trehalose compared to other sugars and hence its enhanced effectiveness as a protectant against drought stress.

SANS studies are reported for aqueous THF at the 1:17 clathrate hydrate-forming composition and on aqueous solutions of the synergist 2-butoxyethanol. Addition of the clathrate hydrate inhibitor polyvinylcaprolactam and a dimeric model compound, 1,3-bis(caprolactamyl)butane, show that the inhibitors do not significantly affect the solution structures of these two important species in clathrate hydrate formation and inhibition. The SANS studies show that 1,3-bis(caprolactamyl)butane is a good model for polyvinylcaprolactam, and both the polymer and model compound exhibit hydrogen bonding interactions with water but do not interact significantly with 2-butoxyethanol in aqueous solution.

Natural gas hydrates occur widely on the ocean-bed and in permafrost regions, and have potential as an untapped energy resource. Their formation and growth, however, poses major problems for the energy sector due to their tendency to block oil and gas pipelines, whereas their melting is viewed as a potential contributor to climate change. Although recent advances have been made in understanding bulk methane hydrate formation, the effect of impurity particles, which are always present under conditions relevant to industry and the environment, remains an open question. Here we present results from neutron scattering experiments and molecular dynamics simulations that show that the formation of methane hydrate is insensitive to the addition of a wide range of impurity particles. Our analysis shows that this is due to the different chemical natures of methane and water, with methane generally excluded from the volume surrounding the nanoparticles. This has important consequences for our understanding of the mechanism of hydrate nucleation and the design of new inhibitor molecules.