New results derived from the experimental method of neutron diffraction and isotopic substitution (NDIS) are presented for the hydration structure of the lithium cation (Li(+)) in aqueous solutions of lithium chloride in heavy water (D2O) at concentrations of 6, 3, and 1 m and at 1.5 m lithium sulfate. By introducing new and more-accurate data reduction procedures than in our earlier studies (I. Howell and G. W. Neilson, J. Phys: Condens. Matter, 1996, 8, 4455-4463), we find, in the first hydration shell of Li(+), ∼4.3(2) water molecules at 6 m, 4.9(3) at 3 m, 4.8(3) at 1 m in the LiCl solutions, and 5.0(3) water molecules in the case of Li2SO4 solution. The general form of the first hydration shell is similar in all four solutions, with the correlations for Li-O and Li-D sited at 1.96 (0.02) Å and 2.58 (0.02) Å, respectively. The results resemble those presented in 1996, in terms of ion-water distances and local coordination, but the hydration number is significantly lower for the case at 1 m than the 6.5 (1.0) given at that time. Thus, experimental and theoretical results now agree that lithium is hydrated by a small number of water molecules (4-5) in the nearest coordination shell.

Neutron scattering experiments were performed on 6 m LiCl solutions in order to obtain the solvation structure around the chloride ion. Molecular dynamics simulations on systems mirroring the concentrated electrolyte conditions of the experiment were carried out with a variety of chloride force-fields. In each case the simulations were run with both full ionic charges and employing the electronic continuum correction (implemented through charge scaling) to account effectively for electronic polarisation. The experimental data were then used to assess the successes and shortcomings of the investigated force-fields. We found that due to the very good signal-to-noise ratio in the experimental data, they provide a very narrow window for the position of the first hydration shell of the chloride ion. This allowed us to establish the importance of effectively accounting for electronic polarisation, as well as adjusting the ionic size, for obtaining a force-field which compares quantitatively to the experimental data. The present results emphasise the utility of performing neutron diffraction with isotopic substitution as a powerful tool in gaining insight and examining the validity of force-fields in concentrated electrolyte solutions.

The method of isotope substitution in neutron diffraction was used to measure the structure of liquid ZnCl2 at 332(5) degrees C and glassy ZnCl2 at 25(1) degrees C. The partial structure factors were obtained from the measured diffraction patterns by using the method of singular value decomposition and by using the reverse Monte Carlo procedure. The partial structure factors reproduce the diffraction patterns measured by high-energy x-ray diffraction once a correction for the resolution function of the neutron diffractometer has been made. The results show that the predominant structural motif in both phases is the corner sharing ZnCl4 tetrahedron and that there is a small number of edge-sharing configurations, these being more abundant in the liquid. The tetrahedra organize on an intermediate length scale to give a first sharp diffraction peak in the measured diffraction patterns at a scattering vector k(FSDP) similar or equal to 1 angstrom(-1) that is most prominent for the Zn-Zn correlations. The results support the notion that the relative fragility of tetrahedral glass forming MX2 liquids is related to the occurrence of edge-sharing units.

Molecular dynamics simulations of a 3molal aqueous solution of d-sorbitol (also called d-glucitol) have been performed at 300K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data support a more bent structure.

Molecular dynamics simulations of pure liquid water under ambient conditions using four common empirical water models have been analyzed to determine how well the oxygen-oxygen radial distribution function, g(OO)(r), used as the sole criterion of congruence with experiment, captures variations in the actual anisotropic collective structuring for these models. The largest systematic deviations from tetrahedrality were found to be due to deformations of the angle between the two closet hydrogen bond donor neighbors, but for intrinsic geometric reasons, these were found to contribute less to g(OO)(r) than deformations of the angles between one hydrogen bond donor neighbor and one hydrogen bond acceptor neighbor. Relying exclusively on a qualitative characterization of the second peak in g(OO)(r) seems to overemphasize the differences between the structuring in some of these models.

Neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations have been used to characterize the structure of aqueous guanidinium carbonate (Gdm2CO3) solutions. The MD simulations found very strong hetero-ion pairing in Gdm2CO3 solution and were used to determine the best structural experiment to demonstrate this ion pairing. The NDIS experiments confirm the most significant feature of the MD simulation, which is the existence of strong hetero-ion pairing between the Gdm+ and CO3(2-) ions. The neutron structural data also support the most interesting feature of the MD simulation, that the hetero-ion pairing is sufficiently strong as to lead to nanometer-scale aggregation of the ions. The presence of such clustering on the nanometer length scale was then confirmed using small-angle neutron scattering experiments. Taken together, the experiment and simulation suggest a molecular-level explanation for the contrasting denaturant properties of guanidinium salts in solution.

Weakly solvated, low charge density, alkali metal cations (K+ and Rb+) destabilize tryptophan zipper (trpzip) peptides with an effectiveness (for Rb+) similar to that of the protein denaturant urea. An analysis of alkali metal cation effects on polypeptides stabilized predominantly either by hydrogen bonds or by the classical hydrophobic effect indicates that the alkali metals attenuate stabilizing interactions involving the tryptophan indole groups. Destabilization does not result from electrolyte screening of the electrostatic component of the indole-indole interaction, but is likely to involve direct interaction of the low charge density cation with the indole group in a cation-pi interaction. The observations highlight a general simplicity in the nature of molecular interactions in solution, in which stabilizing contributions to polypeptide and protein structures are attenuated by solutes of a complementary nature.

The presence of ions in water provides a rich and varied environment in which many natural processes occur with important consequences in biology, geology and chemistry. This article will focus on the structural properties of ions in water and it will be shown how the 'difference' methods of neutron diffraction with isotopic substitution (NDIS) and anomalous X-ray diffraction (AXD) can be used to obtain direct information regarding the radial pair distribution functions of many cations and anions in solution. This information can subsequently be used to calculate coordination numbers and to determine ion–water conformation in great detail. As well as enabling comparisons to be made amongst ions in particular groups in the periodic table, such information can also be contrasted with results provided by molecular dynamics (MD) simulation techniques. To illustrate the power of these 'difference' methods, reference will be made to the alkali group of ions, all of which have been successfully investigated by the above methods, with the exception of the radioactive element francium. Additional comments will be made on how NDIS measurements are currently being combined with MD simulations to determine the structure around complex ions and molecules, many of which are common in biological systems.

A method of neutron diffraction is described which enables the first hydration zone of small cations to be investigated at atomic resolution. It is shown that the cation structures of aqueous electrolyte solutions dissolved in a 'null' mixture of water (H(2)O) and heavy water (D(2)O), can be calculated directly from the neutron scattering patterns. The hitherto unresolved structure around Na(+) is used to illustrate the power of this method, the accuracy of which is discussed formally with reference to standard nickel chloride solutions. Possible applications to a variety of other systems and at different thermodynamic states are proposed.

Recently, it was shown using structural neutron diffraction with isotopic substitutions (NDIS) measurements, combined with molecular dynamics simulations, that in an aqueous solution Of D-Xylose the hydroxyl group on the C4 position does not significantly occupy the position trans to the H4 atom. Here, a similar combination of NDIS and MD studies is described which Uses D-xylose deuterated at the C5 position to further characterize this hydroxyl conformation as being trans to the C5 atom, as predicted by constrained MD simulations, confirming the previous study.

Neutron diffraction experiments and molecular dynamics simulations are used to study the structure of aqueous solutions of two electrolytes: guanidinium sulfate (a mild protein conformation stabilizer) and guanidinium thiocyanate (a powerful denaturant). The MD simulations find the unexpected result that in the Gdm2SO4 solution the ions aggregated into mesoscopic (nanometer-scale) clusters, while no such aggregation is found in the GdmSCN solution. The neutron diffraction studies, the most direct experimental probe of solution structure, provide corroborating evidence that the predicted very strong ion pairing does occur in solutions of 1.5 m Gdm2SO4 but not in 3 m solutions of GdmSCN. A mechanism is proposed as to how this mesoscopic solution structure affects solution denaturant properties and suggests an explanation for the Hofmeister ordering of these solutions in terms of this ion pairing and the ability of sulfate to reverse the denaturant power of guanidinium.

Neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations have been used to examine the pentose D-xylose in aqueous solution. By specifically labeling D-xylose molecules with a deuterium atom at the nonexchangeable hydrogen position on C4, it was possible to extract information about the atomic structuring around just that specific position. The MD simulations were found to give satisfactory agreement with the experimental NDIS results and could be used to help interpret the scattering data in terms of the solvent structuring as well as the intramolecular hydroxyl conformations. Although the experiment is challenging and on the limit of modern instrumentation, it is possible by careful analysis, in conjunction with MD studies, to show that the conformation trans to H4 at 180 degrees is strongly disfavored, in excellent agreement with the MD results. This is the first attempt to use NDIS experiments to determine the rotameric conformation of a hydroxyl group.

Neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations have been used to examine the structuring of solvent around D-glucose in aqueous solution. As expected, no significant tendency for glucose molecules to aggregate was found in either the experiments or the simulation. To the extent that solute pairing does occur as the result of the high concentration, it was found to take place through hydroxyl-hydroxyl hydrogen bonds, in competition with water molecules for the same hydrogen-bonding sites. A detailed analysis of the hydrogen-bonding patterns occurring in the simulations found that the sugar hydroxyl groups are more efficient hydrogen bond donors than acceptors. From the comparison of the MD and NDIS data, it was found that while the modeling generally does a satisfactory job in reproducing the experimental data the force fields may produce sugar rings that are too rigid and thus may require future revisions.

Molecular mechanics (MM) simulations have been used to model two small crystals of cellulose Ibeta surrounded by water. These small crystals contained six different extended surfaces: (110), (11 0), two types of (100), and two types of (010). Significant changes took place in the crystal structures. In both crystals there was an expansion of the unit cell, and a change in the gamma angle to almost orthogonal. Both microcrystals developed a right-hand twist of about 1.5 degrees per cellobiose unit, similar to the twisting of beta-sheets in proteins. In addition, in every other layer, made up of the unit cell center chains, a tilt of the sugar rings of 14.8 degrees developed relative to the crystal plane as a result of a transition of the primary alcohol groups in these layers away from the starting TG conformation to GG. In this conformation, these groups made interlayer hydrogen bonds to the origin chains above and below. No change in the primary alcohol conformations or hydrogen-bonding patterns in the origin chain layers was observed. Strong localization of the adjacent water was found for molecules in the first hydration layer of the surfaces, due to both hydrogen bonding to the hydroxyl groups of the sugar molecules and also due to hydrophobic hydration of the extensive regions of nonpolar surface resulting from the axial aliphatic hydrogen atoms of the 'tops' of the glucose monomers. Significant structuring of the water was found to extend far out into the solution. It is hypothesized that the structured layers of water might present a barrier to the approach of cellulase enzymes toward the cellulose surfaces in enzyme-catalyzed hydrolysis, and might inhibit the escape of soluble products, contributing to the slow rates of hydrolysis observed experimentally. Since the water structuring is different for the different surfaces, this might result in slower hydrolysis rates for some surfaces compared to others.

The combination of neutron diffraction with isotopic substitution (NDIS) experiments and molecular dynamics (MD) simulations to characterize the structuring in an aqueous solution of the denaturant guanidinium chloride is described. The simulations and experiments were carried out at a concentration of 3 m at room temperature, allowing for an examination of any propensity for ion association in a realistic solution environment. The simulations satisfactorily reproduced the principal features of the neutron scattering and indicate a bimodal hydration of the guanidinium ions, with the N-H groups making well-ordered hydrogen bonds in the molecular plane, but with the planar faces relatively deficient in interactions with water. The most striking feature of these solutions is the rich ion-ion ordering observed around the guanidinium ion in the simulations. The marked tendency of the guanidinium ions to stack parallel to their water-deficient surfaces indicates that the efficiency of this ion as a denaturant is due to its ability to simultaneously interact favorably with both water and hydrophobic side chains of proteins.