When a simple alcohol such as methanol or ethanol is mixed with water, the entropy of the system increases far less than expected for an ideal solution of randomly mixed molecules. This well-known effect has been attributed to hydrophobic headgroups creating ice-like or clathrate-like structures in the surrounding water, although experimental support for this hypothesis is scarce. In fact, an increasing amount of experimental and theoretical work suggests that the hydrophobic headgroups of alcohol molecules in aqueous solution cluster together. However, a consistent description of the details of this self-association is lacking. Here we use neutron diffraction with isotope substitution to probe the molecular-scale structure of a concentrated alcohol water mixture (7:3 molar ratio). Our data indicate that most of the water molecules exist as small hydrogen-bonded strings and clusters in a 'fluid' of close-packed methyl groups, with water clusters bridging neighbouring methanol hydroxyl groups through hydrogen bonding. This behaviour suggests that the anomalous thermodynamics of water alcohol systems arises from incomplete mixing at the molecular level and from retention of remnants of the three-dimensional hydrogen-bonded network structure of bulk water.

Neutron diffraction with isotope substitution is used to determine the structures of high (HDA) and low (LDA) density amorphous ice. Both "phases" are fully hydrogen bonded, tetrahedral networks, with local order similarities between LDA and ice Ih, and HDA and liquid water. Moving from HDA, through liquid water and LDA to ice Ih, the second shell radial order increases at the expense of spatial order. This is linked to a fifth first neighbor "interstitial" that restricts the orientations of first shell waters. This "lynch pin" molecule which keeps the HDA structure intact has implications for the nature of the HDA-LDA transition that bear on the current metastable water debate.

Although protein function is thought to depend on flexibility, precisely how the dynamics of the molecule and its environment contribute to catalytic mechanisms is unclear. We review experimental and computational work relating to enzyme dynamics and function, including the role of solvent. The evidence suggests that fast motions on the 100 ps timescale, and any motions coupled to these, are not required for enzyme function. Proteins where the function is electron transfer, proton tunneling, or ligand binding may have different dynamical dependencies from those for enzymes, and enzymes with large turnover numbers may have different dynamical dependencies from those that turn over more slowly. The timescale differences between the fastest anharmonic fluctuations and the barrier-crossing rate point to the need to develop methods to resolve the range of motions present in enzymes on different time- and lengthscales.