A combination of simulations and Fourier transform infrared spectroscopy was used to examine the effect of three ionic solutes ͑KCl, NaCl, and KSCN͒, the polar solute urea, and the osmolyte trimethylamine-N-oxide ͑TMAO͒ on a water structure. The ionic solutes increase the mean waterwater H-bond angle in their first hydration shell concomitantly shifting the OH stretching mode to higher frequency, and shifting the HOH bending mode to lower frequency. TMAO decreases the mean water-water H-bond angle in its first hydration shell, shifts the OH stretching mode frequency down, and shifting the HOH bending mode frequency up. Urea has no effect on the mean H-bond angle, OH stretch, and HOH bend frequencies. These results can be explained in terms of changes in the relative proportions of two H-bond angle populations: Ionic solutes increase the population of more distorted ͑larger angle͒ H bonds relative to the less distorted population, TMAO has the reverse effect, while urea does not affect the H-bond angle probability distribution. The negligible effect of urea on water structure supports the direct binding model for urea-induced protein denaturation
