The Effect of Urea on the Structure of Water: A Molecular Dynamics Simulation

Abstract

This paper reports an analysis using molecular dynamics simulations of the effect of urea on the structure of water. Two definitions of the tetrahedral distributions are used to quantify this effect. The first one is sensitive to the mutual orientation between a reference water molecule and the water molecules forming the tetrahedron, and the second is sensitive to their radial distribution. The analysis shows that increasing urea mole fraction results in a reduction of the structured tetrahedral arrangement contribution in favor of an unstructured one. In order to understand this behavior, we used the nearest neighbor approach which allows us to get unambiguous information on the radial and orientation distributions of the water molecules around a probe one. The results indicate that the decrease of the tetrahedral arrangement of the nearest neighbors around a probe water molecule is associated with both the increase of the fluctuation in their radial distances as well as with the loss of their mutual orientations with respect to those observed in pure water. The tetrahedral distribution of water in the hydration shell of urea as well as that around its carbonyl and amine groups is also discussed.

Structure and Dynamics of Urea/Water Mixtures Investigated by Vibrational Spectroscopy and Molecular Dynamics Simulation

“…42 However, a comparison of the urea and water partial molar volumes measured by densitometry 43 indicates that each urea molecule replaces about 2.45 water molecules, rather than 2, as this hypothesis implies. It is, indeed, natural to suppose that urea cannot be truly neutral towards water structure, and claims linger that urea acts as a slight structure-breaker 14,44,45 or structure-maker 46,47 in water, and that indirect effects might be relevant for denaturation. 14,44,47–51 To cite a few examples, urea has been called a structure-breaker (or “structure disrupter”) on the basis of simulations showing its negative impact on the tetrahedrality of the water oxygen network 45 and of neutron diffraction results revealing a disordering of the second coordination sphere of water around water.…”

“…It is, indeed, natural to suppose that urea cannot be truly neutral towards water structure, and claims linger that urea acts as a slight structure-breaker 14,44,45 or structure-maker 46,47 in water, and that indirect effects might be relevant for denaturation. 14,44,47–51 To cite a few examples, urea has been called a structure-breaker (or “structure disrupter”) on the basis of simulations showing its negative impact on the tetrahedrality of the water oxygen network 45 and of neutron diffraction results revealing a disordering of the second coordination sphere of water around water. 15,52 It has also been called a slight structure-maker on the basis of thermodynamic (Kirkwood-Buff) analysis showing that urea-water interactions become relatively slightly less favorable as the urea concentration increases.…”

Intermolecular hydrogen bonds in urea–water complexes: DFT, NBO, and AIM analysis

“…The possibility of distortion, if any, in the tetrahedral structure of water in presence of urea is analyzed by Idrissi et al [17]. No evidence of urea dimer formation and the hydrogen-bond network of water is considerably changed and sometimes broken.…”

Enthalpic pairwise self-interactions of urea and its four derivatives in (dimethylformamide + water) mixtures rich in water at T = 298.15 K

“…Urea-like compounds have been described as both ''structure makers" and ''structure breakers" with respect to the structure of water in solution [56][57][58][59][60]. Based on the group-additivity approach (SWAG) proposed by Savage and Wood [29], information about modifications of hydrophobic and hydrophilic interactions which are induced by non-electrolytes have been discussed especially by Castronuovo and her co-workers [61,62].…”