Structural Approach to the Solvent Power of Water for Hydrocarbons; Urea as a Structure Breaker

Abstract

The finding of Wetlaufer et al., that addition of urea to water increases the (mole fraction) solubility of hydrocarbon gases (except methane) while making them dissolve with a smaller evolution of heat, is interpreted as a primarily statistical phenomenon. For this purpose, it is treated in terms of a skeleton model in which not only is water represented as a two-species mixture of dense and bulky constituents but the dissolved hydrocarbon is represented as dissolving separately in these constituents, as if it were distributed between two phases, i.e., between a quasiclathrate solution in the bulky constituent and a quasilattice or “regular” solution in the dense one. Added urea is pictured as being able to enter only one of the solutions, the quasilattice one in the dense water, with the result that it acts as a structure breaker. A statistical-thermodynamic analysis of this model leads to equations for the chemical potentials and the partial molal enthalpies and entropies of the hydrocarbon and the urea solutes, and it is found that very simple assumptions suffice to give calculated values for log γ and L̄ of urea, in binary aqueous solutions, in good agreement with experiment. The choice of parameters to fit the results of the Wetlaufer transfer experiments (of hydrocarbon from water to urea-water) leads to calculated values for the partial molal enthalpies and entropies of the hydrocarbons in their hypothetical binary solutions in the bulky (quasiclathrate solution) and dense (quasilattice solution) waters and comparison of these quantities with properties of appropriate real physical systems makes them appear to be acceptable. One inference from this successful result is that the hypothesis of Frank and Evans, that the “extra” negativeness of the S̄2 for hydrocarbon gases in water arises from a structure shift in the latter, may not be unique, but that a similar effect might also arise from the fact that water received some of the hydrocarbon solute into a different type of environment from what it would find in a “normal” solvent.

Effect of urea on the structural dynamics of water

“…The explanations for protein denaturation that are found in the literature follow two distinct viewpoints, which can be traced back to two models from the 1960s. The first viewpoint (14) assumes that urea acts on a protein indirectly, by modifying the hydrogen-bond structure of water and thus perturbing water-mediated hydrophobic interactions. The second viewpoint (24)(25)(26) is based on a direct mechanism in which urea cooperates with water in the solvation of amino acid residues.…”

“…The desire to understand these properties has triggered a great deal of research regarding the structure of aqueous solutions of urea (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). An important question that is encountered throughout the literature is to what extent the hydrogen-bond network of water is perturbed by the incorporation of a urea molecule, as one of the models explaining protein denaturation by urea is built on the assumption that urea strongly alters the hydrogen-bond structure of water (14). The urea-water system has been studied by using a variety of experimental and theoretical techniques, all of which shed light on a different aspect of the system.…”

Preferential Solvation in Urea Solutions at Different Concentrations: Properties from Simulation Studies

“…Given a thermodynamic reference state and concentration scale we use existing methods to measure molecular association (or aggregation). One flexible definition of preferential solvation is the local mole fraction minus the total mole fraction, following the Ben-Naim definition 20,21 (1) Here the local mole fraction x AB is defined as the number of A molecules divided by the number of the total molecules in a sphere on the center of a B molecule within radius R. From the definition the following relations are obtained (2) Preferential solvation can be calculated from Kirkwood-Buff G factors. Such calculations require a sufficiently large R so that (3) where V c is a volume with radius R and the Kirkwood-Buff G ij is defined using the radial distribution function g AB (r) as (4) The direct calculation of high-precision Kirkwood-Buff factors demands long simulation time and large simulation samples due to problematic convergence at larger distances.…”

Urea denaturation by stronger dispersion interactions with proteins than water implies a 2-stage unfolding

“…Insights into the action of urea come largely from experiments that measure transfer free energies of amino acid side chains and peptide backbone (3,7). Based on these experiments, 2 different mechanisms have been proposed: an ''indirect mechanism'' in which urea is presumed to disrupt the structure of water, thus making hydrophobic groups more readily solvated (8)(9)(10)(11)(12)(13); and a ''direct mechanism'' in which urea interacts either directly with the protein backbone, via hydrogen bonds and other electrostatic interactions, or directly with the amino acids through more favorable van der Waals attractions as compared with water (14,15), or both, thus causing the protein to swell, and then denature. Even within the direct mechanism there is controversy over which of the forces is dominant, electrostatic or van der Waals (7,(16)(17)(18).…”