Configuration-dependent heat capacity of pairwise hydrophobic interactions

Hydrophobicity is of central importance to many branches of chemistry, ranging from the low aqueous solubilities of hydrocarbons to properties of polymer solutions, encompassing a broad range of physicochemical and biomolecular phenomena such as the formation of colloid, molecular aggregates, micelles, vesicles, and biological membranes, as well as protein folding and many other self-organization processes.1-3 Recently, much of the interest in hydrophobic interactions,2,3 including their modulation by cosolvents,4 has been motivated by the energetics of proteins and other biomolecules. One of the defining thermodynamic signatures of hydrophobicity is the large and positive heat capacity changes that accompany transfers of nonpolar solutes from pure or nonpolar phases into water.1 For example, because the unfolding of a protein exposes numerous nonpolar groups to water, it has been widely assumed that the positive heat capacity changes associated with it are closely akin to that of small nonpolar solute hydration.3,5,6 Characterization of elemental heat capacity effects is thus essential to ascertaining the role of hydrophobic interactions in more complex phenomena. As “bulk” hydrophobic interactions and the interactions among small nonpolar groups in water can be significantly different,7 to better understand complex hydrophobic phenomena it is necessary to look beyond single-solute hydration and solute transfers between bulk phases. Here we report theoretical calculations of heat capacity effects between pairs of nonpolar solutes, obtained by extensive constant-pressure (NPT) Monte Carlo simulations of TIP4P water8 under atmospheric pressure. Using data from eight simulation temperatures (278 K, 298 K, 313 K, 328 K, 338 K, 348 K, 368 K, and 388 K), we determine the constant-pressure heat capacity change ΔCP upon bringing a pair of nonpolar solutes from infinity to separations (ξ) close to each other. We find that ΔCP(ξ) is significantly nonmonotonic. In particular, at the position of the desolvation free energy barrier (ξ ≈ 5.7 Å) of the two-body potential of mean force (PMF), ΔCP(ξ) has a prominent maximum as high as the hydration heat capacity of an entire methane