The hydration behavior of two planar nanoscopic hydrophobic solutes in liquid water at normal temperature and pressure is investigated by calculating the potential of mean force between them at constant pressure as a function of the solute-solvent interaction potential. The importance of the effect of weak attractive interactions between the solute atoms and the solvent on the hydration behavior is clearly demonstrated. We focus on the underlying mechanism behind the contrasting results obtained in various recent experimental and computational studies on water near hydrophobic solutes. The length scale where crossover from a solvent separated state to the contact pair state occurs is shown to depend on the solute sizes as well as on details of the solute-solvent interaction. We find the mechanism for attractive mean forces between the plates is very different depending on the nature of the solute-solvent interaction which has implications for the mechanism of the hydrophobic effect for biomolecules.

A molecular-level description of the behavior of water in hydrophobic spaces is presented in terms of the coupled effects of solute size and atomic solute-solvent interactions. For model solutes with surface areas near those of protein contacts, we identify three different regions of solute-water interaction to be associated with three distinctly different structural characteristics of water in the intersolute region: dry, oscillating, and wet. A first orderlike phase transition is confirmed from the wet to dry state bridged by a narrow region with liquid-vapor oscillations in the intersolute region as the strength of the solute-water attractive dispersion interaction decreases. We demonstrate that the recent idea that cavitation in the intersolute region of nanoscopic solutes is preceded by the formation of a vapor layer around an individual solute is not the general case. The appearance of density waves pulled up around and outside of a nanoscopic plate occurs at lower interaction strengths than are required to obtain a wet state between such plates. We further show that chemically reasonable estimates of the interaction strength lead to a microscopically wet state and a hydrophobic interaction characterized by traps and barriers to association and not by vacuum induced collapse.

We describe the model dynamical behavior of the solvent between two nanoscopic hydrophobic solutes. The dynamics of the vicinal water in various sized traps is found to be significantly different from bulk behavior. We consider the dynamics at normal temperature and pressure at three intersolute distances corresponding to the three solvent separated minima in the free energy profile between the solutes with attractions. These three states correspond to one, two, and three intervening layers of water molecules. Results are obtained from a molecular dynamics simulation at constant temperature and pressure (NPT) ensemble. Translational diffusion of water molecules trapped between the two solutes has been analyzed from the velocity correlation function as well as from the mean square displacement of the water molecules. The rotational behavior has been analyzed through the reorientational dynamics of the dipole moment vector of the water molecule by calculating both first and second rank dipole-dipole correlation functions. Both the translational and reorientational mobilities of water are found to be much slower at the smaller separation and increases as the separation between solutes becomes larger. The occupation time distribution functions calculated from the trajectories also show that the relaxation is much slower for the smallest intersolute separation as compared to other wider separations. The sublinear trend in mean square displacement and the stretched exponential decay of the relaxation of dipolar correlation and occupation distribution function indicate that the dynamical behavior of water in the confined region between two large hydrophobic solutes departs from usual Brownian behavior. This behavior is reminiscent of the behavior of water in the vicinity of protein surface clefts or trapped between two domains of a protein.

Entropic and enthalpic contributions to the hydrophobic interaction between nanoscopic hydrophobic solutes, modeled as graphene plates in water have been calculated using molecular dynamics simulations in isothermal-isobaric (NPT) ensemble and with free energy perturbation methodology. We find the stabilizing contribution to the free energy of association (contact pair formation) to be the favorable entropic part, the enthalpic contribution being highly unfavorable. The desolvation barrier is dominated by the unfavorable enthalpic contribution in spite of a fairly large favorable entropic compensation. The enthalpic contributions, incorporating the Lennard-Jones solute-solvent terms, largely determine the stability of the solvent separated configuration. We decompose the enthalpy into a direct solute-solute term, the solute-solvent interactions and the remainder that contains pressure-volume work as well as contributions due to solvent reorganization. The enthalpic contribution due to changes in water-water interactions arising from solvent reorganization around the solute molecules is shown to have major contribution in the solvent induced enthalpy change.