Approaches to quantify wetting at the macroscale do not translate to the nanoscale, highlighting the need for new methods for characterizing hydrophobicity at the small scale. We use extensive molecular simulations to study the hydration of homo and heterogeneous self-assembled monolayers (SAMs) and of protein surfaces. For homogeneous SAMs, new pressure-dependent analysis shows that water displays higher compressibility and enhanced density fluctuations near hydrophobic surfaces, which are gradually quenched with increasing hydrophilicity, consistent with our previous studies. Heterogeneous surfaces show an interesting context dependence--adding a single -OH group in a CH3 terminated SAM has a more dramatic effect on water in the vicinity compared to that of a single CH3 group in an -OH background. For mixed -CH3/-OH SAMs, this asymmetry leads to a non-linear dependence of hydrophobicity on the surface concentration. We also present preliminary results to map hydrophobicity of protein surfaces by monitoring local density fluctuations and binding of probe hydrophobic solutes. These molecular measures account for the behavior of protein's hydration water, and present a more refined picture of its hydrophobicity map. At least for one protein, hydrophobin-II, we show that the hydrophobicity map is different from that suggested by a commonly used hydropathy scale.

Liquid water can become metastable with respect to its vapor in hydrophobic confinement. The resulting dewetting transitions are often impeded by large kinetic barriers. According to macroscopic theory, such barriers arise from the free energy required to nucleate a critical vapor tube that spans the region between two hydrophobic surfaces-tubes with smaller radii collapse, whereas larger ones grow to dry the entire confined region. Using extensive molecular simulations of water between two nanoscopic hydrophobic surfaces, in conjunction with advanced sampling techniques, here we show that for intersurface separations that thermodynamically favor dewetting, the barrier to dewetting does not correspond to the formation of a (classical) critical vapor tube. Instead, it corresponds to an abrupt transition from an isolated cavity adjacent to one of the confining surfaces to a gap-spanning vapor tube that is already larger than the critical vapor tube anticipated by macroscopic theory. Correspondingly, the barrier to dewetting is also smaller than the classical expectation. We show that the peculiar nature of water density fluctuations adjacent to extended hydrophobic surfacesnamely, the enhanced likelihood of observing low-density fluctuations relative to Gaussian statistics-facilitates this nonclassical behavior. By stabilizing isolated cavities relative to vapor tubes, enhanced water density fluctuations thus stabilize novel pathways, which circumvent the classical barriers and offer diminished resistance to dewetting. Our results thus suggest a key role for fluctuations in speeding up the kinetics of numerous phenomena ranging from Cassie-Wenzel transitions on superhydrophobic surfaces, to hydrophobically driven biomolecular folding and assembly.capillary evaporation | fluctuations | kinetic barriers | assembly T he favorable interactions between two extended hydrophobic surfaces drive numerous biomolecular and colloidal assemblies (1-5), and have been the subject of several theoretical, computational, and experimental inquiries (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Examples include the association of small proteins to form multimeric protein complexes, of amphiphlic block copolymers, dendrimers, or proteins to form vesicular suprastructures, and of patchy colloidal particles into complex crystalline lattices (23-27). When two such hydrophobic surfaces approach each other, water between them becomes metastable with respect to its vapor at a critical separation, d c , that can be quite large (8,9,(28)(29)(30). For nanometer-sized surfaces at ambient conditions, d c is proportional to the characteristic size of the hydrophobic object, whereas for micron-sized and larger surfaces, d c ∼ 1 μm (29, 30). However, due to the presence of large kinetic barriers separating the metastable wet and the stable dry states, the system persists in the wet state, and a dewetting transition is triggered only at much smaller separations (∼ 1 nm) (13,22,28,30).To uncover the mechanism of dewetting, a numbe...

There is overwhelming evidence that ions are present near the vapor-liquid interface of aqueous salt solutions. Charged groups can also be driven to interfaces by attaching them to hydrophobic moieties. Despite their importance in many self-assembly phenomena, how ion-ion interactions are affected by interfaces is not understood. We use molecular simulations to show that the effective forces between small ions change character dramatically near the water vapor-liquid interface. Specifically, the water-mediated attraction between oppositely charged ions is enhanced relative to that in bulk water. Further, the repulsion between like-charged ions is weaker than that expected from a continuum dielectric description and can even become attractive as the ions are drawn to the vapor side. We show that thermodynamics of ion association are governed by a delicate balance of ion hydration, interfacial tension, and restriction of capillary fluctuations at the interface, leading to nonintuitive phenomena, such as watermediated like charge attraction. "Sticky" electrostatic interactions may have important consequences on biomolecular structure, assembly, and aggregation at soft liquid interfaces. We demonstrate this by studying an interfacially active model peptide that changes its structure from α-helical to a hairpin-turn-like one in response to charging of its ends. T raditional models of an air-water interface of a salt solution present a picture in which salt ions are excluded from the interfacial region (1). However, recent simulations and experiments have shown that certain chaotropic ions, such as iodide, azide, and thiocyanate, can adsorb to the air-water interface (2-7). Even when ions are depleted from the interface, the extent of depletion is limited to a nanometer length scale (8). Charged species can also be driven to an air-water interface by covalently attaching them to hydrophobic moieties, as in ionic surfactants, or interfacially active proteins (9, 10). Thermodynamics of ion adsorption to interfaces are complex, determined by a balance of energetic and entropic contributions (7,11,12). The net energetic contribution can be favorable or unfavorable, depending on the differences between ion-water, ion-ion, and water-water interactions in bulk and at the interface. The entropic contribution is typically unfavorable due to the restriction of water molecules in the hydration shell of the ion and the corresponding pinning of capillary fluctuations at the interface (7,13,14). Solvent structure and fluctuations at the interface are also known to play an important role in ion dissociation pathways in the transport of ions across liquid-liquid interfaces (15). How these factors govern the effective ion-ion interactions near aqueous interfaces and, in turn, influence interfacial self-assembly and aggregation is, however, not understood.We present results from extensive molecular simulations of ion hydration and ion-ion interactions near a water vapor-liquid interface. Our principal results are that solvent-mediated ...

We have studied how primitive hydrophobic interactions between two or more small nonpolar solutes are affected by the presence of surfaces. We show that the desolvation barriers present in the potential of mean force between the solutes in bulk water are significantly reduced near an extended hydrophobic surface. Correspondingly, the kinetics of hydrophobic contact formation and breakage are faster near a hydrophobic surface than near a hydrophilic surface or in the bulk. We propose that the reduction in the desolvation barrier is a consequence of the fact that water near extended hydrophobic surfaces is akin to that at a liquid-vapor interface and is easily displaced. We support this proposal with three independent observations. First, when small hydrophobic solutes are brought near a hydrophobic surface, they induce local dewetting, thereby facilitating the reduction of desolvation barriers. Second, our results and those of Patel et al. (Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 17678-17683) show that, whereas the association of small solutes in bulk water is driven by entropy, that near hydrophobic surfaces is driven by enthalpy, suggesting that the physics of interface deformation is important. Third, moving water away from its vapor-liquid coexistence, by applying hydrostatic pressure, leads to recovery of bulklike signatures (e.g., the presence of a desolvation barrier and an entropic driving force) in the association of solutes. These observations for simple solutes also translate to end-to-end contact formation in a model peptide with hydrophobic end groups, for which lowering of the desolvation barrier and acceleration of contact formation are observed near a hydrophobic surface. Our results suggest that extended hydrophobic surfaces, such as air-water or hydrocarbon-water surfaces, could serve as excellent platforms for catalyzing hydrophobically driven assembly.

We focus on the conformational stability, structure, and dynamics of hydrophobic/charged homopolymers and heteropolymers at the vapor-liquid interface of water using extensive molecular dynamics simulations. Hydrophobic polymers collapse into globular structures in bulk water but unfold and sample a broad range of conformations at the vapor-liquid interface of water. We show that adding a pair of charges to a hydrophobic polymer at the interface can dramatically change its conformations, stabilizing hairpinlike structures, with molecular details depending on the location of the charged pair in the sequence. The translational dynamics of homopolymers and heteropolymers are also different, whereas the homopolymers skate on the interface with low drag, the tendency of charged groups to remain hydrated pulls the heteropolymers toward the liquid side of the interface, thus pinning them, increasing drag, and slowing the translational dynamics. The conformational dynamics of heteropolymers are also slower than that of the homopolymer and depend on the location of the charged groups in the sequence. Conformational dynamics are most restricted for the end-charged heteropolymer and speed up as the charge pair is moved toward the center of the sequence. We rationalize these trends using the fundamental understanding of the effects of the interface on primitive pair-level interactions between two hydrophobic groups and between oppositely charged ions in its vicinity.