1. ``Calculating Free Energies Using a Scaled-force Molecular Dynamics Algorithm,'' E. Darve, M. A. Wilson, and A. Pohorille, Molecular Simulation, 28, 113-144, (2002).

   We propose and test a family of methods to calculate the free energy along a generalized coordinate, x, based on computing the force acting on this coordinate. First, we derive a formula that connects the free energy in unconstrained simulations with the force of constraint that can be readily calculated numerically. Then, we consider two methods, which improve the efficiency of the free energy calculation by yielding uniform or nearly uniform sampling of x. Both rely on modifying the force acting on x. In one method, this force is replaced by a force with zero mean and x is advanced quasistatically. In the second method, the force is augmented adaptively by a biasing force. We provide formulas for calculating the free energy of the unmodified system from the forces acting in these modified, non-Hamiltonian systems. Using conformational transitions in 1,2-dichloroethane as a test case, we show that both methods perform very well.

2. ``Unassisted and assisted ion transport across membranes: Insights from computer simulations,'' A. Pohorille and M. A. Wilson, Cell. Mol. Biol. Lett., 6, 369-374, (2001).

3. ``Electrostatic Properties of Aqueous Interfaces Probed by Small Solutes,'' A. Pohorille, M. A. Wilson, and K. Schweighofer, in Electrostatic Properties of Aqueous Interfaces Probed by Small Solutes, L. R. Pratt and G. Hummer, eds., (AIP, New Yook, 1999) 492-509.

   The excess chemical potentials of methane and its four fluorinated derivatives across the water-hexane, water-octanol, water-glycerol 1-monooleate and water-1-palmitoyl 2-oleoyl sn-glycero 3-phosphatidylcholine (POPC) interfaces are calculated using the particle insertion method. In all cases, the polar species exhibit interfacial minima indicating that these molecules tend to accumulate in the interfacial region, while the non-polar molecules exhibit no such minimum. The excess chemical potentials are further partitioned into electrostatic and non-electrostatic terms. For polar molecules, the electrostatic term changes nearly linearly over the distance of approximately 10 Å in the interfacial region and appears to depend only weakly on the nature of the interface. Solute molecules are not oriented isotropically at the interface, but tend to align themselves with the excess electric field created by the anisotropic interfacial environment. Using dipoles in a cavity as models, it is further shown that, in the water-POPC system, the electrostatic term changes with the size of the dipole according to the predictions of linear response theory. This approximation does not work as well for the other interfacial systems investigated. This may be an artifact due to the neglect of long-range effects in those simulations. The non-electrostatic term, dominated by the reversible work of cavity formation, shows interfacially induced structure. In particular, it is responsible for a maximum of the excess chemical potential on the dense, water side of the water-POPC interface. The results of this study provide guidance to developing simple but accurate implicit models of interfacial systems.

4. ``Insights from computer simulations into the interactions of small molcules with membranes,'' A. Pohorille, M. H. New, K. Schweighofer and M. A. Wilson, in Membrane Permeability: One hundred years since Ernst Overton (Current Topics in Membranes, Volume 48), D. Deamer, ed., (Academic Press, San Diego, 1999), Chapter 3, pp. 49-76.

   Two of Ernest Overton's lasting contributions to biology are the Meyer-Overton relationship between the potency of an anesthetic and its solubility in oil, and the Overton rule which relates the permeability of a membrane to the oil-water partition coefficient of the permeating molecule. A growing body of experimental evidence, however, cannot be reconciled with these theories. In particular, the molecular nature of membranes, unknown to Overton, needs to be included in any description of these phenomena. Computer simulations are ideally suited for providing atomic-level information about the behavior of small molecules in membranes. The authors discuss simulation studies relevant to Overton's ideas. Through simulations it was found that anesthetics tend to concentrate at interfaces and their anesthetic potency correlates better with solubility at the water-membrane interface than with solubility in oil. Simulation studies of membrane permeation revealed the anisotropic nature of the membranes, as evidenced, for example, by the highly nonuniform distribution of free volume in the bilayer. This, in turn, influences the diffusion rates of solutes, which increase with the depth in the membrane. Small solutes tend to move by hopping between voids in the bilayer, and this hopping motion may be responsible for the deviation from the Overton rule of the permeation rates of these molecules.

5. ``Adsorption and Solvation of Ethanol at the water liquid-vapor interface,'' M. A. Wilson and A. Pohorille, J. Phys. Chem., 101, 3130-3135 (1997).

   The free energy profiles of methanol and ethanol at the water liquid-vapor interface at 310 K were calculated using molecular dynamics computer simulations. Both alcohols exhibit a pronounced free energy minimum at the interface, and, therefore, have positive adsorption at this interface. The surface excess was computed from the Gibbs adsorption isotherm, and found to be in good agreement with experimental results. Neither compound exhibits a free energy barrier between the bulk and the surface adsorbed state. Scattering calculations of ethanol molecules from a gas phase thermal distribution indicate that the mass accommodation coefficient is 0.98, and the molecules become thermalized within 10 ps of striking the interface. It was determined that the formation of the solvation structure around the ethanol molecule at the interface is not the rate-determining step in its uptake into water droplets. The motion of an ethanol molecule in a water lamella was followed for 30 ns. The time evolution of the probability distribution of finding an ethanol molecule that was initially located at the interface is very well described by the diffusion equation on the free energy surface.

6. ``Interactions of Alcohols and Anesthetics with the Water-Hexane Interface: a Molecular Dynamics Study,'' A. Pohorille, M. A. Wilson, and C. Chipot, in Progress in Colloid and Polymer Science, 103, 29-40 (1997).

   The free energy profiles characterizing the transfer of nine solutes across the liquid-vapor interfaces of water and hexane, and across the water-hexane interface were calculated from molecular dynamics simulations. Among the solutes were n-butane and three of its halogenated derivatives, as well as three halogenated cyclobutanes. The two remaining molecules, dichlorodifluoromethane and 1,2-dichloroperfluoroethane, belong to series of halo-substituted methanes and ethanes, described in previous studies (J. Chem. Phys., 1996, 104, 3760; Chem. Phys., 1996, 204, 337). Each series of molecules contains structurally similar compounds that differ greatly in anesthetic potency. The accuracy of the simulations was tested by comparing the calculated and the experimental free energies of solvation of all nine compounds in water and in hexane. In addition, the calculated and the measured surface excess concentration of n-butane at the water liquid-vapor interface were compared. In all cases, good agreement with experimental results was found. At the water-hexane interface, the free energy profiles for polar molecules exhibited significant interfacial minima, whereas the profiles for nonpolar molecules did not. The existence of these minima was interpreted in terms of a balance between the free energy contribution arising from solute-solvent interactions and the work to form a cavity that accommodates the solute. These two contributions change monotonically, but oppositely, across the interface. The interfacial solubilities of the solutes, obtained from the free energy profiles, correlate very well with their anesthetic potencies. This is the case even when the Meyer-Overton hypothesis, which predicts a correlation between anesthetic potency and solubility in oil, fails. These results suggest that an interface between polar and nonpolar environments, such as the surface of the neuronal membrane, or a water-exposed portion of a protein receptor, is a more likely site of anesthetic action than the interior of the membrane.

7. ``Interactions of Anesthetics with the Water-Hexane Interface. A Molecular Dynamics Study,'' C. Chipot, M. A. Wilson and A. Pohorille, J. Phys. Chem., 101, 782-791 (1997).

   The transfer of eight solutes across the water-hexane interface is studied using molecular dynamics computer simulations. Four of these solutes are model amphiphiles, straight chain alcohols - methanol, ethanol, butanol and hexanol. The remaining four molecules - cyclopropane, nitrous oxide, isoflurane and desflurane - are non-amphiphilic and polar or weakly polar. All of them are clinical anesthetics. All eight molecules exhibit free energy minima at the interface, indicating that they are interfacially active. Whereas interfacial activity of amphiphiles has been well known, it is shown here that a similar, although somewhat weaker behavior is also characteristic of a wide range of polar solutes. This can be explain as a balance batween electrostatic and non-electrostatic contributions to the free energy, which change monotonically, but oppositely near the interface. Qualitatively similar results are expected for solutes at interfaces between water and other nonpolar liquids or lipid bilayers. Based on the results showing a very good correlation between anesthetic potencies and interfacial concentrations of 20 anesthetic compounds it is proposed that the site of anesthetic action is located near the interface between water and the neuronal membrane.

8. ``Mechanism of Unassisted Ion Transport across Membrane Bilayers,'' M. A. Wilson and A. Pohorille, J. Am. Chem. Soc., 118, 6580-6587 (1996).

   To establish how charged species move from water to the nonpolar membrane interior and to determine the energetic and structural effects accompanying this process, we performed molecular dynamics simulations of the transport of Na⁺ and Cl^- across a lipid bilayer located between two water lamellae. The total length of molecular dynamics trajectories generated for each ion was 10 ns. Our simulations demonstrate that permeation of ions into the membrane is accompanied by the formation of deep, asymmetric thinning defects in the bilayer, whereby polar lipid head groups and water penetrate the nonpolar membrane interior. Once the ion crosses the mid-plane of the bilayer the deformation ``switches sides''; the initial defect slowly relaxes and a defect forms in the outgoing side of the bilayer. As a result, the ion remains well solvated during the process; the total number of oxygen atoms from water and lipid head groups in the first solvation shell remains constant. A similar membrane deformation is formed when the ion is instantaneously inserted into the interior of the bilayer. The formation of defects considerably lowers the free energy barrier to transfer of the ion across the bilayer and, consequently, increases the permeabilities of the membrane to ions, compared to the rigid, planar structure, by approximately 14 orders of magnitude. Our results have implications for drug delivery using liposomes and peptide insertion into membranes.

9. ``Interactions of Anesthetics with the Membrane-Water Interface,'' A. Pohorille, P. Cieplak, and M. A. Wilson, Chem. Phys., 204, 337-345 (1996).

   Although the potency of conventional anesthetics correlates with lipophilicity, an affinity to water also is essential. It was recently found that compounds with very low affinities to water do not produce anesthesia regardless of their lipophilicity. This finding implies that clinical anesthesia might arise because of interactions at molecular sites near the interface of neuronal membranes with the aqueous environment and, therefore, might require increased concentrations of anesthetic molecules at membrane interfaces. As an initial test of this hypothesis, we calculated in molecular dynamics simulations the free energy profiles for the transfer of anesthetic 1,1,2-trifluoroethane and nonanesthetic perfluoroethane across water-membrane and water-hexane interfaces. Consistent with the hypothesis, it was found that trifluoroethane, but not perfluoroethane, exhibits a free energy minimum and, therefore, increased concentrations at both interfaces. The transfer of trifluoroethane from water to the nonpolar hexane or interior of the membrane is accompanied by a considerable, solvent-induced shift in the conformational equilibrium around the C-C bond.

10. ``Excess chemical potential of small solutes across water-membrane and water-hexane interfaces,'' A. Pohorille and M. A. Wilson, J. Chem. Phys., 104, 3760-3773 (1996).

    The excess chemical potentials of five small, structurally related solutes, CH₄, CH₃F, CH₂F₂, CHF₃ and CF₄, across the water-glycerol 1-monooleate bilayer and water-hexane interfaces were calculated at 300, 310 and 340 K using the particle insertion method. The excess chemical potentials of nonpolar molecules (CH₄ and CF₄) decrease monotonically or nearly monotonically from water to a nonpolar phase. In contrast, for molecules that possess permanent dipole moments (CH₃F, CH₂F₂ and CHF₃), the excess chemical potentials exhibit an interfacial minimum that arises from superposition of two monotonically and oppositely changing contributions: electrostatic and nonelectrostatic. The nonelectrostatic term, dominated by the reversible work of creating a cavity that accommodates the solute, decreases, whereas the electrostatic term increases across the interface from water to the membrane interior. In water, the dependence of this term on the dipole moment is accurately described by second order perturbation theory. To achieve the same accuracy at the interface, third order terms must also be included. In the interfacial region, the molecular structure of the solvent influences both the excess chemical potential and solute orientations. The excess chemical potential across the interface increases with temperature, but this effect is rather small. Our analysis indicates that a broad range of small, moderately polar molecules should be surface active at the water-membrane and water-oil interfaces. The biological and medical significance of this result, especially in relation to the mechanism of anesthetic action, is discussed.

11. ``Molecular Modeling of Protocellular Functions,'' A. Pohorille, C. Chipot, M. H. New, and M. A. Wilson, Proceedings of the Symposium on the Evolution of Molecular Structures and the Structure of Molecular Evolution, L. Hunter and T. E. Klein, eds. (World Scientific, Singapore, 1995) pp. 550-569.

    The mechanisms of three protocellular functions have been studied using molecular modeling techniques. These functions are (1) the transport of ions and small, neutral solutes across membranes, (2) the formation of photoactivated proton gradient that could drive chemical synthesis in the protocell, and (3) the organization of small peptides necessary for catalytic activity. In all these processes, membranes play an essential role. The transfer of ions across the barrier formed by protocellular walls is facilitated by the formation of deep, thinning defects in the membrane. The barrier to charged species formed by membranes also allows for retaining proton gradients. These gradients can be generated by a simple transmembrane proton pump consisting of a proton source and two acceptors. The directionality of the pump is ensured by a ``gate-keeping'' mechanism involving a water molecule, conformational change of the primary acceptor or tautomerization of a histidine. The pump can be formed by two transmembrane helices but not one helix. Membranes provide surfaces at which organic molecules concentrate and small peptides can organize into ordered, amphiphilic structures. In general, valuable information about the origins and evolution of protocells can be obtained from the knowledge of physical and chemical principles that govern functioning of contemporary cells.

12. ``Scattering of water from the glycerol liquid-vapor interface,'' I. Benjamin, M. A. Wilson, A. Pohorille, and G. N. Nathanson, Chem. Phys. Lett., 243, 222-228 (1995).

    Molecular dynamics calculations of the scattering of D₂O from the glycerol surface at different collision energies are reported. The results for the trapping probabilities and energy transfer are in good agreement with experiments. The calculations demonstrate that the strong attractive forces between these two strongly hydrogen bonding molecules have only a minor effect on the initial collision dynamics. The trapping probability is influenced to a significant extent by the repulsive hard sphere-like initial encounter with the corrugated surface and, only at a later stage, by the efficiency of energy flow in the multiple interactions between the water and the surface molecules.

13. ``High density amorphous ice, the frost in interstellar grains,'' P. Jenniskens, D. F. Blake, M. A. Wilson, and A. Pohorille, Astrophysical Journal, 455, 389-401 (1995).

    Most water ice in the Universe is in a form which does not occur naturally on Earth and of which only minimal amounts have been made in the laboratory. The authors have encountered this "high-density amorphous ice" in electron diffraction experiments of low-temperature (T<30 K) vapor-deposited water and have subsequently modeled its structure using molecular dynamics simulations. The characteristic feature of high-density amorphous ice is the presence of "interstitial" oxygen pair distances between 3 and 4 Å. However, it is found that the structure is best described as a collapsed lattice of the more familiar low-density amorphous form. These distortions are frozen in at temperatures below 38 K because, the authors propose, it requires the breaking of one hydrogen bond, on average, per molecule to relieve the strain and to restructure the lattice to that of low-density amorphous ice. Several features of astrophysical ice analogs studied in laboratory experiments are readily explained by the structural transition from high-density amorphous ice into low-density amorphous ice. Changes in the shape of the 3.07 m water band, trapping efficiency of CO, CO loss, changes in the CO band structure, and the recombination of radicals induced by low-temperature UV photolysis all covary with structural changes that occur in the ice during this amorphous to amorphous transition. While the 3.07 m ice band in various astronomical environments can be modeled with spectra of simple mixtures of amorphous and crystalline forms, the contribution of the high-density amorphous form nearly always dominates.

14. ``Molecular dynamics studies of simple membrane-water interfaces: structure and functions in the beginning of cellular life,'' A. Pohorille and M. A. Wilson, Orig. Life and Evol. Biosphere, 25, 21-46 (1995).

    Molecular dynamics computer simulations of the structure and functions of a simple membrane are performed in order to examine whether membranes provide an environment capable of promoting protobiological evolution. Our model membrane is composed of glycerol 1-monooleate. It is found that the bilayer surface fluctuates in time and space, occasionally creating thinning defects in the membrane. These defects are essential for passive transport of simple ions across membranes because they reduce the Born barrier to this process by approximately 60%. Negative ions are transferred across the bilayer more readily than positive ions due to favorable interactions with the electric field at the membrane-water interface. Passive transport of neutral molecules is, in general, more complex than predicted by the solubility-diffusion model. In particular, molecules which exhibit sufficient hydrophilicity and lipophilicity concentrate near membrane surfaces and experience ``interfacial resistance'' to transport. The membrane-water interface forms an environment suitable for heterogeneous catalysis. Several possible mechanisms leading to an increase of reaction rates at the interfaces are discussed. We conclude that vesicles have many properties that make them very good candidates for earliest protocells. Some potentially fruitful directions of experimental and theoretical research on this subject are proposed.

15. ``Probing the structure of cometary ice,'' M. A. Wilson, A. Pohorille, P. Jenniskens, and D. Blake, Orig. Life and Evol. Biosphere, 25, 3-19 (1995).

    Computer simulations of bulk and vapor deposited amorphous ices are presented. The structure of the bulk low density amorphous ice is in good agreement with experiments on bulk pressure disordered amorphous ice. Both the low density bulk ice and the vapor deposited ices exhibit strong tetrahedral ordering. Vapor deposition of hot (300 K) water molecules onto a cold (77 K) substrate yields less porous ices than deposition of cold (77 K) water molecules onto a cold substrate. Both vapor deposited ices are more porous than the bulk amorphous ice. The structure of bulk high density amorphous ice is only in fair agreement with experimental results. Attempts to simulate high density amorphous ice via vapor deposition were not successful. Electron diffraction results on vapor deposited amorphous ice indicate that the temperature of the nucleation of the cubic phase depends upon the amount of time between the deposition and the start of the heating. This is interpreted to mean that freshly deposited ice layers reconstruct on times of the order of hours. The relevance of the structure of amorphous ice to the origin of simple organic matter on the early Earth is discussed.

16. ``Interaction of a Model Peptide with a Water-Bilayer System,'' A. Pohorille and M. A. Wilson, in Structure and Reactivity in Aqueous Solutions, ACS Symposium Series 568, C. J. Cramer and D. G. Truhlar, eds., (ACS Books, Washington, DC, 1994) pp 395-408.

    We discuss a molecular dynamics study of the alanine dipeptide at the interface between water and a glycerol-1-monooleate (GMO) bilayer. The dipeptide is interfacially active and incorporates into the bilayer without disrupting its structure. The interfacial region that is readily penetrated by the dipeptide spans the entire head group portion of the bilayer. The polar groups of the alanine dipeptide mostly remain well solvated by water and the oxygen atoms of GMO, and conformations of the dipeptide are characterized by (,) angles typical of -helix and -sheet structures. When the molecule is deeper in the bilayer, the C state also becomes stable. The barrier to the isomerization reaction at the interface is lower than in bulk phases. After 7 ns of trajectories, the system is not fully equilibrated, due to slow collective motions involving GMO head groups. These result in decreased mobility and lower rates of isomerization of the dipeptide at the interface.

17. ``Scattering of Ne from the liquid-vapor interface of glycerol: a molecular dynamics study,'' I. Benjamin, M. A. Wilson, and A. Pohorille, J. Chem. Phys., 100, 6500-6507 (1994).

    A model potential for the scattering of Ne off liquid glycerol is developed. The model is based on a nine-site description of glycerol which takes into account torsional flexibility and hydrogen bonding. This model is used to carry out molecular dynamics calculations of the scattering as a function of collision energy. The results for the sticking probability and energy transfer are in good agreement with experiments. The model predicts a wide angular distribution of the scattered atoms with a mild decrease in the energy transfer as a function of exit angle for a fixed incident angle. The model also provides insight into the importance of the corrugated nature of the surface and the types of liquid modes that play a major role in the energy transfer process.

18. ``Molecular dynamics of a water-lipid bilayer interface,'' M. A. Wilson and A. Pohorille, J. Am. Chem. Soc., 116, 1490-1501 (1994).

    We present results of molecular dynamics simulations of a glycerol 1-monooleate bilayer in water. The total length of analyzed trajectories is 5 ns. The calculated width of the bilayer agrees well with the experimentally measured value. The interior of the membrane is in a highly disordered fluid state. Atomic density profiles, orientational and conformational distribution functions and order parameters indicate that disorder increases toward the center of the bilayer. Analysis of out-of-plane thermal fluctuations of the bilayer surfaces occurring at the time scale of the present calculations reveals that the distribution of modes agrees with predictions of the capillary wave model. Fluctuations of both bilayer surfaces are uncorrelated, yielding Gaussian distribution of instantaneous widths of the membrane. Fluctuations of the width produce transient thinning defects in the bilayer which occasionally spanned almost half of the membrane. The leading mechanism of these fluctuations is the orientational and conformational motion of head groups rather than vertical motion of the whole molecules. Water considerably penetrates the head group region of the bilayer but not its hydrocarbon core. The total net excess dipole moment of the interfacial water points toward the aqueous phase, but the water polarization profile is non-monotonic. Both, water and head groups significantly contribute to the surface potential across the interface. The calculated sign of the surface potential is in agreement with that from experimental measurements but the value is markedly overestimated. The structural and electrical properties of the water-bilayer system are discussed in relation to membrane functions, in particular transport of ions and nonelectrolytes across membranes.

19. ``Isomerization reactions at aqueous interfaces,'' A. Pohorille and M. A. Wilson, in Reaction Dynamics in Clusters and Condensed Phases (Proceedings of the 26 Jerusalem Symposium on Quantum Chemistry and Biochemistry) , B. Pullman and R. Levine, eds., (Kluwer, Dordrecht, 1994), pp. 207-226.

    In this paper we discuss the transfer of small, flexible molecules across the water-hexane interface. The study is motivated by the biological and pharmacological importance of this process in water-membrane systems. We focus on three main issues: (a) what are the free energy profiles for transferring molecules across the interface, (b) how conformational equilibria at the interface differ from those in the bulk phases, and (c) how the rates of isomerization compare to the rates of transfer across the interface. We investigate these problems by molecular dynamics simulations of two systems - 1,2-dichloroethane and alanine dipeptide. Both molecules exhibit a free energy minimum at the interface. As a consequence, the molecules encounter an apparent ``interfacial resistance'', in violation of the solubility-diffusion model. For 1,2-dichloroethane the relaxation time of the isomerization reaction was calculated from the transition state theory and corrected for dynamic effects which included a contribution from quasi-periodic trajectories. This time was found to be much shorter than the lifetime of the solute at the interface, indicating that the conformational equilibrium in this region is readily reached during the transfer. For alanine dipeptide it was found that conformations present in water and in hexane are all populated at the interface, but energy barriers between them are markedly reduced. The description of the transfer across the interface by a simple diffusion model was tested. The model gives satisfactory results for 1,2-dichloroethane but is less accurate for alanine dipeptide.

20. ``Structure of bilayer-water and monolayer-water interfaces: a molecular dynamics study,'' A. Pohorille and M. A. Wilson, Proceedings of the EBSA International Workshop on Water-Biomolecule Interactions, M. U. Palma, M. B. Palma-Vittorelli and F. Parak, eds., (SIF, Bologna, 1993), pp. 227-230.

    We present large-scale molecular dynamics simulations of interfaces between water and bilayers or monolayers of glycerol monooleate. Good agreement between the calculated structural parameters of the bilayer and the corresponding experimental measurements indicate that our description of systems is realistic at a molecular level. We show that (a) water markedly penetrates the headgroup region but not the hydrocarbon core of the amphiphilic phase, (b) water penetration increases with decreasing density of the headgroups at the surface, (c) the width of the water interfacial region in contact with monolayers is the largest at an intermediate headgroup surface coverage, and (d) water molecules at the interface are polarized such that their excess dipole moment points toward the liquid.

21. ``Molecular structure of aqueous interfaces,'' A. Pohorille and M. A. Wilson, J. Mol. Struct., THEOCHEM, 284, 271-298 (1993).

    In this review we summarize recent progress in our understanding of the structure of aqueous interfaces emerging from molecular-level computer simulations. It is emphasised that the presence of the interface induces specific structural effects which, in turn, influence a wide variety of phenomena occurring near the phase boundaries. At the liquid-vapor interface, the most probable orientations of a water molecule is such that its dipole moment lies parallel to the interface, one O-H bond points toward the vapor and the other O-H bond is directed toward the liquid. The orientational distributions are broad and slightly asymmetric, resulting in an excess dipole moment pointing toward the liquid. These structural preferences persist at interfaces between water and nonpolar liquids, indicating that the interactions between the two liquids in contact are weak. It was found that liquid-liquid interfaces are locally sharp but broadened by capillary waves. One consequence of anisotropic orientations of interfacial water molecules is asymmetric interactions, with respect to the sign of the charge, of ions with the water surface. It was found that even very close to the surface ions retain their hydration shells. New features of aqueous interfaces have been revealed in studies of water-membrane and water-monolayer systems. In particular, water molecules are strongly oriented by the polar head groups of the amphiphilic phase, and they penetrate the hydrophilic head-group region, but not the hydrophobic core. At infinite dilution near interfaces, amphiphilic molecules exhibit behavior different from that in the gas phase or in bulk water. This result sheds new light on the nature of hydrophobic effect in the interfacial regions. The presence of interfaces was also shown to affect both equilibrium and dynamic components of rates of chemical reactions. Applications of continuum models to interfacial problems have been, so far, unsuccessful. This, again, underscores the importance of molecular-level information about interfaces.

22. ``Interaction of monovalent ions with the water liquid-vapor interface. A molecular dynamics study,'' M. A. Wilson and A. Pohorille, J. Chem. Phys., 95, 6005-6013 (1991).

    Results of molecular dynamics studies on the ions Na, F, and Cl near the water liquid-vapor interface are reported. The free energies required to move the ions to the interface are presented and shown to depend on the sign of the ionic charge, and not the size of the ion. F and Cl can approach to within 2 molecular layers of the interface without incurring a significant change in free energy, while it costs about 2.5 kcal/mole to move Na this same distance. The free energy differences between the cation and the anions arise from the interaction of the ions with the water molecules in the interfacial region. These water molecules are oriented with a slight preference for their molecular dipoles to point toward the liquid. Thus, the anions approaching the interface disrupt the water structure less than does the cation. The calculated free energy curves were compared with predictions of simple dielectric models. It was shown that these models do not provide a good description of ions at the water surface. The ions were found to retain their first solvation shells at the interface. The anions also retain part of their second solvation shells, while Na does not. As a result, a larger bulge in the water surface is observed above the anions than above Na. The lateral mobilities of the ions increase at the interface, in qualitative agreement with predictions of hydrodynamic models.