Charge asymmetries in hydration of polar solutes

We study the solvation of polar molecules in water. The center of water's dipole moment is offset from its steric center. In common water models, the Lennard-Jones center is closer to the negatively charged oxygen than to the positively charged hydrogens. This asymmetry of water's charge sites leads to different hydration free energies of positive versus negative ions of the same size. Here, we explore these hydration effects for some hypothetical neutral solutes, and two real solutes, with molecular dynamics simulations using several different water models. We find that, like ions, polar solutes are solvated differently in water depending on the sign of the partial charges. Solutes having a large negative charge balancing diffuse positive charges are preferentially solvated relative to those having a large positive charge balancing diffuse negative charges. Asymmetries in hydration free energies can be as large as 10 kcal/mol for neutral benzene-sized solutes. These asymmetries are mainly enthalpic, arising primarily from the first solvation shell water structure. Such effects are not readily captured by implicit solvent models, which respond symmetrically with respect to charge.     

Surface tension of electrolytes: hydrophilic and hydrophobic ions near an interface

We calculate the ion distributions around an interface in fluid mixtures of highly polar and less polar fluids (water and oil) for two and three ion species. We take into account the solvation and image interactions between ions and solvent. We show that hydrophilic and hydrophobic ions tend to undergo a microphase separation at an interface, giving rise to an enlarged electric double layer. We also derive a general expression for the surface tension of electrolyte systems, which contains a negative electrostatic contribution proportional to the square root of the bulk salt density. The amplitude of this square-root term is small for hydrophilic ion pairs but is much increased for hydrophilic and hydrophobic ion pairs. For three ion species, including hydrophilic and hydrophobic ions, we calculate the ion distributions to explain those obtained by x-ray reflectivity measurements.     

Hydrophobic and ionic interactions in nanosized water droplets

A number of situations such as protein folding in confined spaces, lubrication in tight spaces, and chemical reactions in confined spaces require an understanding of water-mediated interactions. As an illustration of the profound effects of confinement on hydrophobic and ionic interactions, we investigate the solvation of methane and methane decorated with charges in spherically confined water droplets. Free energy profiles for a single methane molecule in droplets, ranging in diameter (D) from 1 to 4 nm, show that the droplet surfaces are strongly favorable as compared to the interior. From the temperature dependence of the free energy in D = 3 nm, we show that this effect is entropically driven. The potentials of mean force (PMFs) between two methane molecules show that the solvent separated minimum in the bulk is completely absent in confined water, independent of the droplet size since the solute particles are primarily associated with the droplet surface. The tendency of methanes with charges (M(q+) and M(q-) with q(+) = |q(-)| = 0.4e, where e is the electronic charge) to be pinned at the surface depends dramatically on the size of the water droplet. When D = 4 nm, the ions prefer the interior whereas for D < 4 nm the ions are localized at the surface, but with much less tendency than for methanes. Increasing the ion charge to e makes the surface strongly unfavorable. Reflecting the charge asymmetry of the water molecule, negative ions have a stronger preference for the surface compared to positive ions of the same charge magnitude. With increasing droplet size, the PMFs between M(q+) and M(q-) show decreasing influence of the boundary owing to the reduced tendency for surface solvation. We also show that as the solute charge density decreases the surface becomes less unfavorable. The implications of our results for the folding of proteins in confined spaces are outlined.     

A method for treating the passage of a charged hard sphere ion as it passes through a sharp dielectric boundary

In the implicit solvent models of electrolytes (such as the primitive model (PM)), the ions are modeled as point charges in the centers of spheres (hard spheres in the case of the PM). The surfaces of the spheres are not polarizable which makes these models appropriate to use in computer simulations of electrolyte systems where these ions do not leave their host dielectrics. The same assumption makes them inappropriate in simulations where these ions cross dielectric boundaries because the interaction energy of the point charge with the polarization charge induced on the dielectric boundary diverges. In this paper, we propose a procedure to treat the passage of such ions through dielectric interfaces with an interpolation method. Inspired by the "bubble ion" model (in which the ion's surface is polarizable), we define a space-dependent effective dielectric coefficient, ε(eff)(r), for the ion that overlaps with the dielectric boundary. Then, we replace the "bubble ion" with a point charge that has an effective charge q/ε(eff)(r) and remove the portion of the dielectric boundary where the ion overlaps with it. We implement the interpolation procedure using the induced charge computation method [D. Boda, D. Gillespie, W. Nonner, D. Henderson, and B. Eisenberg, Phys. Rev. E 69, 046702 (2004)]. We analyze the various energy terms using a spherical ion passing through an infinite flat dielectric boundary as an example.     

Theoretical study of the effects of solvent environment on photophysical properties and electronic structure of paracyclophane chromophores

We use first-principles quantum-chemical approaches to study absorption and emission properties of recently synthesized distyrylbenzene (DSB) derivative chromophores and their dimers (two DSB molecules linked through a [2.2]paracyclophane moiety). Several solvent models are applied to model experimentally observed shifts and radiative lifetimes in Stokes nonpolar organic solvents (toluene) and water. The molecular environment is simulated using the implicit solvation models, as well as explicit water molecules and counterions. Calculations show that neither implicit nor explicit solvent models are sufficient to reproduce experimental observations. The contact pair between the chromophore and counterion, on the other hand, is able to reproduce the experimental data when a partial screening effect of the solvent is taken into account. Based on our simulations we suggest two mechanisms for the excited-state lifetime increase in aqueous solutions. These findings may have a number of implications for organic light-emitting devices, electronic functionalities of soluble polymers and molecular fluorescent labels, and their possible applications as biosensors and charge/energy conduits in nanoassemblies.     

Structure formation due to antagonistic salts

Antagonistic salts are composed of hydrophilic and hydrophobic ions. In a mixture solvent (water–oil) such ion pairs are preferentially attracted to water or oil, giving rise to a coupling between the charge density and the composition. First, they form a large electric double layer at a water–oil interface, reducing the surface tension and producing mesophases. Here, the cations and anions are loosely bound by the Coulomb attraction across the interface on the scale of the Debye screening length. Second, on solid surfaces, hydrophilic (hydrophobic) ions are trapped in a water-rich (oil-rich) adsorption layer, while those of the other species are expelled from the layer. This yields a solvation mechanism of local charge separation near a solid. In particular, near the solvent criticality, disturbances around solid surfaces can become oscillatory in space. In mesophases, we calculate periodic structures, which resemble those in experiments.     

Free energy partitioning analysis of the driving forces that determine ion density profiles near the water liquid-vapor interface

Free energy partitioning analysis is employed to explore the driving forces for ions interacting with the water liquid-vapor interface using recently optimized point charge models for the ions and SPC/E water. The Na(+) and I(-) ions are examined as an example kosmotrope/chaotrope pair. The absolute hydration free energy is partitioned into cavity formation, attractive van der Waals, local electrostatic, and far-field electrostatic contributions. We first compute the bulk hydration free energy of the ions, followed by the free energy to insert the ions at the center of a water slab. Shifts of the ion free energies occur in the slab geometry consistent with the SPC/E surface potential of the water liquid-vapor interface. Then the free energy profiles are examined for ion passage from the slab center to the dividing surface. The profiles show that, for the large chaotropic I(-) ion, the relatively flat total free energy profile results from the near cancellation of several large contributions. The far-field electrostatic part of the free energy, largely due to the water liquid-vapor interface potential, has an important effect on ion distributions near the surface in the classical model. We conclude, however, that the individual forms of the local and far-field electrostatic contributions are expected to be model dependent when comparing classical and quantum results. The substantial attractive cavity free energy contribution for the larger I(-) ion suggests that there is a hydrophobic component important for chaotropic ion interactions with the interface.     

Molecular dynamics simulations of electrolyte solutions at the (100) goethite surface

Molecular dynamics simulations of electrolyte solutions in contact with a neutral (100) goethite (alpha-FeOOH) surface were used to probe the structure of the mineral-water interface and gain insight into the adsorption properties of monovalent ions. Three electrolyte solutions were considered: NaCl, CsCl, and CsF. The electrolyte ions were chosen to cover a range of ionic sizes and affinities for the aqueous phase. The molecular dynamics simulations indicate the presence of a structured interfacial region resulting from the strong interaction of water with the mineral surface. The specific arrangement and preferred orientation of water that arise from this interaction create adsorption sites in the interfacial region, i.e., as far as 15 A away from the surface, and hence give rise to a strong correlation between the water and ion distributions. The structure of the hydrated ion, its effect on the water arrangement at the interface, and the strength of the ion-water bond are found to be key factors that determine the location and extent of ion adsorption at the interface. Additionally, in all simulations, we find a build up of positive charges near the surface due to cation adsorption, which is compensated by an accumulation of anions in the next few angstr?ms. This creates an excess of negative charges, which is in turn compensated by an excess of positive charges, and so on. As we modeled a neutral surface, the structure of the electrolyte distribution arises from the complex interplay of the interactions between the surface, water, and the electrolyte ions rather than from the need to neutralize a surface charge. In addition, our simulations indicate that the electrolyte distribution does not resemble that of a classical electrical double layer. Indeed, our calculations predict the presence of several condensed layers and oscillations in the net charge away from the surface.     

Thermodynamic study of small hydrophobic ions at the water-lipid interface

The thermodynamics of binding of two small hydrophobic ions such as norharman and tryptophan to neutral and negatively charged small unilamellar vesicles was investigated at pH 7.4 using fluorescence spectroscopy. Vesicles were formed at room temperature from dimyristoyl phosphatidylcholine (DMPC) or DMPC/dimyristoylphosphatidic acid and DMPC/dimyristoylphosphatidylglycerol. The changes in fluorescence properties were used to obtain association isotherms at variable membrane surface negative charge and at different ionic strengths. The binding of both ions was found to be quantitatively enhanced as the percentage of negative phospholipid increases in the membrane. Also, a decrease in ion binding was found to occur as the concentration of monovalent salt was increased (0.045-0.345 M). If electrostatic effects were ignored, the experimental data showed biphasic behavior in Scatchard plots. When electrostatic effects were taken into account by means of the Gouy-Chapman theory, the same data yielded linear Scatchard plots that were described by a simple partition equilibrium of the hydrophobic ion into the lipid-water interface. We demonstrate that the effective interfacial charge, nu, of the ion is a determinant factor to obtain a unique value of the intrinsic (hydrophobic) binding constant independently of the surface charge density of the lipid membrane.     

Electro-osmosis at inhomogeneous charged surfaces: hydrodynamic versus electric friction

Electrokinetic methods are efficient in probing the electrostatic surface properties of charged systems. However, anomalies observed in experiments indicate that the classical electrokinetic theory should be reconsidered. Using Green's function methods and hydrodynamic simulations, we investigate electro-osmosis driven by electric-field-induced ion motion near a charged planar substrate with smooth or rough boundary. First, a reformulation of electro-osmotic theory for planar charged surfaces employing Green's functions shows that the Helmholtz-Smoluchowski (HS) relation between electrostatic potential and solvent velocity is exact for smooth surfaces, even in the presence of ion correlations. Deviations from HS theory are caused by combined hydrodynamic and electric surface friction, as our hydrodynamic simulations of ions at smooth and corrugated charged surfaces in lateral electric fields demonstrate. Within the simulations, hydrodynamic interactions are treated in the continuum limit and the presence of a no-slip boundary condition at the surface is taken into account. While electrofriction is relevant in highly charged system and/or for multivalent ions, hydrodynamic friction is dominant in systems with moderate surface charge density and/or low ionic valency. We also derive the effective electrokinetic surface charge from the electro-osmotic solvent profiles, which is substantially reduced when compared with the bare value and shows qualitative agreement with the experimental tendency.     

Dynamic surface properties of the solutions of β-casein-surfactant complexes

Dynamic surface elasticity of the solutions of β-casein-surfactant complexes are measured by the oscillation barrier method as functions of surface age and surfactant concentration. Small amounts of added ionic surfactants greatly affect the kinetic dependence of dynamic surface elasticity. The pattern of kinetic dependence is determined by the sign of the charge of surface-active ion. Results obtained can be explained if we take into account the strong electrostatic interaction between charged amine acid residues in the protein and surface-active ions, as well as different distribution of positive and negative charges along the protein chain. The proposed recently mechanism of adsorption of β-casein, which suggests the consecutive formation of loops and tails from relatively hydrophilic and hydrophobic parts of protein molecule, is confirmed.     

Solvent reaction field potential inside an uncharged globular protein: a bridge between implicit and explicit solvent models?

The solvent reaction field potential of an uncharged protein immersed in simple point charge/extended explicit solvent was computed over a series of molecular dynamics trajectories, in total 1560 ns of simulation time. A finite, positive potential of 13-24 kbTec(-1) (where T=300 K), dependent on the geometry of the solvent-accessible surface, was observed inside the biomolecule. The primary contribution to this potential arose from a layer of positive charge density 1.0 A from the solute surface, on average 0.008 ec/A3, which we found to be the product of a highly ordered first solvation shell. Significant second solvation shell effects, including additional layers of charge density and a slight decrease in the short-range solvent-solvent interaction strength, were also observed. The impact of these findings on implicit solvent models was assessed by running similar explicit solvent simulations on the fully charged protein system. When the energy due to the solvent reaction field in the uncharged system is accounted for, correlation between per-atom electrostatic energies for the explicit solvent model and a simple implicit (Poisson) calculation is 0.97, and correlation between per-atom energies for the explicit solvent model and a previously published, optimized Poisson model is 0.99.     

A multiscale coarse‐grained polarizable solvent model for handling long tail bulk electrostatics

A multiscale coarse‐grained approach able to handle efficiently the solvation of microscopic solutes in extended chemical environment is described. That approach is able to compute readily and efficiently very long‐range solute/solvent electrostatic microscopic interactions, up to the 1‐μm scale, by considering a reduced amount of computational resources. All the required parameters are assigned to reproduce available data concerning the solvation of single ions. Such a strategy makes it possible to reproduce with good accuracy the solvation properties concerning simple ion pairs in solution (in particular, the asymptotic behavior of the ion pair potentials of mean force). This new method represents an extension of the polarizable pseudoparticle solvent model, which has been recently improved to account for the main features of hydrophobic effects in liquid water (Masella et al., J. Comput. Chem. 2011 , 32, 2664). This multiscale approach is well suited to be used for computing the impact of charge changes in free energy computations, in terms of both accuracy and efficiency. © 2013 Wiley Periodicals, Inc.     

Molecular dynamics studies of ion distributions for DNA duplexes and DNA clusters: salt effects and connection to DNA melting

We present extensive molecular dynamics simulations of the ion distributions for DNA duplexes and DNA clusters using the Amber force field with implicit water. The distribution of ions and the electrostatic energy of ions around an isolated DNA duplex and clusters of DNA duplexes in different salt (NaCl) concentrations over the range 0.2-1.0 mol/L are determined on the basis of the simulation results. Using the electrostatic energy profile, we determine a local net charge fraction phi, which is found to increase with increasing of salt concentration. For DNA clusters containing two DNA duplexes (DNA pair) or four DNA duplexes, phi increases as the distance between the duplexes decreases. Combining this result with experimental results for the dependence of the DNA melting temperature on bulk salt concentration, we conclude that for a pair of DNA duplexes the melting temperature increases by 5-10 K for interaxis separations of 25-40 A. For a cluster of four DNA duplexes, an even larger melting temperature increase should occur. We argue that this melting temperature increase in dense DNA clusters is responsible for the cooperative melting mechanism in DNA-linked nanoparticle aggregates and DNA-linked polymer aggregates.     

A new charge-associated mechanism to account for the production of fragment ions in the high-energy CID spectra of fatty acids

A new mechanism, termed a charge-assisted process, is proposed as an additional mechanism to the charge-remote process to account for ions of the [M - CnH2n+2] series found in the positive and negative high energy CID spectra of fatty acids and related compounds when ionized as closed-shell ([M - H]- or [M + X]+) species. The new mechanism is based on that commonly invoked to account for similar ions in the electron-impact spectra of derivatized fatty acids whereby the positive charge on the derivative abstracts a hydrogen atom from various positions of the alkyl chain to leave a radical that initiates a radical-induced cleavage of the chain. It is proposed that in the high energy CID spectra of closed-shell ions, similar hydrogen migrations occur but unpairing of electrons is avoided by charge transfer to the alkyl chain. This charge then initiates a concerted cleavage of the chain to give an allylic carbonium (positive ion spectrum) or carbanion (negative ion spectrum). The mechanism avoids the need to involve radicals or loss of hydrogen atoms from even-electron (closed shell) ions and provides a driving force for the reaction, namely, the formation of ions with a stabilized charge. An extension of the mechanism is also proposed to account for the formation of odd-electron ions from these compounds. The charge-assisted mechanism does not rule out the occurrence of other mechanisms that have been accepted for many years but provides an alternative process that can account for some spectral features which were difficult to explain earlier.     

Specific ion binding to macromolecules: effects of hydrophobicity and ion pairing

Using molecular dynamics simulations in an explicit aqueous solvent, we examine the binding of fluoride versus iodide to a spherical macromolecule with both hydrophobic and positively charged patches. Rationalizing our observations, we divide the ion association interaction into two mechanisms: (1) poorly solvated iodide ions are attracted to hydrophobic surface patches, while (2) the strongly solvated fluoride and to a minor extent also iodide bind via cation-anion interactions. Quantitatively, the binding affinities vary significantly with the accessibility of the charged groups as well as the surface potential; therefore, we expect the ion-macromolecule association to be modulated by the local surface characteristics of the (bio-)macromolecule. The observed cation-anion pairing preference is in excellent agreement with experimental data.     

Ion selectivity using membranes comprising functionalized carbon nanotubes

In this paper, we use applied mathematical modelling to investigate the transportation of ions inside functionalized carbon nanotubes, and in particular the transport of sodium and chloride ions. This problem is important for future ion transport and detection, and also arises in ion diffusion inside complex biological channels. Some important future applications of the system for a solvent are ultra-sensitive biosensors and electrolytes for alkaline fuel cells. We model the interactions between the ions and the nanotube by the Lennard-Jones potential and the interactions between the ions and the functional group by the Coulomb potential, while the atomic interactions between the ions is modeled by both the Lennard-Jones and Coulomb potentials. We further assume that the carbon atoms, the charge of the functional group, and the ions are all evenly distributed on the surface of the nanotube, the entry of the nanotube and the envisaged ionic surface, respectively, so that we may use the continuous approximation to calculate the corresponding potential energies. For nanotubes located in salt water, the molecular effects arising from the bulk solution can be extracted from MD simulation studies. Assuming that the solvent is absent, we first determine the acceptance radii for the sodium or chloride ion entering the nanotube, both with and without a functional group, and we then determine the equilibrium positions of two identical ions inside the nanotube. Finally, the transportation time of an intruding ion through the nanotube is deduced from the total axial force. In the presence of a solvent, the molecular effects arising from the bulk solution are examined and we establish that the presence of a solvent stabilizes the selectivity of the ions.     

Co-ion and ion competition effects: ion distributions close to a hydrophobic solid surface in mixed electrolyte solutions

We consider within a modified Poisson-Boltzmann theory an electrolyte, with different mixtures of NaCl and NaI, near uncharged and charged solid hydrophobic surfaces. The parametrized potentials of mean force acting on Na+, Cl-, and I- near an uncharged self-assembled monolayer were deduced from molecular simulations with polarizable force fields. We study what happens when the surface presents negative charges. At moderately charged surfaces, we observe strong co-ion adsorption and clear specific ion effects at biological concentrations. At high surface charge densities, the co-ions are pushed away from the interface. We predict that Cl- ions can also be excluded from the surface by increasing the concentration of NaI. This ion competition effect (I- versus Cl-) may be relevant for ion-specific partitioning in multiphase systems where polarizable ions accumulate in phases with large surface areas.     

Metal-coupled folding of Cys2His2 zinc-finger

Zinc-fingers, which widely exist in eukaryotic cell and play crucial roles in life processes, depend on the binding of zinc ion for their proper folding. To computationally study the zinc-coupled folding of the zinc-fingers, charge transfer and metal induced protonation/deprotonation effects have to be considered. Here, by attempting to implicitly account for such effects in classical molecular dynamics and performing intensive simulations with explicit solvent for the peptides with and without zinc binding, we investigate the folding of the Cys2His2-type zinc-finger motif and the coupling between the peptide folding and zinc binding. We find that zinc ion not only stabilizes the native structure but also participates in the whole folding process. It binds to the peptide at an early stage of folding and directs or modulates the folding and stabilizations of the component beta-hairpin and alpha-helix. Such a crucial role of zinc binding is mediated by the packing of the conserved hydrophobic residues. We also find that the packing of the hydrophobic residues and the coordination of the native ligands are coupled. Meanwhile, the processes of zinc binding, mis-ligation, ligand exchange, and zinc induced secondary structure conversion as well as the water behavior due to the involvement of zinc ion are characterized. Our results are in good agreement with related experimental observations and provide significant insight into the general mechanisms of the metal cofactor dependent protein folding and other metal-induced conformational changes of biological importance.