Effect of dehydration on the interfacial water structure at a charged polymer surface: negligible χ(3) contribution to sum frequency generation signal

Interfacial water structure at charged surfaces plays a key role in many physical, chemical, biological, environmental, and industrial processes. Understanding the release of interfacial water from the charged solid surfaces during dehydration process may provide insights into the mechanism of protein folding and the nature of weak molecular interactions. In this work, sum frequency generation vibrational spectroscopy (SFG-VS), supplemented by quartz crystal microbalance (QCM) measurements, has been applied to study the interfacial water structure at polyelectrolyte covered surfaces. Poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA) chains are grafted on solid surfaces to investigate the change of interfacial water structure with varying surface charge density induced by tuning the solution pH. At pH ≤ 7.1, SFG-VS intensity is linear to the loss of mass of interfacial water caused by the dehydration of PDMAEMA chains, and no reorientation of the strongly bonded water molecules is observed in the light of χ(ppp)/χ(ssp) ratio. χ((3)) contribution to SFG signal is deduced based on the combination of SFG and QCM results. It is the first direct experimental evidence to reveal that the χ((3)) has a negligible contribution to SFG signal of the interfacial water at a charged polymer surface.     

Laser thermal ablation

Continuous wave and pulsed laser ablation of tissue is described as an explosive event. A subsurface temperature maximum and superheated tissue produce high pressures that eject fragments from the tissue. Decreased water content due to dehydration and vaporization decreases thermal conductivity which reduces heat conduction. Also, a decrease in water content dramatically alters the local rate of heat generation of laser radiation above 1.3 microns since water is the primary absorber. In contrast, at UV wavelengths protein and DNA are the primary absorbers so destruction of tissue bonds is due to direct absorption of the laser light rather than heat transfer from water.     

Globular proteins at solid/liquid interfaces

Seven years have passed since one of us (W.N.) published the last comprehensive review on the mechanism of globular protein adsorption to solid/water interfaces. Since that time, annual contributions to the field have steadily increased and substantial progress has been made in a number of important areas. This review takes a fresh look at the driving force for protein adsorption by combining recent advances with key results from the past. The analysis indicates that four effects, namely structural rearrangements in the protein molecule, dehydration of (parts of) the sorbent surface, redistribution of charged groups in the interfacial layer, and protein surface polarity usually make the primary contributions to the overall adsorption behavior.     

Unusual properties of water at hydrophilic/hydrophobic interfaces

The behaviour of water at mosaic hydrophilic/hydrophobic surfaces of different silicas and in biosystems (biomacromolecules, yeast cells, wheat seeds, bone and muscular tissues) was studied in different dispersion media over wide temperature range using 1H NMR spectroscopy with layer-by-layer freezing-out of bulk water (close to 273 K) and interfacial water (180 < T < 273 K), thermally stimulated depolarization current (TSDC) (90 < T < 270 K), infrared (IR) spectroscopy, and quantum chemical methods. Bulk water and water bound to hydrophilic/hydrophobic interfaces can be assigned to different structural types. There are (i) weakly associated interfacial water (1H NMR chemical shift delta(H) = 1.1-1.7 ppm) that can be assigned to high-density water (HDW) with collapsed structure (CS), representing individual molecules in hydrophobic pockets, small clusters and interstitial water with strongly distorted hydrogen bonds or without them, and (ii) strongly associated interfacial water (delta(H) = 4-5 ppm) with larger clusters, nano- and microdomains, and continuous interfacial layer with both HDW and low-density water (LDW). The molecular mobility of weakly associated bound water is higher (because hydrogen bonds are distorted and weakened and their number is smaller than that for strongly associated water) than that of strongly associated bound water (with strong hydrogen bonds but nevertheless weaker than that in ice Ih) that results in the difference in the temperature dependences of the 1H NMR spectra at T < 273 K. These different waters are also appear in changes in the IR and TSDC spectra.     

Adsorption of 1-octanol at the free water surface as studied by Monte Carlo simulation

The adsorption of 1-octanol at the free water surface has been investigated by Monte Carlo computer simulation. Six different systems, built up by an aqueous and a vapor phase, the latter also containing various number of octanol molecules, have been simulated. The number of the octanol molecules has been chosen in such a way that the octanol surface density varies in a broad range, between 0.27 and 7.83 micromol/m(2) in the six systems simulated. For reference, the interfacial system containing bulk liquid octanol in the apolar phase has also been simulated. The results have shown that the formation of hydrogen bonds between the interfacial water and adsorbed octanol molecules is of key importance in determining the properties of the adsorbed layer. At low octanol surface concentration values all the octanol molecules are strongly (i.e., by hydrogen bonds) bound to the aqueous phase, whereas their interaction with each other is negligibly small. Hence, they are preferentially oriented in such a way that their own binding energy (and thus their own free energy) is minimized. In this preferred orientation the O-H bond of the octanol molecule points flatly toward the aqueous phase, declining by about 30 degrees from the interfacial plane, irrespectively from whether the octanol molecule is the H-donor or the H-acceptor partner in the hydrogen bond. Hence, in its preferred orientation the octanol molecule can form at least two low energy hydrogen bonds with water: one as a H-donor and another one as a H-acceptor. Moreover, the preferred orientation of the hydrogen bonded water partners is close to one of the two preferred interfacial water alignments, in which the plane of the water molecule is parallel with the interface. When increasing the octanol surface density, the water surface gets saturated with hydrogen bonded octanols, and hence any further octanol molecule can just simply condense to the layer of the adsorbed octanols. The surface density value at which this saturation occurs is estimated to be about 1.7 micromol/m(2). Above this surface density value the hydrogen bonded octanols and their water partners are oriented in such a way that the number of the water-octanol hydrogen bonds is maximized. Hence, the preferred alignment of the O...O axes of these hydrogen bonds is perpendicular to the interface. This orientation is far from the optimal alignment of the individual octanol molecules, which is also reflected in the observed fact that, unlike in the case of many other adsorbents, the average molecular binding energy of the adsorbed octanol molecules increases (i.e., becomes less negative) with increasing octanol surface density.     

Molecular dynamics study of ion capture from water by a model ionophore, tetraprotonated cryptand SC24

A molecular dynamics study of chloride capture from water by the tetraprotonated cryptand SC24 is presented. The system under study consisted of a cryptand molecule, chloride ion, and 319 water molecules. Calculations were performed for 19 distances between the cryptand and the chloride. For each distance a trajectory of at least 60 ps was obtained. Two anion binding sites of comparable energy were found. The chloride can bind either inside the cryptand cavity or more loosely outside of the ligand. The binding sites are separated by an energy barrier of 20 kcal/mol. Chloride movement toward the cryptand is accompanied by stepwise dehydration of the anion. The energy loss due to this dehydration is offset by the electrostatic attraction between the anion and the ligand and by an increase in favorable water-water interactions. The most striking feature of chloride capture is a rapid cooperative change in the conformation of the cryptand when the Cl- starts to enter the ligand and just as it encounters the energy barrier. The conformational transition is associated with a shift of three N-H bonds from the pure endo orientation, so that they point toward the chloride. The shift provides electrostatic stabilization, which compensates for the loss of the remaining three water molecules from the hydration shell of the anion. The N-H bonds remain directed toward the anion during its further movement into the ligand and guide chloride into a stable position inside the cryptand cavity. The flexibility of the receptor, the stepwise dehydration of an ionic substrate, and the characteristic balance between different energy components in the system all may be features of ion binding common to a wide range of abiotic and biological ionophores.     

Properties of a water layer on hydrophilic and hydrophobic self-assembled monolayer surfaces: A molecular dynamics study

The microscopic behaviors of a water layer on different hydrophilic and hydrophobic surfaces of well ordered self-assembled monolayers (SAMs) are studied by molecular dynamics simulations. The SAMs consist of 18-carbon alkyl chains bound to a silicon(111) substrate, and the characteristic of its surface is tuned from hydrophobic to hydrophilic by using different terminal functional groups ( CH 3 , COOH). In the simulation, the properties of water membranes adjacent to the surfaces of SAMs were reported by comparing pure water in mobility, structure, and orientational ordering of water molecules. The results suggest that the mobility of water molecules adjacent to hydrophilic surface becomes weaker and the molecules have a better ordering. The distribution of hydrogen bonds indicates that the number of water-water hydrogen bonds per water molecule tends to be lower. However, the mobility of water molecules and distribution of hydrogen bonds of a water membrane in hydropho- bic system are nearly the same as those in pure water system. In addition, hydrogen bonds are mainly formed between the hydroxyl of the COOH group and water molecules in a hydrophilic system, which is helpful in understanding the structure of interfacial water.     

Comparative study of the hydration systems formed during interactions of hydrogen phosphate dianions with putrescine, nor-putrescine and magnesium dications

A comparative study of hydration systems, formed as a result of the interaction between hydrogen phosphate dianions and three naturally occurring cations (putrescine (Put), its nor-homologue (nPut) and magnesium), is presented. On the basis of X-ray data and IR, NMR and calorimetric measurements, we have determined how the structure and physicochemical properties of the cations influence the system of phosphate residue hydration. Our study demonstrates that the stability of the hydration systems depends not only on the character of the bonds used by water to link with other salt components (coordinate or hydrogen bonds), but also on the location of the water molecules in the crystal lattice. In addition, contrary to magnesium salts, the dehydration of diamine (Put and nPut) hydrogen phosphates is reversible. Both dehydration and rehydration processes take place in the solid state. During rehydration, the crystalline anhydrous salt absorbs water molecules from the atmosphere. This leads to the reconstruction of the hydrated salt structure; this means that the salt which is the product of rehydration is identical with that obtained by crystallization from water solution.     

Shielded hydrogen bonds as structural determinants of binding kinetics: application in drug design

Time scale control of molecular interactions is an essential part of biochemical systems, but very little is known about the structural factors governing the kinetics of molecular recognition. In drug design, the lifetime of drug-target complexes is a major determinant of pharmacological effects but the absence of structure-kinetic relationships precludes rational optimization of this property. Here we show that almost buried polar atoms--a common feature on protein binding sites--tend to form hydrogen bonds that are shielded from water. Formation and rupture of this type of hydrogen bonds involves an energetically penalized transition state because it occurs asynchronously with dehydration/rehydration. In consequence, water-shielded hydrogen bonds are exchanged at slower rates. Occurrence of this phenomenon can be anticipated from simple structural analysis, affording a novel tool to interpret and predict structure-kinetics relationships. The validity of this principle has been investigated on two pairs of Hsp90 inhibitors for which detailed thermodynamic and kinetic data has been experimentally determined. The agreement between macroscopic observables and molecular simulations confirms the role of water-shielded hydrogen bonds as kinetic traps and illustrates how our finding could be used as an aid in structure-based drug discovery.     

Role of hydrogen bonds in protein-DNA recognition: effect of nonplanar amino groups

Amino groups are one of the various types of hydrogen bond donors, abundantly found in protein main chains, protein side chains, and DNA bases. The polar hydrogen atoms of these groups exhibit short ranged, specific, and directional hydrogen bonds, which play a decisive role in the specificity and stability of protein-DNA complexes. To date, planar amino groups are only considered for the analysis of protein-DNA interfacial hydrogen bonds. This assumption regarding hydrogen atom positions possibly failed to establish the expected role of hydrogen bonds in protein-DNA recognition. We have performed ab initio quantum chemical studies on amino acid side chains and DNA bases containing amino groups as well as on specific hydrogen bonded residue pairs selected from high-resolution protein-DNA complex crystal structures. Our results suggest that occurrences of pyramidal amino groups are more probable in comparison with the usually adopted planar geometry. This increases the quality of the existing hydrogen bonds in almost all cases. Further, detailed analysis of protein-DNA interfacial hydrogen bonds in 107 crystal structures using the in-house program "pyrHBfind" indicates that consideration of energetically more preferred nonplanar amino groups improves the geometry of hydrogen bonds and also gives rise to new contacts amounting to nearly 14.5% of the existing interactions. Large improvements have been observed specifically for the amino groups of guanine, which faces the DNA minor groove and thus helps to resolve the problem of insufficient directional contacts observed in many minor groove binding complexes. Apart from guanine, improvement observed for asparagine, glutamine, adenine, or cytosine also indicates that the consideration of nonplanar amino groups leads to a more realistic scenario of hydrogen bonds occurring between protein and DNA residues.     

Restricted dynamics of water around a protein-carbohydrate complex: Computer simulation studies

Water-mediated protein-carbohydrate interaction is a complex phenomenon responsible for different biological processes in cellular environment. One of the unexplored but important issues in this area is the role played by water during the recognition process and also in controlling the microscopic properties of the complex. In this study, we have carried out atomistic molecular dynamics simulations of a protein-carbohydrate complex formed between the hyaluronan binding domain of the murine Cd44 protein and the octasaccharide hyaluronan in explicit water. Efforts have been made to explore the heterogeneous influence of the complex on the dynamic properties of water present in different regions around it. It is revealed from our analyses that the heterogeneous dynamics of water around the complex are coupled with differential time scales of formation and breaking of hydrogen bonds at the interface. Presence of a highly rigid thin layer of motionally restricted water molecules bridging the protein and the carbohydrate in the common region of the complex has been identified. Such water molecules are expected to play a crucial role in controlling properties of the complex. Importantly, it is demonstrated that the formation of the protein-carbohydrate complex affects the transverse and longitudinal degrees of freedom of the interfacial water molecules in a heterogeneous manner.     

Thermodynamics of water/β-cyclodextrin system

The thermodynamics of β-cyclodextrin dehydration is investigated, by parallel DSC/TG experiments, on both fully and partially hydrated samples. The apparent dehydration enthalpies per mole of water are impossibly high and this fact suggests that another phenomenon, in addition to the rupture of the β-cyclodextrin/H₂O hydrogen bonds, contributes to the peak area. All the experimental evidence agrees with an ‘interaction model’ which assumes that deydration is accompanied by a slow and reversible rearrangement of the β-cyclodextrin structure.     

Origin of repulsive force and structure/dynamics of interfacial water in OEG-protein interactions: a molecular simulation study

Molecular simulations were performed to investigate the origin of the strong repulsive force acting on a protein as the protein approaches an oligo (ethylene glycol) self-assembled monolayer (OEG-SAM) surface. Since the repulsive force is mainly generated from water molecules, the force from the water molecules near the surface was calculated layer by layer to further identify the molecular origin of the repulsive force. Results show that the strong repulsive force acting on the protein near the OEG-SAM surface is dominantly generated by the interfacial water molecules located between the OEG-SAM surface and lysozyme. A hydroxyl-terminated SAM (OH-SAM) surface was used for comparison. No significant repulsive force was observed from the water molecules between the protein and OH-SAM surface. Further studies show that the dipole distribution of the interfacial water molecules is significantly affected by the OEG-SAM surface, as opposed to the negligible impact from the OH-SAM surface. The interfacial water molecules above the OEG-SAM surface stay longer and reorient more slowly than those above the OH-SAM surface. These results from this work support the hypothesis that the OEG-SAM surface interacts strongly with interfacial water molecules and creates a stable hydration layer that prevents proteins from adsorbing to the surface.     

Specific ion effects on interfacial water structure near macromolecules

We investigated specific ion effects on interfacial water structure next to macromolecules with vibrational sum frequency spectroscopy (VSFS). Poly-(N-isopropylacrylamide) was adsorbed at the air/water interface for this purpose. It was found that the presence of salt in the subphase could induce the reorganization of water adjacent to the macromolecule and that the changes depended greatly on the specific identity and concentration of the salt employed. Ranked by their propensity to orient interfacial water molecules, sodium salts could be placed in the following order: NaSCN > NaClO4 > NaI > NaNO3 approximately NaBr > NaCl > pure water approximately NaF approximately Na2SO4. This ordering is a Hofmeister series. On the other hand, varying the identity of the cation exhibited virtually no effect. We also showed that the oscillator strength in the OH stretch region was linearly related to changes in the surface potential caused by anion adsorption. This fact allowed binding isotherms to be abstracted from the VSFS data. Such results offer direct evidence that interfacial water structure can be predominantly the consequence of macromolecule-ion interactions.     

Molecular Structure and Dynamics of Water at the Water–Air Interface Studied with Surface‐Specific Vibrational Spectroscopy

Water interfaces provide the platform for many important biological, chemical, and physical processes. The water–air interface is the most common and simple aqueous interface and serves as a model system for water at a hydrophobic surface. Unveiling the microscopic (<1 nm) structure and dynamics of interfacial water at the water–vapor interface is essential for understanding the processes occurring on the water surface. At the water interface the network of very strong intermolecular interactions, hydrogen‐bonds, is interrupted and the density of water is reduced. A central question regarding water at interfaces is the extent to which the structure and dynamics of water molecules are influenced by the interruption of the hydrogen‐bonded network and thus differ from those of bulk water. Herein, we discuss recent advances in the study of interfacial water at the water–air interface using laser‐based surface‐specific vibrational spectroscopy.     

Intrinsic Surface‐Drying Properties of Bioadhesive Proteins

Sessile marine mussels must “dry” underwater surfaces before adhering to them. Synthetic adhesives have yet to overcome this fundamental challenge. Previous studies of bioinspired adhesion have largely been performed under applied compressive forces, but such studies are poor predictors of the ability of an adhesive to spontaneously penetrate surface hydration layers. In a force‐free approach to measuring molecular‐level interaction through surface‐water diffusivity, different mussel foot proteins were found to have different abilities to evict hydration layers from surfaces—a necessary step for adsorption and adhesion. It was anticipated that DOPA would mediate dehydration owing to its efficacy in bioinspired wet adhesion. Instead, hydrophobic side chains were found to be a critical component for protein–surface intimacy. This direct measurement of interfacial water dynamics during force‐free adsorptive interactions at solid surfaces offers guidance for the engineering of wet adhesives and coatings.     

Local heterogeneous dynamics of water around lysozyme: a computer simulation study

Water present near the surface of a protein exhibits dynamic properties different from that of water in the pure bulk state. In this work, we have carried out atomistic molecular dynamics simulation of an aqueous solution of hen egg-white lysozyme. Attempts have been made to explore the correlation between the local heterogeneous mobility of water around the protein segments and the rigidity of the hydration layers with the microscopic dynamics of hydrogen bonds formed by water molecules with the protein residues. The kinetics of breaking and reformation of hydrogen bonds involving the surface water molecules have been calculated. It is found that the reformations of broken hydrogen bonds are more frequent for the hydration layers of those segments of the protein that are more rigid. The calculation of the low-frequency vibrational modes of hydration layer water molecules reveals that the protein influences the transverse and longitudinal degrees of freedom of water around it in a differential manner. These findings can be verified by appropriate experimental studies.     

Infrared spectra of SF6-.(H2O)n (n=1-3): incipient reaction and delayed onset of water network formation

We present data on the microsolvation of an extended charge distribution with SF(6)(-) as a model system. Infrared spectroscopy, aided by ab initio calculations, shows that the first two water molecules attach to the ion by a combination of single ionic H bonds, sharing one of the F atoms, and weak electrostatic interactions with other F atoms in the ion. No water-water bonds are formed at the dihydrate level, which is an unusual observation, given the strong propensity of water to form H-bonded networks. The onset of water networks occurs with the addition of the third water molecule. Moreover, the attachment of the first two water molecules considerably weakens the SF bond of the F atom involved in bonding to both ligands, indicating a possible mechanism for water-induced reactions.     

Hot spot occlusion from bulk water: a comprehensive study of the complex between the lysozyme HEL and the antibody FVD1.3

Alanine scanning of protein-protein interfaces has shown that there are some residues in the protein-protein interfaces, responsible for most of the binding free energy, which are called hot spots. Hot spots tend to exist in densely packed central clusters, and a hypothesis has been proposed that considers that inaccessibility to the solvent must be a necessary condition to define a residue as a binding hot spot. This O-ring hypothesis is mainly based on the analysis of the accessible surface area (ASA) of 23 static, crystallographic structures of protein complexes. It is known, however, that protein flexibility allows for temporary exposures of buried interfacial groups, and even though the ASA provides a general trend of the propensity for hydration, protein/solvent-specific interactions or hydrogen bonding cannot be considered here. Therefore, a microscopic level, atomistic picture of hot spot solvation is needed to support the O-ring hypothesis. In this study, we began by applying a computational alanine-scanning mutagenesis technique, which reproduces the experimental results and allows for decomposing the binding free energy difference in its different energetic factors. Subsequently, we calculated the radial distribution function and residence times of the water molecules near the hot/warm spots to study the importance of the water environment around those energetically important amino acid residues. This study shows that within a flexible, dynamic protein framework, the warm/hot spot residues are, indeed, kept sheltered from the bulk solvent during the whole simulation, which allows a better interacting microenvironment.     

A computer simulation study of water drying at the interface of protein chains

This study investigated the water drying (cavitation) in the interfacial region of two chains of a dimeric protein by nanosecond molecular dynamics simulations using explicit water representation. Separation-induced cavity of water was directly observed in the region. We evaluated the separation length scale of two chains on which the drying transition occurs, and the average number of water molecules that are expelled from the interfacial region during the transition. The obtained values can be rationalized by Kelvin equation for finite lateral size of confinement [K. Lum and A. Luzar, Phys. Rev. E 56, R6283 (1997)]. Also, we found that the drying transition is accompanied by an exponential reduction in the average hydrogen-bond number per interfacial water molecule. The results of this study may deepen the understanding of how hydrophobic interaction drives the assembly of protein chains.