Spectroscopic evidence for a gold-coloured metallic water solution.

Insulating materials can in principle be made metallic by applying pressure. In the case of pure water, this is estimated1 to require a pressure of 48 megabar, which is beyond current experimental capabilities and may only exist in the interior of large planets or stars2-4. Indeed, recent estimates and experiments indicate that water at pressures accessible in the laboratory will at best be superionic with high protonic conductivity5, but not metallic with conductive electrons1. Here we show that a metallic water solution can be prepared by massive doping with electrons upon reacting water with alkali metals. Although analogous metallic solutions of liquid ammonia with high concentrations of solvated electrons have long been known and characterized6-9, the explosive interaction between alkali metals and water10,11 has so far only permitted the preparation of aqueous solutions with low, submetallic electron concentrations12-14. We found that the explosive behaviour of the water-alkali metal reaction can be suppressed by adsorbing water vapour at a low pressure of about 10-4 millibar onto liquid sodium-potassium alloy drops ejected into a vacuum chamber. This set-up leads to the formation of a transient gold-coloured layer of a metallic water solution covering the metal alloy drops. The metallic character of this layer, doped with around 5 × 1021 electrons per cubic centimetre, is confirmed using optical reflection and synchrotron X-ray photoelectron spectroscopies.

Stability and Reactivity of Aromatic Radical Anions in Solution with Relevance to Birch Reduction.

We investigate the electronic structure of aromatic radical anions in the solution phase employing a combination of liquid-jet (LJ) photoelectron (PE) spectroscopy measurements and electronic structure calculations. By using recently developed protocols, we accurately determine the vertical ionization energies of valence electrons of both the solvent and the solute molecules. In particular, we first characterize the pure solvent of tetrahydrofuran (THF) by LJ-PE measurements in conjunction with ab initio molecular dynamics simulations and G0W0 calculations. Next, we determine the electronic structure of neutral naphthalene (Np) and benzophenone (Bp) as well as their radical anion counterparts Np- and Bp- in THF. Wherever feasible, we performed orbital assignments of the measured PE features of the aromatic radical anions, with comparisons to UV-vis absorption spectra of the corresponding neutral molecules being instrumental in rationalizing the assignments. Analysis of the electronic structure differences between the neutral species and their anionic counterparts provides understanding of the primarily electrostatic stabilization of the radical anions in solution. Finally, we obtain a very good agreement of the reduction potentials extracted from the present LJ-PES measurements of Np- and Bp- in THF with previous electrochemical data from cyclic voltammetry measurements. In this context, we discuss how the choice of solvent holds significant implications for optimizing conditions for the Birch reduction process, wherein aromatic radical anions play crucial roles as reactive intermediates.

Hydration of biologically relevant tetramethylammonium cation by neutron scattering and molecular dynamics.

Neutron scattering and molecular dynamics studies were performed on a concentrated aqueous tetramethylammonium (TMA) chloride solution to gain insight into the hydration shell structure of TMA, which is relevant for understanding its behavior in biological contexts of, e.g., properties of phospholipid membrane headgroups or interactions between DNA and histones. Specifically, neutron diffraction with isotopic substitution experiments were performed on TMA and water hydrogens to extract the specific correlation between hydrogens in TMA (HTMA) and hydrogens in water (HW). Classical molecular dynamics simulations were performed to help interpret the experimental neutron scattering data. Comparison of the hydration structure and simulated neutron signals obtained with various force field flavors (e.g. overall charge, charge distribution, polarity of the CH bonds and geometry) allowed us to gain insight into how sensitive the TMA hydration structure is to such changes and how much the neutron signal can capture them. We show that certain aspects of the hydration, such as the correlation of the hydrogen on TMA to hydrogen on water, showed little dependence on the force field. In contrast, other correlations, such as the ion-ion interactions, showed more marked changes. Strikingly, the neutron scattering signal cannot discriminate between different hydration patterns. Finally, ab initio molecular dynamics was used to examine the three-dimensional hydration structure and thus to benchmark force field simulations. Overall, while neutron scattering has been previously successfully used to improve force fields, in the particular case of TMA we show that it has only limited value to fully determine the hydration structure, with other techniques such as ab initio MD being of a significant help.

Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.

Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.

Valence and Core-Level X-ray Photoelectron Spectroscopy of a Liquid Ammonia Microjet.

Photoelectron spectroscopy of microjets expanded into vacuum allows access to orbital energies for solute or solvent molecules in the liquid phase. Microjets of water, acetonitrile and alcohols have previously been studied; however, it has been unclear whether jets of low temperature molecular solvents could be realized. Here we demonstrate a stable 20 µm jet of liquid ammonia (-60 °C) in a vacuum, which we use to record both valence and core-level band photoelectron spectra using soft X-ray synchrotron radiation. Significant shifts from isolated ammonia in the gas-phase are observed, as is the liquid-phase photoelectron angular anisotropy. Comparisons with spectra of ammonia in clusters and the solid phase, as well as spectra for water in various phases potentially reveal how hydrogen bonding is reflected in the condensed phase electronic structure.

Arginine "Magic": Guanidinium Like-Charge Ion Pairing from Aqueous Salts to Cell Penetrating Peptides.

It is a textbook knowledge that charges of the same polarity repel each other. For two monovalent ions in the gas phase at a close contact this repulsive interaction amounts to hundreds of kilojoules per mole. In aqueous solutions, however, this Coulomb repulsion is strongly attenuated by a factor equal to the dielectric constant of the medium. The residual repulsion, which now amounts only to units of kilojoules per mole, may be in principle offset by attractive interactions. Probably the smallest cationic pair, where a combination of dispersion and cavitation forces overwhelms the Coulomb repulsion, consists of two guanidinium ions in water. Indeed, by a combination of molecular dynamics with electronic structure calculations and electrophoretic, as well as spectroscopic, experiments, we have demonstrated that aqueous guanidinium cations form (weakly) thermodynamically stable like-charge ion pairs. The importance of pairing of guanidinium cations in aqueous solutions goes beyond a mere physical curiosity, since it has significant biochemical implications. Guanidinium chloride is known to be an efficient and flexible protein denaturant. This is due to the ability of the orientationally amphiphilic guanidinium cations to disrupt various secondary structural motifs of proteins by pairing promiscuously with both hydrophobic and hydrophilic groups, including guanidinium-containing side chains of arginines. The fact that the cationic guanidinium moiety forms the dominant part of the arginine side chain implies that the like-charge ion pairing may also play a role for interactions between peptides and proteins. Indeed, arginine-arginine pairing has been frequently found in structural protein databases. In particular, when strengthened by a presence of negatively charged glutamate, aspartate, or C-terminal carboxylic groups, this binding motif helps to stabilize peptide or protein dimers and is also found in or near active sites of several enzymes. The like-charge pairing of the guanidinium side-chain groups may also hold the key to the understanding of the arginine "magic", that is, the extraordinary ability of arginine-rich polypeptides to passively penetrate across cellular membranes. Unlike polylysines, which are also highly cationic but lack the ease in crossing membranes, polyarginines do not exhibit mutual repulsion. Instead, they accumulate at the membrane, weaken it, and might eventually cross in a concerted, "train-like" manner. This behavior of arginine-rich cell penetrating peptides can be exploited when devising smart strategies how to deliver in a targeted way molecular cargos into the cell.

Calcium ions in aqueous solutions: Accurate force field description aided by ab initio molecular dynamics and neutron scattering.

We present a combination of force field and ab initio molecular dynamics simulations together with neutron scattering experiments with isotopic substitution that aim at characterizing ion hydration and pairing in aqueous calcium chloride and formate/acetate solutions. Benchmarking against neutron scattering data on concentrated solutions together with ion pairing free energy profiles from ab initio molecular dynamics allows us to develop an accurate calcium force field which accounts in a mean-field way for electronic polarization effects via charge rescaling. This refined calcium parameterization is directly usable for standard molecular dynamics simulations of processes involving this key biological signaling ion.

Anomalous surface behavior of hydrated guanidinium ions due to ion pairing.

Surface affinity of aqueous guanidinium chloride (GdmCl) is compared to that of aqueous tetrapropylammonium chloride (TPACl) upon addition of sodium chloride (NaCl) or disodium sulfate (Na2SO4). The experimental results have been acquired using the surface sensitive technique X-ray photoelectron spectroscopy on a liquid jet. Molecular dynamics simulations have been used to produce radial distribution functions and surface density plots. The surface affinities of both TPA+ and Gdm+ increase upon adding NaCl to the solution. With the addition of Na2SO4, the surface affinity of TPA+ increases, while that of Gdm+ decreases. From the results of MD simulations it is seen that Gdm+ and SO42- ions form pairs. This finding can be used to explain the decreased surface affinity of Gdm+ when co-dissolved with SO42- ions. Since SO42- ions avoid the surface due to the double charge and strong water interaction, the Gdm+-SO42- ion pair resides deeper in the solutions' bulk than the Gdm+ ions. Since TPA+ does not form ion pairs with SO42-, the TPA+ ions are instead enriched at the surface.

A Non-Exploding Alkali Metal Drop on Water: From Blue Solvated Electrons to Bursting Molten Hydroxide.

Alkali metals in water are always at the brink of explosion. Herein, we show that this vigorous reaction can be kept in a non-exploding regime, revealing a fascinating richness of hitherto unexplored chemical processes. A combination of high-speed camera imaging and visible/near-infrared/infrared spectroscopy allowed us to catch and characterize the system at each stage of the reaction. After gently placing a drop of a sodium/potassium alloy on water under an inert atmosphere, the production of solvated electrons became so strong that their characteristic blue color could be observed with the naked eye. The exoergic reaction leading to the formation of hydrogen and hydroxide eventually heated the alkali metal drop such that it became glowing red, and part of the metal evaporated. As a result of the reaction, a perfectly transparent drop consisting of molten hydroxide was temporarily stabilized on water through the Leidenfrost effect, bursting spectacularly after it had cooled sufficiently.

The conformation of a ribose derivative in aqueous solution: a neutron-scattering and molecular dynamics study.

The structure of aqueous solutions of methyl ß-D-ribofuranoside was investigated by coupling molecular dynamics (MD) simulations and neutron scattering measurements with isotopic substitution. Using a sample of the sugar isotopically-labeled at a single unique position, neutron scattering structure factors and radial distribution functions can be compared with MD simulations constrained to different conformations to determine which conformer best fits the experimental results. Three different simulations were performed with the methyl ether group of the sugar unconstrained and constrained in each of its staggered orientations. The results of the unconstrained simulation showed that the methyl ester group occupied predominantly the 300° position, which is in agreement with the diffraction experimental results. This result suggests that the molecular mechanics force field used in the simulation adequately describes the conformation of the 1-methyl ether group in the methyl ß-D-ribofuranoside.

Ion pairing in aqueous lithium salt solutions with monovalent and divalent counter-anions.

Molecular dynamics simulations of concentrated aqueous solutions of LiCl and Li2SO4 were conducted in order to provide molecular insight into recent neutron scattering data. The structures predicted from the molecular dynamics simulations using standard nonpolarizable force fields provided a very poor fit to the experiment; therefore, refinement was needed. The electronic polarizability of the medium was effectively accounted for by implementing the electronic continuum correction, which practically means rescaling the ionic charges. Consistent with previous studies, we found that this approach in each case provided a significantly improved fit to the experimental data, which was further enhanced by slightly adjusting the radius of the lithium ion. The polarization effect was particularly pronounced in the Li2SO4 solution where the ions in the nonpolarizable simulations tended to cluster unphysically. With the above alterations, the employed force field displayed an excellent fit to the neutron scattering data and provided a useful interpretative framework for the experimental measurements. At the same time, the present study underlines the importance of solvent polarization effects in hydration of ions with high charge density.

Common Cations Are Not Polarizable: Effects of Dispersion Correction on Hydration Structures from Ab Initio Molecular Dynamics.

We employed density functional theory-based ab initio molecular dynamics simulations to examine the hydration structure of several common alkali and alkali earth metal cations. We found that the commonly used atom pairwise dispersion correction scheme D3, which assigns dispersion coefficients based on the neutral form of the atom rather than its actual oxidation state, leads to inaccuracies in the hydration structures of these cations. We evaluated this effect for lithium, sodium, potassium, and calcium and found that the inaccuracies are particularly pronounced for sodium and potassium compared to the experiment. To remedy this issue, we propose disabling the D3 correction specifically for all cation-including pairs, which leads to a much better agreement with experimental data.

Photoelectron Spectroscopy of Benzene in the Liquid Phase and Dissolved in Liquid Ammonia.

We report valence band photoelectron spectroscopy measurements of gas-phase and liquid-phase benzene as well as those of benzene dissolved in liquid ammonia, complemented by electronic structure calculations. The origins of the sizable gas-to-liquid-phase shifts in electron binding energies deduced from the benzene valence band spectral features are quantitatively characterized in terms of the Born-Haber solvation model. This model also allows to rationalize the observation of almost identical shifts in liquid ammonia and benzene despite the fact that the former solvent is polar while the latter is not. For neutral solutes like benzene, it is the electronic polarization response determined by the high frequency dielectric constant of the solvent, which is practically the same in the two liquids, that primarily determines the observed gas-to-liquid shifts.

Complex ion effects on polypeptide conformational stability: chloride and sulfate salts of guanidinium and tetrapropylammonium.

The effects of chloride and sulfate salts of tetrapropylammonium (TPA(+)) and guanidinium (Gdm(+)) on the conformational stabilities of tryptophan zipper (trpzip) and α-helical (alahel) peptides were measured by circular dichroism spectroscopy. Like Gdm(+), TPA(+) interacts with the planar tryptophan indole group, perturbing the conformational stability of trpzip peptides. TPA(+) effects are largely unaffected by sulfate, indicating an absence of the heteroion pairing that is observed in concentrated Gdm(2)SO(4) solutions. TPA(+) stabilizes helical conformations in alahel peptides, indicating exclusion from the peptide bond. The observations are broadly consistent with predictions of molecular dynamics simulations [Mason, P. E.; et al. J. Phys. Chem. B2009, 113, 3227-3234], indicating that the effects of complex ions on proteins are increasingly predictable in terms of ion hydration, complementary interactions with specific protein groups, and ion-pairing contributions.

Topological versus chemical ordering in network glasses at intermediate and extended length scales.

Atomic ordering in network glasses on length scales longer than nearest-neighbour length scales has long been a source of controversy. Detailed experimental information is therefore necessary to understand both the network properties and the fundamentals of glass formation. Here we address the problem by investigating topological and chemical ordering in structurally disordered AX2 systems by applying the method of isotopic substitution in neutron diffraction to glassy ZnCl2. This system may be regarded as a prototypical ionic network forming glass, provided that ion polarization effects are taken into account, and has thus been the focus of much attention. By experiment, we show that both the topological and chemical ordering are described by two length scales at distances greater than nearest-neighbour length scales. One of these is associated with the intermediate range, as manifested by the appearance in the measured diffraction patterns of a first sharp diffraction peak at 1.09(3) A(-1); the other is associated with an extended range, which shows ordering in the glass out to 62(4) A. We also find that these general features are characteristic of glassy GeSe2, a prototypical covalently bonded network material. The results therefore offer structural insight into those length scales that determine many important aspects of supercooled liquid and glass phenomenology.

Resolving the Equal Number Density Puzzle: Molecular Picture from Simulations of LiCl(aq) and NaCl(aq).

The change in number densities of aqueous solutions of alkali chlorides should be qualitatively predictable. Typically, as cations get larger, the number density of the solution decreases. However, aqueous solutions of lithium and sodium chloride exhibit at ambient conditions practically identical number densities at equal molalities despite different ionic sizes. Here, we provide an atomistic interpretation of this experimentally observed anomalous behavior using molecular dynamics simulations. The obtained results show that the rigidity of the Li+ first and second solvation shells and the associated compromised hydrogen bonding result in practically equal average water densities in the local hydration regions for Li+ and Na+ despite different sizes of the cations. In addition, in more distant regions from the cations, the water densities of these two solutions also coincide. These findings thus provide an atomistic interpretation for matching number densities of LiCl and NaCl solutions. In contrast, the number density differences between NaCl and KCl solutions as well as between LiCl and KCl solutions behave in a regular fashion with lower number densities of solutions observed for larger cations.

Sweet taste of heavy water.

Hydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.

Deeply cooled and temperature controlled microjets: Liquid ammonia solutions released into vacuum for analysis by photoelectron spectroscopy.

A versatile, temperature controlled apparatus is presented, which generates deeply cooled liquid microjets of condensed gases, expelling them via a small aperture into vacuum for use in photoelectron spectroscopy (PES). The functionality of the design is demonstrated by temperature- and concentration-dependent PES measurements of liquid ammonia and solutions of KI and NH4I in liquid ammonia. The experimental setup is not limited to the usage of liquid ammonia solutions solely.

Photoelectron spectra of alkali metal-ammonia microjets: From blue electrolyte to bronze metal.

Experimental studies of the electronic structure of excess electrons in liquids-archetypal quantum solutes-have been largely restricted to very dilute electron concentrations. We overcame this limitation by applying soft x-ray photoelectron spectroscopy to characterize excess electrons originating from steadily increasing amounts of alkali metals dissolved in refrigerated liquid ammonia microjets. As concentration rises, a narrow peak at ~2 electron volts, corresponding to vertical photodetachment of localized solvated electrons and dielectrons, transforms continuously into a band with a sharp Fermi edge accompanied by a plasmon peak, characteristic of delocalized metallic electrons. Through our experimental approach combined with ab initio calculations of localized electrons and dielectrons, we obtain a clear picture of the energetics and density of states of the ammoniated electrons over the gradual transition from dilute blue electrolytes to concentrated bronze metallic solutions.

Preferential interactions of guanidinum ions with aromatic groups over aliphatic groups.

Small angle neutron scattering (SANS) and molecular dynamics (MD) simulations were used to characterize the long-range structuring (aggregation) of aqueous solutions of isopropanol (IPA) and pyridine and the effect on structuring of guanidinium chloride (GdmCl). These solutes serve as highly soluble analogs of the nonpolar aliphatic (IPA) and aromatic (pyridine) side chains of proteins. SANS data showed that isopropanol and pyridine both form clusters in water resulting from interaction between nonpolar groups of the solutes, with pyridine aggregation producing longer-range structuring than isopropanol in 3 m solutions. Addition of GdmCl at 3 m concentration considerably reduced pyridine aggregation but had no effect on isopropanol aggregation. MD simulations of these solutions support the conclusion that long-range structuring involves hydrophobic solute interactions and that Gdm(+) interacts with the planar pyridine group to suppress pyridine-pyridine interactions in solution. Hydrophobic interactions involving the aliphatic groups of isopropanol were unaffected by GdmCl, indicating that the planar and weakly hydrated Gdm(+) cation cannot make productive interactions with the highly curved or "lumpy" aliphatic groups of this solute. These observations support the conclusion that the effects of Gdm(+) ions on protein-stabilizing interactions involving aromatic amino acid side chains make significant contributions to the denaturant activity of GdmCl, whereas interactions with the "lumpy" aliphatic side chains are likely to be less important.