Geometries of hydrogen bonds in water-ethanol mixtures from ab initio molecular dynamics simulations.

We outline a simple procedure to determine the geometry of hydrogen bonds between different molecular species in binary mixtures from ab initio molecular dynamics (AIMD) trajectories. Here we determine the geometry of the hydrogen bonds arising from intermolecular OH⋯O interactions between different H-bonded pairs, water-water, ethanol-ethanol and water-ethanol in water-alcohol mixtures at different compositions by plotting the intermolecular non-bonded OH⋯O and O⋯O distances, and the ∠HO⋯O (θ) angles for each of the possible pairs in the ensemble. Two regions separate out in each of the scatter-plots; the one with short OH⋯O and O⋯O intermolecular distances and almost linear ∠HO⋯O angles may be identified as the region where the intermolecular OH⋯O geometry would be favorable for hydrogen bonding. Using the different geometric criteria for each of the three possible H-bonded pairs we estimate the average number of water and ethanol molecules that are hydrogen bonded to a water molecule, and to an ethanol molecule, respectively, at different mole fractions of the mixture. We validate the results from values of the chemical shift of the two OH resonances (water and ethanol) in the proton NMR spectra of the mixtures at different concentrations as these values are known to be sensitive to the local chemical environment of the resonating nuclei.

Search for H-Bonded Motifs in Liquid Ethylene Glycol Using a Machine Learning Strategy.

Trajectories of atomic positions derived from ab initio molecular dynamics (AIMD) simulations of H-bonded liquids contain a wealth of information on dominant structural motifs and recurrent patterns of association. Extracting this information from a detailed search of the trajectories over multiple time frames is, however, a daunting exercise. Here, we use a machine learning strategy based on the neural inspired approach of the self-organizing maps (SOM), a type of artificial neural network that uses unsupervised competitive learning, to analyze the AIMD trajectories of liquid ethylene glycol (EG). The objective was to find whether there are H-bonded fragments, of two or more H-bonded EG molecules, that are recurrent in the liquid and to identify them. The SOM represents a set of high-dimensional data mapped onto a two-dimensional, grid of neurons or nodes, while preserving the topological properties of the input space. We show here that clustering of the fragments by SOM in terms of the molecular conformation of the individual EG molecules of the fragment and their H-bond connectivity pattern facilitates the search for H-bonded motifs. Using this approach, we are able to identify a H-bonded cyclic dimer and a bifurcated H-bonded structure as recurring motifs that appear in the longer H-bonded fragments present in liquid EG.

Ethylene Glycol Dihedral Angle Dynamics: Relating Molecular Conformation to the Raman Spectrum of the Liquid.

The central OCCO dihedral of the ethylene glycol (EG) molecule exists in both trans and gauche geometries in the liquid. The presence of the trans conformer had been inferred from the Raman spectra by interpreting the occurrence of bands in the Raman spectra that were absent in the infrared as evidence for inversion symmetry and hence the trans conformation. The validity of this interpretation is questionable as not all conformations of the EG molecule, where the OCCO dihedral is trans, possess inversion symmetry. We show here that the resolution of the apparent paradox is intimately related to the conformation and dynamics of not just the central OCCO but also the two terminal dihedrals of the EG molecule. Using ab initio molecular dynamics simulations, we show that changes in conformation associated with the three dihedral angles are not infrequent; a number of events are observed during the course of the simulations allowing for a straightforward estimate of the kinetic parameters. More importantly, these parameters allow us to address and resolve the problems in interpreting the Raman spectra and consequently relate molecular conformation to the Raman spectrum of the EG molecule in the liquid state.

Molecular Conformation and Hydrogen Bond Formation in Liquid Ethylene Glycol.

The ethylene glycol (EG) molecule, HOCH2CH2OH, adopts a conformation where the central OCCO dihedral is exclusively gauche in the gaseous and crystalline states, but in the liquid state, for close to 20% of the molecules, the central OCCO adopts the energetically unfavorable trans conformation. Here we report calculations, based on ab initio molecular dynamics simulations, on the thermodynamics associated with hydrogen bond formation in the liquid state of EG between donor-acceptor pairs with different molecular conformations. We establish an operational, geometric definition of hydrogen bonds in liquid EG from an analysis of the proton NMR data and show that the key feature, irrespective of the conformation, is marked directionality with almost linear ∠HO···O angles. The free energy for hydrogen bond formation estimated as the potential of mean force for the reversible work associated with the passage from a hypothetical state where hydrogen bonding is absent and donor-acceptor pairs are randomly oriented to the hydrogen-bonded state where the pairs are oriented showed comparable magnitudes irrespective of the molecular conformation of either the donor or acceptor. The results suggest that the presence of the trans conformer in liquid EG would require an understanding of its role in the extended hydrogen-bonded network of the liquid.

Hydrogen Bonding in the Liquid State of Linear Alcohols: Molecular Dynamics and Thermodynamics.

Linear monohydroxy alcohols are strongly hydrogen-bonded liquids that are considered to be homologues of water. Here, we report ab initio molecular dynamics simulations of the liquid alcohols, methanol to pentanol, and from the combined radial-angular probability distribution of the intermolecular O···O distances and HO···O angles determine the geometrical parameters that define the hydrogen bonds in these systems. The key feature of hydrogen bonds in the liquid alcohols, irrespective of the size of the alkyl group, is the strong orientation dependence with the donor-acceptor HO···O angle being close to zero, similar to that observed in liquid water. Hydrogen bond formation is consequently considered to be the passage from a state where donor-acceptor pairs show no preferred orientation to one where they are almost linear. The potential of mean force, the reversible work associated with this process, is computed from the pair probability density distributions obtained from the simulations and that for a hypothetical state where donor-acceptor pairs are randomly oriented. We find that the magnitude of the free energy for hydrogen bond formation is maximum for ethanol and show that this arises from a larger electrostatic contribution to hydrogen bond formation in ethanol as compared to the other alcohols.

Geometry of OHO interactions in the liquid state of linear alcohols from ab initio molecular dynamics simulations.

Monohydroxy alcohols are strongly associating liquids with the hydrogen bonding associated with the presence of the hydroxyl group having a significant influence on properties. Here we determine the geometry of the hydrogen bond in linear alcohols, methanol to pentanol, arising from intermolecular OHO interactions, from ab initio molecular dynamics trajectories by plotting the intermolecular non-bonded OHO and OO distances, and the ∠HOO (θ) angles for every possible pair of alcohol molecules in the ensemble. Two regions separate out in the scatter-plot; the one with short OHO and OO intermolecular distances and almost linear ∠HOO angles may be identified as the region where the intermolecular OHO geometry would be favorable for hydrogen bonding. We find that the geometry of the hydrogen bond arising from intermolecular OHO interactions in liquid alcohols shows little change with an increase in size of the alkyl group. This observation is in direct contrast to that in the crystalline state where marked departures in the HOO angle from linearity are seen with an increase in the alkyl chain on going from methanol to pentanol.

Geometry of Hydrogen Bonds in Liquid Ethanol Probed by Proton NMR Experiments.

Quantitative information of hydrogen bonding is crucial to our understanding of the structure and properties of associated liquids. Here, we outline a simple procedure to establish the geometry of hydrogen bonds in liquid ethanol using proton nuclear magnetic resonance (NMR) spectroscopy. We do so by exploiting differences in proton chemical shift values, that originate from the secondary isotope effect, to distinguish the methyl and hydroxyl group protons of CH3CH2OH from those of the deuterated CH3CD2OH in the 1H NMR spectra of mixtures of the two. This has allowed us to measure the ratios of the inter- to intramolecular distances between methyl to hydroxyl and methylene to hydroxyl protons using one-dimensional (1D) transient nuclear Overhauser effect NMR measurements as a molecular ruler. We model liquid ethanol by ab initio molecular dynamics simulations and identify all possible pairs of ethanol molecules in the ensemble that satisfied the NMR-determined inter- to intramolecular distance ratio criteria. For these pairs of ethanol molecules, we find the mean value of the hydrogen bonding distance, rOH···O, to be 1.93 Å and the value of the ∠HO···O angle to be 13.3°, thus effectively establishing the geometry of hydrogen bonds in liquid ethanol. An interesting observation that emerges from our study is the linear correlation between hydrogen bond distances and angles in ethanol.

The multiple dissociation constants of glutathione disulfide: interpreting experimental pH-titration curves with ab initio MD simulations.

The hexapeptide glutathione disulfide (GSSG) has six ionizable groups with six associated dissociation constants. The experimentally measured pH-titration curve, however, does not exhibit the six corresponding equivalence points and bears little resemblance to standard textbook examples of acid-base pH-titration curves. The curve highlights the difficulties in determining multiple pKa values of polyprotic acids - typically proteins and peptides - from experiment. The six pKa values of GSSG can, however, be estimated using Car-Parrinello molecular dynamics (CPMD) simulations in conjunction with metadynamics sampling of the underlying free energy landscape of the dissociation reactions. Ab initio MD simulations were performed on a GSSG molecule solvated by 200 water molecules. Using the estimated pKa values the theoretical titration curve was calculated and found to be in good agreement with experiment. The results clearly highlight how dissociation constants estimated from ab initio MD simulations can facilitate the interpretation of the pH-titration curves of complex chemical and biological systems.

Distinguishing Intra- and Intermolecular Interactions in Liquid 1,2-Ethanediol by 1H NMR and Ab Initio Molecular Dynamics.

The central OCCO backbone of the 1,2-ethanediol molecule adopts the gauche conformer in the gaseous and crystalline states but exists in conformational equilibrium between gauche and trans in the liquid; an observation that has been attributed to the competition between intra- and intermolecular interactions. Here, we show that the nuclear Overhauser effect (NOE) has the ability to distinguish inter- from intramolecular interactions in liquid 1,2-ethanediol. We do so by exploiting the secondary isotope effect to distinguish the hydroxyl protons of HOCH2CH2OH and the deuterated HOCD2CD2OH in the 1H NMR spectra of mixtures of the two and, in conjunction with ab initio MD simulations, show how the interplay between inter- and intramolecular interactions gives rise to the conformational isomers in the liquid state of 1,2-ethanediol.

Conformation of Ethylene Glycol in the Liquid State: Intra- versus Intermolecular Interactions.

Ethylene glycol is a typical rotor molecule with the three dihedral angles that allow for a number of possible conformers. The geometry of the molecule in the liquid state brings into sharp focus the competition between intra- and inter-molecular interactions in deciding conformation. Here, we report a conformational analysis of ethylene glycol in the liquid state from ab initio molecular dynamics simulations. Our results highlight the importance of intermolecular hydrogen bonding over intramolecular interactions in the liquid, with the central OCCO linkage adopting both gauche and trans geometries in contrast to the gas phase, wherein only the gauche has been reported. The influence of intermolecular interactions on the conformation of the terminal CCOH moieties is even more striking, with certain regions of conformational space, wherein the ethylene glycol molecule cannot participate with its full complement of intermolecular hydrogen bonds, excluded. The results are in agreement with Raman and NMR spectroscopic studies of liquid ethylene glycol, but at the same time they are able to provide new insights into how intermolecular interactions favor certain conformations while excluding others.

Liquid-Phase Exfoliation of MoS2 Nanosheets: The Critical Role of Trace Water.

Sonication-assisted liquid-phase exfoliation of layered materials in suitable organic solvents offers a simple scalable route for the production of 2D nanomaterials. N-methyl-2-pyrrolidone (NMP) is one of the most efficient solvents for liquid-phase exfoliation of a variety of layered solids, including MoS2. We show here that trace water present in NMP is crucial for the stability of MoS2 nanosheets in NMP dispersions. In the absence of water, the sheets are fragmented and chemically unstable. Using solution NMR techniques, 2D nuclear Overhauser effect and spin-lattice relaxation measurements, supported by classical molecular dynamics simulations, we are able to establish the role of water molecules in stabilizing the dispersion. We show that water molecules are localized at the Mo-terminated edges of the MoS2 sheets, thereby inhibiting chemical erosion of the sheets, and they also exhibit enhanced interactions with the solvent NMP molecules, leading to the stability of the dispersion.

Ab Initio MD Simulations of the Brønsted Acidity of Glutathione in Aqueous Solutions: Predicting pKa Shifts of the Cysteine Residue.

The tripeptide glutathione (GSH) is one of the most abundant peptides and the major repository for nonprotein sulfur in both animal and plant cells. It plays a critical role in intracellular oxidative stress management by the reversible formation of glutathione disulfide with the thiol-disulfide pair acting as a redox buffer. The state of charge of the ionizable groups of GSH can influence the redox couple, and hence the pKa value of the cysteine residue of GSH is critical to its functioning. Here we report ab initio Car-Parrinello molecular dynamics simulations of glutathione solvated by 200 water molecules, all of which are considered in the simulation. We show that the free-energy landscape for the protonation-deprotonation reaction of the cysteine residue of GSH computed using metadynamics sampling provides accurate estimates of the pKa and correctly predicts the shift in the dissociation constant values as compared with the isolated cysteine amino acid.

Ab Initio Molecular Dynamics Simulations of Amino Acids in Aqueous Solutions: Estimating pKa Values from Metadynamics Sampling.

Changes in the protonation and deprotonation of amino acid residues in proteins play a key role in many biological processes and pathways. Here, we report calculations of the free-energy profile for the protonation-deprotonation reaction of the 20 canonical α amino acids in aqueous solutions using ab initio Car-Parrinello molecular dynamics simulations coupled with metadynamics sampling. We show here that the calculated change in free energy of the dissociation reaction provides estimates of the multiple pKa values of the amino acids that are in good agreement with experiment. We use the bond-length-dependent number of the protons coordinated to the hydroxyl oxygen of the carboxylic and the amine groups as the collective variables to explore the free-energy profiles of the Bronsted acid-base chemistry of amino acids in aqueous solutions. We ensure that the amino acid undergoing dissociation is solvated by at least three hydrations shells with all water molecules included in the simulations. The method works equally well for amino acids with neutral, acidic and basic side chains and provides estimates of the multiple pKa values with a mean relative error, with respect to experimental results, of 0.2 pKa units.

Water Dispersible, Positively and Negatively Charged MoS2 Nanosheets: Surface Chemistry and the Role of Surfactant Binding.

Stable aqueous dispersions of atomically thin layered MoS2 nanosheets have been obtained by sonication in the presence of ionic surfactants. The dispersions are stabilized by electrostatic repulsion between the sheets, and we show that the sign of the charge on the MoS2 nanosheets, either positive or negative, can be can be controlled by the choice of the surfactant. Using techniques from solution NMR, we show that the surfactant chains are weakly bound to the MoS2 sheets and undergo rapid exchange with free surfactant chains present in the dispersion. In situ nuclear Overhauser effect spectroscopic measurements provide direct evidence that the surfactant chains lie flat, arranged randomly on the basal plane of the MoS2 nanosheets with their charged headgroup exposed. These results provide a chemical perspective for understanding the stability of these inorganic nanosheets in aqueous dispersions and the origin of the charge on the sheets.

Estimating successive pKa values of polyprotic acids from ab initio molecular dynamics using metadynamics: the dissociation of phthalic acid and its isomers.

Estimation of the dissociation constant, or pKa, of weak acids continues to be a central goal in theoretical chemistry. Here we show that ab initio Car-Parrinello molecular dynamics simulations in conjunction with metadynamics calculations of the free energy profile of the dissociation reaction can provide reasonable estimates of the successive pKa values of polyprotic acids. We use the distance-dependent coordination number of the protons bound to the hydroxyl oxygen of the carboxylic group as the collective variable to explore the free energy profile of the dissociation process. Water molecules, sufficient to complete three hydration shells surrounding the acid molecule, were included explicitly in the computation procedure. Two distinct minima corresponding to the dissociated and un-dissociated states of the acid are observed and the difference in their free energy values provides the estimate for pKa, the acid dissociation constant. We show that the method predicts the pKa value of benzoic acid in good agreement with experiment and then show using phthalic acid (benzene dicarboxylic acid) as a test system that both the first and second pKa values as well, as the subtle difference in their values for different isomers can be predicted in reasonable agreement with experimental data.

Dissociation constants of weak acids from ab initio molecular dynamics using metadynamics: influence of the inductive effect and hydrogen bonding on pKa values.

The theoretical estimation of the dissociation constant, or pKa, of weak acids continues to be a challenging field. Here, we show that ab initio Car-Parrinello molecular dynamics simulations in conjunction with metadynamics calculations of the free-energy profile of the dissociation reaction provide reasonable estimates of the pKa value. Water molecules, sufficient to complete the three hydration shells surrounding the acid molecule, were included explicitly in the computation procedure. The free-energy profiles exhibit two distinct minima corresponding to the dissociated and neutral states of the acid, and the difference in their values provides the estimate for pKa. We show for a series of organic acids that CPMD simulations in conjunction with metadynamics can provide reasonable estimates of pKa values. The acids investigated were aliphatic carboxylic acids, chlorine-substituted carboxylic acids, cis- and trans-butenedioic acid, and the isomers of hydroxybenzoic acid. These systems were chosen to highlight that the procedure could correctly account for the influence of the inductive effect as well as hydrogen bonding on pKa values of weak organic acids. In both situations, the CPMD metadynamics procedure faithfully reproduces the experimentally observed trend and the magnitudes of the pKa values.

Spectral Migration of Fluorescence in Graphene Oxide Aqueous Dispersions: Evidence for Excited-State Proton Transfer.

Aqueous dispersions of graphene oxide (GO) exhibit strong pH-dependent fluorescence in the visible that originates, in part, from the oxygenated functionalities present. Here we examine the spectral migration on nanosecond time-scales of the pH dependent features in the fluorescence spectra. We show, from time-resolved emission spectra (TRES) constructed from the wavelength dependent fluorescence decay curves, that the migration is associated with excited state proton transfer. Both 'intramolecular' and 'intermolecular' transfer involving the quasi-molecular oxygenated aromatic fragments are observed. As a prerequisite to the time-resolved measurements, we have correlated the changes in the steady state fluorescence spectra with the sequence of dissociation events that occur in GO dispersions at different values of pH.

Communication: Benzene dimer--the free energy landscape.

Establishing the relative orientation of the two benzene molecules in the dimer has remained an enigmatic challenge. Consensus has narrowed the choice of structures to either a T-shape, that may be tilted, or a parallel displaced arrangement, but the relatively small energy differences makes identifying the global minimum difficult. Here we report an ab initio Car-Parrinello Molecular Dynamics based metadynamics computation of the free-energy landscape of the benzene dimer. Our calculations show that although competing structures may be isoenergetic, free energy always favors a tilted T-shape geometry at all temperatures where the bound benzene dimer exist.

Engineering new layered solids from exfoliated inorganics: a periodically alternating hydrotalcite-montmorillonite layered hybrid.

Two-dimensional (2D) nanosheets obtained by exfoliating inorganic layered crystals have emerged as a new class of materials with unique attributes. One of the critical challenges is to develop robust and versatile methods for creating new nanostructures from these 2D-nanosheets. Here we report the delamination of layered materials that belonging to two different classes--the cationic clay, montmorillonite, and the anionic clay, hydrotalcite--by intercalation of appropriate ionic surfactants followed by dispersion in a non-polar solvent. The solids are delaminated to single layers of atomic thickness with the ionic surfactants remaining tethered to the inorganic and consequently the nanosheets are electrically neutral. We then show that when dispersions of the two solids are mixed the exfoliated sheets self-assemble as a new layered solid with periodically alternating hydrotalcite and montmorillonite layers. The procedure outlined here is easily extended to other layered solids for creating new superstructures from 2D-nanosheets by self-assembly.