Adjacent Water Molecules Research Articles

Water-Soluble Squaramide Dihydrates: N-Methylation Modulates the Occurrence of One- and Two-Dimensional Water Clusters through Hydrogen Bonding and Dipolar Interactions

Water confined in molecular size domains is distinct to bulk water. The altered interactions between adjacent water molecules, and between water molecules and molecular wall components of the confinement system, determine aspects of important phenomena in material science, biology, and nanotechnology. The structural determination of confined water, however, has proven to be challenging. Here, we describe the crystal structures of three related squaramides 1–3 whose molecular structures are modulated by the gradual incorporation of N-methyl groups to the squaramide moiety. The three squaramides differ in their hydrogen bonding capabilities due to the different degree of N-methylation of each one. Thus, while 1·2H2O forms narrow tapes of water molecules, the monomethylated squaramide 2·2H2O produces two-dimensional water layers, and the dimethylated squaramide 3·2H2O develops polymeric one-dimensional water chains. Our observations show that N-methylation heavily alters the interplay between H-bonding and dipolar stacking, the two supramolecular interactions that govern the structural arrangement of squaramides 1–3, hence modulating the arrangement of the water molecules within the crystals.

Physico-chemical properties of aqueous drug solutions: From the basic thermodynamics to the advanced experimental and simulation results

The physical chemical properties of aqueous solutions of model compounds are illustrated in relation to hydration and solubility issues by using three perspectives: thermodynamic, spectroscopic and molecular dynamics simulations. The thermodynamic survey of the fundamental backgrounds of concentration dependence and experimental solubility results show some peculiar behavior of aqueous solutions with several types of similar solutes. Secondly, the use of a variety of experimental spectroscopic devices, operating under different experimental conditions of dimension and frequency, has produced a large amount of structural and dynamic data on aqueous solutions showing the richness of the information produced, depending on where and how the experiment is carried out. Finally, the use of molecular dynamics computational work is presented to highlight how the different types of solute functional groups and surface topologies organize adjacent water molecules differently. The highly valuable contribution of computer simulation studies in providing molecular explanations for experimental deductions, either of a thermodynamic or spectroscopic nature, is shown to have changed the current knowledge of many aqueous solution processes. While this paper is intended to provide a collective view on the latest literature results, still the presentation aims at a tutorial explanation of the potentials of the three methodologies in the field of aqueous solutions of pharmaceutical molecules.

Structural properties of N-dodecyl-N,N-dimethyl-3-ammonio-1-propane-sulfonate micelle in water by molecular dynamics simulation

ABSTRACTHere we report a molecular dynamics simulation on the structures of N-dodecyl-N,N-dimethyl-3-ammonio-1-propane-sulfonate (SB12-3) micelle. We tracked the formation of the micelle with 90 SB12-3 molecules forming a spherical-like shape. The estimation of average values of moments of inertia and eccentricity value is being used to prove this. Radial distribution function, hydrogen bond, and the deuterium order parameter (SCD) were also used to elucidate the hydrophobic and hydrophilic effects on SB12-3 micelle formation. Radial distribution function and hydrogen bonds indicate the strong interaction of the hydrophilic groups with water molecules. SCD indicates that with the increase of SB12-3 the hydrophobic tail becomes ordered. Carbon atoms of the hydrophobic tail chain pack closely near ; the is “fixed” by the adjacent water molecules and loses the flexibilities together with the hydrophobic tail end atoms. Overall, the obtained results are consistent with the existing experimental findings.

Comparing hydroxide and hydronium at the instantaneous air-water interface using polarizable multi-state empirical valence bond models

A new molecular model for the hydroxide anion was developed and its propensity for the air-water interface was compared with that of the hydronium ion. The multi-state empirical valence bond approach with polarizable potentials was used for both of these, allowing them to share their charge with adjacent water molecules. The hydroxide anion appeared to have a lower propensity for the air-water interface than that of hydronium when comparing its potential of mean force with respect to the Gibbs dividing surface. However, upon further inspection it was found that the hydroxide and hydronium ions had similar free energies at the instantaneous air-water interface. The reason for this discrepancy is that the hydroxide anion has a greater free energy when it was partially solvated. Or in other words, when the hydroxide anion is one molecular layer from the instantaneous air-water interface, but potentially still near the Gibbs dividing surface, it is less stable than the hydronium in a similar configuration. This shows that using the instantaneous interface can provide additional important insights.

Ab initio and density functional theory (DFT) studies on triflic acid with water and protonated water clusters.

The structure, stability and infrared spectral signatures of triflic acid (TA) with water clusters (Wn) and protonated water clusters (TAH+Wn, n = 1 - 6) were computed using DFT and MP2 methods. Our calculations show that a minimum of three water molecules are necessary to stabilize the dissociated zwitterionic form of TA. It can be seen from the results that there is no significant movement of protons in smaller (n = 1 and 2) and linear (n = 1 - 6) types of water clusters. Further, the geometries of TAWn clusters first form a neutral pair (NP) to contact ion pair (CIP), then form a solvent separated ion pair (SSIP) in a water hexamer. These findings reveal that proton transfer may take place through NP to CIP and then CIP to SSIP. The calculated binding energies (BEs) of ion pair clusters is always higher than that of NP clusters (i.e., more stable than the NP). Existing excess proton linear chain clusters transfer a proton to adjacent water molecules via a Grotthuss mechanism, whereas the same isomers in the branched motifs do not conduct protons. Examination of geometrical parameters and infrared frequencies reveals hydronium ion (H3O+ also called Eigen cation) formation in both TAWn and protonated TAWn clusters. The stability of Eigen water clusters is three times higher than that of other non-Eigen water clusters. Our study shows clearly that formation of ion pairs in TAWn and TAH+Wn clusters greatly favors proton transfer to neighboring water molecules and also enhances the stability of these complexes.

Determination of reference enthalpies and thermal expansivity using molecular dynamic simulations in the distortion model of gas hydrates

This work presents the determination of both reference chemical potential and temperature-dependent enthalpy changes of gas hydrates using molecular dynamics simulations. We introduced a method incorporating molecular dynamic (MD) simulations to the Lee-Holder distortion model for calculating the reference properties of single component structure II gas hydrates. The guest molecules affect the interaction between adjacent water molecules distorting the hydrate lattice, which requires diverse values of reference properties for different gas hydrates. We performed the simulation to validate the experimental data determining the reference chemical potential as well as the thermal expansivity of unit cell structure for structure II type gas hydrates. All simulations were performed using TIP4P water molecules at the reference temperature and pressure conditions. As an attempt to apply MD simulation to calculate the reference state of gas hydrate, we demonstrate lattice distortion of structure I and II gas hydrates. The reference chemical potential was generally found to increase with the size of the guest molecule. The temperature effect on the unit cell size, which will be used to calculate the enthalpy change of gas hydrate due to temperature, has been observed.

Handheld energy-efficient magneto-optical real-time quantitative PCR device for target DNA enrichment and quantification

A PCR provides not only valuable genetic information that enables precise differential disease diagnosis but also quantitative data to assess various clinical states. We report the successful integration of novel dual-mode magnetic Fe3O4 nanoclusters that deliver photothermal conversion. The clusters can be excited with pulsed laser light for precision thermal cycle modulation to develop an ultrafast quantitative PCR system. Traditional PCR heats and cools the sample from outside the PCR tube; the heat needs to pass through the heat block, tube wall and transfer to the DNA through water molecules. In contrast, our system uses nanoparticles inside the liquid phase as numerous ‘nanoheaters’; thus the thermal transfer between particles and adjacent water or DNA molecules becomes extremely efficient because of proximity at the molecular level. Moreover, the defective mitochondrial DNA from cybrid cell lines of a patient with chronic progressive external ophthalmoplegia syndrome, a mitochondrial disease, was efficaciously detected. The system has a simple design, is extremely energy efficient and is faster than traditional qPCR. Our finding provides new insight into rapid and accurate quantitative diagnostics for future point-of-care applications. Iron nanoparticles play double duty as ‘nanoheaters’ for DNA amplification and as molecular manipulators in a new point-of-care prototype. Polymerase chain reaction (PCR) devices create multiple copies of small DNA strands for genetic testing, but usually require bulky heating and cooling mechanisms. Dar-Bin Shieh and colleagues from National Cheng Kung University in Taiwan have found that tiny clusters of iron oxide nanocubes can improve heat transfer in PCR devices by entering the liquid phase next to the target DNA. When irradiated by laser light, the iron nanoclusters release heat to precisely modulate DNA temperatures. Furthermore, functionalizing the nanoparticles with nucleotide probes enables them to attach to and extract specific disease-indicating mitochondria using magnetic fields. The portable, battery-powered prototype can wirelessly interface with tablet computers and is twice as efficient at isolating mitochondria as commercial kits. A novel dual-mode magnetic Fe3O4 nanoclusters was developed that exhibit efficient photothermal conversion and superparamagnetism. The particles served as numerous ‘nanoheaters’ in a PCR reaction mixture while enabling effective magnetic-based macromolecular manipulation. The thermal transfer between particles and adjacent water and DNA molecules thus become extremely efficient because of molecular-level proximity and allowed rapid amplification cycle progression. The defective mitochondrial DNA from cybrid cell lines of a patient with chronic progressive external ophthalmoplegia syndrome was efficaciously quantified by fluorescence intensity detection. Our finding provides new insight into rapid and accurate quantitative DNA diagnostics for future point-of-care applications.

The Opposite Effect of Metal Ions on Short-/Long-Range Water Structure: A Multiple Characterization Study.

Inorganic electrolyte solutions are very important in our society as they dominate many biochemical and geochemical processes. Herein, an in-depth study was performed to illustrate the ion-induced effect on water structure by coupling NMR, viscometer, Raman and Molecular Dynamic (MD) simulations. The NMR coefficient (BNMR) and diffusion coefficient (D) from NMR, and viscosity coefficient (Bvis) from a viscometer all proved that dissolved metal ions are capable of enhancing the association degree of adjacent water molecules, and the impact on water structure decreased in the order of Cr3+ > Fe3+ > Cu2+ > Zn2+. This regularity was further evidenced by Raman analysis; however, the deconvoluted Raman spectrum indicated the decrease in high association water with salt concentration and the increase in low association water before 200 mmol·L−1. By virtue of MD simulations, the opposite changing manner proved to be the result of the opposite effect on short-/long-range water structure induced by metal ions. Our results may help to explain specific protein denaturation induced by metal ions.

Proton transfer from water to anion: Free energy profile from first principles metadynamics simulations

We elucidate the characteristic proton transfer process from water to aniline anion, and the free energy profile of the process in aqueous solution from the first principles simulations. We have explored the structure and energetic of hydrated clusters of aniline anion with up to three water molecules by gas phase electronic structure calculations. Our results indicate that the proton transfer in hydrated clusters proceeds more easily as the number of water molecule increases. The presence of minimum three water molecules in the gas phase cluster is sufficient to facilitate the proton transfer process from water to anion. The analysis of trajectories obtained from density functional theory based first principles molecular dynamics simulations of aqueous solution of anion do not show any evident of complete transfer of proton from water to anion due to energy barrier, and cooperativity of other surrounding water molecules. Using biasing potential through first principles metadynamics simulations, we report the observation of proton transfer reaction from water to aniline anion with a barrier height of 27.7kJ/mol. In the aqueous solution of the anion, and beyond the critical number of solvent water molecules in hydrated clusters, one of the adjacent water molecules becomes more acidic and gives its proton to anion. Our observations are in agreement with the observation from experimental study.

A Model of Information Carried over a Neuron Soma.

A series of cellular automata models of amino acid side chains on a neuron soma membrane have been created to simulate their hydropathic influences on adjacent water molecules. The presence of pathways, referred to as water wires, is identified. These pathways are invoked as passage ways across a neuron soma of proton hopping carrying the information from dendrites to the axon hillock.

How Properties of Solid Surfaces Modulate the Nucleation of Gas Hydrate.

Molecular dynamics simulations were performed for CO2 dissolved in water near silica surfaces to investigate how the hydrophilicity and crystallinity of solid surfaces modulate the local structure of adjacent molecules and the nucleation of CO2 hydrates. Our simulations reveal that the hydrophilicity of solid surfaces can change the local structure of water molecules and gas distribution near liquid-solid interfaces, and thus alter the mechanism and dynamics of gas hydrate nucleation. Interestingly, we find that hydrate nucleation tends to occur more easily on relatively less hydrophilic surfaces. Different from surface hydrophilicity, surface crystallinity shows a weak effect on the local structure of adjacent water molecules and on gas hydrate nucleation. At the initial stage of gas hydrate growth, however, the structuring of molecules induced by crystalline surfaces are more ordered than that induced by amorphous solid surfaces.

Investigation of the Ice-Binding Site of an Insect Antifreeze Protein Using Sum-Frequency Generation Spectroscopy.

We study the ice-binding site (IBS) of a hyperactive antifreeze protein from the beetle Dendroides canadensis (DAFP-1) using vibrational sum-frequency generation spectroscopy. We find that DAFP-1 accumulates at the air-water interface due to the hydrophobic character of its threonine-rich IBS while retaining its highly regular β-helical fold. We observe a narrow band at 3485 cm(-1) that we assign to the O-H stretch vibration of threonine hydroxyl groups of the IBS. The narrow character of the 3485 cm(-1) band suggests that the hydrogen bonds between the threonine residues at the IBS and adjacent water molecules are quite similar in strength, indicating that the IBS of DAFP-1 is extremely well-ordered, with the threonine side chains showing identical rotameric confirmations. The hydrogen-bonded water molecules do not form an ordered ice-like layer, as was recently observed for the moderate antifreeze protein type III. It thus appears that the antifreeze action of DAFP-1 does not require the presence of ordered water but likely results from the direct binding of its highly ordered array of threonine residues to the ice surface.

A unique trapping by crystal forces of a hydronium cation displaying a transition state structure

An hydronium cation has been discovered which is unique among all crystallographic such ions of the Cambridge Database. Of composition H 7 O 3 + it has a structure that is totally different from those classically known with structures H 2 O-H 2 O-H 3 O + and H 2 O-(H 3 O + )-H 2 O. Unlike the crystallographically classical ones, the cation discussed here has a bifurcated hydrogen bond. From a central H 3 O + moiety a single hydrogen bond donor extends to two adjacent water molecules. Quantum chemical calculations in absence of the crystal environment demonstrate that the bifurcated hydrogen bond structure is that of a transition state for the H 7 O 3 + complex. Thus remarkably, it appears that crystal forces have captured the ion in what would otherwise be a short-lived and unstable transition state formation.

Crystal structure of 4-(di-methyl-amino)-pyridinium 4-amino-benzoate dihydrate.

In the title hydrated mol­ecular salt, C7H11N2 +·C7H6NO2 −·2H2O, the cation is protonated at the pyridine N atom and the dihedral angle between the benzene ring and the CO2 − group in the anion is 8.5 (2)°. In the crystal, the cation forms an N—H⋯O hydrogen bond to the anion and the anion forms two N—H⋯O hydrogen bonds to adjacent water mol­ecules. Both water mol­ecules form two O—H⋯O hydrogen bonds to carboxyl­ate O atoms. In combination, these hydrogen bonds generate a three-dimensional network and two weak C—H⋯π inter­actions are also observed.

Excited-state proton transfer of photoacids adsorbed on biomaterials.

The interaction between a photoacid (8-hydroxy-1,3,6-pyrenetrisulfonate, HPTS) and the surfaces of biomaterials and the diffusion of protons along the biomaterial surfaces were examined by following the excited-state proton transfer (ESPT) from the photoacid, adsorbed on the surfaces, to water molecules next to it. We chose two different types of biomaterial surfaces, hydrophobic insulin amyloid fibrils and hydrophilic cellulose surfaces. With the help of steady-state and time-resolved fluorescence techniques, we found that the rate of ESPT from HPTS on insulin fibrils to adjacent water molecules is about 1/10 that in bulk water. However, the proton geminate recombination takes place with an efficiency similar to that in bulk water. ESPT from HPTS in wet cellulose to water depends on the weight percentage of water adsorbed by the cellulose. In a semidry sample (<100% weight percentage of water), the ESPT rate is rather low and thus the quantum efficiency of the ESPT is also low within the excited-state lifetime. When the water content is higher, the ESPT rate is almost that of bulk water. We explain these results by the existence of pools of water in cellulose of high water content, in which the triple-negatively charged HPTS molecules desorb from the cellulose surface to these pools. The use of HPTS has allowed us to examine the biological surface and its interaction with water molecules, while obtaining important information regarding the hydration state of the surface that otherwise could not have been obtained. The model that we propose here for the use of photoacids to follow the hydrated state of a given surface is a promising new method of examining the interaction of water molecules with biological surfaces.

Bringing Reactivity to the Aggregation-Volume-Bias Monte Carlo Based Simulation Framework: Water Nucleation Induced by a Reactive Proton.

The development of the aggregation-volume-bias Monte Carlo based simulation technique has led to recent success in studying rare nucleation events, but thus far, this simulation method has been limited to nonreactive systems. This work presents the first application of this technique to study a reactive system of relevance to atmospheric chemistry, i.e., formation of water droplets in the presence of a reactive proton, by combining this approach with a multistate empirical valence bond (MSEVB) description of the excess proton (or the hydronium). It was shown that the ability for the hydronium to share its charge with adjacent water molecules changes dramatically with the cluster size, especially when clusters are small and the distribution of the charge is affected by the presence of an interface, emphasizing the need to use this more sophisticated MSEVB model for such a reactive system. In addition, the simulation results obtained from this system are compared to those with nonreactive hard-sphere ions of different sizes. Overall, the presence of a hydronium or ions appeared to dramatically change the free energy landscape of nucleation compared to the pure water system, leading to the formation of a stable precritical cluster. Although the free energy change due to the addition of the first few water molecules was shown to be very sensitive to the ionic details, the later portion of the free energy profile was found to be nearly independent of the nature of the ion.

Adsorption behaviors of monomer and dimer of formic acid on Pt(111) in the absence and presence of water.

By performing density functional theory (DFT) theory calculations, we studied the adsorption behaviors of the monomer and dimer of formic acid (HCOOH, FA) on the Pt(111) surface with and without the presence of water molecules. The monomer prefers to stand on the surface of Pt(111), and in the most stable adsorption configuration the carbonyl O of HCOOH binds to the atop site of a Pt atom and the hydroxyl H points asymmetrically to two neighboring Pt atoms. The dimer of HCOOH not only exists in the gas-phase but also on Pt(111) surface, and the eight-membered ring dimer is identified as the energetically most favorable dimeric structure of HCOOH both in gas-phase and on Pt(111) surface. With the presence of water molecules, both the monomer and dimer of HCOOH prefer to lie parallel to the surface so as to maximize the number of H-bonds to adjacent water molecules. These results indicate that water molecules significantly influence the initial adsorption manner of HCOOH and further its decomposition reactivity on Pt(111) surface. The present work shows the adsorption behavior of HCOOH dimer on Pt(111) for the first time and also gives several new adsorption configurations of the monomer that are not reported in literature. The theoretical results are expected to provide a valuable input to understand the reactivity of HCOOH on Pt(111).

A Density-Functional Theory Study of the Water−Gas Shift Mechanism on Pt/Ceria(111)

Density-functional theory has been used to model the interactions between ceria(111) and CO adsorbed on platinum in order to provide insights into the mechanism behind the water−gas shift reaction on this material. Morphological studies on ceria show the presence of various defect sites, both cerium and oxygen vacancies, which are believed to be the reason for the catalytic activity of the substrate. Of these defect sites, the reported calculations clearly show the preference for platinum to bind in cerium vacancies, as opposed to a defect-free surface or an oxygen deficiency site. Currently there are two main pathways proposed for this mechanism: a direct redox pathway and a formate-intermediate pathway. In both scenarios the initial step is the same: the oxygen storage capacity of ceria provides the oxygen necessary to oxidize CO into CO2; water then adsorbs and is dissociated in these oxygen vacancies helping reform the ceria surface. The key difference between the two mechanisms is either the desorption of CO2and the formation of H2 when a second water molecule adsorbs at a site where water had been previously dissociated (catalyzed by platinum), or the formation of a formate species from the interaction of the adsorbed CO2 with adjacent water molecules. Energy pathways are mapped for both processes, demonstrating the preference toward the initial direct redox pathway. However, the resulting formation of adsorbed hydroxide species in the oxygen vacancies adjacent to the platinum hinders this pathway. A bifunctional mechanism is then presented as a means to remove these species and thereby form formate. The activation of these adsorbed hydroxides is also studied.

Water influx into cerebrospinal fluid is primarily controlled by aquaporin-4, not by aquaporin-1

Recent studies on cerebrospinal fluid (CSF) homeostasis emphasize the importance of water flux through the pericapillary (Virchow–Robin) space for both CSF production and reabsorption (Oreskovic and Klarica hypothesis), and challenge the classic CSF circulation theory, which proposes that CSF is primarily produced by the choroid plexus and reabsorbed by the arachnoid villi. Active suppression of aquaporin-1 (AQP-1) expression within brain capillaries and preservation of AQP-1 within the choroid plexus together with pericapillary water regulation by AQP-4 provide a unique opportunity for testing this recent hypothesis. We investigated water flux into three representative regions of the brain, namely, the cortex, basal ganglia, and third ventricle using a newly developed water molecular MRI technique based on JJ vicinal coupling between 17O and adjacent protons and water molecule proton exchanges (JJVCPE imaging) in AQP-1 and AQP-4 knockout mice in vivo. The results clearly indicate that water influx into the CSF is regulated by AQP-4, and not by AQP-1, strongly supporting the Oreskovic and Klarica hypothesis.

Mechanistic insights from functional characterization of an unnatural His37 mutant of the influenza A/M2 protein

The influenza A/M2 protein is a homotetrameric single-pass integral membrane protein encoded by the influenza A viral genome. Its transmembrane domain represents both a crucial drug target and a minimalistic model system for transmembrane proton transport and charge stabilization. Recent structural and functional studies of M2 have suggested that the proton transport mechanism involves sequential extraviral protonation and intraviral deprotonation of a highly conserved His37 side chain by the transported proton, consistent with a pH-activated proton shuttle mechanism. Multiple tautomeric forms of His can be formed, and it is not known whether they contribute to the mechanism of proton shuttling. Here we present the thermodynamic and functional characterization of an unnatural amino acid mutant at His37, where the imidazole side chain is substituted with a 4-thiazolyl group that is unable to undergo tautomerization and has a significantly lower solution pKa. The mutant construct has a similar stability to the wild-type protein at pH8 in bilayers and is virtually inactive at external pH7.4 in a semiquantitative liposome flux assay as expected from its lower sidechain pKa. However when the external buffer pH is lowered to 4.9 and 2.4, the mutant shows increasing amantadine sensitive flux of a similar magnitude to that of the wild type construct at pH7.4 and 4.9 respectively. These findings are in line with mechanistic hypotheses suggesting that proton flux through M2 is mediated by proton exchange from adjacent water molecules with the His37 sidechain, and that tautomerization is not required for proton translocation. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.