Association structures of ionic liquid∕DMSO mixtures studied by high-pressure infrared spectroscopy

Using high-pressure infrared methods, we have investigated close interactions of charge-enhanced C-H-O type in ionic liquid∕dimethyl sulfoxide (DMSO) mixtures. The solvation and association of the 1-butyl-3-methylimidazolium tetrafluoroborate (BMI(+)BF(4)(-)) and 1-butyl-2,3-dimethylimidazolium tetrafluoroborate (BMM(+)BF(4)(-)) in DMSO-d(6) were examined by analysis of C-H spectral features. Based on our concentration-dependent results, the imidazolium C-H groups are more sensitive sites for C-H-O than the alkyl C-H groups and the dominant imidazolium C-H species in dilute ionic liquid∕DMSO-d(6) should be assigned to the isolated (or dissociated) structures. As the dilute mixtures were compressed by high pressures, the loss in intensity of the bands attributed to the isolated structures was observed. In other words, high pressure can be used to perturb the association-dissociation equilibrium in the polar region. This result is remarkably different from what is revealed for the imidazolium C-H in the BMM(+)BF(4)(-)∕D(2)O mixtures. DFT-calculations are in agreement with our experimental results indicating that C(4)-H-O and C(5)-H-O interactions seem to play non-negligible roles for BMM(+)BF(4)(-)∕DMSO mixtures.     

Conformational dynamics of ATP∕Mg:ATP in motor proteins via data mining and molecular simulation

The conformational diversity of ATP∕Mg:ATP in motor proteins was investigated using molecular dynamics and data mining. Adenosine triphosphate (ATP) conformations were found to be constrained mostly by inter cavity motifs in the motor proteins. It is demonstrated that ATP favors extended conformations in the tight pockets of motor proteins such as F(1)-ATPase and actin whereas compact structures are favored in motor proteins such as RNA polymerase and DNA helicase. The incorporation of Mg(2+) leads to increased flexibility of ATP molecules. The differences in the conformational dynamics of ATP∕Mg:ATP in various motor proteins was quantified by the radius of gyration. The relationship between the simulation results and those obtained by data mining of motor proteins available in the protein data bank is analyzed. The data mining analysis of motor proteins supports the conformational diversity of the phosphate group of ATP obtained computationally.     

Dissolution of zinc oxide in a protic ionic liquid with the 1-methylimidazolium cation and electrodeposition of zinc from ZnO/ionic liquid and ZnO/ionic liquid–water mixtures

We show that zinc oxide can be dissolved in the protic ionic liquid 1-methylimidazolium trifluoromethylsulfonate, [MIm]TfO at quite a high concentration (~ 2.5 mol/L). FTIR and Raman spectra revealed the association of zinc ions with 1-methylimidazole. The ZnO/[MIm]TfO solutions and their mixtures with water were employed as electrolytes for the electrodeposition of zinc. High current density electrodeposition of zinc can be achieved in the employed electrolytes. Spongy-like zinc structures with a high porosity were obtained in ZnO/[MIm]TfO and the formation of Au_1.2Zn_8.8 alloy was observed. Compact and hexagonal zinc deposits were found in the presence of water. The present results show the potential of ionic liquids as electrolytes for rechargeable zinc–air batteries.     

Liquids intermediate between "molecular" and "ionic" liquids: liquid ion pairs?

Ionic liquids comprised of tetradecyltrihexyl- and tetrabutyl-phosphonium cations paired with chloride or sulfonyl amide anions exhibit properties that reflect strong ion association, including comparatively low viscosity as well as a degree of volatility, and hence exemplify an interesting intermediate state between true ionic and true molecular liquids.     

Behavior of β-amyloid 1-16 at the air-water interface at varying pH by nonlinear spectroscopy and molecular dynamics simulations

The adsorption and aggregation of β-amyloid (1-16) fragment at the air-water interface was investigated by the combination of second harmonic generation (SHG) spectroscopy, Brewster angle microscopy (BAM), and molecular dynamics simulations (MD). The Gibbs free energy of surface adsorption was measured to be -10.3 kcal/mol for bulk pHs of 7.4 and 3, but no adsorption was observed for pH 10-11. The 1-16 fragment is believed not to be involved in fibril formation of the β-amyloid protein, but it exhibits interesting behavior at the air-water interface, as manifested in two time scales for the observed SHG response. The shorter time scale (minutes) reflects the surface adsorption, and the longer time scale (hours) reflects rearrangement and aggregation of the peptide at the air-water interface. Both of these processes are also evidenced by BAM measurements. MD simulations confirm the pH dependence of surface behavior of the β-amyloid, with largest surface affinity found at pH = 7. It also follows from the simulations that phenylalanine is the most surface exposed residue, followed by tyrosine and histidine in their neutral form.     

Exploring the inter-molecular interactions in amyloid-β protofibril with molecular dynamics simulations and molecular mechanics Poisson-Boltzmann surface area free energy calculations

Aggregation of amyloid-β (Aβ) peptides correlates with the pathology of Alzheimer's disease. However, the inter-molecular interactions between Aβ protofibril remain elusive. Herein, molecular mechanics Poisson-Boltzmann surface area analysis based on all-atom molecular dynamics simulations was performed to study the inter-molecular interactions in Aβ(17-42) protofibril. It is found that the nonpolar interactions are the important forces to stabilize the Aβ(17-42) protofibril, while electrostatic interactions play a minor role. Through free energy decomposition, 18 residues of the Aβ(17-42) are identified to provide interaction energy lower than -2.5 kcal/mol. The nonpolar interactions are mainly provided by the main chain of the peptide and the side chains of nine hydrophobic residues (Leu17, Phe19, Phe20, Leu32, Leu34, Met35, Val36, Val40, and Ile41). However, the electrostatic interactions are mainly supplied by the main chains of six hydrophobic residues (Phe19, Phe20, Val24, Met35, Val36, and Val40) and the side chains of the charged residues (Glu22, Asp23, and Lys28). In the electrostatic interactions, the overwhelming majority of hydrogen bonds involve the main chains of Aβ as well as the guanidinium group of the charged side chain of Lys28. The work has thus elucidated the molecular mechanism of the inter-molecular interactions between Aβ monomers in Aβ(17-42) protofibril, and the findings are considered critical for exploring effective agents for the inhibition of Aβ aggregation.     

Micelle–monomer equilibria in solutions of ionic surfactants and in ionic–nonionic mixtures: A generalized phase separation model

On the basis of a detailed physicochemical model, a complete system of equations is formulated that describes the equilibrium between micelles and monomers in solutions of ionic surfactants and their mixtures with nonionic surfactants. The equations of the system express mass balances, chemical and mechanical equilibria. Each nonionic surfactant is characterized by a single thermodynamic parameter — its micellization constant. Each ionic surfactant is characterized by three parameters, including the Stern constant that quantifies the counterion binding. In the case of mixed micelles, each pair of surfactants is characterized with an interaction parameter, β, in terms of the regular solution theory. The comparison of the model with experimental data for surfactant binary mixtures shows that β is constant — independent of the micelle composition and electrolyte concentration. The solution of the system of equations gives the concentrations of all monomeric species, the micelle composition, ionization degree, surface potential and mean area per head group. Upon additional assumptions for the micelle shape, the mean aggregation number can be also estimated. The model gives quantitative theoretical interpretation of the dependence of the critical micellization concentration (CMC) of ionic surfactants on the ionic strength; of the CMC of mixed surfactant solutions, and of the electrolytic conductivity of micellar solutions. It turns out, that in the absence of added salt the conductivity is completely dominated by the contribution of the small ions: monomers and counterions. The theoretical predictions are in good agreement with experimental data.     

Electrooxidation of dextromethorphan on a carbon nanotube–carbon microparticle–ionic liquid composite: applied to determination in pharmaceutical forms

The electrooxidation of dextromethorphan on a composite constructed with carbon nanotube–ionic liquid–carbon microparticles was investigated by cyclic voltammetry in a 100 mM phosphate buffer solution, pH 7.40. In the voltammograms, an irreversible diffusion-controlled anodic peak appeared. The diffusion coefficient of dextromethorphan, the electron-transfer coefficient, and the standard rate constant of the electrooxidation process were found to be 3.45?×?10^?6 cm² s^?1, 0.65, and 1.67?×?10^?3 cm s^?1, respectively. A sensitive and timesaving determination procedure was developed for the analysis of dextromethorphan, and the corresponding analytical parameters were reported. Using this method, dextromethorphan was determined with an LOD and LOQ of 8.81 and 29.36 μM in a linear range of 2.5?×?10^?4 to 3.3?×?10^?3 M, respectively. The proposed amperometric method was successfully applied to the analysis of commercial pharmaceutical products (syrup and oral drop), and the results were in good agreement with the declared values.     

Large scale molecular dynamics simulations of a 4-n-pentyl-4′-cyanobiphenyl (5CB) liquid crystalline model in the bulk and as a droplet

Molecular dynamics simulations for 4-n-pentyl-4′-cyanobiphenyl (5CB) with as many as 944 molecules are reported. The order-N fast multipole method (FMM) is used to treat the long-range interactions. For a droplet of 944 molecules, the simulation shows a correlation between the droplet shape and the nematic order and a strong surface effect; little nematic order is found in a 118 molecule droplet. Simulations of the bulk system result in similar order parameters for both the 118 and 944 molecular ensembles. Although the nematic–isotropic transition was not observed at temperatures as high as 400 K using the CHARMM force field, a modification of the force field using ab initio determined partial atomic charges lowers the order parameters.     

Stereoselective inclusion mechanism of ketoprofen into β-cyclodextrin: insights from molecular dynamics simulations and free energy calculations

The host–guest inclusion mechanism formed between β-cyclodextrin and those poorly water-soluble drug molecules has important applications in supramolecular chemistry, biology and pharmacy. In this work, the chiral recognition ability of β-cyclodextrin to one of nonsteroidal anti-inflammatory drugs, ketoprofen, has been systematically investigated using molecular dynamics and free energy simulation methods. The R- and S-enantiomers of ketoprofen were explicitly bound within the cyclodextrin cavity in our simulations, respectively. In consistent with experimental observations, tiny structural difference between two isomers could be observed. Calculated absolute binding free energies using adapted biasing force (ABF) method and MM/GBSA approach for both isomers are comparable to experimental values. Significant binding fluctuations along the MD trajectory have been observed. The free energy profiles calculated using two different approaches reveal that the ketoprofen prefers binding in the cavity with the carboxylate group facing the wider edge of β-cyclodextrin. Similar free energy profiles for two enantiomers obtained using ABF calculations indicate that it is very hard to separate and identify the chiral conjugates within the framework of the natural β-cyclodextrin.     

Constant pressure molecular dynamics simulations of the crystal–smectic transition in systems of soft parallel spherocylinders as a model for liquid crystals

Abstract

We present the results of constant pressure molecular dynamics simulation under hydrostatic pressure for soft parallel spherocylinders. A clear first order transition from crystal to smectic phase is observed. The anisotropy of the molecular volume plays an important role in this transition. We study the anisotropy of the diffusion process in the smectic phase by the mean-square displacement in each direction. Also the structures before and after the transition are analysed by means of the pair distribution functions.     

How does water affect the dynamics of the room-temperature ionic liquid 1-hexyl-3-methylimidazolium hexafluorophosphate and the fluorescence spectroscopy of Coumarin-153 when dissolved in it?

Molecular dynamics simulations of mixtures of 1-hexyl-3-methylimidazolium hexafluorophosphate ([HMIM+][PF6-]) and water have been performed in order to investigate how small amounts of water affect the translational and rotational dynamics of this ionic liquid (IL). We find that water is closely associated with the anions and that its presence enhances both the translational and rotational dynamics of the IL. In agreement with experiments, we find that the fluorescence spectra of Coumarin-153 is red-shifted because of the presence of water. Small amounts of water enhance the speed of relaxation of the solvent surrounding the solute probe after photoexcitation, but only at a "local environment" level. Interconversion between environments still occurs on a long time scale compared with the fluorescence lifetime of the probe. Excitation wavelength-dependent emission is observed both in the neat IL and in the IL+water mixture.     

Conformational transition and energy landscape of ErbB4 activated by neuregulin1β: one microsecond molecular dynamics simulations

ErbB4, a receptor tyrosine kinase of the ErbB family, plays crucial roles in cell growth and differentiation, especially in the development of the heart and nervous system. Ligand binding to its extracellular region could modulate the activation process. To understand the mechanism of ErbB4 activation induced by ligand binding, we performed one microsecond molecular dynamics (MD) simulations on the ErbB4 extracellular region (ECR) with and without its endogenous ligand neuregulin1β (NRG1β). The conformational transition of the ECR-ErbB4/NRG1β complex from a tethered inactive conformation to an extended active-like form has been observed, while such large and function-related conformational change has not been seen in the simulation on the ECR-ErbB4, suggesting that ligand binding is indeed the active inducing force for the conformational transition and further dimerization. On the basis of MD simulations and principal component analysis, we constructed a rough energy landscape for the conformational transition of ECR-ErbB4/NRG1β complex, suggesting that the conformational change from the inactive state to active-like state involves a stable conformation. The energy barrier for the tether opening was estimated as ~2.7 kcal/mol, which is very close to the experimental value (1-2 kcal/mol) reported for ErbB1. On the basis of the simulation results, an atomic mechanism for the ligand-induced activation of ErbB4 was postulated. The present MD simulations provide a new insight into the conformational changes underlying the activation of ErbB4.     

Stabilizing effect of cholesterol on the state of β2-adrenergic receptor with a broken ionic lock: a molecular dynamics study

A molecular dynamics simulation of the β₂-adrenergic receptor (β₂AR) embedded in a hydrated lipid bilayer showed that the state with a broken ionic lock (salt bridge) between the arginine residue Arg131 and the glutamic acid residue Glu268 is stabilized in the presence of cholesterol molecules. This should be considered as a transient state to the active state of the receptor.     

Diffusion coefficients of first-generation polyamidoamine dendrimer and its β-cyclodextrin conjugate in aqueous solution by means of molecular dynamics simulations

Abstract  

The structure and diffusion behavior of the neutral and charged first-generation polyamidoamine (PAMAM-G1) dendrimer and its β-cyclodextrin (β-CD) conjugate in aqueous solutions were studied by molecular dynamics (MD) simulations. Diffusion coefficients were obtained from mean square displacement data, considering 500-ps intervals of normal diffusive regime within three simulation runs. Calculated diffusion coefficients were compared with experimental values obtained from diffusion ordered spectroscopy (DOSY) experiments for both neutral and charged dendrimer and conjugate structures. Our results show good agreement between calculated and experimental results, accounting for the reliability of our MD simulations.     

Molecular simulation of the phase behaviour of ternary fluid mixtures: the effect of a third component on vapour–liquid and liquid–liquid coexistence

The Gibbs ensemble algorithm is implemented to determine the vapour–liquid and liquid–liquid phase coexistence of dilute ternary fluid mixtures interacting via a Lennard–Jones potential. Calculations are reported for mixtures with a third component characterised by different intermolecular potential energy parameters. Comparison with binary mixture data indicates that the choice of energy parameter for the third component affects the composition range of vapour–liquid substantially. The addition of a third component lowers the energy of liquid phase while slightly increasing the energy of the vapour phase.     

Car-Parinello molecular dynamics simulations of thionitroxide and S-nitrosothiol in the gas phase, methanol, and water—A theoretical study of S-nitrosylation

A dilemma about whether thionitroxide radical (RSNHO) or S-nitrosothiol (RSNO) is observed in protein S-nitrosylation has arisen recently. To illustrate the effect of chemical environment on these structures, this paper presents quantum mechanical molecular dynamics of thionitroxide, and cis-and trans-S-nitrosothiols in the gas phase, methanol, and water. By using Car-Parrinello molecular dynamics (CPMD), we have observed that there is free rotation about the S-N bond at 300 K in thionitroxide, but no such rotation is observed for S-nitrosothiol. The C-S-N-O torsion angle distribution in thionitroxide is s-ignificantly dependent upon the surrounding environment, leading to either gauche-, cis-, or trans-conformation. In the case of S-nitrosothiol the C-S-N-O plane is twisted slightly by 5°-15° in the cis-isomer, while the periplanar structure is well-retained in the trans-isomer. The calculated results are in agreement with the X-ray crystallographic data of small molecular RSNO species. Interestingly, for both compounds, the CPMD simulations show that solvation can cause a decrease in the S-N bond length. Moreover, the oxygen atom of thionitroxide is found to be a good hydrogen-bond acceptor, forming an oxyanion-hole-like hydrogen bonding network.     

Optical pump-terahertz probe spectroscopy of dyes in solutions: probing the dynamics of liquid solvent or solid precipitate?

The optical pump-terahertz probe spectroscopy was used together with ab initio calculations and molecular dynamics simulations to investigate ultrafast dynamics following electronic excitation of Coumarin 153 and TBNC (2,11,20,29-tetra-tert-butyl-2,3-naphtalocyanine) dyes in polar solvents. By scanning the terahertz waveform for different pump-probe delays this experimental technique allows us to obtain two dimensional spectra directly reflecting the temporal response of the system. A distinct signal was obtained for TBNC in chloroform, 2-propanol, and n-butanol, while no signal was recorded for Coumarin 153 in either of these solvents. We explain the nonequilibrium signal detected in TBNC solutions by the presence of a solid, polycrystalline phase of the dye resulting from irradiating the solution by intense optical pulses.     

A survey on the effect of ionic liquid on electrochemical behavior and electrocatalytic activity of a phosphomolybdic acid-ionic liquid-MWCNT–modified glassy carbon electrode

Journal of Solid State Electrochemistry - The surface of a glassy carbon electrode modified with multi-walled carbon nanotubes (GCE/MWCNTs) was coated with a layer of phosphomolybdic acid (PMo12)...