Amide-induced phase separation of hexafluoroisopropanol-water mixtures depending on the hydrophobicity of amides

Amide-induced phase separation of hexafluoro-2-propanol (HFIP)-water mixtures has been investigated to elucidate solvation properties of the mixtures by means of small-angle neutron scattering (SANS), (1)H and (13)C NMR, and molecular dynamics (MD) simulation. The amides included N-methylformamide (NMF), N-methylacetamide (NMA), and N-methylpropionamide (NMP). The phase diagrams of amide-HFIP-water ternary systems at 298 K showed that phase separation occurs in a closed-loop area of compositions as well as an N,N-dimethylformamide (DMF) system previously reported. The phase separation area becomes wider as the hydrophobicity of amides increases in the order of NMF < NMA < DMF < NMP. Thus, the evolution of HFIP clusters around amides due to the hydrophobic interaction gives rise to phase separation of the mixtures. In contrast, the disruption of HFIP clusters causes the recovery of the homogeneity of the ternary systems. The present results showed that HFIP clusters are evolved with increasing amide content to the lower phase separation concentration in the same mechanism among the four amide systems. However, the disruption of HFIP clusters in the NMP and DMF systems with further increasing amide content to the upper phase separation concentration occurs in a different way from those in the NMF and NMA systems.     

A Study of the Solvation Structure of l‐Leucine in Alcohol–Water Binary Solvents through Molecular Dynamics Simulations and FTIR and NMR Spectroscopy

The solvation structures of l ‐leucine (Leu) in aliphatic‐alcohol–water and fluorinated‐alcohol–water solvents are elucidated for various alcohol contents by using molecular dynamics (MD) simulations and IR, and ¹H and ¹³C NMR spectroscopy. The aliphatic alcohols included methanol, ethanol, and 2‐propanol, whereas the fluorinated alcohols were 2,2,2‐trifluoroethanol and 1,1,1,3,3,3‐hexafluoro‐2‐propanol. The MD results show that the hydrophobic alkyl moiety of Leu is surrounded by the alkyl or fluoroalkyl groups of the alcohol molecules. In particular, TFE and HFIP significantly solvate the alkyl group of Leu. IR spectra reveal that the Leu C?H stretching vibration blueshifts in fluorinated alcohol solutions with increasing alcohol content, whereas the vibration redshifts in aliphatic alcohol solutions. When the C?H stretching vibration blueshifts in the fluorinated alcohol solutions, the hydrogen and carbon atoms of the Leu alkyl group are magnetically shielded. Consequently, TFE and HFIP molecules may solvate the Leu alkyl group through the blue‐shifting hydrogen bonds.     

Liquid structure and preferential solvation of metal ions in solvent mixtures of N,N-dimethylformamide and N-methylformamide

Raman spectra of aprotic N,N-dimethylformamide (DMF) and protic N-methylformamide (NMF) mixtures containing manganese(II), nickel(II), and zinc(II) perchlorate were obtained, and the individual solvation numbers around the metal ions were determined over the whole range of solvent compositions. Variation profiles of the individual solvation numbers with solvent composition showed no significant difference among the metal systems examined. In all of these metal systems, no preferential solvation occurs in mixtures with DMF mole fraction of x(DMF) < 0.5, whereas DMF preferentially solvates the metal ions at x(DMF) > 0.5. The liquid structure of the mixtures was also studied by means of small-angle neutron scattering (SANS) and low-frequency Raman spectroscopy. SANS experiments demonstrate that DMF molecules do not appreciably self-aggregate in the mixtures over the whole range of solvent composition. Low-frequency Raman spectroscopy suggests that DMF molecules are extensively hydrogen-bonded with NMF in NMF-rich mixtures, whereas NMF molecules extensively self-aggregate in DMF-rich mixtures, although the liquid structure in neat NMF is partly ruptured. The bulk solvent structure in the mixtures thus varies with solvent composition, which plays a decisive role in developing the varying profiles of the individual solvation numbers of metal ions in the solvent mixtures.     

Structures in solutions from joint experimental-computational analysis: applications to cyclic molecules and studies of noncovalent interactions

The potential of an approach combining nuclear magnetic resonance (NMR) spectroscopy, molecular dynamics (MD) simulations, and quantum mechanical (QM) calculations for full structural characterizations in solution is assessed using cyclic organic compounds, namely, benzazocinone derivatives 1-3 with fused five- and eight-membered aliphatic rings, camphoric anhydride 4, and bullvalene 5. Various MD simulations were considered, using force field and semiempirical QM treatments, implicit and explicit solvation, and high-temperature MD calculations for selecting plausible molecular geometries for subsequent QM geometry optimizations using mainly B3LYP, M062X, and MP2 methods. The QM-predicted values of NMR parameters were compared to their experimental values for verification of the final structures derived from the MD/QM analysis. From these comparisons, initial estimates of quality thresholds (calculated as rms deviations) were 0.7-0.9 Hz for (3)J(HH) couplings, 0.07-0.11 ? for interproton distances, 0.05-0.08 ppm for (1)H chemical shifts, and 1.0-2.1 ppm for (13)C chemical shifts. The obtained results suggest that the accuracy of the MD analysis in predicting geometries and relative conformational energies is not critical and that the final geometry refinements of the structures selected from the MD simulations using QM methods are sufficient for correcting for the expected inaccuracy of the MD analysis. A unique example of C(sp(3))-H···N(sp(3)) intramolecular noncovalent interaction is also identified using the NMR/MD/QM and the natural bond orbital analyses. As the NMR/MD/QM approach relies on the final QM geometry optimization, comparisons of geometric characteristics predicted by different QM methods and those from X-ray and neutron diffraction measurements were undertaken using rigid and flexible cyclic systems. The joint analysis shows that intermolecular noncovalent interactions present in the solid state alter molecular geometries significantly compared to the geometries of isolated molecules from QM calculations.     

Anomalous mixing behavior of polyisobutylene/polypropylene blends: molecular dynamics simulation study

The unusual mixing behavior of polyisobutylene (PIB) with head-to-head (hhPP) and head-to-tail polypropylene (PP) is studied using large-scale molecular dynamics (MD). The heats of mixing and Flory chi parameters were computed from MD simulations of both blends using a united atom model. The chi parameters from the simulations were estimated from the structure factors using the random phase approximation in analogy with neutron scattering (SANS) experiments. MD simulations for syndiotactic hhPP/PIB predicted a lower critical solution temperature with a chi parameter in very good agreement with SANS experiments on the atactic hhPP/PIB blend. MD simulations also predicted that the isotactic PP/PIB blend was immiscible at high molecular weight in qualitative agreement with cloud point measurements on atactic PP/PIB.     

Solvation phenomena of a tetrapeptide in water/trifluoroethanol and water/ethanol mixtures: a diffusion NMR,intermolecular NOE,and molecular dynamics study

Solvation of a tetrapeptide, NAc-Ser-Phe-Val-Gly-OMe (1), in water and in water/alcohol mixtures with 2,2,2-trifluoroethanol (TFE)/water or ethanol (ETH)/water has been studied by diffusion NMR and intermolecular NOE measurements. The experimental results were compared with those obtained from detailed Molecular Dynamics (MD) calculations. Independently, all three methods revealed preferential solvation on the surface of the peptide by TFE in the water/TFE mixtures, but not by ETH in the water/ETH mixtures. The MD calculations show that the TFE concentration coating the peptide is higher than that in the bulk, while for ethanol, the concentration is nearly equal to that in the bulk. Calculated site-specific preferential solvation data between TFE, ETH, and water with the different peptide groups have been compared with the NMR data and shown to be in general agreement with the experimental facts.     

Individual solvation numbers around the nickel(II) ion in an N,N-dimethylformamide and N,N-dimethylacetamide mixture determined by Raman spectrophotometry.

Individual solvation numbers around the nickel(II) ion have been determined by titration Raman spectroscopy in N,N-dimethylformamide (DMF) and N,N-dimethylacetamide (DMA) mixtures at 298 K. The in-plane bending vibration (delta(O=C-N)) of DMF and the stretching vibration (v(N-CH3)) of DMA were used in the present analysis. These Raman bands of solvent molecules shift to higher frequencies upon coordination of the solvent molecules to the metal ion. By analyzing the band intensities of free and bound solvent molecules with increasing concentration of the metal ion, the solvation number around the metal ion can be evaluated. Because the individual solvation numbers of DMF and DMA around the nickel(II) ion in the mixture are determined independently, the total solvation number is obtained as their sum. It was found that the total solvation number remains 6 in all mixtures of the DMA mole fraction x = 0 - 1. Although DMF and DMA have practically the same electron-pair donor capacities, the nickel(II) ion prefers DMF to DMA, and an equal solvation number is attained at x = 0.75. This is ascribed to the solvation steric effect of DMA.     

Excited state hydrogen bond dynamics: coumarin 102 in acetonitrile-water binary mixtures

The time dependent change in the intermolecular response of solvent molecules following photoexcitation of Coumarin 102 (C102) has been measured in acetonitrile-water binary mixtures. Experiments were performed on mixtures of composition x(CH3CN) = 0.25, 0.50, 0.75, and 1.00. At low water concentrations (x(H2O) < or = 0.25) the solvent response is consistent with previous measurements probing dipolar solvation. With increasing water concentration (x(H2O) > or = 0.50) an additional response is found subsequent to dipolar solvation, exhibited as a rapid gain in the solvent's polarizability on a approximately 250 fs time scale. Monte Carlo simulations of the C102:binary mixture system were performed to quantify the number of hydrogen-bonding interactions between C102 and water. These simulations indicate that the probability of the C102 solute being hydrogen bound with two water molecules, both as donors at the carbonyl site, increases in a correlated fashion with the amplitude of the additional response in the measurements. We conclude that excitation of C102 simultaneously weakens and strengthens hydrogen bonding in complexes with two inequivalently bound waters.     

Temperature driven annealing of perforations in bicellar model membranes

Bicellar model membranes composed of 1,2-dimyristoylphosphatidylcholine (DMPC) and 1,2-dihexanoylphosphatidylcholine (DHPC), with a DMPC/DHPC molar ratio of 5, and doped with the negatively charged lipid 1,2-dimyristoylphosphatidylglycerol (DMPG), at DMPG/DMPC molar ratios of 0.02 or 0.1, were examined using small angle neutron scattering (SANS), (31)P NMR, and (1)H pulsed field gradient (PFG) diffusion NMR with the goal of understanding temperature effects on the DHPC-dependent perforations in these self-assembled membrane mimetics. Over the temperature range studied via SANS (300-330 K), these bicellar lipid mixtures exhibited a well-ordered lamellar phase. The interlamellar spacing d increased with increasing temperature, in direct contrast to the decrease in d observed upon increasing temperature with otherwise identical lipid mixtures lacking DHPC. (31)P NMR measurements on magnetically aligned bicellar mixtures of identical composition indicated a progressive migration of DHPC from regions of high curvature into planar regions with increasing temperature, and in accord with the "mixed bicelle model" (Triba, M. N.; Warschawski, D. E.; Devaux, P. E. Biophys. J.2005, 88, 1887-1901). Parallel PFG diffusion NMR measurements of transbilayer water diffusion, where the observed diffusion is dependent on the fractional surface area of lamellar perforations, showed that transbilayer water diffusion decreased with increasing temperature. A model is proposed consistent with the SANS, (31)P NMR, and PFG diffusion NMR data, wherein increasing temperature drives the progressive migration of DHPC out of high-curvature regions, consequently decreasing the fractional volume of lamellar perforations, so that water occupying these perforations redistributes into the interlamellar volume, thereby increasing the interlamellar spacing.     

Li＋在PC＋DMF混合溶剂中优先溶剂化的13C NMR研究

利用¹³C NMR光谱技术研究了Li^＋在碳酸丙烯酯(PC)＋N,N-二甲基甲酰胺(DMF)混合溶剂中的优先溶剂化现象. 根据溶剂分子中碳原子的化学位移随锂盐浓度的变化关系, 确定了与Li^＋发生配位的原子. 碳原子的配位位移值随混合溶剂组成的变化关系表明, 在LiClO₄＋PC＋DMF混合物中, DMF分子对Li^＋的溶剂化作用较PC分子强. 定量计算得到, 在n(PC)∶n(DMF)＝1∶1(摩尔比)的混合溶剂中, PC与DMF分子数在Li^＋第一溶剂化层中的比率为0.12, 说明Li^＋优先被DMF分子溶剂化.     

Structure and dynamics of halogenoethanol-water mixtures studied by large-angle X-ray scattering, small-angle neutron scattering, and NMR relaxation

To clarify the structure of solvent clusters formed in halogenoethanol-water mixtures at the molecular level, large-angle X-ray scattering (LAXS) measurements have been made at 298 K on 2,2,2-trifluoroethanol (TFE), 2,2,2-trichloroethanol (TCE), and their aqueous mixtures in the TFE and TCE mole fraction ranges of 0.002 < or = x(TFE) < or = 0.9 and 0.5 < or = x(TCE) < or = 0.9, respectively. The radial distribution functions (RDFs) for TFE-water mixtures have shown that the structural transition from inherent TFE structure to the tetrahedral-like structure of water takes place at x(TFE) approximately 0.2. In the TCE-water mixtures inherent TCE structure remains in the range of 0.5 < or = x(TCE) < or = 1. Small-angle neutron scattering (SANS) experiments have been performed on CF(3)CH(2)OD- (TFE-d(1)-) D(2)O and CF(3)CD(2)OH- (TFE-d(2)-) H(2)O mixtures in the TFE mole fraction range of 0.05 < or = x(TFE) < or = 0.8. The SANS results in terms of the Ornstein-Zernike correlation length have revealed that TFE and water molecules are most heterogeneously mixed with each other in the TFE-water mixture at x(TFE) approximately 0.15, i.e., both TFE clusters and water clusters are most enhanced in the mixture. To evaluate the dynamics of TFE and ethanol (EtOH) molecules in TFE-water and ethanol-water mixtures, respectively, (1)H NMR relaxation rates for the methylene group within alcohol molecules have been measured by using an inversion-recovery method. The alcohol concentration dependence of the relaxation rates for the TFE-water and ethanol-water mixtures has shown a break point at x(TFE) approximately 0.15 and x(EtOH) approximately 0.2, respectively, where the structural transition from alcohol clusters to the tetrahedral-like structure of water takes place. On the basis of the present results, the most likely structure models of solvent clusters predominantly formed in TFE-water and TCE-water mixtures are proposed. In addition, effects of halogenation of the hydrophobic groups on clustering of alcohol molecules are discussed from the present results, together with the previous ones for ethanol-water and 1,1,1,3,3,3-hexafluoro-2-propanol- (HFIP-) water mixtures.     

Study of the interaction of GFG tripeptide with cesium perfluorooctanoate micelles by means of NMR spectroscopy and MD simulations

The interaction of glycyl-phenylalanyl-glycine (GFG) with bilayers formed by cesium perfluorooctanoate (CsPFO) in water was investigated in the isotropic phase by means of 1H NMR and molecular dynamics (MD) simulations. Details on the preferential location of the different residues of GFG were obtained from selective variations of chemical shift with peptide concentration and of line width in the presence of the paramagnetic ion Mn2+. The analysis of 1H NMR spectra recorded at different concentrations and temperatures allowed the association constant and the enthalpy change upon binding to be evaluated. MD simulations highlighted the hydrogen bonds formed between the different GFG functional groups and the micelle. Both NMR and MD gave indications of high affinity of GFG with the micelle, with the N-terminal residue anchoring on the surface via hydrogen bonds with the micelle COO(-) groups.     

The intermolecular structure of phosphoric acid-N,N-dimethylformamide mixtures as studied by computer simulation

The computer simulation of H(3)PO(4)-N,N-dimethylformamide (DMF) mixtures over the whole concentration range using molecular dynamic (MD) methods has been carried out. The preferential orientations of the nearest neighbors of H(3)PO(4) and DMF molecules were obtained using the ranked radial distribution functions technique. On the basis of MD results, the parameters of hydrogen bonds between molecules in mixture were calculated. The changes of the intermolecular structure of mixture as a function of acid composition over the whole concentration range were analyzed and reported. Analysis of O···H distance distributions and angles between O-H (H(3)PO(4)) and C=O (DMF) or P=O (H(3)PO(4)) vector distributions showed that O(DMF) and O(H(3)PO(4)) may each have two hydrogen bonds.     

NMR studies of carbon dioxide and methane self-diffusion in ZIF-8 at elevated gas pressures

Self-diffusion measurements with methane and carbon dioxide adsorbed in the Zeolitic Imidazolate Framework-8 (ZIF-8) were performed by ¹H and ¹³C pulsed field gradient nuclear magnetic resonance (PFG NMR). The experiments were conducted at 298 K and variable pressures of 7 to 15 bar in the gas phase above the ZIF-8 bed. Via known adsorption isotherms these pressures were converted to loadings of the adsorbed molecules. The self-diffusion coefficients of carbon dioxide measured by PFG NMR are found to be independent of loading. They are in good agreement with results from molecular dynamic (MD) simulations and resume the trend previously found by IR microscopy at lower loadings. Methane diffuses in ZIF-8 only slightly slower than carbon dioxide. Its experimentally obtained self-diffusion coefficients are about a factor of two smaller than the corresponding values determined by MD simulations using flexible frameworks.     

Multivariate estimation between mid and near-infrared spectra of hexafluoroisopropanol-water mixtures.

Multivariate regression based on partial least squares (PLS2) was applied to estimating one spectral dataset from another set having an intrinsic relationship with each other. An estimation was successfully carried out between mid-infrared (IR) spectra in the range of 2980 - 3800 cm(-1) and that of near-infrared (NIR) spectra in the range of 6000 - 7500 cm(-1) for hexafluoroisopropanol (HFIP)-water mixtures. The result demonstrates that, after building a suitable regression model, not only NIR spectra, but also well-resolved IR spectra of HFIP-water mixture can be estimated properly in this way. The use of IR and NIR spectroscopy together with PLS2 regression will not only alleviate laborious and costly measurements, but also open a way to provide easier assignments of generally weak and highly overlapped NIR spectral bands.     

All-atom Molecular Dynamic Simulations and NMR Spectra Study on Intermolecular Interactionsof N,N-dimethylacetamide-Water System

N,N-dimethylacetamide (DMA) has been investigated extensively in studying models of peptide bonds. An all-atom MD simulation and the NMR spectra were performed to investigate the interactions in the DMA-water system. The radial distribution functions (RDFs) and the hydrogen-bonding network were used in MD simulations. There are strong hydrogen bonds and weak C-H￠ ￠ ￠O contacts in the mixtures, as shown by the analysis of the RDFs. The insight structures in the DMA-water mixtures can be classified into different regions by the analysis of the hydrogen-bonding network. Chemical shifts of the hydrogen atom of water molecule with concentration and temperatures are adopted to study the interactions in the mixtures. The results of NMR spectra show good agreement with the statistical results of hydrogen bonds in MD simulations.     

Effect of the TBP and water on the complexation of uranyl nitrate and the dissolution of nitric acid into supercritical CO2. A Theoretical Study

We report theoretical studies on the complexation of uranyl nitrate and the dissolution of nitric acid in supercritical CO2 by TBP. According to quantum mechanical calculations, TBP (modeled by trimethyl phosphate TMP) displays stronger hydrogen-bonding interactions with HNO3 than with H2O, and this has been modeled in force-field calculations. Different combinations of water, TBP, and acid are compared in SC-CO2 and simulated by molecular dynamics (MD), demonstrating the importance of TBP and water concentrations. In MD simulations, which started from "random" mixtures of water, TBP, nitric acid, and uranyl nitrate, complexation of uranyl by TBP is observed and the yield increases with the TBP concentration. TBP molecules are also necessary to dissolve nitric acid in the supercritical phase. Indeed, without TBP, nitric acid alone self aggregates via hydrogen-bonding interactions. Adding water to this solution leads to the formation of water microdomains containing the acid and uranyl salts. The simulations show that a high TBP/nitric acid ratio is needed to fully dissolve the acid in the supercritical phase and to form CO2-philic UO2(NO3)2(TBP)2 complexes. The resulting hydrogen-bonding and solvation patterns are analyzed. The results are consistent with experimental observations and provide microscopic views of this important extraction system.     

The dynamics of water at DNA interfaces: computational studies of Hoechst 33258 bound to DNA

Together, spectroscopy combined with computational studies that relate directly to the experimental measurements have the potential to provide unprecedented insight into the dynamics of important biological processes. Recent time-resolved fluorescence experiments have shown that the time scales for collective reorganization at the interface of proteins and DNA with water are more than an order of magnitude slower than in bulk aqueous solution. The molecular interpretation of this change in the collective response is somewhat controversial some attribute the slower reorganization to dramatically retarded water motion, while others describe rapid water dynamics combined with a slower biomolecular response. To connect directly to solvation dynamics experiments of the fluorescent probe Hoechst 33258 (H33258) bound to DNA, we have generated 770 ns of molecular dynamics (MD) simulations and calculated the equilibrium and nonequilibrium solvation response to excitation of the probe. The calculated time scales for the solvation response of H33258 free in solution (0.17 and 1.4 ps) and bound to DNA (1.5 and 20 ps) are highly consistent with experiment (0.2 and 1.2 ps, 1.4 and 19 ps, respectively). Decomposition of the calculated response revealed that water solvating the probe bound to DNA was still relatively mobile, only slowing by a factor of 2-3, while DNA motion was responsible for the long-time component (approximately 20 ps).     

RbCl由H2O至混合溶剂(H2O-DMF)标准迁移熵的测定

电解质迁移热力学性质的测定,对于离子溶剂化的研究具有重要意义.迁移自由能主要反映离子与溶剂分子间的相互作用,迁移熵则主要反映不同溶剂分子间的相互作用,迁移熵随温度及溶剂组成的改变可为溶剂的原有结构推测及溶液秩序改变提供信息.我们曾运用离子选择性电极测定了部分碱金属卤化物在水及含水混合溶剂中的热力学性质[1-3].本文用离子选择性电极方法,通过测定不同温度下电池的标准电动势,根据溶液热力学原理,求得ＲｂＣｌ由Ｈ2Ｏ至混合溶剂(Ｈ2ＯＤＭＦ)的标准迁移自由能ΔＧｔ及其温度系数,计算ＲｂＣｌ的标准迁移熵ΔＳｔ.结果尚未见…     

Solvation of transmembrane proteins by isotropic membrane mimetics: a molecular dynamics study

Mixtures of organic solvents are often used as membrane mimetics in structure determination of transmembrane proteins by solution NMR; however, the mechanism through which these isotropic solvents mimic the anisotropic environment of cell membranes is not known. Here, we use molecular dynamics simulations to study the solvation thermodynamics of the c-subunit of Escherichia coli F1F0 ATP synthase in membrane mimetic mixtures of methanol, chloroform, and water with varying fractions of components as well as in lipid bilayers. We show that the protein induces a local phase separation of the solvent components into hydrophobic and hydrophilic layers, which provides the anisotropic solvation environment to stabilize the amphiphilic peptide. The extent of this effect varies with solvent composition and is most pronounced in the ternary methanol-chloroform-water mixtures. Analysis of the solvent structure, including the local mole fraction, density profiles, and pair distribution functions, reveals considerable variation among solvent mixtures in the solvation environment surrounding the hydrophobic transmembrane region of the protein. Hydrogen bond analysis indicates that this is primarily driven by the hydrogen-bonding propensity of the essential Asp(61) residue. The impact of the latter on the conformational stability of the solvated protein is discussed. Comparison with the simulations in explicit all-atom models of lipid bilayer indicates a higher flexibility and reduced structural integrity of the membrane mimetic solvated c-subunit. This was particularly true for the deprotonated form of the protein and found to be linked to solvent stabilization of the charged Asp(61).