Macromolecules In Aqueous Solution Research Articles

Ability of the Poisson-Boltzmann equation to capture molecular dynamics predicted ion distribution around polyelectrolytes.

Here, we examine polyelectrolyte (PE) and ion chemistry specificity in ion condensation via all-atom molecular dynamics (MD) simulations and assess the ability of the Poisson-Boltzmann (PB) equation to describe the ion distribution predicted by the MD simulations. The PB model enables the extraction of parameters characterizing ion condensation. We find that the modified PB equation which contains the effective PE radius and the energy of the ion-specific interaction as empirical fitting parameters describes ion distribution accurately at large distances but close to the PE, especially when strongly localized charge or specific ion binding sites are present, the mean field description of PB fails. However, the PB model captures the MD predicted ion condensation in terms of the Manning radius and fraction of condensed counterions for all the examined PEs and ion species. We show that the condensed ion layer thickness in our MD simulations collapses on a single master curve for all the examined simple, monovalent ions (Na+, Br+, Cs+, Cl-, and Br-) and PEs when plotted against the Manning parameter (and consequently the PE line charge density). The significance of this finding is that, contrary to the Manning radius extracted from the mean field PB model, the condensed layer thickness in the all atom detail MD modelling does not depend on the PE chemistry or counterion type. Furthermore, the fraction of condensed counterions in the MD simulations exceeds the PB theory prediction. The findings contribute toward understanding and modelling ion distribution around PEs and other charged macromolecules in aqueous solutions, such as DNA, functionalized nanotubes, and viruses.

Surprising Hofmeister Effects on the Bending Vibration of Water.

The Hofmeister series, which originally described the specific ion effects on the solubility of macromolecules in aqueous solutions, has been a long-standing unsolved and exceptionally challenging mystery in chemistry. The complexity of specific ion effects has prevented a unified theory from emerging. Accumulating research has suggested that the interactions among ions, water and various solutes play roles. However, among these interactions, the binding between ions and solutes is receiving most of the attention, whereas the effects of ions on the hydrogen-bond structure in liquid water have been deemed to be negligible. In this study, attenuated-total-reflectance Fourier transform infrared spectroscopy is used to study the infrared spectra of salt solutions. The results show that the red- and blue-shifts of the water bending band are in excellent agreement with the characteristic Hofmeister series, which suggests that the ions' effects on water structure might be the key role in the Hofmeister phenomenon.

On the existence of two states in liquid water: impact on biological and nanoscopic systems

This work reviews several properties of liquid water, including the dielectric constant and the proton-spin lattice relaxation, and draws attention to a bilinear behaviour defining a crossover in the temperature range 50 ± 10°C between two possible states in liquid water. The existence of these two states in liquid water plays an important role in nanometric and biological systems. For example, the optical properties of metallic (gold and silver) nanoparticles dispersed in water, used as nanoprobes, and the emission properties of CdTe quantum dots (QDs), used for fluorescence bioimaging and tumour targeting, show a singular behaviour in this temperature range. In addition, the structural changes in liquid water may be associated with the behaviour of biological macromolecules in aqueous solutions and in particular with protein denaturation.

Синтез и исследование гидрофобно-модифицированных полимерных бетаинов

Polymeric betaines containing long alkyl chains C 12 H 25 , C 14 H 29 , C 16 H 33 and C 18 H 37 were synthesized by Michael addition reaction of alkylaminocrotonates and methacrylic acid (MAA). They were characterized by FTIR, 13 C NMR, DSC, DLS, GPC, cryo-TEM, viscometry and zeta-potential measurements. The polymers were fully soluble in DMF, THF and DMSO, partially dissolved in aromatic hydrocarbons (benzene, toluene, o-xylene) and formed colloid solutions in aqueous KOH. In aqueous KOH and DMSO solutions, hydrophobically modified polymeric betaines behaved as polyelectrolytes. The average hydrodynamic size and zeta potential of diluted aqueous solutions of hydrophobic polybetainess containing dodecyl-, tetradecyl-, hexadecyl-, and octadecyl groups were studied as a function of pH. Anomalous low values of the isoelectric point (IEP) of amphoteric macromolecules were found to be in the range of pH 2.7-3.4. According to DLS data, the average size of macromolecules tends to decrease with dilution. Zeta-potential of amphoteric macromolecules in aqueous solution is much higher than that in DMSO. The cryo-TEM results revealed that in both aqueous KOH and DMSO media, the micron- and nanosized vesicles existed. The structural organization of vesicles in water and DMSO is discussed. The wax inhibition effect of hydrophobic polybetaines at a decrease of the pour point temperatures of high paraffinic oils was better in comparison with commercial available ethylene-vinylacetate copolymers (EVA).

Temperature- and salt-responsive polyoxometalate-poly(N-isopropylacrylamide) hybrid macromolecules in aqueous solution.

Polyoxometalate (POM) polar head groups were covalently functionalized with poly(N-isopropylacrylamide) (PNIPAM) tails. The macromolecular hybrid demonstrates solution behavior of hydrophilic macroions by self-assembling into blackberry structures at room temperature. The hybrid behaves like an amphiphilic surfactant by forming a vesicular structure when the temperature is above the phase transition of PNIPAM. The reversible self-assembly is also salt-sensitive and the salt-induced smaller vesicular formation results from counterion-association.

NMR Evidence for Unusual Bifurcated Hydrogen Bonding in the TXXH Alpha-Helix N-capping Motif

Hydrogen bonds (H-bonds) are generally weak (< 20 kJ/mol) but ubiquitous interactions that determine in large part the cooperative folding and self-assembly of biological macromolecules in aqueous solution. Although important, most H-bonds are inferred indirectly and modeled using theoretical idealized geometry, therefore leaving instances of bifurcated or strained H-bonds undetected. Here, we present direct solution NMR evidence for an unusual bifurcated H-bonding arrangement comprising threonine Og-H and N-H donor protons and histidine acceptor Nd1 within the conserved TXXH alpha-helix N-capping motif of consensus ankyrin repeat (AR) proteins.The threonine N-H⋯Nd1 histidine H-bonds were detected in the TXXH motif of three and four-repeat AR proteins via 2hJNN hydrogen bond scalar coupling (HBC) NMR correlation experiments. Comparison of the 2hJNN couplings and histidine pKa values demonstrated that the N-H⋯Nd1 H-bonds of internal AR (2hJNN ∼ 4 Hz, pKa < 3) were stronger than those of the solvent-exposed C-terminal AR (2hJNN ∼ 2 Hz, pKa ∼ 5.7). In addition to the N-H⋯Nd1 2hJNN couplings, we also observed distinct 1hJHN HBCs connecting the threonine Og-H and histidine Nd1 within the TXXH motif of internal ARs. Together, the 2hJNN and 1hJHN HBCs supported that a single histidine Nd1 acceptor had two H-bond donors. Accordingly, two-bond reciprocal isotope shifts were detected between the threonine N-H and Og-H protons in solvents with mixed H2O/D2O composition. Finally, a threonine to valine replacement, which eliminated the Og-H⋯Nd1 H-bond and resulted in a destabilized protein, lead to a relaxed valine N-H⋯Nd1 histidine interaction with enhanced 2hJNN (∼5.2 Hz) likely owing to an optimized bonding geometry. Overall, our results provide new insight into the H-bonding ability of histidine and a challenging benchmark for the calculation of HBCs and their relation to H-bond energetics.Supported by NSF grant MCB-1330488

Molar‐Mass Analysis of Dendrigraft Poly(l‐lysine) (DGL) Polyelectrolytes by SEC‐MALLS: The “Cornerstone” Refractive Index Increment

Dendrigraft poly(l‐lysine) (DGL) polyelectrolytes, obtained by iterative polycondensation of N‐trifluoroacetyl‐l‐lysine‐N‐carboxyanhydride, constitute very promising candidates in many biomedical applications. In order to get a better understanding of their structure–property relationships in these applications, their absolute average molecular weights have to be accurately measured. Size‐exclusion chromatography coupled to a multi‐angle laser‐light‐scattering detector (SEC‐MALLS) is known to be the most appropriate analytical tool. These measurements require the determination of the refractive index increment, dn/dc, of these highly branched polycationic macromolecules in aqueous solution. This optical property has to be measured in the same aqueous conditions as SEC‐MALLS eluents. Consequently, data are determined and discussed as a function of different aqueous SEC‐MALLS eluents, as well as different counter‐ions of the many ammonium groups of DGL (generation 3, DGL‐3, used as a model herein). The resulting number‐average molecular weights, , are found to be very dissimilar when the measured dn/dc values are directly considered. In contrast, very close values are obtained (average = 18 700, standard error of 1110 g mol−1) with a low coefficient of variation for such data (ca. 6% for six analyses), when the dn/dc are corrected by the exact lysine amount (measured by the total Kjeldahl nitrogen method). image

Conformational characteristics of polyethylene glycol macromolecules in aqueous solutions according to refractometry data

The aqueous solutions of polyethylene glycols with molecular masses of 600, 1000, 1500, 3000, 6000, and 20000 were studied by refractometry. The conformational polarizabilities, mean-square distances between the ends of the macromolecular chain, segment lengths, and the number of Kuhn segments in a macromolecule were determined using the Lorentz-Lorentz equation. The polarizability of a hydrated macro-molecule was represented as the sum of polarizabilities of the nonhydrated macromolecule with retained conformation and polarizabilities of the water molecules involved in hydration of macromolecules. The size of macromolecules stabilized starting from a certain concentration. It was concluded that the initial concentration of stabilization shifts toward low concentrations as the molecular mass of polyethylene glycol increases. The dependence of the mean-square distance between the ends of the macromolecular chain on the number of Kuhn segments was expressed as the exponential function with index 0.3.

NMR Study of Thermoresponsive Hyperbranched Polymer in Aqueous Solution with Implication on the Phase Transition

High-resolution 1H NMR has been used on the thermoresponsive hyperbranched polyethylenimines (HPEIs) modified with isobutyramide (IBAm) groups (HPEI-IBAm), to study the structure and dynamics of the macromolecules in aqueous solution before and after the phase transition. It shows that the HPEI-IBAm macromolecule having a high IBAm substitution degree has a clear phase transition in aqueous solution, whereas the HPEI-IBAm macromolecule having a low IBAm substitution degree does not. The different phase transition behaviors have been attributed to the content as well as the distribution of the IBAm groups in the macromolecules. In order to deepen the understanding of the phase transition, the hydrophobic–hydrophobic interaction inside the HPEI-IBAm macromolecules was investigated by monitoring the 1H–1H NOEs between the different hydrophobic groups. An enhanced hydrophobic–hydrophobic interaction was observed in the HPEI-IBAm macromolecule having a high IBAm substitution degree after the phase transition, ...

Features of rotational modes of vibrations of water molecules in free and bound states

The paper considers rotational (including librational - dimensional rotational) vibrations and the number of corresponding vibrational modes for molecules of water in its various physical phase states - liquid, ice and bound. The main purpose of the research is comparative analysis of vibrational modes of molecules of water in different phase states, taking into account the results of previous paper [6] on vibrational modes of molecules in liquid water. The analysis of changes in the number of rotational modes of molecules of water for its various phase states and physical consequences of these changes for physical and thermal properties of water was conducted. Increased force of hydrogen bonds of water molecules in ice or ice-like state leads to reducing the number of rotational vibration modes, and accordingly, the number of degrees of freedom of molecules and heat capacity of the phase. State, mobility and structure of macromolecules in aqueous solutions are determined by the strength of ice-like skeleton/corset of their hydration shell formed by bound water molecules.

Entropy–enthalpy compensation of biomolecular systems in aqueous phase: a dry perspective

We survey thermodynamic measurements on processes involving biological macromolecules in aqueous solution, which illustrate well the ubiquitous phenomenon of entropy-enthalpy compensation. The processes include protein folding/unfolding and ligand binding/unbinding, with compensation temperatures varying by about 50 K around an average near 293 K. We show that incorporating both near-exact entropy-enthalpy compensation (due to solvent relaxation) and multi-excitation entropy (from vibrational quanta) leads to a compensation temperature in water of about 230 K. We illustrate a general procedure for subtracting solvent and environment-related terms to determine the bare Gibbs free energy changes of chemical processes.

Development of Methods to Observe a Living Cell and Macromolecules in Aqueous Solution with Scanning Electron Microscope at Nanometer Resolution

In electron microscopy, transparency of specimens against a beam of electrons in TEM or intensity of secondary electrons and so on induced by an incident electron beam in SEM is translated into contrast. Any material surrounding a specimen, which prevents electron beam passing or detection of secondary electrons, obstructs to create an image. Hence, electron microscopy intrinsically requires high voltage electron beam irradiation of specimens and high vacuum under 10-4 Pa in the cell for specimens. Water in samples must be replaced with some resins or completely dried up. These conditions make it difficult to observe wet or living samples like enzymes retaining catalytic activities or living cells in aqueous solution. To image wet and living samples using electron microscopy at nanometer resolution, we are developing a new wet cell for SEM whereby living cells and enzymes can be maintained in aqueous solution. A carbon thin layer with thickness of 20 nm was made by vacuum evaporation. We applied it as a diaphragm withstanding a pressure gap for separating a specimen in solution at atmospheric pressure from high vacuum environment. Cells and enzymes were placed on its surface of the atmospheric side. They were imaged using SEM. The EM photographs show detailed structures of the cell membrane and the enzymes.

Controlling molecular transport through nanopores

Nanopores are emerging as powerful tools for the detection and identification of macromolecules in aqueous solution. In this review, we discuss the recent development of active and passive controls over molecular transport through nanopores with emphasis on biosensing applications. We give an overview of the solutions developed to enhance the sensitivity and specificity of the resistive-pulse technique based on biological and solid-state nanopores.

Application of Molecular Dynamics Simulations in Molecular Property Prediction. 1. Density and Heat of Vaporization

Molecular mechanical force field (FF) methods are useful in studying condensed phase properties. They are complementary to experiment and can often go beyond experiment in atomic details. Even a FF is specific for studying structures, dynamics and functions of biomolecules, it is still important for the FF to accurately reproduce the experimental liquid properties of small molecules that represent the chemical moieties of biomolecules. Otherwise, the force field may not describe the structures and energies of macromolecules in aqueous solutions properly. In this work, we have carried out a systematic study to evaluate the General AMBER Force Field (GAFF) in studying densities and heats of vaporization for a large set of organic molecules that covers the most common chemical functional groups. The latest techniques, such as the particle mesh Ewald (PME) for calculating electrostatic energies, and Langevin dynamics for scaling temperatures, have been applied in the molecular dynamics (MD) simulations. For density, the average percent error (APE) of 71 organic compounds is 4.43% when compared to the experimental values. More encouragingly, the APE drops to 3.43% after the exclusion of two outliers and four other compounds for which the experimental densities have been measured with pressures higher than 1.0 atm. For heat of vaporization, several protocols have been investigated and the best one, P4/ntt0, achieves an average unsigned error (AUE) and a root-mean-square error (RMSE) of 0.93 and 1.20 kcal/mol, respectively. How to reduce the prediction errors through proper van der Waals (vdW) parameterization has been discussed. An encouraging finding in vdW parameterization is that both densities and heats of vaporization approach their "ideal" values in a synchronous fashion when vdW parameters are tuned. The following hydration free energy calculation using thermodynamic integration further justifies the vdW refinement. We conclude that simple vdW parameterization can significantly reduce the prediction errors. We believe that GAFF can greatly improve its performance in predicting liquid properties of organic molecules after a systematic vdW parameterization, which will be reported in a separate paper.

Hydration‐mediated effects of saccharide stereochemistry on poly(N‐isopropylacrylamide) gel swelling

AbstractTo shed new light on the mechanisms of saccharide stereochemistry effect on macromolecules in aqueous solutions, we studied the effect of three monosaccharide stereoisomers, glucose, galactose, and mannose, on the swelling of Poly(N‐isopropylacrylamide) (PNIPA) hydrogels. We equilibrated PNIPA hydrogels in sugar solutions of different concentrations at 25 °C, and determined gel volume and mass swelling ratios, and sugar concentration imbalance. The volume‐phase‐transition occurred at molal concentrations of 0.587 ± 0.004 (galactose), 0.724 ± 0.003 (glucose), and 0.846 ± 0.004 (mannose). The same order of sugars emerged for the gel‐swelling and the magnitude of the sugar concentration‐imbalance, which correlated with sugar isentropic molar compressibility and hydration number. The more hydrated the sugar, the worse a cosolvent it is for the polymer, hence the larger the deswelling and the more negative the sugar concentration imbalance. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2011

Radiation damage to DNA-protein complexes

We review here the advances in understanding the effects of ionizing radiations on DNA, proteins and their complexes, resulting from the collaboration of the authors' teams. It concerns the preponderant indirect effect of low LET ionizing radiations, thus the attack of the macromolecules in aqueous solution by the most aggressive product of water radiolysis, the hydroxyl radical. A model of simulation of the reaction of these radicals with the macromolecules (called RADACK) was developed and was used for calculating the probabilities of damage of each constituent of DNA or proteins (nucleotide or amino-acid). The calculations allowed to draw conclusions from electrophoresis, mutagenesis, spectroscopic (fluorescence, circular dichroïsm) and mass spectrometry experiments. Thus we have shown that the extent and location of the lesions are strongly dependent on the 3D structure of the macromolecules, which in turns is modulated by their sequence and by the binding of some ligands. Molecular dynamics simulation completed our studies in showing the consequences of each lesion on the stability and structure of the proteins and their complexes with DNA.

Aggregation behavior of gemini surfactants and their interaction with macromolecules in aqueous solution

Gemini surfactants are constructed by two hydrophobic chains and two polar/ionic head groups covalently connected by a spacer group at the level of the head groups. Gemini surfactants possess unique structural variations and display special aggregate transitions. Their aggregation ability and aggregate structures can be more effectively adjusted through changing their molecular structures compared with the corresponding monomeric surfactants. Moreover, gemini surfactants exhibit special and useful properties while interacting with polymers and biomacromolecules. Their strong self-aggregation ability can be applied to effectively influence the aggregation behavior of both polymers and biomacromolecules. This short review is focused on the performances of gemini surfactants in aqueous solutions investigated in the last few years, and summarizes the effects of molecular structures on aggregation behavior of gemini surfactants in aqueous solution as well as the interaction of gemini surfactants with polymers and biomacromolecules respectively.

Quadrupole Central Transition 17O NMR Spectroscopy of Biological Macromolecules in Aqueous Solution

We demonstrate a general nuclear magnetic resonance (NMR) spectroscopic approach in obtaining high-resolution (17)O (spin-5/2) NMR spectra for biological macromolecules in aqueous solution. This approach, termed quadrupole central transition (QCT) NMR, is based on the multiexponential relaxation properties of half-integer quadrupolar nuclei in molecules undergoing slow isotropic tumbling motion. Under such a circumstance, Redfield's relaxation theory predicts that the central transition, m(I) = +1/2 ↔ -1/2, can exhibit relatively long transverse relaxation time constants, thus giving rise to relatively narrow spectral lines. Using three robust protein-ligand complexes of size ranging from 65 to 240 kDa, we have obtained (17)O QCT NMR spectra with unprecedented resolution, allowing the chemical environment around the targeted oxygen atoms to be directly probed for the first time. The new QCT approach increases the size limit of molecular systems previously attainable by solution (17)O NMR by nearly 3 orders of magnitude (1000-fold). We have also shown that, when both quadrupole and shielding anisotropy interactions are operative, (17)O QCT NMR spectra display an analogous transverse relaxation optimized spectroscopy type behavior in that the condition for optimal resolution depends on the applied magnetic field. We conclude that, with the currently available moderate and ultrahigh magnetic fields (14 T and higher), this (17)O QCT NMR approach is applicable to a wide variety of biological macromolecules. The new (17)O NMR parameters so obtained for biological molecules are complementary to those obtained from (1)H, (13)C, and (15)N NMR studies.

Solvent-controlled self-assembly of amphiphilic cholic acid-modified PAMAM dendrimers

Here we present the special self-assembly properties of the amphiphilic macromolecules made from G1 PAMAM dendrimers partially modified with cholic acid. These cholic acid-derived macromolecules can self-assemble in both apolar and polar solvents. The aggregates of these macromolecules in toluene can partially extract hydrophilic molecules from water to toluene. The macromolecules in aqueous solutions can form multiple morphological aggregates which are nanoparticles below pH 10.0 and microparticles above pH 13.0. The nanoparticles release methotrexate, an anticancer drug, in a pH-dependent manner. The results indicate that the solvent-controlled self-assemblies may make the macromolecules good candidates for pH-controlled drug release carriers with good cell membrane permeability. This macromolecule may have potential applications in intracellular drug delivery systems.

Influence of pH on the behavior of lignosulfonate macromolecules in aqueous solution

The solution behavior of purified sodium lignosulfonate (PSL) at different pH values were investigated by means of acid–base titration, surface tension, viscosity, fluorescence spectrometry, dynamic light scattering (DLS) and environmental scanning electron microscopy (ESEM) experiments. Fluorescence experiments showed that the critical aggregate concentration (CAC) of PSL was 0.05 g/L. DLS results indicated that the average dimension of PSL molecule and PSL aggregate was about 8 nm and 80 nm, respectively. The surface charge of PSL molecules and the aggregation degree of PSL in solution increased with the increasing of pH due to the ionization of sulfonic and phenolic hydroxyl groups. The size of PSL aggregates and reduced viscosity of PSL solution increased as pH values increased because expansion of the PSL cores. A model for the assembly behavior of PSL was first proposed to explain the influence of pH on the molecular configuration and aggregation behaviors of lignosulfonate in aqueous solutions.