M. V. Fedotova

Hydration and Ion Binding of the Osmolyte Ectoine

Ectoine is a widespread osmolyte enabling halophilic bacteria to withstand high osmotic stress that has many potential applications ranging from cosmetics to its use as a therapeutic agent. In this contribution, combining experiment and theory, the hydration and ion-binding of this zwitterionic compound was studied to gain information on the functioning of ectoine in particular and of osmolytes in general. Dielectric relaxation spectroscopy was used to determine the effective hydration number of ectoine and its effective dipole moment in aqueous solutions with and without added NaCl. The obtained experimental data were compared with structural results from 1D-RISM and 3D-RISM calculations. It was found that ectoine is strongly hydrated, even in the presence of high salt concentrations. Upon addition of NaCl, ions are bound to ectoine but the formed complexes are not very stable. Interestingly, this osmolyte strongly rises the static relative permittivity of its solutions, shielding thus effectively long-range Coulomb interactions among ions in ectoine-containing solutions. We believe that via this effect, which should be common to all zwitterionic osmolytes, ectoine protects against excessive ions within the cell in addition to its strong osmotic activity protecting against ions outside.

Integral Equation Theory of Molecular Solvation Coupled with Quantum Mechanical/Molecular Mechanics Method in NWChem Package.

We have developed a hybrid approach based on a combination of integral equation theory of molecular liquids and quantum mechanical/molecular mechanics (QM/MM) methodology in NorthWest computational Chemistry (NWChem) software package. We have split the evaluations into consequent QM/MM and statistical mechanics calculations based on the one-dimensional reference interaction site model, which allows us to reduce significantly the time of computation. The method complements QM/MM capabilities existing in the NWChem package. The accuracy of the presented method was tested through computation of the water structure around several organic solutes and their hydration free energies. We have also evaluated the solvent effect on the conformational equilibria. The applicability and limitations of the developed approach are discussed.

Ion-binding of glycine zwitterion with inorganic ions in biologically relevant aqueous electrolyte solutions.

The ion-binding between inorganic ions and charged functional groups of glycine zwitter-ion in NaCl(aq), KCl(aq), MgCl2(aq), and CaCl2(aq) has been investigated over a wide salt concentration range by using integral equation theory in the 3D-RISM approach. These systems mimic biological systems where binding of ions to charged residues at protein surfaces is relevant. It has been found that the stability of ion pairs formed by the carboxylate group and added inorganic cations decreases in the sequence Mg(2+)>Ca(2+)>Na(+)>K(+). However, all formed ion pairs are weak and decrease in stability with increasing salt concentration. On the other hand, at a given salt concentration the stability of (-NH3(+):Cl(-))aq ion pairs is similar in all studied systems. The features of ion-binding and the salt concentration effect on this process are discussed.

Structure formation of aqueous electrolyte solutions under extreme conditions by the extended RISM-approach. A possibility of predicting

Abstract In the present study the possibility to use the extended RISM-approach in conjunction with the modified TIPS-water model for predicting structural properties of aqueous electrolyte solutions under extreme conditions (high pressure and high temperatures) is considered. The structural characteristics are computed by the site-site Ornstein-Zernike integral equation in the framework of hypernetted chain closure for aqueous LiCl and NaCl solutions with different state parameters. The effect of temperature and pressure on structure formation of these systems is under observation during the research. The obtained results are compared with experimental structural work data and computer simulations for the same objects. The agreement between our data and those available from the literature proves the possibility to use the extended RISM-approach for predicting structural parameters of liquid state systems in state parameter regions, which are problematic for making experiments.

Ion-selective interactions of biologically relevant inorganic ions with alanine zwitterion: a 3D-RISM study

The ion-molecular association between inorganic ions and the charged groups of alanine zwitterion in biologically relevant aqueous salt solutions, namely NaCl(aq), KCl(aq), MgCl2(aq), and CaCl2(aq), has been investigated over a wide range of electrolyte concentration. The influence of salt concentration on the stability of the formed ion-molecular associates is analyzed. The structure of the formed aggregates and its dependence on salt concentration and chemical nature of the inorganic ion are discussed.

Hydration of methylamine and methylammonium ion: structural and thermodynamic properties from the data of the integral equation method in the RISM approximation

The structural and thermodynamic properties of hydration of methylamine and methyl-ammonium ion were investigated by the integral equations method in the RISM approximation. According to calculations, the average number of water molecules in the first hydration shell of CH3 group is 14.4 for aqueous methylamine and 12.7 for aqueous methylammonium solution. The first hydration shells of the NH2 group of methylamine and the NH3+ group of methylammonium ion contain 6.9 and 5.6 water molecules, respectively. The average number of H-bonds formed by the NH2 group is 2.4 and that formed by the NH3+ group is 3. The results obtained show no H-bonding between the nitrogen atom of NH3+ group of methylammonium and water molecules. The hydrogen atom of water participating in the hydrogen bonding with the nitrogen atom of methylamine now is a constituent of the NH3+ group of methylammonium ion. The hydration free energies and the ionization constant calculated within the framework of the RISM theory are in good agreement with experimental data.

Mobility and association of ions in aqueous solutions: the case of imidazolium based ionic liquids

The mobility and the mechanism of ion pairing of 1,1 electrolytes in aqueous solutions were investigated systematically on nine imidazolium based ionic liquids (ILs) from 1-methylimidazolium chloride, [MIM][Cl], to 1-dodecyl-3-methylimidazolium chloride, [1,3-DoMIM][Cl], with two isomers 1,2-dimethylimidazolium chloride, [1,2-MMIM][Cl], and 1,3-dimethylimidazolium chloride, [1,3-MMIM][Cl]. Molecular dynamics (MD) simulations, statistical mechanics calculations in the framework of the integral equation theory using one-dimensional (1D-) and three-dimensional (3D-) reference interaction site model (RISM) approaches as well as conductivity measurements were applied. From experiment and MD simulations it was found that the mobility/diffusion coefficients of cations in the limit of infinite dilution decrease with an increasing length of the cation alkyl chain, but not linearly. The aggregation tendency of cations with long alkyl chains at higher IL concentrations impedes their diffusivity. Binding free energies of imidazolium cations with the chloride anion estimated by RISM calculations, MD simulations and experiments reveal that the association of investigated ILs as model 1,1 electrolytes in water solutions is weak but evidently dependent on the molecular structure (alkyl chain length), which also strongly affects the mobility of cations.

Characterization of selective binding of biologically relevant inorganic ions with the proline zwitterion by 3D-RISM theory

Selective binding between the charged groups of the proline zwitterion (Pro-ZW) and several biologically relevant mono- and divalent inorganic ions (Na+, K+, Mg2+, Ca2+, Cl−) was studied over a wide range of electrolyte concentrations using integral equation theory in the three-Dimensional Reference Interaction Site Model (3D-RISM) approach. These model samples mimic ion pairing between charged functional groups at protein surfaces and physiologically relevant ions. The effects of salt concentration and chemical nature of the inorganic ion on the stability of the formed ion–molecular associates are analyzed. Additionally, the possible mechanism of ion binding and the structure of the formed aggregates are discussed.

Special features of structure formation of sodium chloride concentrated aqueous solution on its passing to supercritical state

Structural properties of aqueous 4.37 M solution of NaCl under sub-and supercritical conditions (p 25 MPa, T 450–750 K) were studied by the method of integral equations in the atom-atom approximation. The passing of the system to the supercritical state is accompanied by a substantial rearrangements in local structural fragments with hydrogen bonds and in the nearest surrounding of the ions. In this case a transition is observed from the solution structure with hydrated ions and ionic pairs (subcritical region) to the structure with free molecules and low-molecular formations, probably, in the form of clusters (supercritical region).

Hydration structure of osmolyte TMAO: concentration/pressure-induced response

Despite the well-known fact that the natural osmolyte trimethylamine-N-oxide (TMAO) is able to prevent protein denaturation and to stabilize the folded state of proteins in living cells under abiotic stress, much of its molecular mechanism of action remains elusive. At the moment, there is some evidence that osmolytes, including TMAO, do not interact with proteins directly but only through a water layer. It is supposed that their protective mechanism should be mediated and determined largely by their hydration, i.e. by osmolyte interactions with surrounding water. However, to date the details of these interactions are far from being fully understood. To gain further insight into the mechanism behind the protecting effect of osmolytes statistical mechanics calculations in the framework of 1D- and 3D-RISM (reference interaction site model) approaches were performed to yield information on the impact of solute concentration and pressure on the hydration structure of TMAO. An attempt was made to link the structural features of TMAO hydration to its biological role.