Molecular rotation as a tool for exploring specific solute-solvent interactions.

Solute-solvent interactions play an important role in determining the physicochemical properties of liquids and solutions. As a consequence, understanding these interactions has been one of the long-standing problems in physical chemistry. This Minireview describes our approach towards attaining this goal, which is to investigate rotational relaxation of a pair of closely related, medium-sized nondipolar solutes in a set of appropriately chosen solvents. Our studies indicate that solute-solvent hydrogen bonding significantly hinders solute rotation. We have also examined the role of solvent size both in the absence and presence of specific interactions and it has been observed that the size of the solvent has a bearing on solute rotation especially in the absence of specific interactions. Our results point to the fact that only strong solute-solvent hydrogen bonds have the ability to impede the rotation of the solute molecule because, in such a scenario, hydrogen-bonding dynamics and rotational dynamics transpire on comparable time scales. This aspect has been substantiated by measuring the reorientation times of the chosen solutes in solvents such as ethanol and trifluoroethanol, which have distinct hydrogen-bond donating and accepting abilities, and correlating them with solute-solvent interaction strengths. As an alternative treatment, it has been shown that specific interactions between the solute and the solvent can be modeled as dielectric friction with the extended charge distribution model. This approach is not unrealistic considering the fact that specific as well as non-specific interactions are electrostatic by nature and the differences between them are subtle.     

Electrostatic interactions of a neutral dipolar solute with a fused salt: a new model for solvation in ionic liquids

Ionic liquids represent a novel and poorly understood class of solvents, and one challenge in understanding these systems is how one should view the electrostatic character of solute-solvent interactions. The highly structured nature of a fused salt makes a dielectric continuum approximation difficult to implement, and there is no obvious connection between the structure of an individual ion and the polarization character of the medium. We address this problem by making the ansatz that rather than polarizing the medium, the solute may be viewed as intercalating in the charge distribution of the neat liquid such that the solvent screens the electric field of the solute. This approach allows derivation of an analytical expression for the distribution of solvent charge about the solute, and this distribution is found to be a close match to simulation data. The theory also predicts that the electrostatic character of solute-solvent interactions should be determined primarily by the number density of solvent ions, a prediction proven correct by analysis of existing experimental data. The approach represents a new model for the interpretation of solvation phenomena in ionic liquids.     

Solute-solvent interactions in micellar electrokinetic chromatography. Characterization of sodium dodecyl sulfate-Brij 35 micellar systems for quantitative structure-activity relationship modelling.

The solvation parameter model has been applied to the characterization of micellar electrokinetic chromatographic (MEKC) systems with mixtures of sodium dodecyl sulfate and Brij 35 as surfactant. The variation in MEKC surfactant composition results in changes in the coefficients of the correlation equation, which in turns leads to information on solute-solvent and solute-micelle interactions. Since the same solvation model can be used to describe many biological processes, particular MEKC surfactant compositions can be selected that model the solute-solvent interactions of some of these processes. Two different MEKC systems have been selected to model the solute-solvent interactions of two processes of biological interest (octanol-water partition and tadpole narcosis).     

Role of solvent for globular proteins in solution

The properties of the solvent affect the behavior of the solution. We propose a model that accounts for the contribution of the solvent free energy to the free energy of globular proteins in solution. For the case of an attractive square-well potential, we obtain an exact mapping of the phase diagram of this model without solvent to the model that includes the solute-solvent contribution. In particular we find for appropriate choices of parameters upper critical points, lower critical points, and even closed loops with both upper and lower critical points similar to those found before [Macromolecules 36, 5843 (2003)]. In the general case of systems whose interactions are not attractive square wells, this mapping procedure can be a first approximation to understand the phase diagram in the presence of solvent. We also present simulation results for both the square-well model and a modified Lennard-Jones model.     

用离散-连续模型计算NH2-,NH3和NH4+的溶剂化自由能

通过理论计算推测NH2-,NH3和NH4+在水溶液第一溶剂化层中与之直接作用的水分子分别为2,4和4个,并采用离散-连续模型计算了NH2-,NH3,NH3和NH4+在水溶液中的溶剂化自由能.结果表明,由于离散-连续模型在从头算水平考虑了溶质分子与第一溶剂化层溶剂分子之间的作用,能更准确地描述溶剂化作用.此外,采用更加符合溶液中真实情况的溶剂化构型,能得到更准确的溶剂化性质.     

Solvent density inhomogeneities and solvation free energies in supercritical diatomic fluids: a density functional approach

Density functional theory is used to explore the solvation properties of a spherical solute immersed in a supercritical diatomic fluid. The solute is modeled as a hard core Yukawa particle surrounded by a diatomic Lennard-Jones fluid represented by two fused tangent spheres using an interaction site approximation. The authors' approach is particularly suitable for thoroughly exploring the effect of different interaction parameters, such as solute-solvent interaction strength and range, solvent-solvent long-range interactions, and particle size, on the local solvent structure and the solvation free energy under supercritical conditions. Their results indicate that the behavior of the local coordination number in homonuclear diatomic fluids follows trends similar to those reported in previous studies for monatomic fluids. The local density augmentation is particularly sensitive to changes in solute size and is affected to a lesser degree by variations in the solute-solvent interaction strength and range. The associated solvation free energies exhibit a nonmonotonous behavior as a function of density for systems with weak solute-solvent interactions. The authors' results suggest that solute-solvent interaction anisotropies have a major influence on the nature and extent of local solvent density inhomogeneities and on the value of the solvation free energies in supercritical solutions of heteronuclear molecules.     

On the molecular origins of volumetric data

We use a statistical thermodynamic approach and a simple thermodynamic model of hydration to examine the molecular origins of the volumetric properties of solutes. In this model, solute-solvent interactions are treated as a binding reaction. The free energy of hydration of the noninteracting solute species coincides with the free energy of cavity formation, while the free energy of solute-solvent interactions is given by the binding polynomial. By differentiating the relationship for the free energy of hydration with respect to temperature and pressure, one obtains the complete set of equations describing the thermodynamic profile of hydration, including enthalpy, entropy, volume, compressibility, expansibility, and so forth. The model enables one to rigorously define in thermodynamic terms the hydration number and the related concept of hydration shell, which are both widely used as operational definitions in experimental studies. Hydration number, nh, is the effective number of water molecules solvating the solute and represents the derivative of the free energy of hydration with respect to the logarithm of water activity. One traditional way of studying hydration relies on the use of volumetric measurements. However, microscopic interpretation of macroscopic volumetric data is complicated and currently relies on empirical models that are not backed by theory. We use our derived model to link the microscopic determinants of the volumetric properties of a solute and its statistical thermodynamic parameters. In this treatment, the partial molar volume, V degrees, of a solute depends on the cavity volume, hydration number, and the properties of waters of hydration. In contrast, the partial molar isothermal compressibility, K degrees T, and expansibility, E degrees, observables, in addition to the intrinsic compressibility and expansibility of the cavity enclosing the solute, hydration number, and the properties of waters of hydration, contain previously unappreciated relaxation terms that originate from pressure- and temperature-induced perturbation of the equilibrium between the solvated solute species. If significant, the relaxation terms may bring about a new level of nonadditivity to compressibility and expansibility group contributions that goes beyond the overlap of the hydration shells of adjacent groups. We apply our theoretical results to numerical analyses of the volume and compressibility responses to changes in the distribution of solvated species of polar compounds.     

On the mechanism of hydrophobic association of nanoscopic solutes

The hydration behavior of two planar nanoscopic hydrophobic solutes in liquid water at normal temperature and pressure is investigated by calculating the potential of mean force between them at constant pressure as a function of the solute-solvent interaction potential. The importance of the effect of weak attractive interactions between the solute atoms and the solvent on the hydration behavior is clearly demonstrated. We focus on the underlying mechanism behind the contrasting results obtained in various recent experimental and computational studies on water near hydrophobic solutes. The length scale where crossover from a solvent separated state to the contact pair state occurs is shown to depend on the solute sizes as well as on details of the solute-solvent interaction. We find the mechanism for attractive mean forces between the plates is very different depending on the nature of the solute-solvent interaction which has implications for the mechanism of the hydrophobic effect for biomolecules.     

Study of different association processes in the bicyclo[3.2.1]octan-3-ol series by 13C relaxation time measurements

The measurements of T₁ relaxation times in ¹³C NMR spectroscopy are used to determine solute-solvent interactions. endo- and exo-Bicyclo[3.2.1]octan-3-ol and the corresponding bromohydrins are used as substrates. In a non-polar solvent, such as cyclohexane, solute-solvent interactions occur exclusively, whereas in the more polar acetone only solute-solvent interactions are observed. In chloroform, which is of intermediate polarity, the two types of interactions (solute-solute and solute-solvent) occur simultaneously.     

Unexpected high ordering of a [60]Fullerene nitroxide in the nematic phase of 4-4'-azoxyanisole

A nitroxide [60]fullerene adduct containing a pyrrolidine-1-oxyl group has been synthesized. Its orientational order in the nematic phase of the liquid crystal solvent 4,4'-azoxyanisole (PAA) has been measured from the variation of the EPR spectral parameters on passing from the isotropic to the nematic phase. Highly resolved EPR lines allow for precise evaluation of the shifts of the g , a N and a H values. Since the g and the hyperfine tensors are known, the order matrix could be obtained. This is compared with the one calculated with a theoretical model based on short range solute-solvent interactions, which predicts a considerable degree of orientation of the molecular axes, despite the almost spherical shape of the molecule. The agreement with experimental findings is quite good and it is further improved if a bent structure of the pyrrolidine ring is taken into account.     

Confusing cause and effect: energy-entropy compensation in the preferential solvation of a nonpolar solute in dimethyl sulfoxide/water mixtures

We performed molecular simulations to analyze the thermodynamics of methane solvation in dimethyl sulfoxide (DMSO)/water mixtures (298 K, 1 atm). Two contributions to the interaction thermodynamics are studied separately: (i) the introduction of solute-solvent interactions (primary contribution) and (ii) the solute-induced disruption of cohesive solvent-solvent interactions (secondary contribution). The energy and entropy changes of the secondary contribution always exactly cancel in the free energy (energy-entropy compensation), hence only the primary contribution is important for understanding changes of the free energy. We analyze the physical significance of the solute-solvent energy and solute-solvent entropy associated with the primary contribution and discuss how to obtain these quantities from experiments combining solvation thermodynamic and solvent equation of state data. We show that the secondary contribution dominates changes in the methane solvation entropy and enthalpy: below 30 mol % DMSO in the mixture, methane, because of more favorable dispersion interactions with DMSO molecules, preferentially attracts DMSO molecules, which, in response, release water molecules into the bulk, causing an increase in the entropy. This large energy-entropy compensating process easily causes a confusion in the cause for and the effect of preferred methane-DMSO interactions. Methane-DMSO dispersion interactions are the cause, and the entropy change is the effect. Procedures that infer thermodynamic driving forces from analyses of the solvation entropies and enthalpies should therefore be used with caution.     

Hybrid integral equation/simulation model for enhancing free energy computations

Integral equation theory is used for extrapolating free energy data from molecular simulations of a reference state with respect to a modification of the interaction potential. The methodology is applied to the correction of artefacts arising from potential shifting and truncation. Corrective contributions for the hydration free energy with respect to the full potential are analysed for the case that both the solute-solvent as well as the solvent-solvent potentials are truncated and modified by a shifted-force term, reaching beyond the range of the dielectric continuum approximation and simple long-range correction expressions. The model systems argon in water and pure water are used as examples for apolar and polar solutes, revealing significant correction contributions even for the short-ranged dispersive interactions and the magnitude of solute-solvent and solvent-solvent components. In comparison with simulation-based extrapolation techniques the integral equation method is shown to be capable of quantitatively predicting truncation artefacts at negligible computational overhead.     

New stationary phase polarity parameters considering the electric intermolecular interactions in gas chromatographic column

Summary The possibility of evaluation of the parameters representing the dispersive solute-solvent interactions is presented. B_N and B_s values can be used to describe the liquid phase polarity and to predict the retention indices of alcohols when the model polyxyethylene glycol dialkyl ethers and their sulphur analogs are used as stationary phases. The possibility of the first ionization potentials estimation is also presented.     

Theoretical studies of the tautomeric equilibria for five-member N-heterocycles in the gas phase and in solution

Tautomeric equilibria have been studied for five-member N-heterocycles and their methyl derivatives in the gas phase and in different solvents with dielectric constants of epsilon = 4.7-78.4. The free energy changes differently for tautomers upon solvation as compared to the gas phase, resulting in a shift of the equilibrium constant in solution. Solvents with increasing dielectric constant produce more negative solute-solvent interaction energies and increasing internal energies. The methyl-substituted imidazole and pyrrazole form delicate equilibria between two tautomeric forms. Depending on the solvent, the methyl-substituted triazoles and tetrazole have one or two major tautomers in solution. When estimating the relative solvation free energies by means of an explicit solvent model and using the FEP/MC method, one observes that the preferred tautomers differ in several cases from those predicted by the continuum solvent model. The 1,2-prototropic shift, as an intramolecular tautomerization path, requires about 50 kcal/mol activation energy for imidazole in the gas phase, and this route is also disfavored in a solution. The calculated activation free energy along the intramolecular path is 48-50 kcal/mol in chloroform and water as compared to a literature value of 13.6 kcal/mol for pyrrazole in DMSO. A molecular dynamics computer experiment favors the formation of an imidazole chain in chloroform, making the 1,3-tautomerization feasible along an intermolecular path in nonprotic solvents. In aqueous solution, one strong N-H...Ow hydrogen bond is formed for each species, whereas all other nitrogens in the ring form weaker, N...HwOw type hydrogen bonds. The tetrahydrofuran solvent acts as a hydrogen bond acceptor and forms N-H...Oether bonds. Molecules of the dichloromethane solvent are in favorable dipole-dipole interactions with the solute. The results obtained are useful in the design of N-heterocyclic ligands forming specified hydrogen bonds with protein side chains.     

Interactions between phosphate and water in solution: a natural bond orbital based analysis in a QM/MM framework

The natural bond orbital (NBO) and natural energy decomposition analysis (NEDA) calculations are used to analyze the interaction between mono-methyl phosphate-ester (MMP) and its solvation environment in a combined quantum mechanical/molecular mechanical (QM/MM) framework. The solute-solvent configurations are generated using a specific parametrization of the self-consistent-charge density functional tight-binding (SCC-DFTB) model for the MMP and TIP3P for water. The NBO and NEDA calculations are done with several QM/MM partitioning schemes with HF/6-31+G** as the QM level. Regardless of the size of the QM region, a notable amount of charge transfer is observed between MMP and the neighboring water molecules and the charge-transfer interactions are, in the NEDA framework, as important as the electric (electrostatic and polarization) components. This work illustrates that NBO based analyses are effective tools for probing intermolecular interactions in condensed phase systems.     

Solvent effects on glycine. I. A supermolecule modeling of tautomerization via intramolecular proton transfer

The relative stabilities of glycine tautomers involved in the intramolecular proton transfer are investigated computationally by considering glycine-water complexes containing up to five water molecules. The supermolecule results are compared with continuum calculations. Specific solute-solvent interactions and solvent induced changes in the solute wave function are considered using the natural bond orbitals (NBO) method. The stabilization of the zwitterion upon solvation is explained by the changes in the wave functions localized on the forming and breaking bonds as well as by the different interaction energies in the zwitterionic and neutral clusters. Only the neutral species exist in mono- and dihydrated clusters and in the gas phase. In the smaller clusters, zwitterions are mainly stabilized by conformational effects, whereas in larger clusters, in particular when glycine is solvated on both sides of its heavy atom backbone, polarization effects dominate the stability of a given tautomer. Generally, the strength of the solute-solvent interactions is governed by the intermolecular charge transfer interactions. As the solvation progresses, the hypothetical gaseous zwitterion is better solvated than the gaseous neutral, making zwitterion to neutral tautomerization progressively less exothermic for clusters containing up to three water molecules, and endothermic for larger clusters. The neutral isomer does not exist for some solvent arrangements with five water molecules. Only solvent arrangements in which water molecules do not interact with the reactive proton are considered. Hence, the experimentally observed double well potential energy surface may be due to such an interaction or to a different reaction mechanism.     

2-Nitroethanal conformations in solution: AnAb initio SCRF study

The structure of 2-nitroethanal has been studied at the MP2/6-31G^* level in the gas phase and in acetonitrile using a continuum model to represent the electrostatic solute-solvent interactions. The relative energies of the two stable conformations obtained are quite dependent on the media. Indeed, our computations predict a change of the most stable conformation from gas to polar solvent. These results are in agreement with experimental data for the axial/equatorial conformational equilibrium of 2-nitrocyclohexanone.     

Amphiphilic organic ion pairs in solution: a theoretical study.

The macroscopic manifestation of hydrophobic interactions for amphiphilic organic ion pairs (tetraalkylammonium-anion) has been shown experimentally by measuring their association constants and their affinity with the organic phase. Beyond a certain size, there is a direct relation between association constants and chain lengths in tetraalkylammonium ions. We propose to cast a bridge between these results and geometrical properties considered at the level of a single ion pair by means of quantum chemistry calculations performed on model systems: trimethylalkylammonium-pentyl sulfate instead of tetraalkylammonium-dodecyl sulfate. Two limiting cases are considered: head-to-head configurations, which yield an optimal electrostatic interaction between polar heads, and parallel configurations with a balance between electrostatic and hydrophobic interactions. All properties (geometries, complexation energies, and atomic charges) were obtained at the MP2 level of calculation, with water described by a continuum model (CPCM). Dispersion forces link hydrocarbon chains of tetraalkylammonium ions and pentyl sulfate, thus yielding (for the largest ion pairs) parallel configurations favored with respect to head-to-head geometries by solute-solvent electrostatic interactions. Given the small experimental association energies, we probe the accuracy limit of the MP2 and CPCM methods. However, clear trends are obtained as a function of chain length, which agree with the experimental observations. The calculated monotonic stabilization of ion pairs when the hydrocarbon chain increases in length is discussed in terms of electrostatic interactions (between ions and between ion pairs and water), dispersion forces, and cavitation energies.