Hydrophobicity of benzene

The present work tries to clarify the molecular origin of the poor solubility of benzene in water. The transfer of benzene from pure liquid phase into water is dissected in two processes: transfer from gas phase to pure liquid benzene; and transfer from gas phase to liquid water. The two solvation processes are analyzed in the temperature range 5-100 degrees C according to Lee's Theory. The solvation Gibbs energy change is determined by the balance between the work of cavity creation in the solvent, and the dispersive interactions of the inserted benzene molecule with the surrounding solvent molecules. The purely structural solvent reorganization upon solute insertion proves to be a compensating process. The analysis shows that the work of cavity creation is larger in water than in benzene, whereas the attractive energetic interactions are stronger in benzene than in water; this scenario is true at any temperature. Therefore, both terms act in the same direction, contrasting the transfer of benzene from pure liquid phase into water and determining its hydrophobicity.     

Molecular orbital study on the effect of the binding of water to base pair

The effects of binding water to base pairs was studied by means of the CNDO/2 molecular orbital method. The solvation energy is largest when water is bound as a proton donor and is smallest when it is stacked parallel to the plane of the base pair. The effects of two water molecules are nearly additive. The binding of one water molecule to the adenineuracil pair makes one of the two hydrogen bonds stronger and the other weaker. The change in the hydrogen bonding force is explained in terms of electrostatic and charge transfer energies. By the comparison with the adenine-cytosine pair, it is revealed that the binding of water to adenine serves to yield larger solvation energy for the complementary A-U pair than for the non-complementary A-C pair. It was also observed that the solvation energy due to the binding of water to pyrimidine was larger for A-C than for A-U.     

Quantum calculations on water in the KcsA channel cavity with permeant and non-permeant ions

Different ions in the pore of the KcsA channel behave differently, and we relate this to their solvation. We show that the selectivity is dependent, in part, on the solvation in the cavity (sometimes referred to as the vestibule, it is the region containing water molecules between the intracellular gate and the selectivity filter at the extracellular end of the pore). We have shown earlier that potassium is more dependent at the upper end of the cavity region on solvation by the threonines there, while sodium ion has more water molecules as ligands. In addition, sodium ion is placed asymmetrically, while potassium is nearly exactly symmetric with respect to the four-fold symmetry of the channel. We have now extended these calculations to rubidium and cesium ions, and find that rubidium solvation resembles that of potassium (and both are permeant ions), while cesium resembles sodium (and both are non-permeant), in terms of the geometry of up to eight hydrating, and four non-hydrating, water molecules. In each case, a maximum of 12 water molecules are relevant to the calculation. The placement of the water molecules in the two cases is essentially the same as found from the electron density in the X-ray structure of Zhou and MacKinnon. For Na⁺ and K⁺, we show that energy decreases from bulk to the cavity to the lowest position in the selectivity filter (accurate energy could not be calculated for the heavier ions). A separate calculation shows that fixing the Na⁺ ion at the position of the K⁺ minimum, followed by re-optimization produced a significantly modified system, not something that could be produced by thermal fluctuations. Moving the K⁺ into the Na⁺ position in the upper cavity led to a small increase in energy, ≈ 3 k_BT, but was accompanied by large shifts in the positions of hydrating waters, which would create a major kinetic barrier. Therefore, thermal fluctuations could not invalidate the conclusions of the main calculations.     

Solvation thermodynamics of biopolymers. I. Separation of the volume and surface interactions with estimates for proteins

The present paper is a systematic first approach to the problem of solvation thermodynamics of biomolecules. Most previous approaches have been only crude estimates of solvent contributions, and have simply assessed solvation free energy as proportional to surface areas. Here we estimate the various contributions and divide them into (a) hard-core interactions dependent upon the entire volume of solute and (b) the remainder of interactions manifested through surfaces, such as van der Waals, charge-charge, or hydrogen bonds. We have estimated the work to create a cavity with scaled-particle theory (SPT), the van der Waals interactions on the surface, and hydrogen bonds between the surface and the solvent. The conclusion here is that this latter term is the largest component of the solvation free energy of proteins. From estimates on nine diverse proteins, it is clear that the larger the protein, the more dominant is the hydrogen-bond term. In the next paper, we indicate that correlations between hydrogen-bonding groups on the surfaces could increase the magnitude of the hydrogen-bond contribution.     

Computational molecular characterization of the flavonoid Morin and its Pt(II), Pd(II) and Zn(II) complexes

In this work, we make use of a model chemistry within density functional theory (DFT) recently presented, which is called M05-2X, to calculate the molecular structure of the flavonoid Morin and its Pt(II), Pd(II) and Zn(II) complexes, as well to predict their IR and UV-Vis spectra, the dipole moment and polarizability, the free energy of solvation in different solvents as an indication of solubility, the HOMO and LUMO orbitals, and the chemical reactivity parameters that arise from Conceptual DFT. The calculated values are compared with the available experimental data for these molecules.     

Gibbs free energy of transfer of glycine and diglycine from water to alkylurea solutions. Measured vs. calculated values

Ternary systems comprising water (1), glycine (diglycine) (2) and alkylurea (3) have been investigated using vapor pressure osmometry. Equations were obtained in terms of the molalities of the solutes for the activity coefficients of glycine and diglycine in these systems. The alkylureas used were methyl-, ethyl- and N, N'-dimethylurea. Using the activity coefficients the Gibbs free energy of transfer at infinite dilution of component 2 from water to alkylurea solutions was determined. Since the enthalpies of transfer are known, the corresponding entropies could also be obtained. Calculation of the Gibbs free energy of transfer at infinite dilution of component 2 rests on the assumption that it can be divided into two parts: the difference between the Gibbs free energy of cavity formation and that of interaction in the alkylurea solution and water, respectively. The first part was calculated by scaled particle theory using experimental density and surface tension data. The second part was taken to be due mainly to the change in dipole-dipole interactions.     

Aliphatics vs. aromatics hydration thermodynamics

By comparing the hydration thermodynamics of benzene with that of a hypothetical aliphatic hydrocarbon having the same accessible surface area (ASA) of benzene, Makhatadze and Privalov concluded that the whole difference is due to the weak H-bonds that water forms with the aromatic ring. The formation of such H-bonds would be characterized by a negative Gibbs energy change, slightly increasing in magnitude with temperature, and a positive entropy change over a large temperature range. The latter thermodynamic feature is not physically reliable for the formation of H-bonds. In the present article, by using a statistical mechanical dissection scheme of hydration, a microscopic interpretation for the numbers obtained by Makhatadze and Privalov is proposed. The difference in hydration Gibbs energy should be attributed to the different strength of van der Waals interactions that benzene can do with water, owing to the larger polarizability of the aromatic ring with respect to an aliphatic hydrocarbon of equal size. In addition, the difference in hydration entropy should account for the different extent of H-bond reorganization upon the insertion of benzene and the corresponding aliphatic hydrocarbon in water.     

Many-body energies during proton transfer in an aqueous system

The energetics of the mechanism of proton transfer from a hydronium ion to one of the water molecules in its first solvation shell are studied using density functional theory and the Møller–Plesset perturbation (MP2) method. The potential energy surface of the proton transfer mechanism is obtained at the B3LYP and MP2 levels with the 6-311++G** basis set. Many-body analysis is applied to the proton transfer mechanism to obtain the change in relaxation energy, two-body, three-body and four-body energies when proton transfer occurs from the hydronium ion to one of the water molecules in its first solvation shell. It is observed that the binding energy (BE) of the complex decreases during the proton transfer process at both levels of theory. During the proton transfer process, the % contribution of the total two-body energy to the binding energy of the complex increases from 62.9 to 68.09% (39.9 to 45.95%), and that of the total three-body increases from 25.9 to 27.09% (24.16 to 26.17%) at the B3LYP/6-311++G** (MP2/ 6-311++G**) level. There is almost no change in the water–water–water three-body interaction energy during the proton transfer process at both levels of theory. The contribution of the relaxation energy and the total four-body energy to the binding energy of the complex is greater at the MP2 level than at the B3LYP level. Significant differences are found between the relaxation energies, the hydronium–water interaction energies and the four-body interaction energies at the B3LYP and MP2 levels.     

A proposal for the structuring of water

In spite of much work, many of the properties of water remain puzzling. A fluctuating network of water molecules, with localised icosahedral symmetry, is proposed to exist derived from clusters containing, if complete, 280 fully hydrogen-bonded molecules. These are formed by the regular arrangement of identical units of 14 water molecules that can tessellate locally, by changing centres, in three-dimensions and interconvert between lower and higher density forms. The structure allows explanation of many of the anomalous properties of water including its temperature-density and pressure-viscosity behaviour, the radial distribution pattern, the presence of both pentamers and hexamers, the change in properties and 'two-state' model on supercooling and the solvation properties of ions, hydrophobic molecules, carbohydrates and macromolecules. The model described here offers a structure on to which large molecules can be mapped in order to offer insights into their interactions.     

Effective water model for Monte Carlo simulations of proteins

We present an effective theory for water. Our goal is to formulate on accurate model for the effects of solvation on protein dynamics, without incurring the huge computational cost and the slow temporal evolution typical of molecular dynamics simulations of liquids. We replace the individual water molecules in an all-atom potential with a local dielectric density field, with self interactions given by the Landau-Ginzburg free energy and external interactions by Lennard-Jones forces at the surface of the protein atoms. We explore conformational space with finite temperature Monte Carlo dynamics, using parallel Langevin and Fourier acceleration algorithms well suited to data-parallel computer architectures such as the Connection Machine. To establish the validity of our approximations, we compare our electrostatic contribution to the solvalion energy with the results of Lim, Bashford, and Karplus using a conventional static continuum dielectric cavity model, and the non electrostatic contributions with estimates of hydrophohic surface free energy. Our model can also accommodate ionic charges and temperature fluctuations, We propose future investigations extending our effective theory of solvation to include explicit orientational entropy and hydroxen-bonding terms. © 1995 John Wiley & Sons, Inc.     

Thermodynamics of the hydrophobic effect. III. Condensation and aggregation of alkanes, alcohols, and alkylamines

Knowledge of the energetics of the low solubility of non-polar compounds in water is critical for the understanding of such phenomena as protein folding and biomembrane formation. Solubility in water can be considered as one leg of the three-part thermodynamic cycle - vaporization from the pure liquid, hydration of the vapor in aqueous solution, and aggregation of the substance back into initial pure form as an immiscible phase. Previous studies on the model compounds n-alkanes, 1-alcohols, and 1-aminoalkanes have noted that the thermodynamic parameters (Gibbs free energy, DeltaG; enthalpy, DeltaH; entropy, DeltaS; and heat capacity, DeltaC(p)) associated with these three processes are generally linear functions of the number of carbons in the alkyl chains. Here we assess the accuracy and limitations of the assumption of additivity of CH(2) group contributions to the thermodynamic parameters for vaporization, hydration, and aggregation. Processes of condensation from pure gas to liquid and aqueous solution to aggregate are compared. Hydroxy, amino, and methyl headgroup contributions are estimated, liquid and solid aggregates are distinguished. Most data in the literature were obtained for compounds with short aliphatic hydrocarbon tails. Here we emphasize long aliphatic chain behavior and include our recent experimental data on long chain alkylamine aggregation in aqueous solution obtained by titration calorimetry and van't Hoff analysis. Contrary to what is observed for short compounds, long aliphatic compound aggregation has a large exothermic enthalpy and negative entropy.     

水/乙醇溶剂中阿奇霉素的热力学及多晶型研究

在278.2~308.2 K温度范围内,测定阿奇霉素在水/乙醇混合溶剂中的溶解度,根据固液平衡理论建立了该体系的溶解度修正模型。采用X线粉末衍射法和差示扫描量热法,对阿奇霉素在不同温度、不同体积比的水/乙醇混合溶剂中得到的晶体进行鉴别。同时利用溶解度数据估算了阿奇霉素在水/乙醇体系中的溶解热(-25.26~-16.11 k J/mol)、混合热(-9.94~-3.25 k J/mol)。通过溶液化学理论推导了阿奇霉素溶剂化平衡常数K与活度系数γ2的方程:γ2=1/(1+K),建立了溶剂化焓与温度、水/乙醇两者体积比(φ)之间的关系式,为ΔH=RTln(17.86exp(3.4φ)-1)。采用溶析结晶方法得到的6种阿奇霉素晶体,均属单斜晶系,但具有不同的晶胞参数且其密度和熔点也不同。同时发现温度越高,水/乙醇体积比越大,得到的晶体稳定性越差(晶体的熔点和密度降低)。在水/乙醇混合溶剂的溶析结晶体系中,产生阿齐霉素多晶型的现象与溶剂化作用的强弱有关。     

Picosecond-resolved solvent reorganization and energy transfer in biological and model cavities

Water molecules in hydrophobic biological cleft/cavities are of contemporary interest for the biomolecular structure and molecular recognition of hydrophobic ligands/drugs. Here, we have explored picosecond-resolved solvation dynamics of water molecules and associated polar amino acids in the hydrophobic cleft around Cys-34 position of Endogenous Serum Albumin (ESA). While site selective acrylodan labeling to Cys-34 allows us to probe solvation in the cleft, Förster resonance energy transfer (FRET) from intrinsic fluorescent amino acid Trp 214 to the extrinsic acrylodan probes structural integrity of the protein in our experimental condition. Temperature dependent solvation in the cleft clearly shows that the dynamics follows Arrhenius type behavior up to 60 °C, after which a major structural perturbation of the protein is evident. We have also monitored polarization gated dynamics of the acrylodan probe and FRET from Trp 214 to acrylodan at various temperatures. The dynamical behavior of the immediate environments around the probe acrylodan in the cleft has been compared with a model biomimetic cavity of a reverse micelle (w₀ = 5). Using same fluorescent probe of acrylodan, we have checked the structural integrity of the model cavity at various temperatures using picosecond-resolved FRET from Trp to acrylodan in the cavity. We have also estimated possible distribution of donor-acceptor distances in the protein and reverse micelles. Our studies reveal that the energetics of the water molecules in the biological cleft is comparable to that in the model cavity indicating a transition from bound state to quasibound state, closely consistent with a recent MD simulation study.     

Overall charge and local charge density of pectin determines the enthalpic and entropic contributions to complexation with β-lactoglobulin

The complex formation between β-lactoglobulin and pectins of varying overall charge and local charge density were investigated. Isothermal titration calorimetry experiments were carried out to determine the enthalpic contribution to the complex formation at pH 4.25 and various ionic strengths. Complex formation was found to be an exothermic process for all conditions. Combination with previously published binding constants by Sperber et al. (Sperber, B. L. H. M.; Cohen Stuart, M. A.; Schols, H. A.; Voragen, A. G. J.; Norde, W. Biomacromolecules 2009, 10, 3246-3252) allows for the determination of the changes in the Gibbs energy and the change in entropy of the system upon complex formation between β-lactoglobulin and pectin. The local charge density of pectin is found to determine the balance between enthalpic and entropic contributions. For a high local charge density pectin, the main contribution to the Gibbs energy is of an enthalpic nature, supported by a favorable entropy effect due to the release of small counterions. A pectin with a low local charge density has a more even distribution of the enthalpic and entropic part to the change of the Gibbs energy. The enthalpic part is reduced due to the lower charge density, while the relative increase of the entropic contribution is thought to be caused by a change in the location of the binding place for pectin on the β-lactoglobulin molecule. The association of the hydrophobic methyl esters on pectin with an exposed hydrophobic region on β-lg results in the release of water molecules from the hydrophobic region and surrounding the methyl esters of the pectin molecule. An increase in the ionic strength decreases the enthalpic contribution due to the shielding of electrostatic attraction in favor of the entropic contribution, supporting the idea that the release of water molecules from hydrophobic areas plays a part in the complex formation.     

Cuticular wax profiles of leaves of some traditionally used African Bignoniaceae

Bignoniaceae, Newbouldia laevis, Markhamia acuminata, Spathodea campanulata and Kigelia africana were analysed by GC-MS. The principal constituents were represented by a homologous series of n-alkanes (C23-C33), n-alcohols (C18-C30) and related carboxylic acids (C16-C36). For N. laevis and M. acuminata, ursolic and oleanolic acid were the most abundant wax components (52 and 60%, respectively), followed by the C29, the C31 and the C33 n-alkanes. The predominant components of S. campanulata were n-alcohols (35%), with octacosanol and triacontanol as the most abundant ones, while K. africana is distinguished from these three members by the conspicuous absence of triterpenoic acids and the predominance of n-alkanes (70%) with hentriacontane and tritriacontane as the main representatives. Other notable constituents were sterols, albeit present in trace amounts. The wax profiles are discussed in terms of taxonomic characters.     

Solvent reorganization contribution to the transfer thermodynamics of small nonpolar molecules.

The experimental thermodynamic data for the dissolution of five simple hydrocarbon molecules in water were combined with the solute-solvent interaction energy from a computer simulation study to yield data on the enthalpy change of solvent reorganization. Similar data were generated for dissolving these same solute molecules in their respective neat solvents using the equilibrium vapor pressure and the heat of vaporization data for the pure liquid. The enthalpy and the free energy changes upon cavity formation were also estimated using the temperature dependence of the solute-solvent interaction energy. Both the enthalpy and T delta S for cavity formation rapidly increase with temperature in both solvent types, and the free energy of cavity formation can be reproduced accurately by the scaled particle theory over the entire temperature range in all cases. These results indicate that the characteristic structure formation around an inert solute molecule in water produces compensating changes in enthalpy and entropy, and that the hydrophobicity arises mainly from the difference in the excluded volume effect.     

Prediction of the aqueous solvation free energy of organic compounds by using autocorrelation of molecular electrostatic potential surface properties combined with response surface analysis

Several quantitative structure-property relationship (QSPR) approaches have been explored for the prediction of aqueous solubility or aqueous solvation free energies, DeltaG(sol), as crucial parameter affecting the pharmacokinetic profile and toxicity of chemical compounds. It is mostly accepted that aqueous solvation free energies can be expressed quantitatively in terms of properties of the molecular surface electrostatic potentials of the solutes. In the present study we have introduced autocorrelation molecular electrostatic potential (autoMEP) vectors in combination with nonlinear response surface analysis (RSA) as alternative 3D-QSPR strategy to evaluate the aqueous solvation free energy of organic compounds. A robust QSPR model (r(cv)=0.93) has been obtained by using a collection of 248 organic chemicals. An external test set based on 23 molecules confirmed the good predictivity of the autoMEP/RSA model suggesting its further applicability in the in silico prediction of water solubility of large organic compound libraries.     

Water penetration in the low and high pressure native states of ubiquitin

Theoretical studies on the solvation of methane molecules in water have shown that the effect of increased pressure is to stabilize solvent separated contacts relative to direct contacts. This suggests that high pressure stabilizes waters that have penetrated into a protein's core, indicating a mechanism for the high pressure denaturation of proteins. We test this theory on a folded protein by studying the penetration of water into the native state of ubiquitin at low and high pressures, using molecular dynamics. An ensemble of conformations sampled in the folded state of ubiquitin has been determined by NMR at two pressures below the protein's denaturation pressure, 30 atm and 3000 atm. We find that 1-5 more waters penetrate the high pressure conformations than the low pressure conformations. Low volume configurations of the system are favored at high pressures, but different components of the system may experience increases or decreases in their specific volumes. We find that penetrating waters have a higher volume per water than bulk waters, but that the volume per protein residue may be lowered by solvation. Furthermore, we find that penetration of the protein by water at high pressures is driven by the difference in the pressure dependence of the probability of cavity opening in the protein and pressure dependence of the probability of cavity opening in the bulk solvent. The volume changes associated with cavity opening and closing indicate that each penetrating water reduces the volume of the system by about 12 mL/mol. The experimental volume change going from the low pressure to the high pressure native state of ubiquitin is 24 mL/mol. Our results indicate that this volume change can be explained by penetration of the protein by two water molecules.     

Exploring the structure and dynamics of nano-confined water molecules using molecular dynamics simulations

Confinement effects can lead to drastic changes in the structural and dynamical properties of water molecules. In this work, we have performed classical molecular dynamics simulations of endohedral fullerenes of type (H₂O)_n@C_m (n = 1, 12, 21, 62, 108 and m = 60, 180, 240, 500 and 720) to explore the effects of spherical confinement on water properties. It is shown that these confined water molecules can form distinct solvation pattern depending upon the available space inside the fullerene cavity. For the systems with smaller diameter, cage-like structure is predominant whereas bulk-like structure is observed for larger fullerenes. The orientational relaxation of these confined water molecules showed slower relaxation as the cavity diameter increases except for the (H₂O)₂₁@C₂₄₀. In this case, stable cage-like structure hinders the overall dynamics of the trapped water molecules. Finally, we have calculated the hydrogen bond lifetimes from the hydrogen bond time correlation functions and compared with that of bulk water.