Free Energy Of Water Research Articles

Arginine increases the solubility of alkyl gallates through interaction with the aromatic ring

We have recently proposed the application of solubilizing effects of arginine to poorly soluble aromatic compounds for drug discovery research. In this study, we compared the solubilizing effects of arginine with those of other amino acids, salts and a surfactant using alkyl gallates as model drug substances of low aqueous solubility. The solubilizing effects of arginine on the alkyl gallates were distinct compared with those of other amino acids and salts; the effects were even greater than those achieved using a strongly chaotropic guanidinium ion. Transfer free energy of the alkyl gallates from water to arginine solution depended weakly on their dissolution free energy in water, which is in contrast to sodium dodecyl sulphate that showed strong dependence. The present results suggest that arginine solubilizes alkyl gallates through interaction with the aromatic moiety and sodium dodecyl sulphate does so by interacting with alkyl groups.

Differential Solvation Free Energies of Oxonium and Ammonium Ions: Insights from Quantum Chemical Calculations

We have employed computational protocols to determine the differential solvation free energy in water of oxonium and ammonium ions. We have focused our analysis on pairs of onium ions having the same hydrocarbon content and substitutional pattern (HCSP pairs). In agreement with previous suggestions (Taft, R. W.; Wolf. J. F.; Beauchamp, J. L.; Scorrano, G.; Arnett, E. M. J. Am. Chem. Soc. 1978, 100, 1240), we found that cavitation and van der Waals terms do not contribute to the differential solvation free energy. Moreover, we observe that oxonium ions are more strongly solvated than the analogous ammonium ions even though the former ones have fewer H-bond donor sites. The performance of two different continuum solvation models, PCM and SMD, is discussed.

Evaluation of the 1-octanol/water partition coefficient of nucleoside analogs via free energy estimated in quantum chemical calculations

The partition coefficients (logP) of nucleoside analogs determined by the difference in the free energies of hydration and solvation in water-saturated octanol using the thermodynamic integration method are reported. The logP values calculated in this approach are closer to the experimental values compared to other ab initio methods. Solvation free energy in water and octanol, free energy of cavity formation in water and Henry’s constants, and some other parameters are estimated at the density functional theory (DFT) and Hartree-Fock level with 6–31G*, 6–31G, and 6–31+G basis sets. Surface area, mass, refractivity, volume, polarizability, and dipole moment are calculated for some drugs with HF and DFT methods. The results show that log P decreases with the decrease in polarizability and the increase in dipole moment.

Ecophysiological responses of five emergent-wetland plants to diminished water supply: an experimental microcosm study

Freshwater wetlands are fundamentally tied to hydrology as they are often found along the boundaries between terrestrial uplands and open waters. Although wetland systems are frequently prone to extended periods of flooding and exposure, the degree of water deprivation may intensify during periods of low precipitation or drought. Therefore, the purpose of this study was to evaluate plant–water relations in five emergent macrophytes (Carex alata, Juncus effusus, Peltandra virginica, Saururus cernuus, and Justicia americana) to simulated drought conditions. Weekly evaluations of tissue water content and xylem water potential (free energy of water in xylem tissues) were conducted on plants grown in experimental microcosms over a 9-week period. Plant performance was also evaluated in each species by monitoring the changes in plant biomass, leaf area, and survival. The results indicate that J. effusus and P. virginica performed better in both flooded and moderately dry conditions, and plants that maintained higher water content in water logged soils (i.e., J. americana) were less tolerant to drying conditions. This study also illustrates the importance of periodic water withdrawal on plant performance. In general, plants that were subjected to both flooded and dry conditions responded better physiologically than plants that were either continuously flooded or received extended droughts (≥4 weeks). Therefore, provided the duration of water deficit is not extensive, short periods of water withdrawal can enhance the performance and water relations in some emergent-wetland plant species.

MD Study of SN1 Reactivity of 2-Chloro-2-methylpropane in the Room-Temperature Ionic Liquid 1-Ethyl-3-methylimidazolium Hexafluorophosphate

The S(N)1 ionization reaction RX --> R(+) + X(-) for 2-chloro-2-methylpropane in ionic liquid 1-ethyl-3-methylimidazolium hexafluorophosphate ([emim](+)P(-)(6)) is studied via molecular dynamics computer simulations. By employing a two-state valence-bond description for electronic structure variations of the reaction complex, the free energy curve relevant to its SN1 ionization in [emim](+)P(-)(6)) is computed via the thermodynamic integration method and compared with those in water and in acetonitrile. It is found that the detailed reaction mechanism differs among the three solvents. To be specific, the dissociation of 2-chloro-2-methylpropane in [emim](+)P(-)(6)) is a stepwise process consisting of the formation of a solvent-separated ion pair and ensuing dissociation, while that in acetonitrile appears to proceed without any stable reaction intermediates. The S(N)1 pathway in water on the other hand is characterized by the formation of a contact ion pair, followed by dissociation to free ions. The activation free energy in water is much lower than those in [emim](+)P(-)(6)) and acetonitrile. Between the two latter solvents, the barrier height is lower in [emim](+)P(-)(6)) than in acetonitrile, indicating that the S(N)1 reactivity of 2-chloro-2-methylpropane would be higher in [emin](+)P(-)(6)) than in acetonitrile. Its implication for solvolysis in these solvents is briefly discussed.

Computational Studies of Liquid Water and Diluted Water in Carbon Tetrachloride

Molecular dynamics simulations were carried out to study solvent effects on the energetic and dynamical properties of water molecules in liquid water and in carbon tetrachloride (CCl4). In these studies, the free-energy profiles or potentials of mean force (PMF) for water dimers in both solvents were computed. The computed PMF results showed a stable minimum near 3 A for the O-O separation, with a minimum free energy of about -2.8 kcal/mol in CCl4, as compared to a value of -0.5 kcal/mol in liquid water. The difference in free energy in water as compared to that in CCl4 was expected and is the result of competition from surrounding water molecules that are capable of forming hydrogen bonds in the liquid water. This capability is absent in the diluted water found in CCl4. We found that the rotational motions of H2O/D2O were nonisotropic, with the out-of-plane vector correlation times in H2O/D2O varying from 5.6/5.8 ps at 250 K to 0.57/0.56 ps at 350 K and the corresponding OH/OD bond vectors varying from 6.5/7.7 ps to 0.75/0.75 ps. The results compare reasonably well to the available NMR experimental and computer simulation data on the same system (Farrar; Skinner; et al. J. Am. Chem. Soc. 2001, 123, 8047). For diluted water in CCl4, we found the computed rotational correlation times also were nonisotropic and much longer than the corresponding NMR experimental values at the same concentration (Farrar; et al. J. Phys. Chem. A 2007, 111, 6146). Upon analyzing the water hydrogen-bonding patterns as a function of water concentration, we conclude that the differences in the rotational correlation times mainly result from the formation of water hydrogen-bonding networks as the water concentration is increased in liquid CCl4. In addition, we found the rotational correlation times to be substantially faster in liquid CCl4 than in liquid water.

DFT Calculation on 76 Polychlorophenazines: Their Thermodynamic Function and Implication of Cl Substituted Position

Thermodynamic functions, including enthalpy (Hθ) and entropy (Sθ) for 76 polychlorophenazines (PCPZs) in the gas state at 298.15 K and 101.325 kPa, have been calculated using the B3LYP/6-31G∗level with Gaussian 03 program, and considered on solvation affects. Total free energy in water (Gw) was calculated with the same program. Based on these data, the isodesmic reactions were designed to calculate the standard formation heat (ΔfHθ) and standard free energy of formation in water(ΔfGwθ). The dependences of these thermodynamic parameters on the numbers and positions of chlorine substitution (NPCS) were discussed. It is suggested thatSθ, ΔfHθ, andΔfGwθof PCPZs varied greatly withNPCS. Moreover, the values of molar heat capacity at constant pressure (Cp,m) from 200 to 1800 K for PCPZ congeners were calculated using a statistical thermodynamics calculation program based on Gaussian output files, and the temperature-dependence relation ofCp,mwas obtained using the least-squares method. In addition, according to the relative magnitude of theirΔfGwθ, the relative stability order of PCPZ congeners was theoretically proposed.

Hydration forces and liquid-like layer on the ice/metal interface

A model to describe the phenomenon of the liquid-like layer is proposed. It is based on thetheory of the hydration forces proposed by Gruen and Marcelja (1983 J. Chem. Soc.Faraday Trans. II 79 225), taking into account the influence of ions on the free energy ofwater. The model was applied to experimental data obtained with the quartz-crystalmicrobalance, in a study of the liquid-like layer between metal and frozen aqueouselectrolytes and between metal and ice.

Conformational structure, dynamics, and solvation energies of small alanine peptides in water and carbon tetrachloride

The rate-limiting barrier for peptide transport across lipid bilayers is the nonpolar hydrocarbon interior. Permeating peptides may undergo conformational changes during their transfer from an aqueous solution into the barrier domain, thus facilitating peptide transport. To test this hypothesis, all-atom and explicit-solvent molecular dynamics (MD) simulations have been conducted on a series of small peptides, p-toluyl-Ala(n) (n = 0-3) used previously in transport experiments, to explore their conformational structures, dynamics and solvation free energies in water and carbon tetrachloride (CCl(4)). The conformations of the p-toluyl alanine di- and tri-peptides in water were found to be far from random coils, with P(II) and alpha(R) dominating but with smaller populations of seven-membered (c(7)) and five-membered rings (c(5)). In contrast, the seven-membered ring, c(7), along with c(5) dominated in CCl(4). These results indicate that the conformational preferences of the alanine peptides are highly sensitive to solvent. Dynamically, stable seven-membered ring formation occurred on a time scale of 10 ps while larger ring-sizes (e.g., 10-membered rings) were observed much less frequently. The values of adjacent torsional angles (phi(1), psi(1)) were dependent on neighboring torsional angles. Thermal motions of neighboring torsions leading to transitions between c(7), c(5), alpha(R), and P(II) conformers were highly cooperative while longer range correlations between transitions of adjacent sets of torsions (phi(1), psi(1)) and (phi(2), psi(2)) were less evident. Peptide folding in CCl(4) lowers the intramolecular electrostatic energies. This, along with hydrophobic interactions, favors partitioning into CCl(4). These effects only partially offset other types of intramolecular interactions and peptide-solvent polar interactions that are more favorable in water, leading to net transfer free energies (3-7 kcal/mol) that disfavor peptide transfer from water into carbon tetrachloride.

Thermodynamics of Rhodium Hydride Reactions with CO, Aldehydes, and Olefins in Water: Organo-Rhodium Porphyrin Bond Dissociation Free Energies

Tetra(p-sulfonato-phenyl) porphyrin rhodium hydride ([(TSPP)Rh-D(D2O)](-4)) (1) reacts in water (D2O) with carbon monoxide, aldehydes, and olefins to produce metallo formyl, alpha-hydroxyalkyl, and alkyl complexes, respectively. The hydride complex (1) functions as a weak acid in D2O and partially dissociates into a rhodium(I) complex ([(TSPP)Rh(I)(D2O)](-5)) and a proton (D+). Fast substrate reactions of 1 in D2O compared to reactions of rhodium porphyrin hydride ((por)Rh-H) in benzene are ascribed to aqueous media promoting formation of ions and supporting ionic reaction pathways. The regioselectivity for addition of 1 to olefins is predominantly anti-Markovnikov in acidic D2O and exclusively anti-Markovnikov in basic D2O. The range of accessible equilibrium thermodynamic measurements for rhodium hydride substrate reactions is substantially increased in water compared to that in organic media through exploiting the hydrogen ion dependence for the equilibrium distribution of species in aqueous media. Thermodynamic measurements are reported for reactions of a rhodium porphyrin hydride in water with each of the substrates, including CO, H2CO, CH3CHO, CH2=CH2, and sets of aldehydes and olefins. Reactions of rhodium porphyrin hydrides with CO and aldehydes have nearly equal free-energy changes in water and benzene, but alkene reactions that form hydrophobic alkyl groups are substantially less favorable in water than in benzene. Bond dissociation free energies in water are derived from thermodynamic results for (TSPP)Rh-organo complexes in aqueous solution for Rh-CDO, Rh-CH(R)OD, and Rh-CH2CH(D)R units and are compared with related values determined in benzene.

The sulfur oxygenase reductase fromAcidianus ambivalens

The microbial oxidation of reduced inorganic sulfur compounds and elemental sulfur to sulfate is one of the major reactions in the global sulfur cycle. Despite its importance, only limited information is available about molecular details of the enzymes involved. The present work was aimed to contribute to the understanding of the underlying molecular mechanisms by investigating the function and structure of the sulfur oxygenase reductase (SOR) from the thermoacidophilic crenarchaeote Acidianus ambivalens. The expression of the sor gene in Escherichia coli resulted in active, soluble SOR and in inclusion bodies from which active SOR could be refolded as long as ferrous ions were present in the refolding solution. The wild type and recombinant SOR preparations possessed indistinguishable properties when analyzed for activity and by gel permeation chromatography, CD spectroscopy and electron microscopy. The analysis of the quaternary structure showed a multi-subunit shell-like assembly with a central hollow core. The subunits formed homodimers as the building blocks of the holoenzyme, as shown by denaturation experiments. Conformational stability studies showed that the apparent unfolding free energy in water was ~5 kcal mol-1, at pH 7. Iron was found in the wild type enzyme at a stoichiometry of one iron per subunit. EPR spectroscopy of the colorless SOR resulted in a single isotropic signal at g = 4.3 characteristic of high-spin ferric iron. The signal disappeared upon reduction with dithionite or incubation with sulfur at elevated temperature. The iron center had a reduction potential of E0´ = -268 mV at pH 6.5. Protein database inspection identified five SOR protein homologues which allowed the prediction of amino acids putatively involved in catalysis. The recombinant SOR was crystallized by the sitting drop vapor diffusion method. The crystal structure was determined at 1.7 A resolution. The homo-icosatetrameric holoenzyme was a highly symmetrical hollow protein particle with 432 point group symmetry and a molecular mass of 871 kDa. The subunits were αβ-proteins and comprised a central β-barrel surrounded by α-helices. Each monomer contained one mononuclear non-heme iron site with the ligands H85, H89, E113 and two water molecules in an octahedral arrangement. The protein ligands formed a 2-His-1-carboxylate facial triad for iron binding. The cysteines C30, C100 and C103 were in the vicinity of the iron site and located along the same cavity within the interior of the subunit, therefore defining the enzyme´s active site. C30 was persulfurated. The 24 active sites were spacially separated from each other, making an electronic interaction during catalysis unlikely. They were accessible solely via the inner compartment. Access of substrate to the inner compartment is most probably provided by six hydrophobic channels along the four-fold symmetry axes of the particle. Furthermore, the structure suggested that a linear polysufide species and not the cyclic α-S8 is the substrate of the SOR. Crystal structures of the SOR in complex with the inhibitors p-hydroxy-mercury-benzoic acid and iodoacetamide identified the cysteines as the inhibitor binding sites. The iron-binding residues H85, H89 and E113 and the three cysteines C30, C100 and C103 were altered by site-directed mutagenesis and the mutant proteins were analyzed for activity and iron content. Mutations of the iron ligands and C30 resulted in inactive enzyme, whereas mutations of C100 and C103 resulted in a reduced activity. All mutations affected the oxygenase and reductase partial reactions to a similar degree. These analyses allowed the first detailed insight into the mode of action of this self-compartmentalizing metalloenzyme. C30 is most probably the sulfur binding residue which aligns the substrate for the initial oxygenation catalyzed by the Fe site. The role of C100 and C103 is not clear, but they might act in the subsequent sulfur disproportionation reaction. The comparison of the SOR with SoxAX, the only other sulfur compound oxidizing enzyme from prokaryotes for which a high resolution structure is available, showed no structural similarity. SoxAX and other sulfur oxidizing enzymes contain different cofactors, demonstrating the diversity of mechanistic approaches utilized for sulfur compound oxidation. In contrast, a basic functional principle seems to be the central role of cysteine residues, acting as covalent binding sites for the substrate.

Solvation Free Energies and Transfer Free Energies for Amino Acids from Hydrophobic Solution to Water Solution from a Very Simple Residue Model

Solvation free energies of neutral amino acids in water and in chloroform were computed from extensive molecular dynamics simulations using multiconfiguration thermodynamic integration. The values computed for the AMBER force field are in very good agreement with available experimental data (rms differences of 5.1 kJ mol-1 for the solvation free energies and 6.4 kJ mol-1 for the transfer free energies of amino acids between water and chloroform) and with existing calculations. We derived an additive residue-scale solvation model formulated as the sum of a nonpolar term that is proportional to the molecular surface area and an electrostatic term (Kirkwood−Onsager model) for the hydration free energy of a dipole in a solvated cavity. This model can surprisingly well describe the solvation free energies in water and chloroform as well as the transfer free energies of amino acids between the two solvents when suitably adapted cavity radii are used. Root-mean-square differences of the predicted values with res...

Transition state stabilization by general acid catalysis, water expulsion, and enzyme reorganization in Medicago savita chalcone isomerase.

In aqueous solution, Medicago savita chalcone isomerase (CHI) enhances the reaction rate for the unimolecular rearrangement of chalcone (CHN) into flavanone by seven orders of magnitude. Conformations of CHN and their relative free energies in water and CHI were investigated by the thermodynamic perturbation method. In water, CHN adopts two conformations (I and II) with conformation I being higher in energy than conformation II by 3 kcal/mol. Only I can give rise to a near attack conformer (NAC) where the nucleophile O2' and the electrophile C9 are placed in proximity. In CHI, I binds less tightly than II by approximately 2 kcal/mol, resulting in the free energy for NAC formation being approximately 2 kcal/mol higher in the enzyme than in water. This unfavorable feature in the ground state of the CHI reaction requires the predominant catalytic advantage to be taken in the step of NAC --> transition state (TS). From the molecular dynamics simulations of apo-CHI, CHI complexed with CHN (CHI.CHN) and CHI.TS, we found: (i) Lys-97-general-acid catalysis of the O2'(-) nucleophilic addition; (ii) expulsion of three water molecules in the process of TS formation; (iii) release of enzyme structural distortion on TS formation. In the conclusion, CHI's remarkable efficiency of stabilizing the TS and its relatively poor ability in organizing the ground state is compared with chorismate mutase whose catalytic prowess, when compared with water, originates predominantly from the enhanced NAC population at the active site.

Hydrogen Atom Addition to Cytosine, 1-Methylcytosine, and Cytosine−Water Complexes. A Computational Study of a Mechanistic Dichotomy

Combined ab initio and density functional theory calculations at the B3-MP2/6-311++G(3df,2p) level of theory are used to investigate the structures and energetics of radicals produced by hydrogen atom addition to cytosine tautomers, 1-methylcytosine, and cytosine−water complexes. H-atom adducts to the N-3 positions are the most stable radical isomers derived from cytosine tautomer (1), 1-methylcytosine, and cytosine−water complexes in the gas phase. Solvent effects on radical stabilities are addressed by calculations that use the polarizable continuum model. Solvation by bulk water favors C-5 and C-6 adducts which have free energies in water that are comparable to those of the N-3 adducts. H-atom additions to the C-5 positions have the lowest activation energies for all cytosine derivatives under study and are predicted to be kinetically predominant. H-atom additions to the N-3 and C-6 positions are solvent dependent. In the absence of solvation, N-3 is more reactive than C-6 in cytosine and 1-methylcytos...

Calculation of the free energy of solvation for neutral analogs of amino acid side chains

The ability of the GROMOS96 force field to reproduce partition constants between water and two less polar solvents (cyclohexane and chloroform) for analogs of 18 of the 20 naturally occurring amino acids has been investigated. The estimations of the solvation free energies in water, in cyclohexane solution, and chloroform solution are based on thermodynamic integration free energy calculations using molecular dynamics simulations. The calculations show that while the force field reproduces the experimental solvation free energies of nonpolar analogs with reasonable accuracy the solvation free energies of polar analogs in water are systematically overestimated (too positive). The dependence of the calculated free energies on the atomic partial charges was also studied.

A molecular-based theory for the thermodynamic properties of water

Following the rules set by the molecular theories of fluids, a perturbed form of the Helmholtz free energy for water has been developed. The reference term corresponds to short range water, and is approximated by the properties of a primitive model; the perturbation term is given by contributions of the dispersion forces and the dipole-dipole interaction. The method is first verified by applying it to TIP4P water and then used for real water without reference to any specific potential. The parameters of the model are determined in order to obtain the best representation of the vapour pressure and coexistence liquid densities from the triple point to 643.15K; no attempt is made to fit the critical region. Despite a number of approximations employed, the accuracy of the equation of state is comparable with that of the modified Redlich-Kwong-Soave equation and SAFT Yukawa-dipole-dipole equation, and considerably better than the accuracy of SAFT-HS and SAFT-VR equations. Because of its true molecular footing, the equation remains reliable also for various thermodynamic properties outside the coexistence region. It reproduces the anomaly in the isothermal compressibility, locating its minimum at T = 38 °C (versus the experimental value T = 46 °C) for P = 1 bar. It also predicts a density maximum, but outside the experimental temperature range (at temperatures below the triple-point temperature).

Solvation Model Based on Weighted Solvent Accessible Surface Area

We have developed a fast procedure to predict solvation free energies for both organic and biological molecules. This solvation model is based on weighted solvent accessible surface area (WSAS). Least-squares fittings have been applied to optimize the weights of SAS for different atom types in order to reproduce the experimental solvation free energies. Good agreement with experimental results has been obtained. For the 184-molecule set (model I), for which there are experimental solvation free energies in 1-octanol, we have achieved an average error of 0.36 kcal/mol, better than that of the SM5.42R universal solvation model1 by Li et al. For the 245-molecule set (model II) that has experimental aqueous solvation free energies, our WSAS model achieves an average error of 0.48 kcal/mol, marginally larger than that of Li's model (0.46 kcal/mol). We have used a 401-molecule set, the largest training set (model IV) that we know of solvation model development, to derive the SAS weights in order to reproduce the experimental solvation free energies in water. For this model, we have achieved an average unsigned error of 0.54 kcal/mol and an RMS error of 0.79 kcal/mol.The advantage of this model lies in its simplicity and independence of charge models. We have successfully applied this model to predict the relative binding free energies for the five binding modes of HIV-1RT/efavirenz. The most favorable binding mode, which has an RMSD of 1.1 Å (for 54 Cα around the binding site) compared to the crystal structure, has a binding free energy at least 10 kcal/mol more negative than the other binding modes. Moreover, the solvation free energies with WSAS have a high correlation (the correlation coefficient is 0.92) to the solvation free energies calculated by the Poisson−Boltzmann/surface area (PBSA) model. As an efficient and fast approach, WASA is also attractive for protein modeling and protein folding studies. We have applied this model to predict the solvation free energies of the 36-mer villin headpiece subdomain in its native structure, a compact folding intermediate, and a random coil. The rank order of the solvation free energies and the free energies for the three kinds of conformational clusters are in reasonable agreement with those found by MM-PBSA, a widely used solvation free energy model.

Theory of the Self-Exchange Electron Transfer in the Dioxygen/Superoxide System in Water

Theoretical investigation of the rate constant and activation energy of the charge-transfer reaction in water is performed. Equations for these kinetic characteristics of the reaction obtained in the framework of quantum mechanical theory are presented. The equations take into account a quantum character of the O−O vibration and the fact that the dielectric spectrum of water has an absorption in the quantum frequency range. Parameters of these equations, such as the reactants' interaction free energy in water, U(R), electron coupling matrix element, Vfi, and reorganization energies are calculated in terms of appropriate models for several mutual geometries of the reactants. For each of these geometries, the distance dependence of the parameters is investigated and used for numerical estimation of the rate constant and activation energy. Results of the theoretical analysis are in a reasonable agreement with experimental data.

Formation of natural gas hydrates in marine sediments: 2. Thermodynamic calculations of stability conditions in porous sediments

A thermodynamic model for hydrate formation is used to compute the solubility of methane in pore water in equilibrium with gaseous methane or methane hydrate or both. Free energy of water in the hydrate phase and of methane in gas bubbles are corrected to account for salt effects and capillary effects. Capillary effects increase the solubility of methane in fluid in equilibrium with either hydrate or gas. Natural sediments have a broad distribution of pore sizes, and the effective pore size for capillary effects is a function of the fraction of the pore space filled by hydrate or gas (phase fraction). The equilibrium conditions for hydrate + water + gas equilibrium thus depend on hydrate and gas phase fraction. Data acquired on Blake Ridge during Ocean Drilling Program Leg 164 show that the base of the hydrate stability there is shifted by −2°C or more with respect to the expected temperature and this shift has been attributed to capillary effects. We show that this explanation would require a very small effective pore radius (20 nm at 30 MPa). Mercury porosimetry indicates that the percolation threshold for Blake Ridge silty claystone is reached at 20–25% phase fraction and corresponds to a 100 nm pore radius. Hydrate and gas phase fraction determined with several independent methods are all lower than this percolation threshold, implying that gas and hydrate fill pores larger than 100 nm. We conclude that additional inhibition factors other than pore size effects must be involved to explain the −2°C bottom‐simulating reflector (BSR) shift as an equilibrium phenomenon. Capillary effects may, however, explain other observations such as large variations of the gas hydrate content in the sediment with lithology and porosity and the distribution of hydrate between interstitial hydrate and segregated masses. Capillary effects should also oppose the migration of gas bubbles when gas phase fraction is less than the percolation threshold and make unnecessary the assumption of a hydrate seal impermeable to fluids. Alternatively, we can go some way to explaining the offset position of the BSR by relaxing the assumption that the system is in thermodynamic equilibrium. Nucleation kinetics of hydrate and/or free gas bubbles may be inhibited by confinement of the methane‐bearing fluid in small pores. Equilibration may also be limited by possible rates of diffusional transport of gas, water, and salt components or be perturbed by significant flows of fluid or heat through the sediments.

Determination of the free energy of water at room temperature by parallel grand canonical Monte Carlo

Determination of the free energy of water at room temperature by parallel grand canonical Monte Carlo