Free Energy Of Solution Research Articles

Thermodynamic analysis of celecoxib in amphiprotic and amphiprotic-aprotic solvent mixtures at several temperatures

The solubilities of celecoxib (CLX), a COX-2 selective nonsteroidal anti-inflammatory drug, were determined in water-ethanol and ethanol-ethyl acetate mixtures at several temperatures (288.15-308.15 K). The solubility curves as a function of ethanol ratio were studied at five temperatures, they showed a single maximum located at 50% ethanol-ethyl acetate (δ1 = 22.50 MPa1/2). The measurements of the variation of inherent drug solubility with temperature were used to estimate different thermodynamic parameters, enthalpy, entropy and Gibbs free energy of solution (ΔHS,ΔSS and ΔGShm, respectively). The apparent enthalpies of the solution were a nonlinear function of the ethanol ratio in aqueous mixture. Non-linear enthalpy-entropy compensation analysis was observed indicating different dissolution mechanism with the variation in mixtures composition. The solubility enhancement is entropy driven at water-rich region (0-40% v/v ethanol) and enthalpy controlled at ethanol-rich region (40–100% v/v ethanol), likely due to water-structure loss around nonpolar moieties of the drug and for the ethanol-rich mixtures it is the enthalpy, probably due to the drug better solvation.

Theory of Multi-Ion Transport and Thermodynamic Phenomena in Solvent-Filled Membranes

Solvent-filled membranes, such as Nafion, are an important class of polymer electrolytes because the imbibed solvent imbues the material with high ionic conductivity, while still allowing the membrane to maintain its mechanical stability. Both of these attributes are essential for membrane electrolytes in numerous energy-storage and -conversion devices including redox-flow batteries. The transport phenomena is complicated due to the multiple ions in the electrolytes employed in these applications and the higher concentrations desired for energy density. Furthermore, while there is understanding on the single-ion transport in these materials, there is a need to develop a self-consistent theory for describing the ion transport and ion partitioning and thermodynamics when interacting with the charged polymer membrane. Moreover, there are few quantitative material design guides for polymers that balance the movement of certain species that are desirable, such as current-carrying ions, against transport of contaminants, additives, or redox-active species, which decrease device performance. To address the above gaps and provide material design insights, this work describes the theory of multi-ion transport in polymer-electrolyte membranes. To specify the thermodynamics of the system, we formulate the membrane and electrolyte solution free energies. The model accounts for long-range electrostatic and short-range solvation and physical interactions between ions. Externally validated solution and membrane properties parameterize the model. The model calculations agree with measured water and ion uptake in dilute and concentrated binary and ternary salt electrolytes, with the uptake being a balance between osmotic and elastic pressures that are impacted by ion specificity and membrane pretreatment.1-2 To model the transport phenomena, we use Stefan-Maxwell-Onsager theory. To connect performance to the molecular-level structure of the polymer, hydrodynamic theory provides constitutive relations for the involved ion/solvent and ion/ and solvent/polymer friction coefficients, with classical porous-media theories scaling tortuosity. The model compares favorably to a number of published measured membrane transport properties1-2 (i.e. conductivity, transference numbers, electroosmosis, and water-transport coefficient) in dilute and concentrated binary and ternary electrolytes. Importantly, the model isolates the contribution of each type of molecular-scale to the measured properties. Acknowledgements: This study was funded with support of the Fuel Cell Performance and Durability Consortium (FC-PAD) funded by the Energy Efficiency and Renewable Energy, Fuel Cell Technologies Office, of the U.S. Department of Energy under contract number DE-AC02- 05CH11231 and, in part, by the Advanced Research Projects Agency - Energy (ARPA-E), U.S. Department of Energy (DOE) under Award Number DEAR0000149 . References Okada, T.; Satou, H.; Okuno, M.; Yuasa, M., Ion and Water Transport Characteristics of Perfluorosulfonated Ionomer Membranes with H+ and Alkali Metal Cations. J. Phys. Chem. B 2002, 106 (6), 1267-1273.Tang, Z.; Svoboda, R.; Lawton, J. S.; Aaron, D. S.; Papandrew, A. B.; Zawodzinski, T. A., Composition and Conductivity of Membranes Equilibrated with Solutions of Sulfuric Acid and Vanadyl Sulfate. J. Electrochem. Soc. 2013, 160 (9), F1040-F1047.

How to Model Inter- and Intramolecular Hydrogen Bond Strengths with Quantum Chemistry.

This article presents the computation of both inter- and intramolecular hydrogen bond strengths from first-principles. Quantum chemical calculations conducted at the dispersion-corrected density functional theory level including free energy and solvation contributions are conducted for (i) one-to-one hydrogen-bonded complexes of alcohols to N-methyl pyrrolidinone measured by an infrared spectroscopy method and (ii) a set of experimental intramolecular hydrogen bond-forming phenol and pyrrole compounds, with intramolecular hydrogen bond strengths derived from a nuclear magnetic resonance method. The computed complexation free energies in solution show a correlation to experiment of R2 = 0.74 with a root mean square error of 4.85 kJ mol-1. The intramolecular hydrogen bonding free energies in solution show a correlation of R2 = 0.79 with a root mean square error of 5.51 kJ mol-1. The results of this study can be used as a guide on how to build reliable quantum chemical databases for computed hydrogen bonding strengths.

Hydrogen-Bonding and Hydrophobic Groups Contribute Equally to the Binding of Hyperactive Antifreeze and Ice-Nucleating Proteins to Ice.

Hyperactive insect antifreeze proteins and bacterial ice-nucleating proteins are arguably the most potent ice-binding molecules in nature. These highly effective proteins bind ice through amphiphilic ice-binding sites based on arrays of threonine residues. It remains poorly understood how hydrophilic and hydrophobic groups of the binding site contribute to the ice affinity of proteins. Here, we use molecular simulations to demonstrate that the hydrogen-bonding and hydrophobic groups at the ice-binding site of the antifreeze protein TmAFP of Tenebrio molitor and extended ice-nucleating protein surfaces contribute distinctively yet almost equally in magnitude to their binding free energy to ice. The methyl groups rigidize the ice-binding site, slow the water dynamics at the ice-binding surface, and stabilize the clathrate-like water in the anchored clathrate motif that binds these proteins to ice. We find that hydrophobic dehydration of the methyl group does not contribute to the binding free energy of the protein to ice. The role of the hydroxyl groups is to anchor the clathrate-like water through direct hydrogen-bonding, positioning and slowing the dynamics of water at the trough of the binding site. We uncover a correlation between slower dynamics of water at the binding site for the protein in solution and stronger free energy of binding of the protein to ice. The synergy between hydrophobic and hydrophilic groups unveiled by this study provides guidance for the design of synthetic ice-binding molecules with enhanced ice nucleation and antifreeze activity.

The Study of the Octanol-Water Partition Coefficient by the Computational Chemistry Method

The octanol–water partition coefficient (logP) is not only an important index value of the hydrophobicity (or hydrophilicity) of a substance, but it is possible to predict the absorbability and accumulation of organic compounds in the living body, and application to the development of new drugs can be expected. In this paper, the logP values of compounds were predicted by solvation free energy calculation using packaged software, Gaussian09. In calculations of free energy in solution, we used CPCM, IEFPCM and SMD methods in the SCRF methods and compared the logP calculated by those methods with that observed by experiments. The results suggest that the SMD method gave better results than the other two.

Gaussian Process Regression Models for the Prediction of Hydrogen Bond Acceptor Strengths.

We present two approaches for the computation of hydrogen bond acceptor strengths, one by machine-learning and one by a composite quantum-mechanical protocol, both based on the well-established pKBHX scale and dataset. The QM calculations after a necessary linear fit reproduce the complexation free energies in solution with an RMSE of 2.6 kJ mol-1 , not far off the expected error of 2 kJ mol-1 obtained from the comparison of experimental data from two different sources. The second approach is by Gaussian Process Regression (GPR) machine-learning. We describe the hydrogen bond acceptor atoms by a radial atomic reactivity descriptor that encodes their electronic and steric environment. The performance of the GPR model on an external test set corresponds to 3.3 kJ mol-1 , which is also close to the experimental error. We apply the GPR model built on experimental data to model the hydrogen bond acceptor strengths of a series of hydrogen bond acceptor sites of 10 phosphodiesterase 10 A inhibitors. The predicted values correlate well with the experimentally measured IC50 values.

An improved methodology to compute surface site interaction points using high density molecular electrostatic potential surfaces.

The theoretical calculation of Surface Site Interaction Points (SSIP) has been used successfully in some applications in the solid and liquid phase. In this work we propose a new set of optimizations for the search of SSIP using the Molecular Electrostatic Potential Surfaces (MEPS) calculated with Density Functional Theory and B3LYP/6-31*G basis set. The measures that have been implemented are based on the search for the best agreement between experimental H-bond donor and acceptor parameters (α and β) and the MEPS extremes exploring a range of electron density levels. Additionally, a parameterization as a function of atom types has been performed. The results show that the MEPS calculated at 0.01 au electron density level slightly improves the correlation with experimental data in comparison with the calculation over other density values. This fact is related to the bigger contribution of local electrostatics at higher density levels. The refinement has provided significant improvements to the correlation between theoretical and experimental data. Moreover, the proposed calculation over 0.01 au is six times faster on average than the computation at 0.002 au. The proposed methodology has been developed with the purpose to obtain high precision SSIP in a fast way and to improve their applications in virtual cocrystal screening, calculation of free energies in solution and molecular docking. © 2018 Wiley Periodicals, Inc.

The Structure and Dynamics of C. elegans Tubulin Reveals the Mechanistic Basis of Microtubule Growth

The dynamic instability of microtubules is a conserved and fundamental mechanism in eukaryotes. Yet microtubules from different species diverge in their growth rates, lattice structures, and responses to GTP hydrolysis. Therefore, we do not know what limitsmicrotubule growth, what determines microtubule structure, or whether the mechanisms of dynamic instability are universal. Here, we studied microtubules from the nematode C.elegans, which have strikingly fast growth rates and non-canonical lattices invivo. Using a reconstitution approach, we discovered that C.elegans microtubules combine intrinsically fast growth with very frequent catastrophes. We solved the structure of C.elegans microtubules to 4.8Å and discovered sequence divergence in the lateral contact loops, one of which is ordered in C.elegans but unresolved in other species. We provide direct evidence that C.elegans tubulin has a higher free energy in solution and propose a model wherein the ordering of lateral contact loops activates tubulin for growth.

Below the room temperature measurements of solubilities in ester absorbents for CO2 capture

Six ester absorbents were selected for CO2 capture, such as methyl benzoate, methyl heptanoate, ethyl hexanoate, butyl butyrate, triethyl phosphate and tributyl phosphate. CO2 solubilities in these absorbents were determined under temperatures of 273.15–283.15 K, and pressures up to 1.2 MPa. Henry’s constants of CO2 + the selected absorbent systems at 273.15 K and 283.15 K were calculated and compared with those at higher temperature. It seemed that decreasing the absorption temperature is obviously beneficial for enhancing absorption performance. In order to assess the absorption capacity for different physical absorbents, Henry’s constants and volumetric solubilities of the selected absorbents were compared with ionic liquids, common solvents and the selected absorbents in our previous work. The result showed that tributyl phosphate and triethyl phosphate were found to be relatively good absorbents by mole and volumetric fraction respectively, and they have potential value for CO2 capture. Moreover, thermodynamic properties such as entropy of solution, enthalpy of solution and Gibbs free energy of solution for the selected systems were calculated and assessed to study the absorption behavior.

Cocrystal Ternary Phase Diagrams from Density Functional Theory and Solvation Thermodynamics

Several solid–liquid ternary phase diagrams consisting of an active ingredient, an excipient (coformer), and a solvent have been computed by means of density functional theory and COSMO-RS solvation thermodynamics. In all these ternary systems, cocrystal formation occurs; furthermore, the active ingredient and coformer are capable of forming strong, concerted hydrogen bonds in solution. The formation of such exceptionally strong bonds in solution has been taken into account by the introduction of an additional binary interaction parameter. This approach leads to a good agreement with experimental data using a minimum set of fit parameters. Quantum-chemically computed interaction enthalpies between solutes are of similar magnitude as the optimized interaction parameters and computed free energies in solution corroborate the existence of a significant population of aggregated drug–coformer complexes. The outlined procedure provides detailed insights into solvation and solubility enhancement effects at the m...

Direct Measurements of Surface Free Energy of Solid Solutions: Phase Transitions and Complexions

Surfaces are key elements of nanomaterials and catalysts. The main thermodynamic properties of surfaces are their chemical composition and energy. To determine the composition of the surface, there are a number of effective methods such as AES, XPS, TEM. Direct measurements of the interfacial free energy of “solid–gas” interface are practically not carried out. This is related to experimental difficulties. We have developed a method for in situ measurements of the surface energy of solid metals and alloys. We conducted the experiments on two-component Cu-based systems in an inert or reducing gas atmosphere. The measurements on Cu [Ag] and Cu [Co] solid solutions show the presence of phase transitions on the surfaces. The isotherms of the surface energy have singularities (the minimum in the case of copper solid solutions with silver and the maximum in the case of solid solutions with cobalt). In both cases, the surface phase transitions lead to the surface miscibility gap: a monolayer (multilayer) formation (Cu–Ag) or formation of nanoscale particles (Cu–Co). In accordance with the bulk phase diagrams, the concentration and temperature of the surface phase transitions correspond to the solid solution in the bulk. Experiments on similar systems (Cu–Fe, Cu–Pb) lead to the conclusion that in all peritectic systems, an increase in the surface energy by adding a component with a higher melting point and surface phase transitions “surface solid solution—two-phase surface with particles” should be expected. In eutectic systems, the component with a lower melting point decreases the surface energy and forms continuous layers.

Below the room temperature measurements of CO 2 solubilities in six physical absorbents

Abstract An isothermal synthetic apparatus was established as the absorbing device. Six physical absorbents with ether and ester groups were selected: ethylene glycol methyl ether acetate (EGMEA), propylene glycol methyl ether acetate (PGMEA), 3-methoxy butyl acetate (MBA), diethylene glycol diethyl ether (DGDE), ethylene glycol butyl ether acetate (EGBEA) and carbitol acetate (CA). CO2 solubilities in the selected absorbents were measured at temperatures of 273.15–283.15 K, and pressures up to 1.2 MPa. Henry’s constants of CO2 + selected absorbents systems at 273.15 K and 283.15 K were regressed and compared with those at higher temperature. It turned out that decreasing the temperature has a large effect on improving absorption capacity. Henry’s constants and volumetric solubilities of the selected absorbents were compared with other solvents and ionic liquids for the purpose of judging the absorption capacity. CA and EGMEA were found to be relatively good absorbents by mole and volumetric fraction respectively, and they have potential value for CO2 capture. In order to study absorption behavior, thermodynamic properties such as entropy of solution, enthalpy of solution and Gibbs free energy of solution for the selected systems were calculated and assessed.

Calculation of Reaction Free Energies in Solution: A Comparison of Current Approaches.

The result of the application of different approaches based on the ideal gas/rigid rotor/harmonic oscillator (IGRRHO) model, commonly used in popular software packages, for the calculation of free energies in solution is compared with that of ab initio molecular dynamics for a process involving ligand exchange in palladium complexes. The IGRRHO-based approaches considered differ in most cases in the extent to which the rotational and translational contributions are included in the correction. Our study supports the use the free energy values directly obtained from dispersion-corrected DFT functionals without any correction or with minor corrections at most.

Reduction Potential of RuIII-Based Complexes with Potential Antitumor Activity and Thermodynamics of their Hydrolysis Reactions and Interactions with Possible Biological Targets: a Theoretical Investigation

In this article density functional theory (DFT)-based calculations were employed to investigate the electrochemistry of the antitumor ruthenium complexes trans-tetrachloro(dimethylsulfoxide)imidazole ruthenate(III) (NAMI-A) and trans-[tetrachlorobis(1.-indazole)ruthenate(III)] (KP1019), their hydrolysis products as well as their interactions with biological S-donors and N-donors targets as cysteine, glutathione and guanine nucleobase. The compounds exhibit different electrochemical behavior upon hydrolysis. While the reduction potential of NAMI-A increases up to 0.8 V upon hydrolysis, the reduction potential of KP1019 remains almost constant after the first hydrolysis. NAMI-A and KP1019 complexes have thermodynamic preference to be reduced prior to undergoing hydrolysis and, strong preference to undergo successive hydrolysis instead of interacting with the S-donor and N-donor ligands. Interaction with S-donor ligands in the unprotonated form is highly unfavorable, with the free energy in solution (ΔGsol) ≥ 18 kcal mol-1. For both complexes, the interaction with the guanine and glutathione are of the same magnitude (ΔGsol ca. –0.6 kcal mol-1) meaning that these ligands can compete for binding to the metallodrug.

How Bound and Free Fatty Acids in Cellulose Films Impact Nonspecific Protein Adsorption.

The effect of fatty acids and fatty acid esters to impair nonspecific protein adsorption on cellulose thin films is investigated. Thin films are prepared by blending trimethylsilyl cellulose solutions with either cellulose stearoyl ester or stearic acid at various ratios. After film formation by spin coating, the trimethylsilyl cellulose fraction of the films is converted to cellulose by exposure to HCl vapors. The morphologies and surface roughness of the blends were examined by atomic force microscopy revealing different feature shapes and sizes depending on the blend ratios. Nonspecific protein adsorption at the example of bovine serum albumin toward the blend thin films was tested by means of surface plasmon resonance spectroscopy in real-time. Incorporation of stearic acid into the cellulose leads to highly protein repellent surfaces regardless of the amount added. The stearic acid acts as a sacrificial compound that builds a complex with bovine serum albumin thereby inhibiting protein adsorption. For the blends where stearoyl ester is added to the cellulose films, the cellulose:cellulose stearoyl ester ratios of 3:1 and 1:1 lead to much lower nonspecific protein adsorption compared to pure cellulose, whereas for the other ratios, adsorption increases. Supplementary results were obtained from atomic force microscopy experiments performed in liquid during exposure to protein solution and surface free energy determinations.

Thermodynamics of solution of L-valine in water

This paper focuses on the accurate thermodynamic study of solution of L-valine in water in a wide temperature range. Enthalpies of solution of L-valine in water have been calorimetrically determined between T=279K and T=323 К. Standard enthalpies and heat capacities of solution as well as standard partial molal heat capacities have been calculated and compared with available literature values. The free energy of solution and its enthalpic and entropic terms have been computed using the combination of solubility and calorimetric data via the Gibbs-Helmholtz equation from T=280K to T=360K. The temperature dependence of solubility of the amino acid has been also computed and compared with experimental quantities. The satisfactory agreement is found between experimental and predicted solubility values.

Solubility in Zr-Nb alloys from first-principles

The thermodynamic properties of the Zr-Nb alloy are investigated at temperatures below 890 K with ab initio calculations. The solution energies of the bcc Nb-rich and hcp Zr-rich solid solutions obtained within the framework of density functional theory are in good agreement with experimental data, although insufficient for a quantitative description of the miscibility gap, for which non configurational entropy has to be accounted for. Whereas electronic free energies can be neglected, we show, using the harmonic approximation and the density functional perturbation theory, that both solution free energies are strongly modified by the contribution related to atomic vibrations. Considering this vibrational free energy leads to a good description of the phase diagram.

Utility of chemical computations in predicting solution free energies of metal ions

Here, we study quasi-chemical theory (QCT) for the free energies of divalent alkaline earth ions (Ba, Sr, Ca, Mg) in water, emphasizing that: (a) interactions between metal ions and proximal water molecules are as strong as traditional chemical effects; (b) QCT builds directly from accessible electronic structure calculations but rests on fully elaborated molecular statistical thermodynamics; (c) QCT offers choices of convenience in identifying coordination numbers for analysis. We investigate utilisation of direct QCT with inner-shell conditioning , alternative to the traditional conditioning motivated by a generalised van der Waals view. The alternative works well: deleterious non-Gaussian effects of van der Waals repulsive interactions are not serious, and the alternative conditioning improves the convenience of QCT calculations. Comparison between ab initio and force field molecular dynamics (AIMD and FFMD) with standard models suggests that FFMD likely exaggerates the anharmonicity in the thermal motion of inner-shell ion-water clusters. Together with the general encouraging support for the harmonic approximations implied by the conditioning, that observation helps explain the remarkable success of the cluster-based QCT solution free energies, which do not require assessment of all inner-shell occupancies by simulation.

Structure and hydrophilicity of azo‐dye‐derived rotaxane: density functional theory approach

We investigated the most probable molecular structure, energy, and corresponding properties, including the solvation energy and binding free energy in solution, for non‐encapsulated azo dyes using quantum mechanical density functional theory (DFT). The structures of non‐encapsulated azo dyes with six conformations were optimised to find the most stable conformation with the lowest energy, but the energy differences among the conformations were within ~2.2 kcal mol−1. The LUMO–HOMO gaps were also similar, meaning that their interaction with light would be similar. The energies of alpha‐cyclodextrin (α‐CD) encircling the phenyl ring fragments were significantly higher than other conformations, because α‐CD tends preferably to encircle azo fragments to create a thermodynamically stable form. From solvation free energy calculations, the hydrophobic non‐encapsulated azo dye and hydrophilic α‐CD showed reasonable values for solvation free energy with respect to dimethyl sulphoxide (DMSO) and water: the former has more solvation in DMSO, while the latter has more solvation in water. Rotaxane formation is thermodynamically feasible in water (−3.06 kcal mol−1) but not in DMSO (25.56 kcal mol−1) according to calculation of binding free energy in solution state.

Commentary on “Correlation of solubility of hexamethylene-1,6-bisthiosulphate disodium salt dihydrate versus dielectric constants of water + ethanol mixtures”

Apelblat model equation coefficients reported by Song and coworkers [Fluid Phase Equilib. 384 (2014) 143–149] are found to give calculated mole fractions that exceed unity for the solubility of hexamethylene-1,6-bisthiosulphate disodium salt dihydrate dissolved in binary aqueous-ethanol solvent mixtures. The calculated mole fraction solubilities are approximate ten thousand times the experimental values. A polemic is also given regarding the authors' interpretation of an observed mathematical relationship between the experimental mole fraction solubility data and the dielectric constant of the binary solvent mixture. The authors' interpreted one of the curve-fit equation coefficients as the free energy of solute at the thermodynamic equilibrium state. An unit analysis examination shows that the unit of the curve-fit equation coefficient must be J/(mol K) which is inconsistent with free energy.