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This article presents an in-depth investigation into the influence of anionic structures of ionic liquids (ILs) on gas-ionic liquid partition coefficients (log K ) of organic solutes in three ILs. While the primary objective was to examine whether there is a relationship between the molecular structure of the IL anion component and log K , additionally it was looked at whether the molecular descriptors of the anion in the relationships encode possible molecular interactions during the miscibility and partitioning in the IL. The research involves the compilation of data series of experimental log K values, where the cation component is constant. Such representative data series were obtained for three solutes─benzene, cyclohexane, and methanol─in three ILs with a uniform cationic component of methylimidazoliums. Using multiple linear regression models enhanced with machine learning techniques, the relationship between anionic structures and log K values was successfully quantified and modeled. Systematically selected molecular descriptors describing the anion structure show that in the case of methanol log K is strongly dependent on hydrogen bonds and Coulomb-dipolar interactions with the anion component, while in the case of benzene and cyclohexane the dispersion forces of the anion component are dominant. The outlier analysis and data interpretation highlight the need for extensive experimental data. The results confirm the initial hypothesis and provide valuable information on the role of the structure of the anionic component in determining the partitioning behavior of organic solutes. This knowledge is important for the design and optimization of ILs for specific applications, particularly as solvents in various industrial processes. The research also provides useful information about molecular interactions taking place in the interfaces of IL and organic additives in complex liquid media such as multicomponent electrolyte solutions, for example in energy storage applications.

A polemic is given regarding several of the calculated curve-fit parameters that Zhou and coworkers reported in their published paper. The calculated curve-fit parameters for the Combined Nearly Ideal Binary Solvent/Redlich-Kister, Jouyban-Acree-van't Hoff, Sun and modified Apelblat models were found to give mole fraction solubilities that exceeded unity. Our analysis also found that the mean relative absolute percent deviations provided by the authors were significantly underestimated., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A new set of solute parameters derived from a correlation model using Catalan parameters. The parameters represent the interaction of the solute with the mono-solvents at 298.15K. The computational procedure was adopted from Abraham's solvation model and the obtained results are promising. In this work, the calculated parameters were used to back-calculate the drugs solubility in various mono-solvents at different temperatures employing the van't Hoff's model as the skeleton on the derived model. The obtained mean percentage deviations (MPDs) were in the range of 3.1 to 88.5% with the overall MPD of 29.1%. (1) Derivation of a new set of solute parameters from a correlation model using Catalan parameters; (2) adoption of the calculation method of Abraham's solvation model with the skeleton of van't Hoff's equation; (3) using the achieved parameters for back-calculation of drugs solubility in various mono-solvents; (4) obtaining an overall acceptable mean percentage deviation of 29.1% from calculations., (Copyright © 2023 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Rosuvastatin (RST) is a poorly water-soluble drug responsible for limited in vivo dissolution and subsequently low oral systemic absorption (poor bioavailability). The mole fraction solubility values of RST in various ratios of binary mixtures "{PEG400 (1) + water (2)}" at 298.15 K were employed to investigate the preferential solvation (PS) of RST (3) by the binary components. Moreover, the GastroPlus program predicted the drug dissolution/absorption rates, plasma drug concentration, and compartmental regional drug absorbed from a conventional tablet as compared to the RST-loaded (PEG400 + water) mixture (at x 1 = 0.5) in healthy subjects (considering the fast condition). Fedors' method was adopted to estimate the values of molar volume (314.8 cm 3 ·mol -1 ) and Hildebrand solubility parameter (28.08 MPa 1/2 ) of RST. The results of inverse Kirkwood-Buff integrals showed the PS of RST by PEG400 as observed in all studied ratios of the binary mixture. The highest PS value (δ x 1,3 = 1.65 × 10 -2 ) for RST by PEG400 was attained at x 1 = 0.5. Finally, the GastroPlus program predicted the maximum dissolution rate [20 mg within 15 min as compared to pure RST (1.5 mg within 15 min)]. Moreover, the program predicted increased in vivo oral absorption (1.2 μg/mL) and enhanced regional absorption (95.3%) of RST from upper segments of the gastrointestinal tract for the RST-loaded PEG400 + water mixture in humans as compared to conventional tablets (87.5% as total regional absorption and 0.88 μg/mL as in vivo absorption). Hence, the present binary system ferrying RST can be a promising strategy to control systemic dyslipidemia after oral or subcutaneous administration., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Meloxicam is an analgesic and anti-inflammatory drug widely prescribed in current therapeutics that exhibits very low solubility in water. Thus, this physicochemical property has been studied in N -methyl-pyrrolidone (NMP)-aqueous mixtures at several temperatures to expand the solubility database about pharmaceutical compounds in aqueous-mixed solvents. The flask-shake method and UV-vis spectrophotometry were used for meloxicam solubility determination as a function of temperature and mixture composition. Several cosolvency models, including the Jouyban-Acree model, were challenged for equilibrium solubility correlation and/or prediction. The van't Hoff and Gibbs equations were employed here to calculate the apparent standard thermodynamic quantities for the dissolution and mixing processes of this drug in these aqueous mixtures. Inverse Kirkwood-Buff integrals were employed to calculate the preferential solvation parameters of meloxicam by NMP in all mixtures. Meloxicam equilibrium solubility increased with increasing temperature, and maximal solubilities were observed in neat NMP at all temperatures. The mole fraction solubility of meloxicam increased from 1.137 × 10 -6 in neat water to 3.639 × 10 -3 in neat NMP at 298.15 K. The Jouyban-Acree model correlated the meloxicam solubility in these mixtures very well. Dissolution processes were endothermic and entropy-driven in all cases, except in neat water, where nonenthalpy- nor entropy-driven was observed. Apparent Gibbs energies of dissolution varied from 34.35 kJ·mol -1 in pure water to 7.99 kJ·mol -1 in pure NMP at a mean harmonic temperature of 303.0 K. A nonlinear enthalpy-entropy relationship was observed in the plot of dissolution enthalpy vs dissolution Gibbs energy. Meloxicam is preferentially hydrated in water-rich mixtures but preferentially solvated by NMP in the composition interval of 0.16 < x 1 < 1.00., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Ionic liquids (ILs) are known for their unique characteristics as solvents and electrolytes. Therefore, new ILs are being developed and adapted as innovative chemical environments for different applications in which their properties need to be understood on a molecular level. Computational data-driven methods provide means for understanding of properties at molecular level, and quantitative structure-property relationships (QSPRs) provide the framework for this. This framework is commonly used to study the properties of molecules in ILs as an environment. The opposite situation where the property is considered as a function of the ionic liquid does not exist. The aim of the present study was to supplement this perspective with new knowledge and to develop QSPRs that would allow the understanding of molecular interactions in ionic liquids based on the structure of the cationic moiety. A wide range of applications in electrochemistry, separation and extraction chemistry depends on the partitioning of solutes between the ionic liquid and the surrounding environment that is characterized by the gas-ionic liquid partition coefficient. To model this property as a function of the structure of a cationic counterpart, a series of ionic liquids was selected with a common bis-(trifluoromethylsulfonyl)-imide anion, [Tf2N] - , for benzene, hexane and cyclohexane. MLR, SVR and GPR machine learning approaches were used to derive data-driven models and their performance was compared. The cross-validation coefficients of determination in the range 0.71-0.93 along with other performance statistics indicated a strong accuracy of models for all data series and machine learning methods. The analysis and interpretation of descriptors revealed that generally higher lipophilicity and dispersion interaction capability, and lower polarity in the cations induces a higher partition coefficient for benzene, hexane, cyclohexane and hydrocarbons in general. The applicability domain analysis of models concluded that there were no highly influential outliers and the models are applicable to a wide selection of cation families with variable size, polarity and aliphatic or aromatic nature.

Abraham model solute descriptors have been determined for nisoldipine, nizatidine, loratadine, zonisamide, oxaprozin, rebamipide, domperidone, temozolomide, 'florfenicol', florfenicol A, dapsone, chrysin, benorilate, β-lapachone, and Ipriflavone based on published partition coefficients, molar solubilities and gas chromatographic retention indices. The calculated solute descriptors, combined with our previously published Abraham model correlations, are used to predict several important physicochemical and biological properties, such as air-water, air-blood, air-lung, air-fat, air-skin, water-lipid, water-membrane and water-skin partition coefficients, as well as permeation from water through skin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

An important factor affecting the model accuracy is the unit expression type for solute and solvent concentrations. One can report the solute and solvent concentration in various units and compare them with various error scales. In order to investigate the unit and error scale expression effects on the accuracy of the Jouyban-Acree model, in the current study, seventy-nine solubility data sets were collected randomly from the published articles and solute and solvent concentrations in the investigated systems were expressed in various units. Mass fraction, mole fraction, and volume fraction were the employed concentration units for the solvent compositions, and mole fraction, molar, and gram/liter were the investigated concentration units for the solutes. The solubility data, with various solute/solvent concentration units, were correlated using the Jouyban-Acree model, and the accuracy of each model for correlating the data was investigated by calculating different error scales and discussed.

( Z )- N -Benzyl-2-{2,4-dioxo-5-(4-prop-2-yl-1-yloxyl)benzylidene)thiazolin-3-yl)}acetamide (SE415) is a novel aldose reductase inhibitor used in the management of diabetes mellitus (DM) and associated complications. Herein, the drug was solubilized (mole fraction solubility) in a "PEG 400 (polyethylene glycol 400) + water" mixture of various ratios at 298.15 K. We reported the preferential solvation of SE415 by PEG 400 using Kirkwood-Buff integrals, the thermodynamic functional parameter, in vitro dissolution, and GastroPlus-based predictions for in vivo performance. The result of Hansen solubility parameter analysis suggested PEG 400 as a suitable solvent for SE415 solubilization at 298.0 K, followed by prediction of several physicochemical properties. In the preferential solvation study, the molar volume, Hildebrand solubility parameters, and the molecular radius of SE415 were estimated as 258.4 cm 3 ·mol -1 , 27.62 MPa 1/2 , and 0.468 nm, respectively, using Fedors' method. The inverse Kirkwood-Buff integrals indicated that the preferential solvation of SE415 by PEG 400 occurred in all studied ratios of the (PEG 400 + water) mixtures. The maximum value (δ x 1,3 = 1.21 × 10 -2 ) of the preferential solvation of SE415 by PEG 400 was achieved at x 1 = 0.15. Then, using GastroPlus software, the maximum dissolution, improved in vivo oral absorption, and high regional compartmental absorption (total 99.0%) of SE415 in humans were predicted. Finally, the solubility data were correlated/predicted using various cosolvency models with satisfactory results. Thus, the binary cosolvent system can be a promising approach for enhanced oral absorption in controlling DM and associated complications in humans., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

The calculation of the heats of combustion ΔH° c and formation ΔH° f of organic molecules at standard conditions is presented using a commonly applicable computer algorithm based on the group-additivity method. This work is a continuation and extension of an earlier publication. The method rests on the complete breakdown of the molecules into their constituting atoms, these being further characterized by their immediate neighbor atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting calculus using the experimental data of 5030 molecules from literature. The applicability of this method has been tested by a subsequent ten-fold cross-validation procedure, which confirmed the extraordinary accuracy of the prediction of ΔH° c with a correlation coefficient R 2 and a cross-validated correlation coefficient Q 2 of 1, a standard deviation σ of 18.12 kJ/mol, a cross-validated standard deviation S of 19.16 kJ/mol, and a mean absolute deviation of 0.4%. The heat of formation ΔH° f has been calculated from ΔH° c using the standard enthalpies of combustion for the elements, yielding a correlation coefficient R 2 for ΔH° f of 0.9979 and a corresponding standard deviation σ of 18.14 kJ/mol.

Experimental solvation free energies are nowadays commonly included as target properties in the validation of condensed-phase force fields, sometimes even in their calibration. In a previous article [Kashefolgheta et al., J. Chem. Theory. Comput., 2020, 16, 7556-7580], we showed how the involved comparison between experimental and simulation results could be made more systematic by considering a full matrix of cross-solvation free energies . For a set of N molecules that are all in the liquid state under ambient conditions, such a matrix encompasses N×N entries for considering each of the N molecules either as solute (A) or as solvent (B). In the quoted study, a cross-solvation matrix of 25 × 25 experimental value was introduced, considering 25 small molecules representative for alkanes, chloroalkanes, ethers, ketones, esters, alcohols, amines, and amides. This experimental data was used to compare the relative accuracies of four popular condensed-phase force fields, namely GROMOS-2016H66, OPLS-AA, AMBER-GAFF, and CHARMM-CGenFF. In the present work, the comparison is extended to five additional force fields, namely GROMOS-54A7, GROMOS-ATB, OPLS-LBCC, AMBER-GAFF2, and OpenFF. Considering these nine force fields, the correlation coefficients between experimental values and simulation results range from 0.76 to 0.88, the root-mean-square errors (RMSEs) from 2.9 to 4.8 kJ mol -1 , and average errors (AVEEs) from -1.5 to +1.0 kJ mol -1 . In terms of RMSEs, GROMOS-2016H66 and OPLS-AA present the best accuracy (2.9 kJ mol -1 ), followed by OPLS-LBCC, AMBER-GAFF2, AMBER-GAFF, and OpenFF (3.3 to 3.6 kJ mol -1 ), and then by GROMOS-54A7, CHARM-CGenFF, and GROMOS-ATB (4.0 to 4.8 kJ mol -1 ). These differences are statistically significant but not very pronounced, and are distributed rather heterogeneously over the set of compounds within the different force fields.

The calculation of the vapour pressure of organic molecules at 298.15 K is presented using a commonly applicable computer algorithm based on the group-additivity method. The basic principle of this method rests on the complete breakdown of the molecules into their constituting atoms, further characterized by their immediate neighbour atoms. The group contributions are calculated by means of a fast Gauss-Seidel fitting algorithm using the experimental data of 2036 molecules from literature. A ten-fold cross-validation procedure has been carried out to test the applicability of this method, which confirmed excellent quality for the prediction of the vapour pressure, expressed in log(pa), with a cross-validated correlation coefficient Q 2 of 0.9938 and a standard deviation σ of 0.26. Based on these data, the molecules' standard Gibbs free energy ΔG° vap has been calculated. Furthermore, using their enthalpies of vaporization, predicted by an analogous group-additivity approach published earlier, the standard entropy of vaporization ΔS° vap has been determined and compared with experimental data of 1129 molecules, exhibiting excellent conformance with a correlation coefficient R 2 of 0.9598, a standard error σ of 8.14 J/mol/K and a medium absolute deviation of 4.68%.

This article is the first of three projected IUPAC Technical Reports resulting from IUPAC Project 2011-037-2-100 (Reference Materials for Phase Equilibrium Studies). The goal of that project was to select reference systems with critically evaluated property values for the validation of instruments and techniques used in phase equilibrium studies for mixtures. This Report proposes seven systems for liquid-liquid equilibrium studies, covering the four most common categories of binary mixtures: aqueous systems of moderate solubility, non-aqueous systems, systems with low solubility, and systems with ionic liquids. For each system, the available literature sources, accepted data, smoothing equations, and estimated uncertainties are given.

Experimental solvation free energies are nowadays commonly included as target properties in the validation and sometimes even in the calibration of condensed-phase force fields. However, this is often done in a nonsystematic fashion, by considering available solvation free energies involving an arbitrary collection of solutes in a limited set of solvents (e.g., water, octanol, chloroform, cyclohexane, or hexane). Here, this approach is made more systematic by introducing the concept of cross-solvation free energies Δ s G A:B ⊖ for a set of N molecules that are all in the liquid state under ambient conditions, namely the matrix of N 2 entries for Δ s G A:B ⊖ considering each of the N molecules either as a solute (A) or as a solvent (B). Relying on available experimental literature followed by careful data curation, a complete Δ s G A:B ⊖ matrix of 625 entries is constructed for 25 molecules with one to seven carbon atoms representative for alkanes, chloroalkanes, ethers, ketones, esters, alcohols, amines, and amides. This matrix is then used to compare the relative accuracies of four popular condensed-phase force fields: GROMOS-2016H66, OPLS-AA, AMBER-GAFF, and CHARMM-CGenFF. In broad terms, and in spite of very different force-field functional-form choices and parametrization strategies, the four force fields are found to perform similarly well. Relative to the experimental values, the root-mean-square errors range between 2.9 and 4.0 kJ·mol -1 (lowest value of 2.9 for GROMOS and OPLS), and the average errors range between -0.8 and +1.0 kJ·mol -1 (lowest magnitude of 0.2 for AMBER and CHARMM). These differences are statistically significant but not very pronounced, especially considering the influence of outliers, some of which possibly caused by inaccurate experimental data.

A polemic is given regarding the calculated thermodynamic quantities reported in the published paper by Farschi and coworkers. The graph used to calculate the molar heat of sorption of organic probe molecules onto the liquid DL-limonene stationary phase erroneously plots the reciprocal of the centigrade temperatures, rather than the reciprocal of the Kelvin temperatures. Molar heats of vaporization of the organic probe molecules reported in the paper are abnormally small and are not in accord with published values determined from calorimetric and vapor pressure measurements., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The physics-based molecular force field (PMFF) was developed by integrating a set of potential energy functions in which each term in an intermolecular potential energy function is derived based on experimental values, such as the dipole moments, lattice energy, proton transfer energy, and X-ray crystal structures. The term "physics-based" is used to emphasize the idea that the experimental observables that are considered to be the most relevant to each term are used for the parameterization rather than parameterizing all observables together against the target value. PMFF uses MM3 intramolecular potential energy terms to describe intramolecular interactions and includes an implicit solvation model specifically developed for the PMFF. We evaluated the PMFF in three ways. We concluded that the PMFF provides reliable information based on the structure in a biological system and interprets the biological phenomena accurately by providing more accurate evidence of the biological phenomena.

We have used gas chromatographic retention data together with other data to obtain Abraham descriptors for 30 terpene esters. These include the air-water partition coefficient, as log Kw, for which no experimental values are available for any terpene ester. The other descriptors are the ester dipolarity, S, the hydrogen bond basicity, B, (the ester hydrogen bond acidity is zero for the esters studied), and L the logarithm of the air-hexadecane partition coefficient. Both S and B are larger than those for simple aliphatic esters, as expected from the terpene ester structures that include ring systems and ethylenic double bonds. These descriptors can then be used to obtain a large number of physicochemical and environmental properties of terpene esters. We have analyzed experimental results on human odor detection thresholds and have constructed another equation for the calculation of these thresholds, to go with a previous equation that we have reported. Then the descriptors for terpene esters can be used to estimate the important odor detection thresholds., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The literature data on solubilities and water-solvent partition coefficients have been used to obtain properties or "Absolv descriptors" for zwitterionic α-aminoacids: glycine, α-alanine (α-aminopropanoic acid), α-aminobutanoic acid, norvaline (α-aminopentanoic acid), norleucine (α-aminohexanoic acid), valine (α-amino-3-methylbutanoic acid), leucine (α-amino-4-methylpentanoic acid), and α-phenylalanine. Together with equations that we have previously constructed, these descriptors can be used to estimate further solubilities and partition coefficients in a variety of organic solvents and in water-methanol and water-ethanol mixtures. It is shown that equations for neutral solutes are inadequate for the description of solubilities and partition coefficients for these α-aminoacids, and our equations developed for use with both neutral and ionic solutes must be used. The Absolv descriptors include those for hydrogen-bond acidity, A , and hydrogen-bond basicity, B . We find that both of these descriptors are far smaller in value than those for compounds that contain the corresponding ionic groups. Thus, A for α-alanine is 0.28, but A for the ethylammonium cation is 1.31; B for α-alanine is 0.83, and yet B for the acetate anion is no less than 2.93. The additional descriptors that we developed for equations that involve ions, J + and J - , are very significant for the α-aminoacids, although numerically smaller than for ionic species such as EtNH 3 + and CH 3 CO 2 - ., Competing Interests: The authors declare no competing financial interest.

The solubility of drugs is a crucial physicochemical property in the drug discovery or development process and for improving the bioavailability of drugs. There are various methods for evaluating the solubility of drugs including manual measurement methods, mathematical methods, and smart methods. Manual measurement and mathematical methods have some defects which make the smart systems more reliable and important in this field. In this review, various instruments used for the solubility determination, along with the smart systems, have been discussed. Mechanism and applications of each method have been elaborated in detail. Moreover, unique characteristics as well as some limitations of discussed methods are also described.

In computer simulations of solvation effects on chemical reactions, continuum modeling techniques regain popularity as a way to efficiently circumvent an otherwise costly sampling of solvent degrees of freedom. As effective techniques, such implicit solvation models always depend on a number of parameters that need to be determined earlier. In the past, the focus lay mostly on an accurate parametrization of water models. Yet, non-aqueous solvents have recently attracted increasing attention, in particular, for the design of battery materials. To this end, we present a systematic parametrization protocol for the Self-Consistent Continuum Solvation (SCCS) model resulting in optimized parameters for 67 non-aqueous solvents. Our parametrization is based on a collection of ≈6000 experimentally measured partition coefficients, which we collected in the Solv@TUM database presented here. The accuracy of our optimized SCCS model is comparable to the well-known universal continuum solvation model (SMx) family of methods, while relying on only a single fit parameter and thereby largely reducing statistical noise. Furthermore, slightly modifying the non-electrostatic terms of the model, we present the SCCS-P solvation model as a more accurate alternative, in particular, for aromatic solutes. Finally, we show that SCCS parameters can, to a good degree of accuracy, also be predicted for solvents outside the database using merely the dielectric bulk permittivity of the solvent of choice.

This study aimed to provide a rational experimental design to collect a minimum number of experimental data points for a drug dissolved in a given binary solvent mixture at various temperatures, and to describe a computational procedure to predict the solubility of the drugs in any solvent composition and temperature of interest. We gathered available solubility data sets from papers published from 2012 to 2016 (56 data sets, 3488 data points totally). The mean percentage deviations (MPD) used to check the accuracy of predictions was calculated by Eq. 10. Fifty-six datasets were analyzed using 8 training data points which the overall MPD was calculated to be 15.5% ± 15.1%, and for 52 datasets after excluding 5 outlier sets was 12.1% ± 8.9%. The paired t test was conducted to compare the MPD values obtained from the models trained by 7 and 8 training data points and the reduction in prediction overall MPD (from 17.7% to 15.5%) was statistically significant (p < 0.04). To further reduction in MPD values, the computations were also conducted using 9 training data points, which did not reveal any significant difference comparing to the predictions using 8 training data points (p > 0.88). This observation revealed that the model adequately trained using 8 data points and could be used as a practical strategy for predicting the solubility of drugs in binary solvent mixtures at various temperatures with acceptable prediction error and using minimum experimental efforts. These sorts of predictions are highly in demand in the pharmaceutical industry.

We have used literature data on the solubility of cyclooctasulfur in a number of solvents to drive Abraham descriptors for cyclooctasulfur. These can then be used in linear free-energy relationships that we have already constructed to predict partition coefficients and solubilities in a very large number of additional solvents. Cyclooctasulfur is very hydrophobic, has zero hydrogen bond acidity and zero hydrogen bond basicity, and dissolves best in nonpolar or only moderately polar solvents. We have also obtained enthalpies of solvation of cyclooctasulfur in solvents; again our linear free-energy relationships can be used to predict enthalpies of solvation in further solvents., Competing Interests: The authors declare no competing financial interest.

The calculation of the surface tension of ordinary organic and ionic liquids, based on a computer algorithm applying a refined group-additivity method, is presented. The refinement consists of the complete breakdown of the molecules into their constituting atoms, further distinguishing them by their immediate neighbour atoms and bond constitution. The evaluation of the atom-groups' contributions was carried out by means of a fast Gauss-Seidel fitting method, founded upon the experimental data of 1893 compounds from literature. The result has been tested for plausibility using a 10-fold cross-validation (cv) procedure. The direct calculation and the cv test proved the applicability of the present method by the close similarity and excellent goodness of fit R² and Q² of 0.9039 and 0.8823, respectively. The respective standard deviations are ±1.99 and ±2.16 dyn/cm. Some correlation peculiarities have been observed in a series of ordinary and ionic liquids with homologous alkyl chains, as well as with di- and trihydroxy-groups-containing liquids, which have been discussed in detail, exhibiting the limit of the present method.

To describe the physically realistic solvation free energy surface of a molecule in a solvent, a generalized version of the solvation free energy density (G-SFED) calculation method has been developed. In the G-SFED model, the contribution from the hydrogen bond (HB) between a solute and a solvent to the solvation free energy was calculated as the product of the acidity of the donor and the basicity of the acceptor of an HB pair. The acidity and basicity parameters of a solute were derived using the summation of acidities and basicities of the respective acidic and basic functional groups of the solute, and that of the solvent was experimentally determined. Although the contribution of HBs to the solvation free energy could be evenly distributed to grid points on the surface of a molecule, the G-SFED model was still inadequate to describe the angle dependency of the HB of a solute with a polarizable continuum solvent. To overcome this shortcoming of the G-SFED model, the contribution of HBs was formulated using the geometric parameters of the grid points described in the HB coordinate system of the solute. We propose an HB angle dependency incorporated into the G-SFED model, i.e., the G-SFED-HB model, where the angular-dependent acidity and basicity densities are defined and parametrized with experimental data. The G-SFED-HB model was then applied to calculate the solvation free energies of organic molecules in water, various alcohols and ethers, and the log P values of diverse organic molecules, including peptides and a protein. Both the G-SFED model and the G-SFED-HB model reproduced the experimental solvation free energies with similar accuracy, whereas the distributions of the SFED on the molecular surface calculated by the G-SFED and G-SFED-HB models were quite different, especially for molecules having HB donors or acceptors. Since the angle dependency of HBs was included in the G-SFED-HB model, the SFED distribution of the G-SFED-HB model is well described as compared to that of the G-SFED model.

We have set out an equation for partition of 87 neutral molecules from water to o -nitrophenyl octyl ether, NPOE, an equation for partition of the 87 neutral molecules and 21 ionic species from water to NPOE, and an equation for partition of 87 neutral molecules from the gas phase to NPOE. Comparison with equations for partition into other solvents shows that, as regards partition of neutral (nonelectrolyte) compounds, NPOE would be a good model for 1,2-dichloroethane and for nitrobenzene. In terms of partition of ions and ionic species, NPOE is quite similar to 1,2-dichloroethane and not far away from other aprotic solvents such as nitrobenzene.

The application of a commonly used computer algorithm based on the group-additivity method for the calculation of the liquid viscosity coefficient at 293.15 K and the activity coefficient at infinite dilution in water at 298.15 K of organic molecules is presented. The method is based on the complete breakdown of the molecules into their constituting atoms, further subdividing them by their immediate neighborhood. A fast Gauss-Seidel fitting method using experimental data from literature is applied for the calculation of the atom groups' contributions. Plausibility tests have been carried out on each of the calculations using a ten-fold cross-validation procedure which confirms the excellent predictive quality of the method. The goodness of fit (Q²) and the standard deviation (σ) of the cross-validation calculations for the viscosity coefficient, expressed as log(η), was 0.9728 and 0.11, respectively, for 413 test molecules, and for the activity coefficient log(γ) ∞ the corresponding values were 0.9736 and 0.31, respectively, for 621 test compounds. The present approach has proven its versatility in that it enabled the simultaneous evaluation of the liquid viscosity of normal organic compounds as well as of ionic liquids., Competing Interests: The authors declare no conflict of interest.

The calculation of the standard enthalpies of vaporization, sublimation and solvation of organic molecules is presented using a common computer algorithm on the basis of a group-additivity method. The same algorithm is also shown to enable the calculation of their entropy of fusion as well as the total phase-change entropy of liquid crystals. The present method is based on the complete breakdown of the molecules into their constituting atoms and their immediate neighbourhood; the respective calculations of the contribution of the atomic groups by means of the Gauss-Seidel fitting method is based on experimental data collected from literature. The feasibility of the calculations for each of the mentioned descriptors was verified by means of a 10-fold cross-validation procedure proving the good to high quality of the predicted values for the three mentioned enthalpies and for the entropy of fusion, whereas the predictive quality for the total phase-change entropy of liquid crystals was poor. The goodness of fit ( Q ²) and the standard deviation (σ) of the cross-validation calculations for the five descriptors was as follows: 0.9641 and 4.56 kJ/mol ( N = 3386 test molecules) for the enthalpy of vaporization, 0.8657 and 11.39 kJ/mol ( N = 1791) for the enthalpy of sublimation, 0.9546 and 4.34 kJ/mol ( N = 373) for the enthalpy of solvation, 0.8727 and 17.93 J/mol/K ( N = 2637) for the entropy of fusion and 0.5804 and 32.79 J/mol/K ( N = 2643) for the total phase-change entropy of liquid crystals. The large discrepancy between the results of the two closely related entropies is discussed in detail. Molecules for which both the standard enthalpies of vaporization and sublimation were calculable, enabled the estimation of their standard enthalpy of fusion by simple subtraction of the former from the latter enthalpy. For 990 of them the experimental enthalpy-of-fusion values are also known, allowing their comparison with predictions, yielding a correlation coefficient R ² of 0.6066.

We have used equations for partition coefficients of compounds from water and the gas phase to various solvents to obtain descriptors for pentane-2,4-dione and 21 of its derivatives. These descriptors can then be used to estimate further partition coefficients into a wide variety of solvents. The descriptors also yield information about the properties of pentane-2,4-dione and its derivatives. Pentane-2,4-dione and its alkyl derivatives are quite polar, with substantial hydrogen bond basicity but with no hydrogen bond acidity. In contrast 1,1,1-trifluoropentane-2,4-dione and hexafluoropentan-2,4-dione have significant hydrogen bond acidities.

Linear free energy relationships, LFERs, have been constructed for water-triolein partition coefficients for neutral species. It is shown that separate equations are required for wet and dry triolein. From a comparison of the equation coefficients for water-wet triolein with those for 52 other water-solvent systems it is shown that there is little correspondence between triolein and any of the 52 other solvents - only the water-isopropyl myristate system is close to the water-wet triolen system. A comparison of equation coefficients for the water-wet triolein system with LFER coefficients of 16 environmentally important processes shows that wet triolein is not a suitable model for any of the processes, although a number of other water-solvent systems are possible models for some of the environmental processes. A comparison of LFER coefficients with those of 17 aqueous toxicological processes reveals that most of the water-solvent systems, including water-wet triolein, will be poor models for any of the toxicological systems, but the water-lower alcohol systems show promise as models for a number of the toxicological systems. Our method of comparison of coefficients for LFERs that have exactly the same independent variables can be extended to various other types of system., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The determination of Abraham descriptors for single ions is reviewed, and equations are given for the partition of single ions from water to a number of solvents. These ions include permanent anions and cations and ionic species such as carboxylic acid anions, phenoxide anions and protonated base cations. Descriptors for a large number of ions and ionic species are listed, and equations for the prediction of Abraham descriptors for ionic species are given. The application of descriptors for ions and ionic species to physicochemical processes is given; these are to water-solvent partitions, HPLC retention data, immobilised artificial membranes, the Finkelstein reaction and diffusion in water. Applications to biological processes include brain permeation, microsomal degradation of drugs, skin permeation and human intestinal absorption. The review concludes with a section on the determination of descriptors for ion-pairs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Equation coefficients in the Abraham linear free energy relationship have been obtained for a number of parallel artificial membrane permeability assays, PAMPA, and have been compared to equation coefficients for several biological processes and a large number of water-solvent partitions. From a principal component analysis of the equation coefficients we show that one particular PAMPA (Wohnsland and Faller, 2001) is a good model for human intestinal absorption, but we could find no PAMPA that was a good model for rat brain permeation, mouse brain permeation, blood-brain distribution, skin permeation or water-skin partition, although models that include PAMPA and other descriptors may be useful. The water-octanol system is a poor model for all the biological process we have studied, but water-nonpolar solvent partitions are good models for permeation through egg lecithin membranes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Blood-tissue partition coefficients indicate how a chemical will distribute throughout the body and are an important part of any pharmacokinetic study. They can be used to assess potential toxicological effects from exposure to chemicals and the efficacy of potential novel drugs designed to target certain organs or the central nervous system. In vivo measurement of blood-tissue partition coefficients is often complicated, time-consuming, and relatively expensive, so developing in vitro systems that approximate in vivo ones is desirable. We have determined such systems for tissues such as brain, muscle, liver, lung, kidney, heart, skin, and fat., Results: Several good (p < 0.05) blood-tissue partition coefficient models were developed using a single water-solvent system. These include blood-brain, blood-lung, blood-heart, blood-fat, blood-skin, water-skin, and skin permeation. Many of these partition coefficients have multiple water-solvent systems that can be used as models. Several solvents-methylcyclohexane, 1,9-decadiene, and 2,2,2-trifluoroethanol-were common to multiple models and thus a single measurement can be used to estimate multiple blood-tissue partition coefficients. A few blood-tissue systems require a combination of two water-solvent partition coefficient measurements to model well (p < 0.01), namely: blood-muscle: chloroform and dibutyl ether, blood-liver: N-methyl-2-piperidone and ethanol/water (60:40) volume, and blood-kidney: DMSO and ethanol/water (20:80) volume., Conclusion: In vivo blood-tissue partition coefficients can be easily estimated through water-solvent partition coefficient measurements.Graphical abstract:Predicted blood-brain barrier partition coefficients coloured by measured log BB value.

Lipid membrane-water partitions (e.g., immobilized artificial membrane systems where the lipid membrane is a neutral phospholipid monolayer bound to gel beads) were compared to various organic solvent-water partitions using linear free energy relationships. To this end, we also measured the retention factors of 36 compounds (including neutral and ionic species) from water to liposomes made up of 3-sn-phosphatidylcholine and 3-sn-phosphatidyl-l-serine (80:20, mol/mol), employing liposome electrokinetic chromatography in this work. The results show that lipid membranes exhibit a considerably different chemical environment from those of organic solvents. For both neutral species and ionic species, partitions into the more polar hydroxylic solvents are chemically closer to partition into the lipid membrane as compared to partitions into the less polar hydroxylic solvents and into aprotic solvents. This means that solutes partition into the polar parts of lipid membranes, regardless of whether they are charged or not. In addition, cerasome (i.e., liposome composed mainly of stratum corneum lipids) was compared with regular phospholipid liposomes as a possible model for human stratum corneum in partitions. It was found that the cerasome-water partition exhibits a better chemical similarity to skin permeation. This is probably due to the unique structures of ceramides that occur in cerasome and in the stratum corneum lipid domain. We further show that membranes in membrane-water partitions exhibit very different properties., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Abraham model correlation for describing the partitioning behavior of solutes between water and hexadecane was redetermined using the measured partition coefficient data and solute descriptors derived from experimental data. The newly derived correlation provides a much better mathematical description of the observed partition coefficient data than the correlation given in the published paper.

Background: The Abraham general solvation model can be used in a broad set of scenarios involving partitioning and solubility, yet is limited to a set of solvents with measured Abraham coefficients. Here we extend the range of applicability of Abraham's model by creating open models that can be used to predict the solvent coefficients for all organic solvents., Results: We created open random forest models for the solvent coefficients e, s, a, b, and v that had out-of-bag R(2) values of 0.31, 0.77, 0.92, 0.47, and 0.63 respectively. The models were used to suggest sustainable solvent replacements for commonly used solvents. For example, our models predict that propylene glycol may be used as a general sustainable solvent replacement for methanol., Conclusion: The solvent coefficient models extend the range of applicability of the Abraham general solvation equations to all organic solvents. The models were developed under Open Notebook Science conditions which makes them open, reproducible, and as useful as possible. Graphical AbstractChemical space for solvents with known Abraham coefficients.

Background: Calculating Abraham descriptors from solubility values requires that the solute have the same form when dissolved in all solvents. However, carboxylic acids can form dimers when dissolved in non-polar solvents. For such compounds Abraham descriptors can be calculated for both the monomeric and dimeric forms by treating the polar and non-polar systems separately. We illustrate the method of how this can be done by calculating the Abraham descriptors for both the monomeric and dimeric forms of trans-cinnamic acid, the first time that descriptors for a carboxylic acid dimer have been obtained., Results: Abraham descriptors were calculated for the monomeric form of trans-cinnamic acid using experimental solubility measurements in polar solvents from the Open Notebook Science Challenge together with a number of water-solvent partition coefficients from the literature. Similarly, experimental solubility measurements in non-polar solvents were used to determine Abraham descriptors for the trans-cinnamic acid dimer., Conclusion: Abraham descriptors were calculated for both the monomeric and dimeric forms of trans-cinnamic acid. This allows for the prediction of further solubilities of trans-cinnamic acid in both polar and non-polar solvents with an error of about 0.10 log units. Graphical abstractMolar concentration of trans-cinnamic acid in various polar and non-polar solvents.

A simple method is reported for the estimation of in vivo air-tissue partition coefficients of VOCs and of in vitro blood-tissue partition coefficients for volatile organic compounds and other compounds. Linear free energy relationships for tissues such as brain, muscle, liver, lung, kidney, heart, skin and fat are available and once the Abraham descriptors are known for a compound, no more than simple arithmetic is required to estimate air-tissue and blood-tissue partitions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Abraham descriptors for 40 phthalate esters have been calculated from a variety of experimental data, including water-solvent partition coefficients, high performance liquid chromatographic and gas chromatographic retention times. These descriptors can then be used to calculate a large number of physicochemical and biochemical properties of the esters; values are given for dinonyl phthalate as an example. Once the Abraham descriptors have been obtained for a given phthalate ester, no more than simple arithmetic is needed to calculate values of a huge range of properties. The 'three solubility method' yields data that are consistent for a particular physicochemical property, but not necessarily correct data. Previous literature values for air-water partition coefficients for the higher phthalates are likely to be incorrect by several orders of magnitude., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

(1)H NMR chemical shifts have been obtained in the solvents deuterochloroform and dimethyl sulfoxide. The difference in the chemical shifts of an OH or NH group in these two solvents, Δδ = δ(DMSO) - δ(CDCl3), can be converted into the hydrogen bond acidity, A, of the group using the equation A = 0.0065 + 0.133Δδ. The NMR A value, ANMR, can be used as a quantitative assessment of intramolecular hydrogen bonding. We list values of Δδ and ANMR for 55 compounds containing an OH group and 60 compounds with an NH group. For the hydroxy compounds, if A > 0.5 then the OH group is not part of an intramolecular hydrogen bond, but if A < 0.1 then the OH group forms part of an intramolecular hydrogen bond. For NH compounds, if A > 0.16 the NH group is not part of an intramolecular hydrogen bond, and if A < 0.05 the NH group is part of an intramolecular hydrogen bond. No comparison compounds are needed, and the method is extremely simple. We further show how it is possible to relate intramolecular hydrogen bonding to the actual effect on values of a number of physicochemical, environmental, and biochemical properties.

Background: There is considerable interest in the blood-tissue distribution of agrochemicals, and a number of researchers have developed experimental methods for in vitro distribution. These methods involve the determination of saline-blood and saline-tissue partitions; not only are they indirect, but they do not yield the required in vivo distribution., Results: The authors set out equations for gas-tissue and blood-tissue distribution, for partition from water into skin and for permeation from water through human skin. Together with Abraham descriptors for the agrochemicals, these equations can be used to predict values for all of these processes. The present predictions compare favourably with experimental in vivo blood-tissue distribution where available. The predictions require no more than simple arithmetic., Conclusions: The present method represents a much easier and much more economic way of estimating blood-tissue partitions than the method that uses saline-blood and saline-tissue partitions. It has the added advantages of yielding the required in vivo partitions and being easily extended to the prediction of partition of agrochemicals from water into skin and permeation from water through skin., (© 2013 Society of Chemical Industry.)

Using literature data on solubilities, equations have been constructed for the correlation of solubilities of liquids and solids in dry octanol, as log Soct (M). The best equation statistically uses Abraham descriptors together with the compound melting point. For 282 compounds the equation standard deviation is no more than 0.47 log units. If the melting point term is omitted the standard deviation rises to 0.63 log units. It is suggested that if Abraham descriptors are available, these equations represent the most satisfactory equations for the correlation and estimation of solubilities in dry octanol. If these descriptors are not available, then the simple equation of Yalkowsky can be used, although for 223 compounds the equation standard deviation rises to 0.71 log units., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Retention data on an immobilised artificial membrane have been taken from the work of Li et al. and from Liu et al., and have been correlated with a set of descriptors that includes descriptors for ionized species, that is anions from deprotonated acids and cations from protonated bases. Log k(IAM) values can be predicted for acids or bases that are partially ionized at the experimental pH and log k(IAM) values for acids and bases can be predicted as a function of the fraction present as the ionized species, equivalent to prediction as a function of pH. It is shown that anions reduce the value of log k(IAM) by about 1.1 log units but that cations have almost no effect by comparison to the neutral species. By comparison to non-polar solvents, carboxylate anions and protonated base cations are considerably stabilized by both water and the IAM phase to about 6-8 log units and so the rather small influence of anions (-1.1 log unit) and cations (-0.1 log unit) on log k(IAM) is due to substantial cancellation of these stabilization effects. Indeed, the effect of change of phase from water to IAM on the neutral species is at least as large as the effect of change of phase on the ionic species., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Gas chromatographic retention data on 107 terpene hydrocarbons from the literature together with other data have been used to obtain a set of Abraham descriptors for these 107 compounds. For 88 aliphatic cyclic terpene hydrocarbons, a fragmentation scheme was constructed that allows key descriptors to be estimated just from structure. The total set of descriptors, including those estimated by the fragmentation schemes, were then used to predict water-octanol partition coefficients for the 88 compounds, there being good agreement with values calculated from a number of well-known programs. For a small number of terpene hydrocarbons, there was good agreement between predicted and experimental values of nasal pungency thresholds, and predicted and experimental gas-blood, gas-oil, and gas-water partition coefficients. It is suggested that the descriptors obtained for the 107 terpene hydrocarbons can be used to predict water-solvent partition coefficients, gas-solvent partition coefficients, and partition coefficients in a number of biological systems., (Copyright © 2013 Elsevier B.V. All rights reserved.)