COSMO-RS

Thermophysical properties of solvent are set of data that are essential for designing processes in industry. But in the absence of experimental data, an accurate predictive method is required. In this context, density () and viscosity () of sulfolane with glycerol and 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide have been measured over the entire range of composition with temperature ranging from 298.15 K to 363.15 K at atmospheric pressure. From these experimental values, thermal expansion (), excess molar volume (V E), viscosity deviation () and Gibbs free energy (G) were calculated. The predicted values were close to the corresponding experimental data with all the standard deviation lower than 1 × 10 −3. Quantum chemical based COSMO-RS was used to predict the molecular interaction and non-ideal liquid phase activity coefficient for all mixtures. It has been interpreted that strong interaction for the sulfolane + [BMIM][NTf 2 ] system, meanwhile weak interaction was deduced for the sulfolane + glycerol system. The molar enthalpy (H), entropy (S) and Gibbs free energy of activation (G) of viscosity were calculated. Simultaneous effects of composition and temperature for the binary mixtures were also reported.

New protocol for screening efficient and environmentally friendly solvents was proposed and experimentally verified. The guidance for solvent selection comes from computed solubility via COSMO-RS approach. Furthermore, solute-solvent affinities computed using advanced quantum chemistry level were used as a rationale for observed solvents ranking. The screening protocol pointed out that 4-formylomorpholine (4FM) is an attractive solubilizer compared to commonly used aprotic solvents such as DMSO and DMF. This was tested experimentally by measuring the solubility of the title compounds in aqueous binary mixtures in the temperature range between 298.15 K and 313.15 K. Additional measurements were also performed for aqueous binary mixtures of DMSO and DMF. It has been found that the solubility of studied aromatic amides is very high and quite similar in all three aprotic solvents. For most aqueous binary mixtures, a significant decrease in solubility with a decrease in the organic fraction is observed, indicating that all systems can be regarded as efficient solvent-anti-solvent pairs. In the case of salicylamide dissolved in aqueous-4FM binary mixtures, a strong synergistic effect has been found leading to the highest solubility for 0.6 mole fraction of 4-FM.

The cocrystallization landscape of benzamide and urea interacting with aliphatic and aromatic carboxylic acids was studied both experimentally and theoretically. Ten new cocrystals of benzamide were synthesized using an oriented samples approach via a fast dropped evaporation technique. Information about types of known bi-component cocrystals augmented with knowledge of simple binary eutectic mixtures was used for the analysis of virtual screening efficiency among 514 potential pairs involving aromatic carboxylic acids interacting with urea or benzamide. Quantification of intermo-lecular interaction was achieved by estimating the excess ther-modynamic functions of binary liquid mixtures under supercooled conditions within a COSMO-RS framework. The smoothed histograms suggest that slightly more potential pairs of benzamide are characterized in the attractive region compared to urea. Finally, it is emphasized that prediction of cocrystals of urea is fairly direct, while it remains ambiguous for benzamide paired with carboxylic acids. The two known simple eutectics of urea are found within the first two quartiles defined by excess thermodynamic functions, and all known cocrystals are outside of this range belonging to the third or fourth quartile. On the contrary, such a simple separation of positive and negative cases of benzamide miscibility in the solid state is not observed. The difference in properties between urea and benzamide R2,2(8) heterosynthons is also documented by alterations of substituent effects. Intermolecular interactions of urea with para substituted benzoic acid analogues are stronger compared to those of benzamide. Also, the amount of charge transfer from amide to aromatic carboxylic acid and vice versa is more pronounced for urea. However, in both cases, the greater the electron withdrawing character of the substituent, the higher the binding energy, and the stronger the supermolecule polarization via the charge transfer mechanism.

The solubility of Sulfanilamide in binary mixtures comprising water and five organic solvents was studied at different temperatures using a spectrophotometric method. Additionally, the differential scanning calorimetry (DSC) measurements were performed to characterize the non-dissolved portion of Sulfanilamide obtained after shake-flask experiments. The Buchowski-Ksiazczak solubility model was applied to interpret the obtained experimental results. The model was successful in reproducing experimental data, as it was evidenced by several statistical measures, including the Akaike Information Criterion. The obtained parameters of the λh-equation were used for calculating the values of enthalpy of mixing. It was observed that the minimum value of enthalpy of mixing for each system is associated with those binary solvent compositions which result in the highest solubility of Sulfanilamide. Also the maximum value of the λ parameter corresponds to the composition of the mixture yielding the highest solubility. The application of COSMO-RS methodology revealed the sensitivity of solute activities and solvation Gibbs free energies to solvent-cosolvent composition. Also, there was noticed a strong correlation of these thermodynamic properties. It happened that low values of Sulfanilamide activities and their monotonous variations with the composition of considered binary solutions are associated with monotonous solubility profiles and also the reverse conclusion holds. Besides, differences in solvation of monomers and intermolecular complexes are the very probable origins of the observed trends in excess enthalpies of saturated solutions. The advanced quantum chemistry computations, including electron correlation and extended basis set, were used for quantification of affinities of systems components toward pairs formation. From the obtained values of activity equilibrium constants it was concluded that the highest affinity in all studied conditions should be attributed to Sulfanilamide dimers. It was also observed that pairs formed by Sulfanilamide with water are more thermodynamically stable than the ones with cosolvent molecules with only one exception, namely 1,4-dioxane.

In this study, the temperature-dependent solubility of nicotinamide (niacin) was measured in six neat solvents and five aqueous-organic binary mixtures (methanol, 1,4-dioxane, acetonitrile, DMSO and DMF). It was discovered that the selected set of organic solvents offer all sorts of solvent effects, including co-solvent, synergistic, and anti-solvent features, enabling flexible tuning of niacin solubility. In addition, differential scanning calorimetry was used to characterize the fusion thermodynamics of nicotinamide. In particular, the heat capacity change upon melting was measured. The experimental data were interpreted by means of COSMO-RS-DARE (conductor-like screening model for realistic solvation-dimerization, aggregation, and reaction extension) for concentration dependent reactions. The solute-solute and solute-solvent intermolecular interactions were found to be significant in all of the studied systems, which was proven by the computed mutual affinity of the components at the saturated conditions. The values of the Gibbs free energies of pair formation were derived at an advanced level of theory (MP2), including corrections for electron correlation and zero point vibrational energy (ZPE). In all of the studied systems the self-association of nicotinamide was found to be a predominant intermolecular complex, irrespective of the temperature and composition of the binary system. The application of the COSMO-RS-DARE approach led to a perfect match between the computed and measured solubility data, by optimizing the parameter of intermolecular interactions.