Computational modeling is of great importance in solvent selection for new active pharmaceutical ingredients (APIs), with the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state being among the most popular tools for modeling the API solubility. The PC-SAFT parameters for APIs are traditionally fitted to experimental solubility data, leaving the PC-SAFT performance for other thermodynamic properties of pure APIs and API−solvent mixtures unknown. Therefore, the intention of this study was to investigate the PC-SAFT performance for the solubility as well as pure component properties (liquid density and vapor pressure) of five model APIs: paracetamol, ibuprofen, naproxen, indomethacin, and dibenzofuran. To this end, five different parametrization strategies were defined, the corresponding new parameter sets were identified (using the simulated annealing technique), and their impact on the PC-SAFT performance was evaluated. These strategies differed mainly in the combination of properties included in the parameter regression. The results showed that the API parameters fitted only to solubility data provided a very poor estimation of the pure API properties, whereas those fitted to the liquid density and vapor pressure provided not only an accurate description of such properties but, in many cases, solubility predictions comparable to those obtained using parameters based merely on the solubility. It was also revealed that the inclusion of the vapor pressure in addition to solubility improved the solubility prediction for API−solvent systems not included in the parameter regression. Moreover, the effect of explicitly accounting for the API dipole moment in the PC-SAFT framework was examined.

Low volatility of ionic liquids (ILs), being one of their most valuable properties, is also the principal factor making reliable measurements of vapor pressures and vaporization (or sublimation) enthalpies of ILs extremely difficult. Alternatively, vaporization enthalpies at the temperature of the triple point can be obtained from the enthalpies of sublimation and fusion. While the latter can be obtained calorimetrically with a fair accuracy, the former is in principle accessible through ab initio computations. This work assesses the performance of the first-principles calculations of sublimation properties of ILs. Namely, 3 compounds, coupling the 1-ethyl-3-methylimidazolium cation [emIm] with either tetrafluoroborate [BF 4 ], hexafluorophosphate [PF 6 ], or bis(trifluoromethylsulfonyl)imide [NTf 2 ] anions were selected for a case study. A computational methodology, originally developed for molecular crystals, is adopted for crystals of ILs. It exploits periodic density functional theory (DFT) calculations of the unit-cell geometries and quasi-harmonic phonons and many-body expansion schemes for ab initio refinements of the lattice energies of crystalline ILs. The vapor phase is treated as the ideal gas whose properties are obtained combining the rigid rotor−harmonic oscillator model with corrections from the one-dimensional hindered rotors and molecular-dynamics simulations capturing the contributions from the interionic interaction modes. Although the given computational approach enables one to reach the chemical accuracy (4 kJ mol −1 ) of calculated sublimation enthalpies of simple molecular crystals, reaching the same level of accuracy for ionic liquids proves challenging as crystals of ionic liquids are bound appreciably stronger than common molecular crystals, the underlying cohesive energies of solid ionic liquids is up to 1 order of magnitude larger. Still, combination of the mentioned computational and experimental frameworks results in a novel promising scheme that is expected to generate reliable and accurate temperature-dependent data on sublimation (and vaporization) of ILs.

Liquid−liquid equilibrium data in binary systems γ-valerolactone + hydrocarbon (n-heptane, n-decane, n-dodecane, cyclohexane, and 2,4,4-trimethyl-1-penetene) were determined by direct analytical and cloud-point methods. The experimental data were smoothed by the extended scaling law equation which respects nonclassical behavior of fluid mixtures in critical loci. The nonrandom two-liquid equation's parameters were evaluated from the data obtained, as well. Since the molecule of γ-valerolactone retains a quite high dipole moment, the acquired experimental data on liquid−liquid equilibrium were used for the testing of predictive capabilities of the perturbed-chain polar SAFT equation of state (PCP-SAFT) in comparison to the original PC-SAFT model. Vapor pressures of γ-valerolactone in the temperature range from 264 K to 313 K and its liquid densities at temperatures from 288 K to 363 K were measured and utilized for evaluation of the PCP-SAFT and PC-SAFT parameters. It was found that prediction of liquid−liquid equilibrium performed by the polar PCP-SAFT equation with pure component parameters can be classified as relatively successful. ■ INTRODUCTIONγ-Valerolactone (GVL) is a natural compound which can be found for example in fruits. Recently this compound has gained attention as a versatile sustainable liquid which can be efficiently produced from biomass, preferentially from lignocellulose. The versatility of GVL is very wide. GVL can be utilized as liquid fuel, green solvent, and food additive or as an organic intermediate in the syntheses of other chemicals. To produce GVL from biomass, different technologies are studied. A pioneering technology suggested by Horvath et. al 1 involves a high pressure hydrogenation step which is rather costly for large-scale production of GVL. Romań et al. 2 devised a less expensive method to synthesize the key biofuel component, which could make its industrial production much more costeffective. From this point of view the utilization of GVL as fuel, fuel additive, or fuel precursor seems to be very promising. GVL can be converted to lower molecular weight valerate esters (methyl-, ethyl-, and propyl valerate) suitable for use as a gasoline additive and higher esters (butyl and pentyl valerate) that could be used directly as a diesel fuel or as a diesel additive. 3 Alternatively GVL can be converted to butane molecules which can be further combined to yield longer hydrocarbon chains for diesel or jet fuels. 4 A comparison of GVL with absolute ethanol as a gasoline additive was done by Horvath et al. 5 It was found that most of the data for GVL are comparable with that of ethanol. The lower vapor pressure of GVL even leads to improved performance. According to experiments carried out by Bereczky et al., 6 the addition of GVL to diesel fuels had relatively little effect on engine performance and NO x emission, but it significantly reduced the exhaust concentration of CO, unburned fuel, and smoke. The use of GVL as direct additive to gasoline can be restricted however because of t...

were measured by a static method near ambient temperatures over an operating pressure range from 0.5 to 1270 Pa, thus complementing literature vapor pressure data obtained by ebulliometry at higher temperatures. Liquid heat capacities of 1-octanol, 1-nonanol, and 1decanol were determined by Tian−Calvet calorimetry. Ideal-gas thermodynamic properties of 1-alkanols up to 1-heptanol were obtained by a combination of quantum chemistry and statistical mechanics and validated against available experimental data. Ideal-gas heat capacities and entropies for longer homologues were obtained by deriving a methylene increment due to having a too complex conformational shape for analogical treatment. The thermodynamic consistency of available data was validated by simultaneous correlation of selected vapor pressures, literature enthalpies of vaporization, and heat capacity differences between the ideal gaseous and the liquid phase. The results are represented by the Cox equation and compared with available literature data. Moreover, the results were used to examine the perturbed-chain statistical associating fluid theory (PC-SAFT) equation of state for its performance in describing vapor pressures, enthalpies of vaporization, residual liquid heat capacities, and liquid densities of neat 1-alkanols from 1-hexanol to 1-decanol. A new PC-SAFT parameter set for each of them was also regressed that improves the PC-SAFT performance for the studied properties in comparison to existing parameters published in the literature.

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