Evaluation of the OPLS-AA Force Field for the Study of Structural and Energetic Aspects of Molecular Organic Crystals

Motivated by the need for reliable experimental data for the assessment of theoretical predictions, this work proposes a data set of enthalpies of sublimation determined for specific crystalline structures, for the validation of molecular force fields (FF). The selected data were used to explore the ability of the OPLS-AA parametrization to investigate the properties of solid materials in molecular dynamics simulations. Furthermore, several approaches to improve this parametrization were also considered. These modifications consisted in replacing the original FF atomic point charges (APC), by values calculated using quantum chemical methods, and by the implementation of a polarizable FF. The obtained results indicated that, in general, the best agreement between theoretical and experimental data is found when the OPLS-AA force field is used with the original APC or when these are replaced by ChelpG charges, computed at the MP2/aug-cc-pVDZ level of theory, for isolated molecules in the gaseous phase. If a good description of the energetic relations between the polymorphs of a compound is required then either the use of polarizable FF or the use of charges determined taking into account the vicinity of the molecules in the crystal (combining the ChelpG and MP2/cc-pVDZ methods) is recommended. Finally, it was concluded that density functional theory methods, like B3LYP or B3PW91, are not advisable for the evaluation of APC of organic compounds for molecular dynamic simulations. Instead, the MP2 method should be considered

Evaluation of the OPLS-AA Force Field for the Study of Structural and Energetic Aspects of Molecular Organic Crystals

Motivated by the need for reliable experimental data for the assessment of theoretical predictions, this work proposes a data set of enthalpies of sublimation determined for specific crystalline structures, for the validation of molecular force fields (FF). The selected data were used to explore the ability of the OPLS-AA parametrization to investigate the properties of solid materials in molecular dynamics simulations. Furthermore, several approaches to improve this parametrization were also considered. These modifications consisted in replacing the original FF atomic point charges (APC), by values calculated using quantum chemical methods, and by the implementation of a polarizable FF. The obtained results indicated that, in general, the best agreement between theoretical and experimental data is found when the OPLS-AA force field is used with the original APC or when these are replaced by ChelpG charges, computed at the MP2/aug-cc-pVDZ level of theory, for isolated molecules in the gaseous phase. If a good description of the energetic relations between the polymorphs of a compound is required then either the use of polarizable FF or the use of charges determined taking into account the vicinity of the molecules in the crystal (combining the ChelpG and MP2/cc-pVDZ methods) is recommended. Finally, it was concluded that density functional theory methods, like B3LYP or B3PW91, are not advisable for the evaluation of APC of organic compounds for molecular dynamic simulations. Instead, the MP2 method should be considered

Kinetics and Mechanism of the Thermal Dehydration of a Robust and Yet Metastable Hemihydrate of 4‑Hydroxynicotinic Acid

Hydrates are the most common type of solvates and certainly the most important ones for industries such as pharmaceuticals which strongly rely on the development, production, and marketing of organic molecular solids. A recent study indicated that, in contrast with thermodynamic predictions, a new hemihydrate of 4-hydroxynicotinic acid (4HNA·0.5H₂O) did not undergo facile spontaneous dehydration at ambient temperature and pressure. The origin of this robustness and the mechanism of dehydration were investigated in this work, through a combined approach which involved kinetic studies by thermogravimetry (TGA), crystal packing analysis based on X-ray diffraction data, and microscopic observations by hot stage microscopy (HSM), scanning electron microscopy (SEM), and atomic force microscopy (AFM). The TGA results indicated that the resilience of 4HNA·0.5H₂O to water loss is indeed of kinetic origin, c.f., due to a significant activation energy, <i>E</i>_a, which increased from 85 kJ·mol^–1 to 133 kJ·mol^–1 with the increase in particle size. This <i>E</i>_a range is compatible with the fact that four moderately strong hydrogen bonds (typically 20–30 kJ·mol^–1 each) must be broken to remove water from the crystal lattice. The dehydration kinetics conforms to the Avrami-Erofeev A2 model, which assumes a nucleation and growth mechanism. Support for a nucleation and growth mechanism was also provided by the HSM, SEM, and AFM observations. These observations further suggested that the reaction involves one-dimensional nucleation, which is rarely observed. Finally, a statistical analysis of Arrhenius plots for samples with different particle sizes revealed an isokinetic relationship between the activation parameters. This is consistent with the fact that the dehydration mechanism is independent of the sample particle size

Polymorphic Phase Transition in 4′-Hydroxyacetophenone: Equilibrium Temperature, Kinetic Barrier, and the Relative Stability of <i>Z</i>′ = 1 and <i>Z</i>′ = 2 Forms

Particularly relevant in the context of polymorphism is understanding how structural, thermodynamic, and kinetic factors dictate the stability domains of polymorphs, their tendency to interconvert through phase transitions, or their possibility to exist in metastable states. These three aspects were investigated here for two 4′-hydroxyacetophenone (HAP) polymorphs, differing in crystal system, space group, and number and conformation of molecules in the asymmetric unit. The results led to a Δ_f<i>G</i>_m°-<i>T</i> phase diagram highlighting the enantiotropic nature of the system and the fact that the <i>Z</i>′ = 1 polymorph is not necessarily more stable than its <i>Z</i>′ = 2 counterpart. It was also shown that the form II → form I transition is entropy driven and is likely to occur through a nucleation and growth mechanism, which does not involve intermediate phases, and is characterized by a high activation energy. Finally, although it has been noted that conflicts between hydrogen bond formation and close packing are usually behind exceptions from the hypothesis of <i>Z</i>′ = 1 forms being more stable than their higher <i>Z</i>′ analogues, in this case, the HAP polymorph with stronger hydrogen bonds (<i>Z</i>′ = 2) is also the one with higher density