Can We Predict the Pressure Induced Phase Transition of Urea? Application of Quantum Molecular Dynamics

Abstract

Crystalline urea undergoes polymorphic phase transition induced by high pressure. Form I, which is the most stable form at normal conditions and Form IV, which is the most stable form at 3.10 GPa, not only crystallize in various crystal systems but also differ significantly in the unit cell dimensions. The aim of this study was to determine if it is possible to predict polymorphic phase transitions by optimizing Form I at high pressure and Form IV at low pressure. To achieve this aim, a large number of periodic density functional theory (DFT) calculations were performed using CASTEP. After geometry optimization of Form IV at 0 GPa Form I was obtained, performing energy minimization of Form I at high pressure did not result in Form IV. However, employing quantum molecular isothermal–isobaric (NPT) dynamics calculations enabled to accurately predict this high-pressure transformation. This study shows the potential of different approaches in predicting the polymorphic phase transition and points to the key factors that are necessary to achieve the success.

Molecular Simulation and Statistical Learning Methods toward Predicting Drug–Polymer Amorphous Solid Dispersion Miscibility, Stability, and Formulation Design

“…As a computational modeling tool for studying solid-state pharmaceutical compounds, periodic DFT computations have seen increased applications in the literature [ 82 ]. Furthermore, combined DFT/MD methods may also be applied (e.g., Car–Parrinello MD) in which standard empirical force fields (see Section 3.2.1 ) are replaced with an ab initio description of the electronic structure [ 83 , 84 , 85 , 86 ]. Pure QM approaches commonly seen in ASD modeling produce a static snapshot and therefore require adequate, often manual, sampling of the conformational space as a prerequisite.…”

Periodic DFT Calculations—Review of Applications in the Pharmaceutical Sciences

“…However, employing MD dynamics calculations enabled to accurately predict this high-pressure transformation ( Figure 5). Recently, periodic DFT MD calculations have been used in one of our studies to model the polymorphism of urea [160]. Crystalline urea undergoes polymorphic phase transition induced by the high pressure.…”

“…The results were found to be in agreement with the experimental data as Form I is metastable and transforms into Form IV at 3.10 GPa. Source: author's archive, more details[160].…”

Confirmation of Phase Transitions and Laser-Assisted Chemical Reaction for Pyridine under High Pressure

“…Recently, research interest in the properties of molecular crystals under high pressure has continued to rise. , External high pressure reduces intermolecular distances, enhances intermolecular and intramolecular interactions, modifies properties, and induces structure phase transformation in molecular crystals . High-pressure research methods typically include both experimental and computational components. − The experimental method based on diamond anvil cells (DAC) generates a high-pressure environment for a sample and can provide the evolution of phase transitions, atomic coordinates, and unit cell parameters of molecular crystals, combined with synchrotron XRD, Raman and infrared spectroscopy, photoluminescence, etc. − Computational methods, including density functional theory (DFT) − and force field (FF) groups, can provide the energetic characteristics of investigated materials and explain the nature of phase transitions on the basis of the critical parameters from experimental measurements for molecular crystals. , Significant progress in engineering made these experiments possible and even routine in some sense, but they were still very time-consuming and complicated. These experiments give the atomic coordinates and cell parameters of molecular crystals.…”