Yongsheng Zhao

The solvent is the most important external influence on crystal morphology. Correctly interpreting solvent effects is essential to engineer the desired crystal morphology with specific properties. In this study, we propose a method based on quantum mechanical calculated gas phase interaction + Solvation Model Based on Density (SMD) calculated solvation free energy to predict the solvent‐modified bond energies to predict the morphology of crystals grown from solvents. We also calculate the solvent‐modified bond energy by combining molecular force fields, including the Generalized Amber Force Field and the Coulomb–London–Pauli force field (to calculate gas phase interaction) and SMD (to calculate solvation free energy). We validate these methods using mechanistic models to predict morphologies of four crystals grown from various solvents. Good agreement between the predicted crystal morphologies and the experimental results indicates the reliability of the proposed methods.

All‐atom force fields are important for calculating interaction energies between growth units to predict crystal morphology. Our group at UCSB developed the ADDICT morphology design software to predict crystal morphology using mechanistic growth models driven by the generalized Amber force field (GAFF). In this study, the universal force field (UFF), the consistent force field (CFF), and the Coulomb‐London‐Pauli (CLP) force field are incorporated into ADDICT. We systematically test the lattice energies and crystal morphologies of olanzapine, adipic acid, rubrene, biphenyl, and naphthalene using all these force fields. The unit cells for these crystals are represented by the original CSD experimental structure, as well as optimized structures. Considering the high accuracy of CLP, its wide range of applications, and the fact that ADDICT can automatically specify the atomic charge and type required for this force field, we find that CLP is the best all‐atom model to drive morphology calculations.