Predicting the solvent effect on crystal morphology via quantum mechanical methods

Abstract 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.