Research On Polymorphic Molecular Stability Based On Quantum Mechanical Fragmentation Method

Molecular crystal plays an important role in many fields of science technology and materials,which enables one to understand,rationalize and engineer the bulk properties of solids.But it often crystallizes in different polymorphs with different physical and chemical properties.To guide the experimental synthesis of candidate materials,the atomic-scale model is frequently used to predict the most stable polymorph and its structural properties.The CSP method is widely used to search the most stable crystal structures of pharmaceutical molecules.Pioneering CSP works have successfully assisted pharmaceutical industries and researchers to find thermodynamic favorable crystal packing with advanced efficacy.However,most of them are based on calculations of the lattice energy,which usually neglects the effects of entropy and temperatures when evaluating the stability of crystal polymorphs.Here,we show how an ab initio method can be used to achieve a rapid and accurate prediction of sulfathiazole?an antibiotic drug?and p-Tol₂S₂?energy storage and lubricating materials?crystal polymorphs,based on the Gibbs free energy calculation and Raman spectra analysis.At the atmospheric pressure and the temperature of 300 K,we demonstrate that form III?FIII?is the most stable structure of sulfathiazole.The agreement between the predicted and experimental crystal structures corresponds to the order of stability for five sulfathiazole polymorphs as FI<FV<FIV<FII<FIII,which is achieved by employing the density functional theory?DFT?calculations.By comparing the Gibbs free energies between predicted and experimental structures,we found that phase?is the most stable structure for p-Tol₂S₂ crystal at ambient temperature and standard atmospheric pressure.Furthermore,we provide an efficient method to discriminate different polymorphs based on the Raman/IR spectra.The proposed work enable us to evaluate the quality of various crystal polymorphs rapidly.