Study On The Regulation Of Polymorphs Of Linezolid And Chlorfenapyr

In the crystallization process,the use of effective methods to regulate polymorphism and crystal morphology is of great significance for industrial production.In this paper,based on the solution crystallization process,Linezolid and Chlorfenapyr were selected as the model.Combining the experiments with simulation methods,the study of the regulation of polymorphs,the nucleation mechanism and morphology prediction for Linezolid and Chlorfenapyr in solution system were developed.The rapid-cooling crystallization method was carried out to study the effect of solvent on the crystallization of Linezolid.It was found that in the solvents of methanol and ethanol facilitate the production of the needle-shape Form II crystal,while in the solvents of ethyl acetate and butyl acetate are suitable to produce the platelet-shape Form IV crystal.The nucleation mechanism of selective crystallization of Linezolid in different solvents was disclosed by molecular dynamics simulation method.It is illustrated that with the solvent of methanol there appears the N1H(LZ)···O3(LZ)and CH(LZ)···π(Aromatic-LZ)interactions between solute-solute molecules,which promotes the formation of Linezolid Form II crystal.Whereas with the solvent of ethyl acetate,there exists the N1H(LZ)···O3(LZ)and CH(LZ)···O(LZ)interactions between solute-solute molecules,which facilitates the formation of Linezolid Form IV crystal.Secondly,a new crystal form of Chlorfenapyr(Form II)was obtained by solventing-out crystallization method in ethanol-water system.The evolution characteristics of the radial distribution function were analyzed by molecular dynamics simulation to reveal the aggregation process and nucleation mechanism of chlorfenapyr in solution.The results show that the π(Aromatic-CF)···π(pyrrole-CF)interaction between the benzene ring and the pyrrole ring in the molecule of Chlorfenapyr is formed,which promotes the formation of Form II crystal.After considering the influence of solvents on the crystal morphology,the attachment energy model was modified,and thus the morphology of Chlorfenapyr polymorphic were accurately predicted.