Study On The Morphology Control Of Solution Crystallization Processes For Organic Compound

As well as the purity and yield, polymorphism, habit and crystal size distribution ofthe solid state are of specific importance. Both have a pronounced influence on theproduct quality and production index of economic and technology. Controlling thepolymorphism and habit by selecting proper solvent or additives and optimizing thesolution crystallization process are the main parts of the crystal engineering.In order to control the morphology of solid product, the molecular modeling methodwas used to study the effects of solvent and additives on the crystal habit andpolymorphism in this thesis.Molecular modeling is also known as computer experiment method, its softwareprovides functions to calculate and optimize the interaction energy between atoms andmolecules, which made it possible to study the crystal structure, crystal-liquidinterface interaction and the key problems of crystal nucleation and growth on thescale of atoms or molecules. By the advantages of the powerful graph interface, theinternal crystal structure, the atom arrangement on the surface, and even the outsideappearance derived by the relative growth rate can be observed directly. Themicrostructure can be visualized, providing better ideas for research.The interface layer model, which composed by crystal layer and solvent layer, wasestablished. The interaction between two layers was estimated by molecular methodand molecular dynamic method, and was also used to estimate the interaction betweensolvent and different surfaces of crystal. Combined with the crystal growth theory, anew model was developed to describe the influence of solvent on habit. In this model,both the interaction of solvent -crystal surface and interaction of solvent-solvent wereconsidered. Compared with the single molecule model, this new model is closer to theactual situation. Area factor S is used to describe the volume effect of solventmolecule. This model can be applied to crystal habit prediction under several ofsolvents and solvent mixtures (with various ratios). It has been verified when it wasused to analyze the habit of α L-glutamic acid,β L-glutamic acid and urea grownfrom solution crystallization.The solution structure near the solute molecule was studied by means of molecularmodeling. The results should the difference distribution of solvents are main influencefactor for the change on solubility and conformation of the solute molecules.Grand Canonical Monte Carlo simulations have been performed to model theadsorption of additives on the crystal surface. The study results of equilibriumadsorption amount, potential adsorbed sites, adsorption energy, density and distanceof adsorbed additive molecules showed that the contribution of additives at differentconcentration can be estimated by the Langmuir equation, in which the coefficient isdepended on adsorption energy. It was applied to calculate the modified habit ofL-glutamic acid with different additives and the habit of 6APA in present of phenylacetic acid (PAA ) as impurity at a series concentration.The environment effects on the polymorph have been discussed. Taking L-glutamicacid as an example compound, lattice energy was used to determine the relativestability. Molecular dynamic method was applied to study the conformation of thesolute molecule in the solution at different temperature. It was shown that the ratio ofdifferent conformations varied with temperature, and elucidated why L-glutamic acidcrystalline being different polymorph at different temperature. The additive effects onpolymorph selection in solution crystallization have also been studied in detail. It hasbeen proved that using proper additives, which could restrain the existence ofunexpected polymorph or accelerate phase transformation into desired polymorph.