Mechanism And Application Of Crystal Nucleation At Solid-liquid Interface

In the field of fine chemicals,especially pharmaceuticals,crystallization is an important part of the process of product separation and purification.Among them,nucleation serves as the basis of crystallization.The research on the nucleation mechanism has also been a hot spot in recent years.In this paper,we used experiments combined with molecular dynamics simulation to study the nucleation mechanism of organic molecular crystals at different interfaces.Based on this,the nucleation mechanism is used to predict the nucleation trend of different crystals on different surfaces.The details are as follows:Using small organic molecule glycine as the model compound,experiments and molecular dynamics simulation(MD)methods were applied to study the crystal nucleation mechanism in milliliter-scale tubular crystallizers of different materials.Four different commercial tubular crystallizer materials including polytetrafluoroethylene(PTFE),polyvinyl chloride(PVC)and silicone rubber(Silicon)were used as research objects.The degree of nucleation and adhesion of tubes of different materials was investigated by observing the nucleation of crystals in the tube,the adhesion of crystals on the wall of the tube,and the experimental methods of measuring the outlet concentration of the tubes of different materials.The factors that affect the nucleation and attachment of crystals on the inner surface of the tube were discussed from a chemical and physical point of view.The main factor that determines the degree of crystal adhesion in the tubular crystallizer is the interaction energy between the crystal-tubing interface,and the other factor is the roughness of the tubing surface inside.In the end,the clogging trends of different tubes are as follows:silicon rubber > polyvinyl chloride > polytetrafluoroethylene.This study provides a method for selecting the inner surface materials of the crystallizers,which will help solve the clogging problem in the continuous tubular crystallizers.Then,the same simulation method was used to predict the nucleation and adhesion trends of glass and steel,which are commonly used as equipment materials in the industry.It was concluded that glycine crystals had the highest adhesion on stainless steel and the lowest adhesion on glass.And through experimental verification,it proved the accuracy of molecular simulation methods in predicting the nucleation trend.The protein in crystal form has the advantages of good drug stability,high concentration of active ingredients of the drug and easy controlled release of the drug.To obtain the polymers that can promote protein crystallization,we need to screen template molecules for protein crystal nucleation.For the nucleation prediction of organic macromolecular proteins,the most common protein lysozyme is used as the model,which mainly predicts the trend of polyaspartic acid(PASP),polyethyleneimine(PEI),and sodium chondroitin sulfate(Cs-Na)influencing on lysozyme crystallization.Using the molecular dynamics simulation method,the interaction energy between the polymer interface and the selected lysozyme random coil structure was calculated by the structure optimization method.The hydrogen bond at the interface between the random coil of lysozyme and the polymer was analyzed.The simulation results indicated that the polymer interface could interact with specific amino acids in the random coil of the selected lysozyme and have a significant effect on the molecular conformation of the random coil of the lysozyme.Finally,it was predicted that the influence trend of the three polymers on the nucleation of lysozyme crystals is: PEI <PASP <Cs-Na.