Study On Molecular Conformation Changes During Nucleation Of Crystals

Crystal nucleation occurs in the early stage of crystallization and plays a crucial role in the formation of polymorphs and different forms of salts,eutectics,and solvent compounds.The study of molecular self-assembly,molecular conformation and solvation state before nucleation has important theoretical and practical application value for further understanding of nucleation process.In this paper,5-nitrofurazone was selected as the research object.The preparation and transformation of different crystal forms,thermodynamic properties,crystal transformation process and molecular morphology changes during nucleation were studied.In the study of polymorphic preparation and transformation,nitrofurazone form α was prepared by ultrasonic assisted solvent-mediated transformation.The effects of solvent,temperature and ultrasonic on product quality were studied.Form γ was prepared by solution-cooling coupled crystallization.The effect of solvent and temperature on product quality were studied.On this basis,the relationship between mutual transformation and mutual preparation of different forms was studied.In the thermodynamic study of 5-nitrofurazone,the solubility data of form γ in 9 pure solvents and 2 binary mixed solvent systems were determined by UV method.The solubility of form γ in pure solvent was correlated with the modified Apelblat equation and the NRTL model.The solubility data in the binary mixed solvent was correlated with the λh equation and the NRTL model.The mixed thermodynamic properties and dissolution thermodynamic properties in pure solvent and binary mixed solvent were calculated.In the study of 5-nitrofurazone crystal transformation process,the solventmediated crystal transfer process of form β to form γ crystal was monitored by on-line laser Raman spectroscopy.By measuring the solubility of two crystal forms of nitrofurazone,the thermodynamic driving force of the crystal transformation process in different solvents was studied.Ultraviolet spectroscopy was used to determine the change of solution concentration in this process,and the rate control procedure of the process was determined by combining the online Raman data.The effects of solvent,temperature,solid phase loading and stirring rate were studied.In the study of molecular conformation changes in nucleation process,conformational polymorphisms were prepared by cooling crystallization,and the crystal structure differences were analyzed.The spectral changes of different crystal form saturated solutions and their dilution processes were detected by Raman spectroscopy;the 2D-NOESY spectrum and 1HNMR on its dilution process of 5-nitrofurazone saturation was detected by NMR;the possible conformation and the energy of them were determined by quantum chemical calculation;the radial distribution function was calculated by molecular dynamics simulation.The conformation contained in the solution was analyzed by the above method,and the molecular conformation changes of the nucleation process of nitrofurazone were summarized.