Study On Self-assembly Process Of Molecular Aggregates During Crystal Nucleation

Crystal nucleation is a key process affecting the design and preparation of crystal products.Molecular aggregates play an important role in the crystal nucleation,it is very important to study the mechanism and precise regulation of the crystal nucleation.However,most of the researches on pre-nucleation molecular aggregates focus on proteins and inorganic systems,few researchers have conducted special,comprehensive and systematic experimental and theoretical studies on the structural evolution of molecular aggregates during the crystal nucleation of small organic molecules.In order to solve the above problems,in this paper,two organic small molecules PNBA and OTBN were used as model compounds to investigate the self-assembly process of molecular aggregates during nucleation.First,the relationship between solution chemistry and nucleation kinetics of PNBA in seven different solvents was investigated.Density functional theory(DFT)and solvation energy calculation were adopted to evaluate the strength of solute-solvent interactions.Experiental methods combined with molecular simulation were applied to reveal the pre-assembly species in the solution.Based on above results,it was analyzed and proved that the similarity between the existence form of solute in solution and the crystal product,the interaction of characteristic sites and the total free energy of solvation jointly affect the difficulty of crystal nucleation.The presence of nano-scattered particles in PNBA solution was observed by DLS,NTA and ~1H NMR.These scattering particles were characterized and analyzed to be solute-rich pre-nucleation clusters.The effects of time,filtration and solvent type on the size of clusters were investigated,and clusters were proved to be the key location for crystal nucleation by cooling crystallization experiments.To demonstrate that the emergence of PNBA clusters is not an isolated case,similar pre-nucleation clusters in OTBN solution were analyzed and characterized by scattering technique.It was demonstrated that the change in the solvation effect would drive the pre-nucleation clusters to exhibit very different structures.The molecular dynamics evolution of clusters,the effect of initial mixing process on clusters and nucleation dynamics were investigated systematically.The results suggested that the dynamics of nucleation could be regulated by changing the structure and size of the pre-nulceation clusters.In order to understand the composition of complex mesoscopic solute-rich clusters,the existence of oligomers in the clusters was proved by SLS and free energy analysis.By DFT simulation and NMR experiments,it was further proved that the oligomers in solution were the dimer structure in crystal unit.The presence of solvent molecules in the clusters was confirmed by longitudinal relaxation time and 2D NMR spectroscopy.Finally,the formation and stability mechanism of clusters and associated physico-chemical rules were studied in detail.The parameter values such as the monomer-dimer reaction rate constants the diffusion coefficients of both species were obtained by reaction-diffusion kinetics and DOSY results.The evolution of cluster radius as a function of time,the qualitative spatial distributions of monomers and dimers densities under steady states were plotted to better understand the formation process and the nature of the clusters.