Unveiling the self-association and desolvation in crystal nucleation.

Danning Li,Yongli Wang,Shuyi Zong,Ting Wang,Xin Li,Na Wang,Xin Huang,Yuyuan Dong,Hongxun Hao

doi:10.1107/s2052252521003882

Abstract

As the first step in the crystallization process, nucleation has been studied by many researchers. In this work, phenacetin (PHEN) was selected as a model compound to investigate the relationship between the solvent and nucleation kinetics. Induction times at different supersaturation in six solvents were measured. FTIR and NMR spectroscopy were employed to explore the solvent-solute interactions and the self-association properties in solution. Density functional theory (DFT) was adopted to evaluate the strength of solute-solvent interactions and the molecular conformations in different solvents. Based on these spectroscopy data, molecular simulation and nucleation kinetic results, a comprehensive understanding of the relationship between molecular structure, crystal structure, solution chemistry and nucleation dynamics is discussed. Both the solute-solvent interaction strength and the supramolecular structure formed by the self-association of solute molecules affect the nucleation rate. The findings reported here shed new light on the molecular mechanism of nucleation in solution.

Highlights

Crystallization from solution is one of the most widely used unit operations and has been extensively used in the food, chemical, dye, pharmaceutical and agrochemical industries
Investigations on the relationship between solution chemistry and nucleation kinetics have been carried out using PHEN as a model compound
We found that form I of PHEN could be obtained in acetonitrile, methanol, toluene, chloroform, DMA and dimethyl sulfoxide (DMSO)

Summary

Introduction

Crystallization from solution is one of the most widely used unit operations and has been extensively used in the food, chemical, dye, pharmaceutical and agrochemical industries. Nucleation is crucial as the first step of the crystallization process. Davey and Trout used FTIR to study the existing form of butynoic acid in different solvents. In chloroform it is a carboxyl hydrogen-bonded dimer, whereas in ethanol, though the solute has the potential to form hydrogen bonds, it does not participate in the formation of dimers.

Results

Discussion

Conclusion