Date Published: October 01, 2019
Publisher: International Union of Crystallography
Author(s): Shuyi Zong, Jingkang Wang, Hao Wu, Qi Liu, Yunhui Hao, Xin Huang, Dehui Wu, Guanchen Zhou, Hongxun Hao.
The pathway and hybrid control mechanism of crystal nucleation were studied through both experimental and computational investigation on the role of pre-assembly and desolvation in the nucleation process.
Nucleation is a key step in the crystallization process which has decisive influence on the crystal-size distribution and polymorphism of the final products. Unfortunately, although crystal nucleation from solution is common, there is insufficent understanding of the early stage in the crystal formation process and the nucleation mechanism is still not fully understood from the molecular level. In recent years, solution chemistry has turned out to be a useful tool to explore the molecular assembly path in the nucleation process due to the significant influence of solute–solvent interactions on the molecular self-assembly process (Du et al., 2015 ▸; Gebauer et al., 2014 ▸; Davey et al., 2013 ▸). Besides, the rapid development of computational techniques and the notable improvement of analysis techniques have made it possible to study larger molecular clusters more efficiently. Plenty of work therefore has been carried out to interpret the evolution of the so-called ‘growth units’ in the crystallization nucleation process (Gavezzotti et al., 1997 ▸; Chen & Trout, 2008 ▸; Tommaso, 2013 ▸; Zeglinski et al., 2018 ▸). The structural correlation between solution aggregates and crystal syntheses has been investigated by studying the structural evolution process from solute molecules to supramolecular syntheses (Parveen et al., 2005 ▸; Byrn et al., 1976 ▸; Bernstein & Hagler, 1978 ▸; Habgood, 2012 ▸).
In this work, investigations on the relationship between solution chemistry and nucleation kinetics were carried out by using p-nitrobenzoic acid (PNBA) as model compound. It was found that form (I) of PNBA could be obtained in chloroform, acetonitrile and methanol while corresponding solvates would be formed in DMSO, DMF, NMP and DMA. The crystal structures of all these forms were analyzed and discussed. NMR and FTIR spectroscopies were used to analyze the solute species in solution and the results showed that carboxylic acid dimers of PNBA were thermodynamically favoured in chloroform, whereas the solvated forms were favoured in acetonitrile, methanol, DMSO, DMF, NMP and DMA. The solute species in chloroform, DMSO, DMF, NMP and DMA were crystal-like while the conformation of solute in acetonitrile and methanol was unlike that in the crystal. In acetonitrile and methanol, one thermodynamically driven desolvation step was required to form the dense crystal nuclei containing only PNBA molecules.