(42f) Insight into the Role of Pre-Assembly and Desolvation in Crystal Nucleation: A Case of p-Nitrobenzoic Acid

Crystal nucleation from solution is of central importance but not well understood phenomena in chemistry science. Increasing interest was focus on the relationship between solution chemistry and nucleation dynamics recently [1]. Our current work take p-nitrobenzoic acid (PNBA) as the model compound, studing how pre-assembly species and desolvation process govern the crystal nucleation from solution, and it first consider the case of solvates. The nucleation behaviors and dynamics of PNBA in chloroform, acetonitrile, methanol, DMSO, DMF, NMP and DMA were studied. Vibration spectroscopy, combined with computational method are applied to reveal the pre-assembly species in the solution, which may be retained in the mature crystal structure or undergo rearrangement. Further analysis of density functional theory (DFT) and solvation energy calculation reflect the strength of solute-solvent interactions. Based on above results, the more comprehensive correlation of molecular structure, crystal structure, solution chemistry and nucleation dynamics was established. The finding suggests that the structural similarity between solution chemistry and crystal structure, the specific site interaction and overall solvation strength have a combined influence on the nucleation process, however, none of them should be regarded as the rate-limiting factor.