Investigating the Role of Solvent in the Formation of Vacancies on Facets

Surface defects play a crucial role in the process of crystal growth, as incorporation of growth units generally takes place on undercoordinated sites on the growing crystal facet. In this work, we use molecular simulations to obtain information on the role of the solvent in the roughening of three morphologically relevant crystal faces of form I of racemic ibuprofen. To this aim, we devise a computational strategy to evaluate the energetic cost associated with the formation of a surface vacancy for a set of ten solvents, covering a range of polarities and hydrogen bonding propensities. We find that the mechanism as well as the work of defect formation are markedly solvent and facet dependent. Based on Mean Force Integration and Well Tempered Metadynamics, the methodology developed in this work has been designed with the aim of capturing solvent effects at the atomistic scale while maintaining the computational efficiency necessary for implementation in high-throughput in-silico screenings of crystallization solvents.

Automated summary

Surface defects play a crucial role in crystal growth. In this study, molecular simulations are used to investigate the impact of solvents on the roughening of crystal faces in racemic ibuprofen. A computational strategy is developed to evaluate the energy cost of surface vacancy formation in different solvents. The results show that the mechanism and energy of defect formation depend on both the solvent and crystal face. This methodology provides a way to capture solvent effects at the atomistic level for high-throughput screening of crystallization solvents.