On the Role of Solvent in the Formation of Vacancies on Ibuprofen Crystal Facets

Abstract

Surface defects play a crucial role in the process of crystal growth, as the incorporation of growth units generally takes place on under-coordinated sites on the growing crystal facet. In this work, we use molecular dynamics 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 based on combining independent Well Tempered Metadynamics with Mean Force Integration. This approach enables us 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 ability. We find that both the mechanism of defect formation on these facets and the work associated with the process are indeed markedly solvent-dependent. 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 computational screenings of crystallization solvents.