Marinova Veselina, Wood Geoffrey P F, Marziano Ivan, Salvalaglio Matteo
Department of Materials Science and Engineering, The University of Sheffield, Sheffield S1 3JD, United Kingdom.
Pfizer Worldwide Research and Development, Groton Laboratories, Groton, Connecticut 06340, United States.
Cryst Growth Des. 2022 May 4;22(5):3034-3041. doi: 10.1021/acs.cgd.1c01479. Epub 2022 Apr 22.
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.
