Solution and nanoscale structure selection: implications for the crystal energy landscape of tetrolic acid

Abstract

Solution and growth effects are in many cases critical in determining which crystal structure (polymorph) a molecule will adopt. Contemporary crystal structure prediction (CSP) rarely address formation and growth in a systematic way, relying instead on bulk thermodynamic stabilities. In this study, it is shown that analysis of simulated solutions of tetrolic acid in combination with calculation of stabilities for nanoscale clusters cut from bulk structures can distinguish between four computationally predicted crystal structures, including the two known forms and two speculative forms, rationalizing the formation of one structure rather than another on grounds other than bulk lattice energies. It is concluded that modelling of both solution-based supramolecular species and nanocrystal stabilities are necessary to explain the selection of one structure over another during crystal formation, and that they are sufficient for the specific case of tetrolic acid.