Molecular, Crystal, and Surface Chemistry of the Conformational Polymorphic Forms of <scp>l</scp> -isoleucine

l-isoleucine exists in two enantiotropically related polymorphs, α and β, which are both zwitterionic in crystalline and solution states. These forms are conformational polymorphs, distinguished by their hydrogen bonding networks, where the α form exhibits a parallel arrangement, while the β form displays nonparallel interactions, reflecting differences between their respective crystal packings. The crystal morphology, molecular conformation and stability, intermolecular (synthonic) interactions, and surface chemistry of both l-isoleucine polymorphs are examined using synthonic and crystallographic modeling. The β form is found to have stronger intermolecular interactions due to its more efficient arrangement of hydrogen bonds, better packing coefficient, and less void space. This is reflected in the lattice energy for the β form, which is about 15% higher than that for the α form, reflecting its shorter and more linear hydrogen bond network. The NH3+···O hydrogen bonding is found to be the strongest bulk (intrinsic) synthon for both forms, reflecting the higher % contribution to their lattice energies. The predicted morphologies for the two forms are found to be almost identical, i.e., displaying a hexagonal cross-section elongated along the b-axis. The anisotropic growth of the morphology reflects the large variation in the attachment energy values for the important morphological facets of both forms. The anisotropic nature of the growth morphology in both forms is further rationalized through examination of the extrinsic (surface-terminated) synthon contributions to the crystal habit surfaces, where the synthons contributing to respective attachment energies are found to be stronger at the capping surfaces than at the more morphologically dominant surfaces.