Exploring the Crystal Structure Landscape with a Heterosynthon Module: Fluorobenzoic Acid:1,2-Bis(4-pyridyl)ethylene 2:1 Cocrystals

The crystal structure landscape of the 2:1 benzoic acid:dipyridylethylene cocrystal (BA:DPE-I) is explored experimentally with fluoro-substituted benzoic acids and extended with studies employing the Cambridge Structural Database (CSD). The interpretation of the cocrystal landscape is facilitated by considering the kinetically favored and robust acidpyridine heterosynthon as a modular unit. Information based on high-throughput crystallography shows that polymorphs and pseudopolymorphs may belong to the same landscape but arise from different crystallization pathways because of complex and different kinetic features, and secondary synthon preferences. Using the CSD as a guide, the coformer was changed from 1,2-bis(4-pyridyl)ethylene (DPE-I) to 1,2-bis(4-pyridyl)ethane (DPE-II) and this provides an extended interpretation of the BA:DPE-I cocrystal landscape, also highlighting the complexity of the kineticthermodynamic dichotomy during the molecule-to-crystal progression.