Structural Landscape of α-Acetamidocinnamic Acid Cocrystals with Bipyridine-Based Coformers: Influence of Crystal Packing on Their Thermal and Photophysical Properties

Controlling the supramolecular synthon outcome in systems with different functionalities has been a key factor for the design of supramolecular materials, which also affected their physicochemical properties. In this contribution, we have analyzed the structural landscape of α-acetamidocinnamic acid (HACA) aiming to find its synthon outcome from the competitivity between its acidic and amidic groups. We prepared four multicomponent forms including one dihydrate (HACA·2H₂O) and three cocrystals bearing different bipyridine coformers with formulas (HACA)₂(1,2-bpe) (1), (HACA)₂(4,4'-azpy) (2), and (HACA)₂(4,4'-bipy)₃ (3) (1,2-bpe = 1,2-bis(4-pyridyl)ethylene; 4,4'-azpy = 4,4'-azopyridine; 4,4'-bipy = 4,4'-bipyridine). First, we applied a virtual screening approach to assess the feasibility of cocrystal formation. Then, we synthesized the cocrystals, via liquid-assisted grinding (LAG) (1 and 2) or solvothermal (3) techniques, and single crystals of HACA, and their four multicomponent forms were obtained showing different synthons and crystal packings. Besides, a Cambridge Structural Database (CSD) search of the cocrystals presenting bipyridine-type coformers and molecules with acid and amide functionalities was performed, and the observed synthon occurrences as well as the possibility of synthon modification by tuning the H-donor/H-acceptor propensity of the acidic and amidic groups were shown. Finally, we measured their thermal and photophysical properties, which were correlated with their structural features.