Interplay of Hydrogen, Halogen, and Aromatic interactions in Schiff Base Cocrystals: A Hirshfeld surface and energy-based study

• Two Schiff base–carboxylic acid cocrystals were synthesized and structurally characterized. • Substitution with para -F and para -Br atoms modulates supramolecular interactions. • Cooperative O–H···N, C–H···F, Br···Br, and π – π contacts govern crystal packing. • Fusion enthalpies and melting points correlate with lattice energies and interaction strength. • Energy frameworks and Hirshfeld surfaces reveal the interplay of hydrogen, halogen, and π−π forces. Two cocrystals formed between Schiff base derivatives and biphenyl-4-carboxylic acid were synthesized and structurally characterized. The Schiff bases differ by para -substitution with either fluorine or bromine on a perfluorinated aromatic ring. Single-crystal X-ray diffraction revealed a complex interplay. This study examines supramolecular interactions, including classical O–H···N hydrogen bonds, C–H···F contacts, halogen contacts (e.g., Br···π and Br···Br), and π–π stacking interactions. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to visualize and quantify the predominant intermolecular contacts, while energy framework calculations estimated the energetic contributions to crystal packing. Differential scanning calorimetry revealed that the brominated cocrystal exhibits a slightly higher melting enthalpy and temperature, consistent with its larger lattice energy and increased halogen-bonding contribution to crystal cohesion. The nature and geometry of the para-substituent significantly influence the supramolecular architecture, illustrating the competitive and cooperative roles of hydrogen, halogen, and aromatic interactions in cocrystal formation.