Polymorphism and Isostructurality of the Series of 3‑(4,5- Diaryl‑4H‑1,2,4-triazole-3-yl)propenoic Acid Derivatives

Polymorphism of four biologically active 3-(4,5-diaryl-4H-1,2,4-triazole-3-yl)propenoic acid derivatives has been investigated. Traditional solution-based solid-state forms screening revealed three anhydrous forms of 3-[4-phenyl-5-(2-pyridyl)-4H-1,2,4-triazole-3-yl]propenoic acid. Noteworthy, two pairs of concomitant polymorphs were detected for this system. Two other compounds were found to be dimorphic. The molecular and crystal structures of all obtained crystal forms were established by single-crystal X-ray diffraction. The resulting crystal structures were analyzed in terms of molecular conformation, intermolecular interaction patterns, and crystal packing motifs. The experimental studies were supported by extended lattice and interaction energy calculations. It was found that the carboxylic group adopts the anti conformation in all studied forms and is involved in the intramolecular O–H···Ntriazole hydrogen bonding. In consequence, the association modes are dominated by the weak C–H···O, C–H···N hydrogen bonds further supported by effective π-stacking interactions between the overlapping triazole-propenoic acid units. Substantial conformational differences between polymorphs result from rotation around the triazole-aryl bonds. The thermodynamic relationships between polymorphs were investigated by variable-temperature powder diffraction and differential scanning calorimetry. The studies revealed four pairs of enantiotropically related polymorphs. Transformations between the polymorphs occur in the single-crystal-to-single-crystal mode.