SYNTHESIS, CRYSTAL STRUCTURE, AND HIRSHFELD AND ENERGETIC ANALYSIS OF INTERMOLECULAR INTERACTIONS OF A NEW COCRYSTAL BASED ON 3-AMINO-1,2,4-TRIAZOLE AND 6-AMINO-1,3-DIMETHYL-5- NITROSOPYRIMIDINE-2,4-DIONE

Abstract

The development of pharmaceutical and supramolecular cocrystals has become one of the most promising directions in crystal engineering because cocrystallization enables modification of physicochemical properties without altering the molecular structures of the parent compounds. Understanding the crystal packing, hydrogen-bonding patterns, and intermolecular interaction energies of heterocyclic compounds such as 3-amino-1,2,4-triazole and 6-amino-1,3-dimethyl-5-nitrosopyrimidine-2,4-dione is essential for designing stable supramolecular architectures. Purpose. To synthesize a novel cocrystal based on 3-amino-1,2,4-triazole and 6- amino-1,3-dimethyl-5-nitrosopyrimidine-2,4-dione, determine its crystal structure by single- crystal X-ray diffraction, and investigate the intermolecular interaction effects using Hirshfeld surface analysis and energy framework calculations. Methodology. The cocrystal was synthesized by solution crystallization under controlled experimental conditions. Its molecular and crystal structures were characterized using FT-IR spectroscopy and single-crystal X-ray diffraction. The supramolecular organization was investigated through Hirshfeld surface analysis, two-dimensional fingerprint plots, and intermolecular interaction energy calculations using CrystalExplorer 17.5 software. Originality. A new heterocyclic cocrystal composed of 3-amino-1,2,4-triazole and 6- amino-1,3-dimethyl-5-nitrosopyrimidine-2,4-dione was obtained for the first time. The relationship between hydrogen-bonding motifs, crystal packing, and lattice stabilization was quantitatively established through combined Hirshfeld surface and energy framework analyses. Findings. Single-crystal X-ray diffraction confirmed the formation of a well-defined supramolecular cocrystal stabilized by an extended hydrogen-bonding network involving N– H···O and N–H···N interactions. Hirshfeld surface analysis revealed that O···H/H···O and N···H/H···N contacts constitute the dominant intermolecular interactions responsible for crystal packing. Two-dimensional fingerprint plots provided quantitative contributions of the major contacts, while energy framework calculations demonstrated that electrostatic and dispersion interactions collectively govern the stability of the crystal lattice.