Origins of salt formation and cocrystallization: A combined experimental and theoretical study

Three DNP (3,4-dinitropyrazole) salts and one DNP cocrystal were synthesized and characterized by IR, elemental analysis, and single-crystal X-ray diffraction. DSC analysis shows that hydrazine hydrate (HH), ethanediamine (ED), aminoguanidine (AG), and urea (U) all make DNP prone to decomposition, demonstrating that salt formation and cocrystallization are two strategies to modulate the thermal stability and the coformers play a vital role in the performance of the target products. Hirshfeld surfaces suggest that O···H close contacts make the greatest contribution to the stabilization of I-IV. Electrostatic potential and pKa values give a reasonable explanation that DNP forms salts I-III with HH, ED, and AG, while it forms cocrystal IV with U. The hydrogen-bonding interactions were evaluated by the quantum theory of atoms-in-molecules (AIM) and the independent gradient model (IGM), further revealing that DNP and U prefer to form a cocrystal, rather than a salt or as the individual compounds. The systematic experimental and theoretical work gives a clear comparison of the salt and cocrystal formation processes and explains their origins on the atomic scale, which can prompt the development of the design and synthesis of new salts and cocrystals.