Progress in Predicting Ionic Cocrystal Formation: The Case of Ammonium Nitrate

Abstract

In contrast to the mature predictive frameworks applied to neutral cocrystals, ionic cocrystals, those including an ion pair, are difficult to design. Furthermore, they are generally excluded categorically from studies which correlate specific molecular properties to cocrystal formation, leaving the prospective ionic cocrystal engineer with few clear avenues to success. Herein ammonium nitrate, an energetic oxidizing salt, is targeted for cocrystallization in a potential coformer group selected based on likely interactions with the nitrate ion as revealed in the Cambridge Structural Database; six novel ionic cocrystals were discovered. Molecular descriptors previously identified as being related to neutral cocrystal formation were examined across the screening group but showed no relationship with ionic cocrystal formation. High packing coefficient is shown to be a constant among the successful coformers in the set and is utilized to directly target two more successful coformers, bypassing the need for a large screening group.

Cocrystals by Design: A Rational Coformer Selection Approach for Tackling the API Problems

“…Every entry in the CSD contains information on chemical structure and crystallographic data (such as space groups, lattice, symmetry, and crystal systems), crystal packing, molecular dimensions, molecular geometry, stereochemistry, structure representation, and conformational analysis [37]. Based on the understanding of geometries and preferred orientations of current intermolecular interactions, coformers can be chosen for cocrystallization with the APIs [34,38].…”

Perchlorate-Free Energetic Oxidizers Enabled by Ionic Cocrystallization

“…21,23 Cocrystallization of AN with a variety of small-molecule coformers has recently been accomplished and shown to mitigate the phase transition. 24 Although cocrystallization can address the major deficiencies of AN, maintaining positive oxygen content of the resultant cocrystals is an unmet challenge; no cocrystals of AN, or indeed any nonperchlorate oxidizing salt (for a successful example using sodium perchlorate, see Inoue et al 25 ), have yet achieved a positive oxygen balance, making them nonfunctional as oxidizers. Energetic molecules with excess oxygen content are rare and generally ill-suited for cocrystallization due to an overabundance of nitro groups and a lack of exposed hydrogen bond donors, impeding cocrystal design based on intermolecular interactions.…”

“…AP is currently the state-of-the-art oxidizer for solid rocket propellants due to its impressive oxygen content (OB +34.0%), good burning properties, and low cost of manufacture. , However, health concerns related to unburned perchlorates as well as environmental and tactical issues stemming from HCl generation have spurred widespread efforts to replace AP in propellant formulations. − One chlorine-free oxidizing salt that has been considered as a replacement is AN (Figure ). AN is inexpensive to manufacture and has good oxygen content (OB +20.0%) but suffers from handling issues related to hygroscopicity, poor morphology, and, critically, exhibits a solid state phase transition accompanied by a 3% change in volume during exposure to typical operating temperatures. , AN is also a notoriously poor burning material with an endothermic dissociation to nitric acid and ammonia that inhibits self-sustained burning. , Cocrystallization of AN with a variety of small-molecule coformers has recently been accomplished and shown to mitigate the phase transition . Although cocrystallization can address the major deficiencies of AN, maintaining positive oxygen content of the resultant cocrystals is an unmet challenge; no cocrystals of AN, or indeed any nonperchlorate oxidizing salt (for a successful example using sodium perchlorate, see Inoue et al), have yet achieved a positive oxygen balance, making them nonfunctional as oxidizers.…”

“…The first consideration when selecting an energetic coformer capable of ionic cocrystal formation is the presence of the appropriate functionality to disrupt interactions within the salt. Recently, interactions involving both the ammonium and nitrate ions have been catalogued individually , from the Cambridge Structural Database (CSD) and analyzed in order to develop strategies for ionic cocrystal prediction. Regardless of counterion, ammonium was found to interact most often with N-heterocycles whereas nitrate most often interacts with amines; the presence of one or both of these functionalities is therefore a useful predictor of coformer success.…”

“…The class of energetic molecules based on high-nitrogen ring structures (e.g., azoles) tend toward neutral or slightly negative oxygen balance while commonly featuring the sought-after functionalities in the form of heterocyclic imines and azolic NH groups, , making them an ideal choice for cocrystallization with AN. Cocrystallization of AN with N-heterocycles (including azoles) has previously been shown to be related to the crystalline packing efficiency of the coformers, expressed in terms of the Kitaigorodsky packing coefficient ( C k ) . Higher C k was correlated with a greater likelihood of successful cocrystal formation.…”