Theoretical and Structural Understanding of the Different Factors Influencing the Formation of Multicomponent Crystals of 2,4-Dichlorophenoxyacetic Acid with N-heterocyclic Compounds

The formation of multicomponent crystals depends on many factors; therefore it is extremely challenging to predict and select the appropriate coformers (CCFs) to prepare functional multicomponent crystals. In this study, we selected the 2,4-dichiorophenoxyacetic acid (2,4-D) molecule and 10 N-heterocyclic compounds with similar structures to investigate the main factors affecting the synthesis of multicomponent crystals. On screening of multicomponent crystals by solution crystallization, we obtained nine b of multicomponent crystals of 2,4-D with different colors, including a hydrate of the 2,4-D-PYE cocrystal. However, 1,3-bis(4-pyridyl)propane (BPP) failed to form multicomponent crystals with 2,4-D using the solution crystallization methods. The influence of CCF on the formation of multicomponent crystals was discussed from three aspects: hydrogen bond donor and acceptor capacity (molecular electrostatic potential (MEP) surface, hydrogen bond acceptor ability h_ema calculated by Molecular Operating Environment software, and interaction site-pairing energy differences (Delta Esite-pair)), thermodynamic enthalpy (the excess enthalpy Delta H-ex), and structural factors (molecular complementarity (MC) and molecular flexibility (Kier flex)). Molecular flexibility is the main reason no multicomponent crystals are formed between BPP and 2,4-D. A logistic regression calculation indicates that the formation of multicomponent crystals of 2,4-D is mainly affected by Delta Esite-pair and MEP values. The cases considered in this study not only expand the crystal structure landscape of the 2,4-D but also provide a reference for the effective prediction and design of multicomponent crystals, in general.

Automated summary

The formation of multicomponent crystals is influenced by various factors, making it challenging to predict and select suitable coformers for their preparation. This study investigated the main factors affecting the synthesis of multicomponent crystals using 2,4-dichlorophenoxyacetic acid (2,4-D) and 10 N-heterocyclic compounds. The results showed that molecular flexibility is the main factor preventing the formation of multicomponent crystals between certain compounds. Furthermore, the interaction energy differences and molecular electrostatic potential values play important roles in the formation of multicomponent crystals of 2,4-D.