Practical crystal engineering using halogen bonding: A hierarchy based on calculated molecular electrostatic potential surfaces

• 36 co-crystallizations on compounds with two different acceptors were performed.
• An interaction hierarchy was established using calculated electrostatic potentials.
• All 10 structures obtained display best donor/acceptor halogen bonds.
• Halogen bonds with iodine are more effective than the bromo-analogues.

A series of co-crystallization experiments were performed using four multi-topic N-heterocyclic acceptor molecules and nine aromatic halogen-bond donors in order to establish how effectively a ranking of bond strength based on calculated molecular electrostatic potential surfaces translates into predictable primary interactions in the solid state. A total of ten new crystal structures were obtained, and in each case, the observed interaction took place between the best acceptor (with the larger negative electrostatic potential) on the N-heterocycle and the halogen-bond donor. The supramolecular yield (number of successful co-crystallizations) is 70% for iodine-donors whereas none of the bromo-substituted donors produced a co-crystal which underscores the importance of the magnitude of the electrostatic potential and of the polarizability of the halogen-bond donor in the context of successful practical crystal engineering.