Inclusion of Pentamidine in Carboxylated Pillar[5]arene: Late Sequential Crystallization and Diversity of Host–Guest Interactions

Here we describe the inclusion of the minor-groove binding drug pentamidine in its extended conformation into the macrocyclic cavity of water-soluble carboxylated pillar[5]­arene. The artificial host–guest system is manifested as an ensemble of three crystalline forms differing in the pillar[5]­arene–pentamidine interaction mode, solvation type, and even stoichiometry. The strong hydrogen bonds of various types of amidinium–carboxylate (between pentamidine and pillar[5]­arene) and carboxylic–carboxylate (between adjacent pillar[5]­arenes) are realized in all complexes, rigidifying the assembly. However, it seems that more subtle effects, such as local solvation/desolvation, a certain degree of flexibility of both the host and guest, and variable protonation/deprotonation state of the pillar[5]­arene substituents, play significant roles in the peculiar crystallization behavior of the system. The snapshots of three crystal structures highlighting various binding geometries and intermolecular interaction modes between the same host and guest present exciting opportunities in terms of more holistic models of the host–guest systems, shifting from focusing our attention on “visible interactions” in one crystal structure to the appreciation of many subtle effects playing a combined role in the host–guest chemistry.