Two new polymorphs (forms VIII and IX) of piroxicam were discovered through poly(ethylene glycol) (PEG)-assisted melt crystallization, and their structures were revealed by 3D electron diffraction (3D ED). This discovery provides insight into the potential of PEG in pharmaceutical polymorph discovery and verifies the significance of 3D ED as an essential technique for structural determination of pharmaceuticals. Furthermore, the direct contribution of intermolecular hydrogen bonding to melting points was discussed based on the structural divergency between the newly solved form VIII and the previously reported form IV. Combining PEG-assisted melt crystallization and 3D ED not only accelerated the discovery of new polymorphs but also provided unique opportunities for understanding structure-property relationships in pharmaceutical crystals.

Zeolites are crystalline microporous materials constructed by corner-sharing tetrahedra (SiO₄ and AlO₄), with many industrial applications as ion exchangers, adsorbents and heterogeneous catalysts. However, the presence of micropores impedes the use of zeolites in areas dealing with bulky substrates. Introducing extrinsic mesopores, that is, intercrystal/intracrystal mesopores, in zeolites is a solution to overcome the diffusion barrier. Still, those extrinsic mesopores are generally disordered and non-uniform; moreover, acidity and crystallinity are always, to some extent, impaired. Thus, synthesizing thermally stable zeolites with intrinsic mesopores that are of uniform size and crystallographically connected with micropores, denoted here as intrinsic mesoporous zeolite, is highly desired but still not achieved. Here we report ZMQ-1 (Zeolitic Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, no. 1), an aluminosilicate zeolite with an intersecting intrinsic meso-microporous channel system delimited by 28 × 10 × 10-rings, in which the 28-ring has a free diameter of 22.76 Å × 11.83 Å, which reaches the mesopore domain. ZMQ-1 has high thermal and hydrothermal stability with tunable framework Si/Al molar ratios. ZMQ-1 is the first aluminosilicate zeolite with an intrinsic meso-microporous channel system. The Brønsted acidity of ZMQ-1 imparts high activity and unique selectivity in the catalytic cracking of heavy oil. The position of the organic structure-directing agent (OSDA) used for ZMQ-1 synthesis was determined from three-dimensional electron diffraction (3D ED) data, which shows the unique structure-directing role of the OSDA in the formation of the intrinsic meso-microporous zeolite. This provides an incentive for preparing other stable mesopore-containing zeolites.

A series of new isostructural aluminum monocarboxylates, denoted as CAU-71-X (X = -Ac, -Prop and -TGA), with the framework composition [Al9(µ3-O)2(µ-OH)12(RCOO)12] · x H2O (R = -CH3, -C2H5, -C2H4SH) were obtained by investigating a chemical system involving an aluminum salt, a series of monocarboxylic acids (acetic acid (Ac), propionic acid (Prop), and thioglycolic acid (TGA)) and sodium hydroxide in aqueous solutions. Since the CAU-71 materials were obtained as nano- to microcrystalline products, the structure determination was carried out by 3D electron diffraction (3DED). To cope with the flexibility of the functional groups of ligands, low-dose 3DED was combined with cyro-EM to stabilize the functional group. With the stabilization from both low electron fluence and cryo-protection, the structures of three isostructural aluminum monocarboxylates were determined completely with refined positional disorder of coordinating monocarboxylates. One prominent feature of this structure is the 18-ring, which consists of 18 [AlO6] octahedra held together by edge-sharing oxygen atoms and 24 monocarboxylate ligands.  This 18-ring structure forms a 2D porous layer, which is further packed into a 3D crystal by hydrogen bonding. Porosity of the CAU-71 compounds was confirmed by H2O and CO2 sorption experiments and maximum uptake capacities of 60 mg/g (~ 6 mol/mol) and 8 cm3/g [JX1] were found for CAU-71-Prop.