Structure determination, thermal stability and dissolution rate of δ-indomethacin.

The structure solution of the δ-polymorph of indomethacin was obtained using three-dimensional electron diffraction. This form shows a significantly enhanced dissolution rate compared with the more common and better studied α- and γ-polymorphs, indicating better biopharmaceutical properties for medicinal applications. The structure was solved in non-centrosymmetric space group P21 and comprises two molecules in the asymmetric unit. Packing and molecule conformation closely resemble indomethacin methyl ester and indomethacin methanol solvate. Knowledge of the structure allowed the rational interpretation of spectroscopic IR and Raman data for δ-polymorph and a tentative interpretation for still unsolved indomethacin polymorphs. Finally, we observed a solid-solid transition from δ-polymorph to α-polymorph that can be driven by similarities in molecular conformation.

The structure of kaliophilite KAlSiO4, a long-lasting crystallographic problem.

Kaliophilite is a feldspathoid mineral found in two Italian magmatic provinces and represents one of the 12 known phases with composition close to KAlSiO4. Despite its apparently simple formula, the structure of this mineral revealed extremely complex and resisted structure solution for more than a century. Samples from the Vesuvius-Monte Somma and Alban Hills volcanic areas were analyzed through a multi-technique approach, and finally the crystal structure of kaliophilite was solved using 3D electron diffraction and refined against X-ray diffraction data of a twinned crystal. Results were also ascertained by the Rietveld method using synchrotron powder intensities. It was found that kaliophilite crystallizes in space group P3 with unit-cell parameters a = 27.0597 (16), c = 8.5587 (6) Å, V = 5427.3 (7) Å3 and Z = 54. The kaliophilite framework is a variant of the tridymite topology, with alternating SiO4 and AlO4 tetrahedra forming sheets of six-membered rings (63 nets), which are connected along [001] by sharing the apical oxygen atoms. Considering the up (U) and down (D) orientations of the linking vertex, kaliophilite is the first framework that contains three different ring topologies: nine (1-3-5) (UDUDUD) rings, six (1-2-3) (UUUDDD) rings and twelve (1-2-4) (UUDUDD) rings. This results in a relatively open (19.9 tetrahedra nm-3) channel system with multiple connections between the double six-ring cavities. Such a framework requires a surprisingly large unit cell, 27 times larger than the cell of kalsilite, the simplest phase with the same composition. The occurrence of some Na for K substitution (3-10%) may be related to the characteristic structural features of kaliophilite. Micro-twinning, pseudo-symmetries and anisotropic hkl-dependent peak broadening were also detected, and they may account for the elusive character of the kaliophilite crystal structure.

Electron Diffraction on Flash-Frozen Cowlesite Reveals the Structure of the First Two-Dimensional Natural Zeolite.

Cowlesite, ideally Ca6Al12Si18O60·36H2O, is to date the only natural zeolite whose structure could not be determined by X-ray methods. In this paper, we present the ab initio structure determination of this mineral obtained by three-dimensional (3D) electron diffraction data collected from single-crystal domains of a few hundreds of nanometers. The structure of cowlesite consists of an alternation of rigid zeolitic layers and low-density interlayers supported by water and cations. This makes cowlesite the only two-dimensional (2D) zeolite known in nature. When cowlesite gets in contact with a transmission electron microscope vacuum, a phase transition to a conventional 3D zeolite framework occurs in few seconds. The original cowlesite structure could be preserved only by adopting a cryo-plunging sample preparation protocol usually employed for macromolecular samples. Such a protocol allows the investigation by 3D electron diffraction of very hydrated and very beam-sensitive inorganic materials, which were previously considered intractable by transmission electron microscopy crystallographic methods.

3D electron diffraction techniques.

3D electron diffraction is an emerging technique for the structural analysis of nanocrystals. The challenges that 3D electron diffraction has to face for providing reliable data for structure solution and the different ways of overcoming these challenges are described. The route from zone axis patterns towards 3D electron diffraction techniques such as precession-assisted electron diffraction tomography, rotation electron diffraction and continuous rotation is also discussed. Finally, the advantages of the new hybrid detectors with high sensitivity and fast readout are demonstrated with a proof of concept experiment of continuous rotation electron diffraction on a natrolite nanocrystal.

Daliranite, PbHgAs2S5: determination of the incommensurately modulated structure and revision of the chemical formula.

The incommensurately modulated crystal structure of the mineral daliranite has been determined using 3D electron diffraction data obtained on nanocrystalline domains. Daliranite is orthorhombic with a = 21, b = 4.3, c = 9.5 Šand shows modulation satellites along c. The solution of the average structure in the Pnma space group together with energy-dispersive X-ray spectroscopy data obtained on the same domains indicate a chemical formula of PbHgAs2S5, which has one S fewer than previously reported. The crystal structure of daliranite is built from columns of face-sharing PbS8 bicapped trigonal prisms laterally connected by [2+4]Hg polyhedra and (As3+2S5)4- groups. The excellent quality of the electron diffraction data allows a structural model to be built for the modulated structure in superspace, which shows that the modulation is due to an alternated occupancy of a split As site.