Determination of the Crystal Structure of a New Polymorph of Theophylline

A new approach to crystal structure determination, combining crystal structure prediction and transmission electron microscopy, was used to identify a potential new crystal phase of the pharmaceutical compound theophylline. The crystal structure was determined despite the new polymorph occurring as a minor component in a mixture with Form II of theophylline, at a concentration below the limits of detection of analytical methods routinely used for pharmaceutical characterisation. Detection and characterisation of crystallites of this new form were achieved with transmission electron microscopy, exploiting the combination of high magnification imaging and electron diffraction measurements. A plausible crystal structure was identified by indexing experimental electron‐diffraction patterns from a single crystallite of the new polymorph against a reference set of putative crystal structures of theophylline generated by global lattice energy minimisation calculations.     

Polymorph Identification and Crystal Structure Determination by a Combined Crystal Structure Prediction and Transmission Electron Microscopy Approach

Electron diffraction offers advantages over X‐ray based methods for crystal structure determination because it can be applied to sub‐micron sized crystallites, and picogram quantities of material. For molecular organic species, however, crystal structure determination with electron diffraction is hindered by rapid crystal deterioration in the electron beam, limiting the amount of diffraction data that can be collected, and by the effect of dynamical scattering on reflection intensities. Automated electron diffraction tomography provides one possible solution. We demonstrate here, however, an alternative approach in which a set of putative crystal structures of the compound of interest is generated by crystal structure prediction methods and electron diffraction is used to determine which of these putative structures is experimentally observed. This approach enables the advantages of electron diffraction to be exploited, while avoiding the need to obtain large amounts of diffraction data or accurate reflection intensities. We demonstrate the application of the methodology to the pharmaceutical compounds paracetamol, scyllo‐inositol and theophylline.     

Electrodeposited quantum dots IV. Epitaxial short-range order in amorphous semiconductor nanostructures

The structure of diffraction-amorphous CdSe (a-CdSe) quantum dots (QDs) electrodeposited on evaporated Pd substrate was studied by high resolution transmission electron microscopy (HRTEM), and compared with epitaxial (crystalline) QDs obtained by the same procedure on Au, as well as with a simulated image of random a-CdSe. Digital analysis of HRTEM images established the existence of repeating ordered motifs in a-CdSe QDs on Pd substrates, in the form of epitaxial sub-nanometre to nanometre size clusters. The QDs are shown to be intermediate between crystalline and random amorphous material. Digital Fourier analysis indicated epitaxial relationship with the 111inPd substrate, rotated 30° relative to the orientational relationship on 111_Au.     

Facile mechanosynthesis of amorphous zeolitic imidazolate frameworks

A fast and efficient mechanosynthesis (ball-milling) method of preparing amorphous zeolitic imidazolate frameworks (ZIFs) from different starting materials is discussed. Using X-ray total scattering, N(2) sorption analysis, and gas pycnometry, these frameworks are indistinguishable from one another and from temperature-amorphized ZIFs. Gas sorption analysis also confirms that they are nonporous once formed, in contrast to activated ZIF-4, which displays interesting gate-opening behavior. Nanoparticles of a prototypical nanoporous substituted ZIF, ZIF-8, were also prepared and shown to undergo amorphization.