Chemists of all fields currently publish about 50 000 crystal structures per year, the vast majority of which are X‐ray structures. We determined two molecular structures by employing electron rather ...than X‐ray diffraction. For this purpose, an EIGER hybrid pixel detector was fitted to a transmission electron microscope, yielding an electron diffractometer. The structure of a new methylene blue derivative was determined at 0.9 Å resolution from a crystal smaller than 1×2 μm2. Several thousand active pharmaceutical ingredients (APIs) are only available as submicrocrystalline powders. To illustrate the potential of electron crystallography for the pharmaceutical industry, we also determined the structure of an API from its pill. We demonstrate that electron crystallography complements X‐ray crystallography and is the technique of choice for all unsolved cases in which submicrometer‐sized crystals were the limiting factor.
Electrons instead of X‐rays: An electron diffractometer was tailored and employed for de novo structure determination from submicrometer‐sized crystals. A new methylene blue derivative was analysed together with a microcrystalline extract of an active pharmaceutical ingredient from a pill. The results obtained on submicrometer‐sized samples complement X‐ray crystallography.
Derzeit publizieren Chemiker aller Fachrichtungen ca. 50 000 Kristallstrukturen pro Jahr, von denen es sich bei der überwältigenden Mehrheit um Röntgenstrukturen handelt. Wir setzen Elektronen‐ statt ...Röntgenbeugung ein, um die Struktur zweier molekularer Verbindungen zu bestimmen. Zu diesem Zweck wurde ein EIGER‐Hybridpixeldetektor an ein Transmissionselektronenmikroskop angebaut und so ein Elektronendiffraktometer konstruiert. Die Struktur eines neuen Methylenblauderivates wurde aus einem Kristall kleiner als 1×2 μm2 mit einer Auflösung von 0.9 Å bestimmt. Mehrere tausend Wirkstoffe sind nur als submikrokristallines Pulver verfügbar. Um das Potenzial für die pharmazeutische Industrie zu verdeutlichen, haben wir die Struktur eines Wirkstoffs direkt aus einer Tablette bestimmt. Wir demonstrieren, dass Elektronenkristallographie die Röntgenkristallographie ergänzt und die Methode der Wahl ist für alle ungelösten Strukturen von submikrometergroßen Kristallen. Die Größe der Kristalle ist uns hier wichtig als Kriterium für die Elektronenbeugung.
Elektronen ersetzen Röntgen‐Strahlen bei der De‐novo‐Strukturbestimmung an submikrometergroßen Kristallen mit einem Elektronendiffraktometer. Auf diese Weise wurden ein Methylenblauderivat und ein mikrokristallines Wirkstoffextrakt aus einer Pille untersucht und Details der dreidimensionalen Molekülstruktur ermittelt. Die mithilfe von submikrometergroßen Proben erhaltenen Ergebnisse ergänzen die Röntgen‐Kristallographie.
3D electron diffraction has reached a stage where the structures of chemical compounds can be solved productively. Instrumentation is lagging behind this development, and to date dedicated electron ...diffractometers for data collection based on the rotation method do not exist. Current studies use transmission electron microscopes as a workaround. These are optimized for imaging, which is not optimal for diffraction studies. The beam intensity is very high, it is difficult to create parallel beam illumination and the detectors used for imaging are of only limited use for diffraction studies. In this work, the combination of an EIGER hybrid pixel detector with a transmission electron microscope to construct a productive electron diffractometer is described. The construction not only refers to the combination of hardware but also to the calibration of the system, so that it provides rapid access to the experimental parameters that are necessary for processing diffraction data. Until fully integrated electron diffractometers become available, this describes a setup for productive and efficient operation in chemical crystallography.
Installation of the EIGER X 1M detector onto an electron microscope and system calibration for data collection turns a transmission electron microscope into an electron diffraction instrument. Data can be collected and processed with a throughput that meets the requirements of a modern X‐ray facility. The setup described here offers access to single‐crystal structure determination from microcrystalline powder when large single crystals cannot be produced.
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