The ultimate productivity tool

AutoChem is the ultimate productivity tool for small molecule chemists, offering fast, fully automatic structure solution and refinement during data collection. Developed in collaboration with OlexSys Ltd (Durham University, UK), AutoChem works in conjunction with Olex2 where more advanced structure solution and refinement functionality exists. AutoChem is seamlessly integrated within CrysAlisPro and forms an integral part of our ‘What is this?’ feature. The ‘What is this?’ feature gives you structures in seconds and ensures you are not wasting time collecting full datasets on known samples or starting materials. It is an alternative pre-experiment option, which is used to plan your full data collections using structural information in addition to diffraction statistics. AutoChem now features workflows for the Crystalline Sponge Method (CSM) and improved support for electron diffraction data.

Three-dimensional electron diffraction (3D-ED), equivalently referred to as microcrystal electron diffraction (MicroED) is a revolutionary technique, which allows for solving atomic structures from single sub-micron crystals within minutes. This is achieved by conducting single-crystal diffraction with electrons instead of X-rays, which not only interact up to six orders of magnitude more strongly with matter, but also are less damaging to sensitive materials. Hence, even for challenging samples such as pharmaceuticals, mesoporous compounds or proteins, 3D-ED/MicroED offers an excellent alternative to synchrotron or PXRD, if only micro- or nanocrystals are available. Sophisticated data collection and processing techniques have been developed over the last years, which furthermore allow for determination of absolute configuration, as well as mapping of polymorph mixtures. 3D-ED/MicroED can be conducted within adapted electron microscopes, or, more recently, in dedicated electron diffractometers, such as Rigaku’s XtaLAB Synergy-ED.

Notable papers

• 3D Electron Diffraction: The Nanocrystallography Revolution by Mauro Mauro Gemmi, Enrico Mugnaioli, Tatiana E. Gorelik, Ute Kolb, Lukas Palatinus, Philippe Boullay, Sven Hovmöller, and Jan Pieter Abrahams.

This article reviews most important 3D electron diffraction (3D-ED/MicroED) applications for different kinds of samples and problematics, related with both materials and life sciences.

• Electron diffraction determines molecular absolute configuration in a pharmaceutical nanocrystal by Petr Brázda, Lukáš Palatinus and Martin Babor
• Chirality and accurate structure models by exploiting dynamical effects in continuous-rotation 3D ED data by Paul Klar,Yasar Krysiak, Hongyi Xu, Gwladys Steciuk, Jung Cho, Xiaodong Zou, Lukáš Palatinus

Determination of the absolute configuration of organic molecules is essential in drug development and the subsequent approval process. In Brázda et al. it was shown for first time, that this determination is possible through electron diffraction using nanocrystalline material, making use of dynamical diffraction effects.

Building upon this ground-breaking result, in Klar et al., it is demonstrated that significant improvement of refinement quality and determination of absolute structures via dynamical diffraction can be applied routinely to a wide range of sample classes.

• Microcrystal electron diffraction in macromolecular and pharmaceutical structure determination by Max T. B. Clabbers, Hongyi Xu
• MicroED for the study of protein–ligand interactions and the potential for drug discovery by Lisa J. Clark, Guanhong Bu, Brent L. Nannenga & Tamir Gonen

The review papers by Clabbers et al. and Clark et al. specifically discuss the new opportunities opened up by 3D-ED/MicroED for drug discovery, fragment screening, and study of protein-ligand complexes

• Can 3D electron diffraction provide accurate atomic structures of metal–organic frameworks? by Zhehao Huang, Meng Ge, Francesco Carraro, Christian Doonan, Paolo Falcaro and Xiaodong Zou

Mesoporous framework structures pose a particular challenge for crystallographic structure determination due to their small crystal sizes and high radiation sensitivity. These issues can be readily overcome by 3D-ED/MicroED, which has been shown for the example of a metal-organic frameworks in the article by Huang et al.

• Towards automated diffraction tomography: Part I—Data acquisition by U.Kolb, T.Gorelik, C.Kübel, M.T.Otten, & D.Hubert
• Collecting 3D electron diffraction data by the rotation method by Daliang Zhang, Peter Oleynikov, Sven Hovmöller and Xiaodong Zou
•  Three-dimensional electron crystallography of protein microcrystals by Dan Shi, Brent L Nannenga, Matthew G Iadanza, Tamir Gonen
• A Medipix quantum area detector allows rotation electron diffraction data collection from submicrometre three-dimensional protein crystals by I. Nederlof, E. van Genderen, Y.-W. Li and J. P. Abrahams

The foundations of modern 3D-ED/MicroED techniques have been laid by groups from, among others, Mainz, Stockholm, HHMI Janelia and Leiden,  who creatively combined approaches from electron microscopy and single-crystal X-ray diffraction. These publications from the early days of 3D-ED/MicroED present their ground-breaking research.

 

Micro-ED is new emerging field that is game changer in structural characterization, especially in pharmaceutical field. In our field, it is not uncommon that we have form that is unstable, cannot be made as single crystal, etc while having crystal structure is unequivocally important for project decision. We used to solve the structure from PXRD data, but access to synchrotron and time needed to solve and refine the structure are sometimes not suitable for early drug development where speed matters.

Rigaku is forefront in making instrumentation for MicroED and development of Synergy ED is a real game changer. I have been working with different companies offering MicroED, and so far Rigaku provides the best support and data with the quickest turn around. The service is exceptional! The service is also a good way to provide real case to acquire this capability in-house or with the collaboration with local partner.

--Researcher from pharmaceutical company