Rotation Electron Diffraction Data Research Articles

Structural Elucidation and Absolute Stereochemistry for Pharma Compounds Using MicroED.

Microcrystal electron diffraction (microED) is an emerging technique for rapid crystallographic analysis of small molecule micro- and nanocrystals. In this report, we evaluate the applicability of microED to pharmaceutical compounds through the analysis of 30 samples obtained from the process and medicinal chemistry groups at Amgen Inc. Using only 40 h of microscope time, 15 of 30 crystal structures were elucidated. From these crystal structures, all chiral compounds had the correct absolute stereochemistry assigned by dynamical refinement of continuous rotation electron diffraction data, confirming dynamical refinement as a promising tool for the absolute stereochemistry determination of pharmaceutically relevant compounds.

STEM SerialED: achieving high-resolution data for ab initio structure determination of beam-sensitive nanocrystalline materials.

Serial electron diffraction (SerialED), which applies a snapshot data acquisition strategy for each crystal, was introduced to tackle the problem of radiation damage in the structure determination of beam-sensitive materials by three-dimensional electron diffraction (3DED). The snapshot data acquisition in SerialED can be realized using both transmission and scanning transmission electron microscopes (TEM/STEM). However, the current SerialED workflow based on STEM setups requires special external devices and software, which limits broader adoption. Here, we present a simplified experimental implementation of STEM-based SerialED on Thermo Fisher Scientific STEMs using common proprietary software interfaced through Python scripts to automate data collection. Specifically, we utilize TEM Imaging and Analysis (TIA) scripting and TEM scripting to access the STEM functionalities of the microscope, and DigitalMicrograph scripting to control the camera for snapshot data acquisition. Data analysis adapts the existing workflow using the software CrystFEL, which was developed for serial X-ray crystallography. Our workflow for STEM SerialED can be used on any Gatan or Thermo Fisher Scientific camera. We apply this workflow to collect high-resolution STEM SerialED data from two aluminosilicate zeolites, zeolite Y and ZSM-25. We demonstrate, for the first time, ab initio structure determination through direct methods using STEM SerialED data. Zeolite Y is relatively stable under the electron beam, and STEM SerialED data extend to 0.60 Å. We show that the structural model obtained using STEM SerialED data merged from 358 crystals is nearly identical to that using continuous rotation electron diffraction data from one crystal. This demonstrates that accurate structures can be obtained from STEM SerialED. Zeolite ZSM-25 is very beam-sensitive and has a complex structure. We show that STEM SerialED greatly improves the data resolution of ZSM-25, compared with serial rotation electron diffraction (SerialRED), from 1.50 to 0.90 Å. This allows, for the first time, the use of standard phasing methods, such as direct methods, for the ab initio structure determination of ZSM-25.

A Crystalline Three-Dimensional Covalent Organic Framework with Flexible Building Blocks.

The construction of three-dimensional covalent organic frameworks (3D COFs) has proven to be very challenging, as their synthetic driving force mainly comes from the formation of covalent bonds. To facilitate the synthesis, rigid building blocks are always the first choice for designing 3D COFs. In principle, it should be very appealing to construct 3D COFs from flexible building blocks, but there are some obstacles blocking the development of such systems, especially for the designed synthesis and structure determination. Herein, we reported a novel highly crystalline 3D COF (FCOF-5) with flexible C-O single bonds in the building block backbone. By merging 17 continuous rotation electron diffraction data sets, we successfully determined the crystal structure of FCOF-5 to be a 6-fold interpenetrated pts topology. Interestingly, FCOF-5 is flexible and can undergo reversible expansion/contraction upon vapor adsorption/desorption, indicating a breathing motion. Moreover, a smart soft polymer composite film with FCOF-5 was fabricated, which can show a reversible vapor-triggered shape transformation. Therefore, 3D COFs constructed from flexible building blocks can exhibit interesting breathing behavior, and finally, a totally new type of soft porous crystals made of pure organic framework was announced.

Polymorph evolution during crystal growth studied by 3D electron diffraction.

3D electron diffraction (3DED) has been used to follow polymorph evolution in the crystallization of glycine from aqueous solution. The three polymorphs of glycine which exist under ambient conditions follow the stability order β < α < γ. The least stable β polymorph forms within the first 3 min, but this begins to yield the α-form after only 1 min more. Both structures could be determined from continuous rotation electron diffraction data collected in less than 20 s on crystals of thickness ∼100 nm. Even though the γ-form is thermodynamically the most stable polymorph, kinetics favour the α-form, which dominates after prolonged standing. In the same sample, some β and one crystallite of the γ polymorph were also observed.

High-throughput continuous rotation electron diffraction data acquisition via software automation.

Single-crystal electron diffraction (SCED) is emerging as an effective technique to determine and refine the structures of unknown nano-sized crystals. In this work, the implementation of the continuous rotation electron diffraction (cRED) method for high-throughput data collection is described. This is achieved through dedicated software that controls the transmission electron microscope and the camera. Crystal tracking can be performed by defocusing every nth diffraction pattern while the crystal rotates, which addresses the problem of the crystal moving out of view of the selected area aperture during rotation. This has greatly increased the number of successful experiments with larger rotation ranges and turned cRED data collection into a high-throughput method. The experimental parameters are logged, and input files for data processing software are written automatically. This reduces the risk of human error, and makes data collection more reproducible and accessible for novice and irregular users. In addition, it is demonstrated how data from the recently developed serial electron diffraction technique can be used to supplement the cRED data collection by automatic screening for suitable crystals using a deep convolutional neural network that can identify promising crystals through the corresponding diffraction data. The screening routine and cRED data collection are demonstrated using a sample of the zeolite mordenite, and the quality of the cRED data is assessed on the basis of the refined crystal structure.

Synthesis and Structure of a Layered Fluoroaluminophosphate and Its Transformation to a Three-Dimensional Zeotype Framework.

Two-dimensional zeolitic materials have drawn increasing attention because of their structural diversity, high accessible surface areas, and potential as precursors to form novel three-dimensional (3D) structures. Here we report a new layered fluoroaluminophosphate, denoted as EMM-9 (ExxonMobil Material #9), synthesized in the same synthesis system as that for a previously reported 3D framework structure EMM-8 (framework-type code: SFO) using an F- medium and 4-(dimethylamino)pyridine (DMAP) as the organic structure-directing agent. The structure of EMM-9 was solved from rotation electron diffraction data and refined against synchrotron powder X-ray diffraction data. The fluoroaluminophosphate layer of EMM-9 is composed of sti composite building units. The DMAP cations are located between the layers. π-π interactions between the DMAP cations and hydrogen bonding between the DMAP cations and layers were identified. The layered EMM-9 structure is closely related to the 3D framework structure of EMM-8 and can be transformed to EMM-8 by calcination.

On the quality of the continuous rotation electron diffraction data for accurate atomic structure determination of inorganic compounds

The continuous rotation electron diffraction (cRED) method has the capability of providing fast three-dimensional electron diffraction data collection on existing and future transmission electron microscopes; unknown structures could be potentially solved and refined using cRED data collected from nano- and submicrometre-sized crystals. However, structure refinements of cRED data using SHELXL often lead to relatively high R1 values when compared with those refined against single-crystal X-ray diffraction data. It is therefore necessary to analyse the quality of the structural models refined against cRED data. In this work, multiple cRED data sets collected from different crystals of an oxofluoride (FeSeO3F) and a zeolite (ZSM-5) with known structures are used to assess the data consistency and quality and, more importantly, the accuracy of the structural models refined against these data sets. An evaluation of the precision and consistency of the cRED data by examination of the statistics obtained from the data processing software DIALS is presented. It is shown that, despite the high R1 values caused by dynamical scattering and other factors, the refined atomic positions obtained from the cRED data collected for different crystals are consistent with those of the reference models refined against single-crystal X-ray diffraction data. The results serve as a reference for the quality of the cRED data and the achievable accuracy of the structural parameters.

Accurate determination of crystal orientation from rotation electron diffraction data

Accurate determination of crystal orientation from rotation electron diffraction data

Accurate unit cell determination from rotation electron diffraction data

Accurate unit cell determination from rotation electron diffraction data

Improving rotation electron diffraction data quality by data merging

Improving rotation electron diffraction data quality by data merging

Improved accuracy of unit-cell determination for rotation electron diffraction data

Improved accuracy of unit-cell determination for rotation electron diffraction data

Accurate structure determination of a borosilicate zeolite EMM-26 with two-dimensional 10 × 10 ring channels using rotation electron diffraction

A novel borosilicate zeolite structure was solved from rotation electron diffraction data and preferential boron positions could also be identified.

Optimization of rotation electron diffraction data collection and data processing

Optimization of rotation electron diffraction data collection and data processing

A zeolite family with expanding structural complexity and embedded isoreticular structures.

The prediction and synthesis of new crystal structures enable the targeted preparation of materials with desired properties. Among porous solids, this has been achieved for metal-organic frameworks, but not for the more widely applicable zeolites, where new materials are usually discovered using exploratory synthesis. Although millions of hypothetical zeolite structures have been proposed, not enough is known about their synthesis mechanism to allow any given structure to be prepared. Here we present an approach that combines structure solution with structure prediction, and inspires the targeted synthesis of new super-complex zeolites. We used electron diffraction to identify a family of related structures and to discover the structural 'coding' within them. This allowed us to determine the complex, and previously unknown, structure of zeolite ZSM-25 (ref. 8), which has the largest unit-cell volume of all known zeolites (91,554 cubic ångströms) and demonstrates selective CO2 adsorption. By extending our method, we were able to predict other members of a family of increasingly complex, but structurally related, zeolites and to synthesize two more-complex zeolites in the family, PST-20 and PST-25, with much larger cell volumes (166,988 and 275,178 cubic ångströms, respectively) and similar selective adsorption properties. Members of this family have the same symmetry, but an expanding unit cell, and are related by hitherto unrecognized structural principles; we call these family members embedded isoreticular zeolite structures.

Phase identification and structure determination from multiphase crystalline powder samples by rotation electron diffraction

Phase identification and structure characterization are important in synthetic and materials science. It is difficult to characterize the individual phases from multiphase crystalline powder samples, especially if some of the phases are unknown. This problem can be solved by combining rotation electron diffraction (RED) and powder X-ray diffraction (PXRD). Four phases were identified on the same transmission electron microscopy grid from a multiphase sample in the Ni–Se–O–Cl system, and their structures were solved from the RED data. Phase 1 (NiSeO3) was found in the Inorganic Crystal Structure Database using the information from RED. Phase 2 (Ni3Se4O10Cl2) is an unknown compound, but it is isostructural to Co3Se4O10Cl2, which was recently solved by single-crystal X-ray diffraction. Phase 3 (Ni5Se6O16Cl4H2) and Phase 4 (Ni5Se4O12Cl2) are new compounds. The fact that there are at least four different compounds in the as-synthesized material explains why the phase identification and structure determination could not be done by PXRD alone. The RED method makes phase identification from such multiphase powder samples much easier than would be the case using powder X-ray diffraction. The RED method also makes structure determination of submicrometre-sized crystals from multiphase samples possible.

Structural study of disordered SiC nanowires by three-dimensional rotation electron diffraction

The structure of disordered SiC nanowires was studied by using the three-dimensional rotation electron diffraction (RED) technique. The streaks shown in the RED images indicated the stacking faults of the nanowire. High-resolution transmission electron microscopy imaging was employed to support the results from the RED data. It suggested that a 2H polytype is most possible for the nanowires.

When two bad data sets are better than one

High-resolution synchrotron X-ray powder diffraction (SXPD) data alone are sometimes not enough to solve the structure of a complex polycrystalline material. Such was the case for the high-silica zeolites SSZ-61 and SSZ-87, where combining data from different sources, in particular XPD and electron microscopy, was vital to success. For SSZ-61, the SXPD data feature broad peaks and a resolution of ca. 1.2 Å. Although the pattern could be indexed, structure determination failed both with the charge flipping routine in SUPERFLIP [1] and with the zeolite-specific program FOCUS [2]. The unit cell parameters and HRTEM images indicated a relationship with ZSM-12 (MTW) and SSZ-59 (SFN), so several models derived from these two frameworks were built. Eventually, after considering Si-29 MAS NMR data and the size of the organic structure directing agent (SDA), a framework model that fits all the data emerged. To complete the structure, the SDA was included as a rigid-body, and its location and orientation optimized using simulated annealing. Subsequent Rietveld refinement confirmed the structure. In contrast to SSZ-61, the SXPD pattern for SSZ-87 was quite good, and it could be indexed with a C-centered cell. However, structure solution failed, probably because of the very high degree of reflection overlap (93%). Therefore, rotation electron diffraction (RED) data [3] were collected, but they proved to be of low resolution and poor quality. Only 2 of the 7 data sets could be indexed, and these had different unit cells. Neither fit the XPD pattern directly. The problem was traced to large errors in the RED cell parameters, and eventually one RED cell could be transformed to one similar to the SXPD cell. The RED data with this cell was only 15% complete up to a resolution of 1.22 Å. Even so, the structure could be solved using a recently developed version of FOCUS that works with ED data. The SDA was found as for SSZ-61, and the structure then confirmed by Rietveld refinement.

Single Crystal 3D Rotation Electron Diffraction from Nano-sized Crystals

Electron crystallography is an important technique for structure analysis of nano-sized materials. Crystals too small or too complicated to be studied by X-ray diffraction can be investigated by electron crystallography. However, conventional TEM methods requires high TEM skills and strong crystallographic knowledge, which many synthetic materials scientists and chemists do not have. We recently developed the software-based Rotation Electron Diffraction (RED) method for automated collection and processing of 3D electron diffraction data. Complete single crystal 3D electron diffraction data can be collected from nano- and micron-sized crystals in less than one hour by combining electron beam tilt and goniometer tilt, which are controlled by the RED – data collection software.3 The unit cell, possible space groups and electron diffraction intensities can be obtained from the RED data using the RED data processing software. The figure below illustrates the data collection and data processing of a zeolite silicalite-1 by RED. 1427 ED frames were collected in less than 1 hour from a crystal of 800 x 400 x 200 nm in size. A 3D reciprocal lattice of silicalite-1 was reconstructed from the ED frames, from which the unit cell parameters and space group were determined (P21/n, a=20.02Å, b=20.25Å, c=13.35Å, alfa=90.130, beta=90.740, gamma=90.030. It was possible to cut the 3D reciprocal lattice perpendicular to any directions and study the reflection conditions. The reflection intensities could be extracted. The structure of the calcined silicalite-1 could be solved from the RED data by routine direct methods using SHELX-97. All 78 unique Si and O atoms could be located and refined to an accuracy better than 0.08 Å. The RED method has been applied for structure solution of a wide range of crystals and shown to be very powerful and efficient. Now a structure determination can be achieved within a few hours, from the data collection to structure solution. We will present several examples including unknown inorganic compounds, metal-organic frameworks and organic structures solved from the RED data. Different parameters that affect the RED data quality and thus the structure determination will be discussed. The methods are general and can be applied to any crystalline materials.

Why was the structure of the niobium silicate AM-11 so difficult to solve?

The synthesis of the polycrystalline niobium silicate catalyst AM-11 was first reported in 1998 [1], but its structure proved to be elusive. In 2007 we received two samples from the Aveiro group. At the time, we were looking for a material suitable for the application of the texture method of structure solution, and AM-11 seemed to be ideal for this purpose. One of the samples had needle and the other platelet morphology, and textured samples could be prepared in both cases. The conventional powder diffraction pattern could be indexed on a hexagonal, an orthorhombic or a monoclinic unit cell, so this was the first issue to be resolved. The texture measurements quickly revealed that the crystal system was orthorhombic, but the structure resisted solution. We then tried applying the precession electron diffraction technique in combination with high-resolution powder diffraction data, but beyond confirming the orthorhombic symmetry, these data did not help us to solve the structure. Another attempt was made with a new sample and an improved texture setup, but to no avail. Rotation electron diffraction data and high-resolution transmission electron microscopy images showed that some disorder was present and helped to define the space group, but the structure remained a mystery. The powder charge-flipping routine in Superflip [2], yielded tantalizingly clear electron density maps, but they could not be interpreted sensibly. The unit cell parameters were seen to be related to those of the titanium silicate zorite [3] (one axis doubled in AM-11), so the problem was taken up once again last year. By starting with a simplified zorite framework structure with Nb in place of Ti, and performing what amounts to manual Fourier recycling, the surprisingly simple structure (1Nb, 3 Si, 9 O), which is significantly different from zorite, finally revealed itself. There is some stacking disorder, but the structure is otherwise innocuous. What made it so difficult to solve?

SSZ-45: A High-Silica Zeolite with Small Pore Openings, Large Cavities, and Unusual Adsorption Properties

Separations of small molecules such as CO2 and N2 or CH4 and CO2 are key to many industrial processes, but it is not always easy to find a molecular sieve that can discriminate between these molecules and withstand the harsh conditions often required. The high-silica zeolite SSZ-45, which was synthesized using N-cyclopentyldiazabicyclooctane as the structure directing agent (SDA), was found to exhibit excellent thermal stability and rather unusual adsorption properties under pressure. That is, it has potential in the area of small molecule separations. Of particular interest, therefore, was the structural basis for its peculiar adsorption behavior. The relatively complex silicate framework structure of SSZ-45 was determined from a combination of synchrotron powder diffraction and rotation electron diffraction data. Once the framework was known, it was possible to locate the organic SDA in the cavities and to better understand its contribution to the formation of the zeolite. Here we describe the synthesis of SSZ-45, the analysis of its structure, and the subsequent investigation of its small molecule separation properties.