Structure determination of small molecule compounds by an electron diffractometer for 3D ED/MicroED

3D electron diffraction (3D ED) has emerged as an alternative to x-ray diffraction for structure elucidation of crystals in the submicrometer range [1].With scattering cross-sections typically 10 4 times larger than x-rays, data can be routinely collected from nanosized grains.Experiments performed in transmission electron microscopes or electron diffractometers allow to focus electron beams into diameters of tens of nanometers, allowing to collect single crystal data from microcrystalline samples.Further advantages include direct determination of absolute structure [2], easier localisation of light atoms including hydrogens [3] and an increased sensitivity to atomic charges [4].Dynamical refinements taking multiple scattering of electrons into account allow to obtain precise structure models with R-factors comparable to x-ray diffraction [5].

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.

A new lanthanum oxide, KLa5O5(VO4)2, was synthesized using a flux growth technique that involved solid-state reaction under an air atmosphere at 900 °C. The crystal structure was solved and refined using an innovative approach recently established and based on three-dimensional (3D) electron diffraction data, using precession of the electron beam and then validated against Rietveld refinement and denisty functional theory (DFT) calculations. It crystallizes in a monoclinic unit cell with space group C2/m and has unit cell parameters of a = 20.2282(14) Å, b = 5.8639(4) Å, c = 12.6060(9) Å, and β = 117.64(1)°. Its structure is built on Cresnel-like two-dimensional (2D) units (La5O5) of 4*3 (OLa4) tetrahedra, which run parallel to (001) plane, being surrounded by isolated VO4 tetrahedra. Four isolated vanadate groups create channels that host K(+) ions. Substitution of K(+) cations by another alkali metal is possible, going from lithium to rubidium. Li substitution led to a similar phase with a primitive monoclinic unit cell. A complementary selected area electron diffraction (SAED) study highlighted diffuse streaks associated with stacking faults observed on high-resolution electron microscopy (HREM) images of the lithium compound. Finally, preliminary catalytic tests for ethanol oxidation are reported, as well as luminescence evidence. This paper also describes how solid-state chemists can take advantages of recent progresses in electron crystallography, assisted by DFT calculations and powder X-ray diffraction (PXRD) refinements, to propose new structural types with potential applications to the physicist community.

Rare earth nanominerals in bentonite deposits of the Eocene Texas coastal plains

The emerging field of 3D electron diffraction (3D ED) opens new opportunities for structure determination from sub-micrometre-sized crystals. Although the foundations of this technology emerged earlier, the past decade has seen developments in cryo-electron microscopy and (X-ray) crystallography that particularly enable the widespread use of 3D ED. This Perspective describes to chemists and chemical crystallographers just how similar electron and X-ray diffraction are and discusses their complementary aspects. We wish to establish 3D ED in the broader chemistry community, such that electron crystallography becomes a common part of the analytical chemistry toolkit. With a suitable instrument at their disposal, every skilled crystallographer can quickly learn to perform structure determinations using 3D ED.

The effect of the acceleration voltage on the quality of structure determination by 3D-electron diffraction

The new zeolite, COE-11, was synthesized at 155 °C to 168 °C by hydrothermal synthesis from a reaction mixture of SiO2/tetraethylammonium hydroxide/H3BO3/NaOH/H2O. Because tetraethylammonium is an unspecific structure directing agent, COE-11 crystallizes in all cases together with at least one impurity phase from a selection of phases: zeolite types *BEA, CHA, FER, MFI, MOR, MTW; the layered silicates magadiite and kenyaite; and searlsite and silica polymorph quartz. The crystal structure was solved from 3D electron diffraction (3D ED) data. Subsequent structure refinements of X-ray powder diffraction (PXRD) data and single crystal electron diffraction data converged to residual values of RF = 0.039, chi2 = 3.6 (PXRD) and RF = 21.81% (3D ED) confirming the structure model. COE-11 crystallizes in space group C2 with unit cell dimensions of a0 = 17.3494(11) Å, b0 = 17.3409(11) Å, c0 = 14.2789(4) Å and β = 113.762(2) °. The structure of COE-11 is characterized by a microporous borosilicate framework with intersecting, highly elliptical 12-ring channels running parallel (110) and (1–10) and forming a two-dimensional pore system. The Rietveld refinement provided a hint that boron partly substitutes silicon on three specific T sites of the framework. The idealized chemical composition of as-made COE-11 is [(CH3CH2)4N]4[B4Si62O132] per unit cell. Physico-chemical characterization using solid-state NMR spectroscopy, SEM, TG-DTA, and ATR-FTIR spectroscopy confirmed that COE-11 is a microporous borosilicate zeolite. COE-11 is structurally closely related to zeolite beta polymorph B but differs concerning the dimensionality of the pore system, which is 2D instead of 3D.

Uranotungstite is an uranyl-tungstate mineral that was until recently only partially characterized with a formula originally given as (Fe2+,Ba,Pb)(UO2)2(WO4)(OH)4·12H2O and an unknown crystal structure. This mineral has been reinvestigated by electron microprobe analysis coupled with three-dimensional electron diffraction. According to the electron microprobe data, the holotype material from the Menzenschwand uranium deposit (Black Forest, Germany) has the empirical formula (Ba0.35Pb0.27)Σ0.62[(U6+O2)2(W0.986+☐0.75)O4.7(OH)2.5(H2O)1.75](H2O)1.67 (average of 8 points calculated on the basis of 2U apfu; H2O content derived from the structure). According to the precession-assisted 3D ED data, holotype uranotungstite from Menzenschwand is monoclinic, P21/m, with a = 6.318(5) Å, b = 7.388(9) Å, c = 13.71(4) Å, β = 99.04(13)°, and V = 632(2) Å3 (Z = 2). The structure refinement of the 3D ED data using the dynamical approach (Robs = 0.0846 for 3287 independent observed reflections) provided a structure model composed of heteropolyhedral sheets. A β-U3O8-type sheet of idealized composition [(UO2)2W6+Fe0.253+☐0.75O4.75(OH)1.5(H2O)1.75]0.25– is composed of UO7 polyhedra linked by (W,Fe)O5 polyhedra in which the W:Fe ratio is variable as well as the bulk occupancy of this site; the W site may also host a minor proportion of Cu, Mg, or V. In uranotungstite, the interlayer spaces between adjacent U-W-O sheets host water on one side and, on the other side, a partially occupied cation site mostly occupied by Ba and, to a lesser extent, Pb, as well as a partially occupied H2O site. This work is the first structural description of a natural uranyl-tungstate mineral and confirms the great structural and chemical flexibility of β-U3O8 type of sheets.

Mechanochemistry finds application in the synthesis of new organic and metal-organic materials such as molecular crystals, salts, cocrystals and polymeric structures.This method allows the formation of products, polymorphs and topologies different from those obtained in solution.However, the structural characterisation of the obtained products is one of the main challenges related to this synthetic approach, due to the presence of nanometric crystals that cannot be analysed by conventional single-crystal X-ray diffraction.Furthermore, powder diffraction methods can be extremely difficult to apply in the case of large unit cells, low symmetry and polyphasic systems.Electron crystallography, especially 3D electron diffraction (3D ED), is an emerging characterisation technique that, due to the most recent developments, can be successfully employed to obtain the structure of nanocrystalline species.This has allowed the structural characterisation of different types of materials, spanning from porous MOFs, COFs and zeolites, to pharmaceutical APIs [1,3].The 3D electron diffraction analysis is usually performed in transmission electron microscopes (TEMs); however, the growing interest in 3D ED also prompted the development of dedicated electron diffractometers.In this contribution, we present a combined approach based on mechanochemistry and 3D ED analysis for the synthesis and structural characterisation of new reticular compounds.In particular, we studied a tetrahedral pyridyl-based SOF [4,5], zinc(II) and 2,6-pyridine dicarboxylic acid coordination polymers (CPs) [6] and MOFs based on copper(II) and phenolic ligands [7].The single-crystal 3D ED analyses of metal-organic compounds were performed in a TEM, whereas one of the SOFs was characterised in a new electron diffractometer.The comparison between 3D ED and X-ray powder diffraction data is also discussed.Figure 1.Schematic view of the combined use of mechanochemistry and 3D electron crystallography.

3D electron crystallography has emerged as a method with great potential for the structure determination of small molecules and macromolecules complementing traditional single-crystal X-ray crystallography and powder X-ray diffraction (PXRD). It offers the unique capability of determining the structures of small molecules and macromolecules from micro- and nanocrystals. In this study, using 3D electron diffraction (3DED), we determined the single-crystal structure of commercially sourced arginine directly from its bottle. The 3DED analysis of micro-sized single crystals identified two distinct forms: the L-arginine enantiomer and the racemic mixture DL-arginine. At the time of writing, neither the Cambridge Structural Database nor the Crystallographic Open Database contain a single-crystal structure of isolated L-arginine (sum formula C6H14N4O2), which has been solved in this work by 3DED. We also present a comparison of the structures of these molecules solved by 3DED and PXRD.

Crystal structure determination of a new LaPO4 phase in a multicomponent glass ceramic via 3D electron diffraction

We present new transmission electron microscopy (TEM) based electron diffraction characterization techniques (orientation imaging combined with 3D precession electron diffraction tomography-ADT) applied on cultural heritage materials. We have determined precisely unit cell parameters, crystal symmetry, atomic structure, and orientation/phase mapping of various pigment/opacifier crystallites at nm scale which are present in green and white Roman glass tesserae. Such TEM techniques can be an alternative to Synchrotron based techniques, and allow to distinguish accurately at nm scale between different crystal structures even in cases of same/very close chemical composition, where is also possible to visualize between different crystal orientations and amorphous/crystalline phases. This study additionally demonstrates that although opacifiers in green and white tesserae are found to have average Pb2Sb2O7 cubic and CaSb2O6 trigonal structures, their pyrochlore related framework can host many other elements like Cu, Ca, Fe through ionic exchanges at high firing temperatures which in turn may also contribute to the tesserae colour appearance.

Since the Science nomination for “Breakthrough of the year 2018” [1], electron diffraction (3D ED, known also as micro-ED) for structural elucidation of organic compounds has been gaining a lot of momentum. 3D ED has been rapidly evolving as a complementary technique for SCXRD experiments [2]. Especially for those cases where single crystals of suitable size for XRD experiments are not obtained. Dedicated electron diffractometers [3] make the technique more accessible, resulting in many recent publications where these commercial electron diffractometers have been used [4].3D ED / Micro-ED’s ease of use and its potential for various applications is presented in multiple studies, especially in the pharmaceutical industry where it is having a high impact [5,6]. We would highlight some case studies where electron diffraction has helped the pharmaceutical industry obtain structural information not available before by other means [4b, 6]. Furthermore, we’ll delve and showcase other applications like: Characterization of meta-stable polymorphic forms, identifying crystallinity in amorphous solid dispersions, finding new polymorphic forms, identifying polymorphic forms for litigation purposes, impurities and phase identification using crystal mapping, and more.

ELECTRON crystallography has two important advantages over X-ray crystallography for the determination of atomic positions in crystal structures: crystallographic phases can be determined directly from images1, and extremely small samples can be analysed. On the other hand, the strong interaction between electrons and matter gives rise to dynamical effects2 which complicate quantitative analysis of the experimental data. This has led to a pessimistic view of the possibility of direct crystal structure determination by electron crystallography3,4, especially for compounds containing heavy elements. The atomic structures of a few inorganic crystals, mainly oxides, have been determined from electron microscopy images5–7, but in no case was the atomic structure refined. Here we report the complete determination of an unknown structure, for the compound Ti11Se4, by electron crystallography. These results show that crystals that are too small for single-crystal X-ray diffraction and difficult to solve by powder diffraction may nevertheless be amenable to accurate structure determination by electron crystallography.

The stratosphere at altitudes ranging from 30 to 40 km is one of the most suitable and accessible environments to collect pristine interplanetary and interstellar dust particles, where the terrestrial dust component, e.g. volcanic, aeolian and anthropogenic aerosol, is negligible [1-3]. The DUSTER (Dust in the Upper Stratosphere Tracking Experiment and Retrieval) project is a balloon-borne sampling instrument specifically developed to collect Interplanetary Dust Particles (IDPs) with minimal contamination and structural integrity, at collection speed of 7 m/s and flow rates > 1 m3/h. DUSTER includes an adhesive-free collection substrate (Collector), fitted with 13 Transmission Electron Microscope (TEM) grids, directly exposed to the stratospheric airflow. The collection strategy is designed to ensure low-speed impact and capture, avoiding particle fragmentation or heating. The Collector and the Blank, i.e. an identical but unexposed collector, are imaged pre- and post-flight to identify possible pre-existing non-stratospheric particles to be excluded from the sample collection, if observed on the Collector, and to be considered as contaminants, if observed on the Blank. The conceived stringent contamination control protocol positions DUSTER as the only system capable of returning ultra-clean cosmic dust for high-resolution up-to-date laboratory investigations. Four DUSTER stratospheric balloon campaigns have successfully collected IDPs: Svalbard, Norway (2008) and Kiruna, Sweden (2011, 2019, 2021) [4,5]. We focus here on particles coming from the most recent campaigns (Kiruna, 2019 and 2021). These collections yielded hundreds of particles ranging in size from 0.1 to 50 µm, with a predominance in the 1 µm range. The preliminary SEM-based morpho-classification reveals a compositional and structural diversity including compact mineral fragments, porous aggregates, and spherules. Energy-dispersive X-ray (EDX) analyses confirmed the presence of silicates and carbonates, [4,5].Figure 1. Schematic overview of the DUSTER collection concept: Interplanetary Dust Particles (IDPs) from comets, asteroids, and meteoroid collisions, as well as interstellar dust from supernovae and dense molecular clouds, enter Earth’s atmosphere. Most man-made and terrestrial materials, e.g. volcanic, remain confined to the troposphere or lower stratosphere. The high-altitude stratospheric window, 30 - 40 km, is a unique reservoir for extraterrestrial matter, allowing DUSTER to collect stratospheric particles in a near-contamination-free environment, enabling the recovery of pristine IDPs and possible interstellar dust, intercepted due to the solar system's motion within the Milky Way. Figure 2. SEM and EDX elemental maps of a stratospheric particle collected by DUSTER. The right image shows a secondary electron micrograph of the collected particle, highlighting its irregular morphology and fragile structure. Elemental maps obtained via EDX reveal the distribution of major elements: calcium (Ca), oxygen (O), aluminum (Al), silicon (Si), and iron (Fe). The PRIN 2022 research project “Cosmic Dust II: Cosmochemistry and Space Tweezers Technologies for Solar System Science and Exploration", uses this collection to investigate the cosmochemical and mineralogical characteristics of extraterrestrial particles with sizes ranging from about 0.5 µm to 50 µm, a dimension gap yet to be filled. Within this framework, selected subsets of DUSTER IDPs i.e., a total of 11 particles with sizes > 10 µm and of 10 particles with sizes < 5 µm, are undergoing a comprehensive multi-analytical technique campaign. These particles have been selected based on their size, morphology, mineralogy, and surface preservation. For particles larger than 10 µm in size an initial high-resolution SEM imaging, followed by non-destructive spectroscopic techniques, including micro-Infrared (µIR), micro-Raman, and nano-Raman spectroscopy are employed. This facilitates the mapping of mineral phases and organic functional groups, allowing us to identify silicates, sulfides, and carbonaceous matter. IDPs smaller than 5 µm in size are observed with high-resolution transmission electron microscopy (HR-TEM) and 3D electron diffraction tomography (EDT), offering structural and chemical characterization at nanometer scale and discriminate of amorphous versus crystalline domains. A subset of particles will undergo destructive analytical techniques, including nano-scale Secondary Ion Mass Spectrometry (nanoSIMS) for measurement of isotopic compositions at sub-micron scale. This last analysis is critical for tracing potential presolar grains and to understand the source-region signatures within the solar system, but also very challenging when applied to DUSTER collections. Through this correlated microscopic protocol we aim to build an integrated dataset for each particle, allowing us to characterize its composition, formation history, and potential astrobiological significance. These results are expected to have implications not only for understanding the composition of the near-Earth dust complex and identifying its parent bodies, but also for the broader goals of astrobiology, planetary geology, and Solar System exploration.