Small-molecule Crystallography Research Articles

Repositioning small-molecule crystallography in higher education

Repositioning small-molecule crystallography in higher education

Copper acetate small-molecule crystallography undergraduate experiments

Copper acetate small-molecule crystallography undergraduate experiments

Contributions of Professor Tayur N. Guru Row to Research in Small-Molecule Crystallography

ADVERTISEMENT RETURN TO ARTICLES ASAPEditorialNEXTContributions of Professor Tayur N. Guru Row to Research in Small-Molecule CrystallographyDeepak Chopra*Deepak Chopra*Email: [email protected]More by Deepak Choprahttps://orcid.org/0000-0002-0018-6007, Sajesh P. Thomas*Sajesh P. Thomas*Email: [email protected]More by Sajesh P. Thomas, and Giuseppe Resnati*Giuseppe Resnati*Email: [email protected]More by Giuseppe Resnatihttps://orcid.org/0000-0002-0797-9296Cite this: Cryst. Growth Des. 2023, XXXX, XXX, XXX-XXXPublication Date (Web):April 28, 2023Publication History Received25 November 2022Published online28 April 2023https://doi.org/10.1021/acs.cgd.2c01383Published 2023 by American Chemical SocietyRIGHTS & PERMISSIONSArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1002 KB) Get e-AlertsSUBJECTS:Crystal structure,Crystallography,Crystals,Diffraction,Electrical properties Get e-Alerts

Reliability and reproducibility in small-molecule crystallography

Reliability and reproducibility in small-molecule crystallography

Repositioning small-molecule crystallography to educate next generation of users

Repositioning small-molecule crystallography to educate next generation of users

CELLOPT: improved unit-cell parameters for electron diffraction data of small-molecule crystals.

Electron diffraction enables structure determination of organic small molecules using crystals that are too small for conventional X-ray crystallography. However, because of uncertainties in the experimental parameters, notably the detector distance, the unit-cell parameters and the geometry of the structural models are typically less accurate and precise compared with results obtained by X-ray diffraction. Here, an iterative procedure to optimize the unit-cell parameters obtained from electron diffraction using idealized restraints is proposed. The cell optimization routine has been implemented as part of the structure refinement, and a gradual improvement in lattice parameters and data quality is demonstrated. It is shown that cell optimization, optionally combined with geometrical corrections for any apparent detector distortions, benefits refinement of electron diffraction data in small-molecule crystallography and leads to more accurate structural models.

Chemical crystallography by serial femtosecond X-ray diffraction

Inorganic–organic hybrid materials represent a large share of newly reported structures, owing to their simple synthetic routes and customizable properties1. This proliferation has led to a characterization bottleneck: many hybrid materials are obligate microcrystals with low symmetry and severe radiation sensitivity, interfering with the standard techniques of single-crystal X-ray diffraction2,3 and electron microdiffraction4–11. Here we demonstrate small-molecule serial femtosecond X-ray crystallography (smSFX) for the determination of material crystal structures from microcrystals. We subjected microcrystalline suspensions to X-ray free-electron laser radiation12,13 and obtained thousands of randomly oriented diffraction patterns. We determined unit cells by aggregating spot-finding results into high-resolution powder diffractograms. After indexing the sparse serial patterns by a graph theory approach14, the resulting datasets can be solved and refined using standard tools for single-crystal diffraction data15–17. We describe the ab initio structure solutions of mithrene (AgSePh)18–20, thiorene (AgSPh) and tethrene (AgTePh), of which the latter two were previously unknown structures. In thiorene, we identify a geometric change in the silver–silver bonding network that is linked to its divergent optoelectronic properties20. We demonstrate that smSFX can be applied as a general technique for structure determination of beam-sensitive microcrystalline materials at near-ambient temperature and pressure.

Resolving Space-Group-Choice Dilemma in Small-Molecule Crystallography for Chemistry Students Using Case-Based Learning Modules

Despite advances in software development, symmetry-related topics are among the most important yet confusing concepts in crystallography training for chemistry students who routinely use small-molecule crystallography in their scientific study. The case-based learning approach is very effective in stimulating students’ interests in self-exploring the course material and critically processing information to arrive at the most reasonable result. Learning modules such as applying concepts of the 17 two-dimensional space groups in Escher drawings and critically judging crystallography misconceptions can engage chemistry students and invoke their confidence in handling the crystal structures encountered in their research.

NSF's ChemMatCARS Advanced Crystallography Program – a dedicated advanced small-molecule crystallography beamline

NSF's ChemMatCARS Advanced Crystallography Program – a dedicated advanced small-molecule crystallography beamline

The lower energy diffraction and scattering side-bounce beamline for materials science at the Canadian Light Source

A new diffraction beamline for materials science has been built at the Canadian Light Source synchrotron. The X-ray source is an in-vacuum wiggler with a 2.5 T peak magnetic field at 5.2 mm gap. The optical configuration includes a toroidal mirror, a single side-bounce Bragg monochromator, and a cylindrical mirror, producing a sub-150 µm vertical× 500 µm horizontal focused beam with a photon energy range of 7-22 keV and a flux of 1012 photons per second at the sample position. Three endstations are currently open to general users, and the techniques available include high-resolution powder diffraction, small molecule crystallography, X-ray reflectivity, in situ rapid thermal annealing, and SAXS/WAXS. The beamline design parameters, calculated and measured performance, and initial experimental results are presented to demonstrate the capabilities for materials science.

Inversion of Many-Beam Bragg Intensities for Phasing by Iterated Projections: Removal of Multiple Scattering Artifacts from Diffraction Data.

An iterated projection algorithm (N-Phaser) is developed that reconstructs a scattering potential from N-beam multiple Bragg scattered intensities. The method may be used to eliminate multiple scattering artifacts from electron diffraction data, solving the phase problem and increasing the thicknesses of samples used in materials science, solid-state chemistry, and small molecule crystallography. For high-energy transmission electron diffraction, we show that the algorithm recovers accurate complex structure factors from a wide range of thicknesses, orientations, and relativistic beam energies, and does not require known thickness or atomic-resolution data if sufficient multiple scattering occurs. Extensions to Cryo-electron microscopy and Micro-electron diffraction are suggested.

Towards synergy of macromolecular and small-molecule crystallography

Towards synergy of macromolecular and small-molecule crystallography

High-impact small-molecule crystallography skills development through local undergraduate curriculum and regional workshops and schools

High-impact small-molecule crystallography skills development through local undergraduate curriculum and regional workshops and schools

Teaching Crystallography by Determining Small Molecule Structures and 3-D Printing: An Inorganic Chemistry Laboratory Module

Experimental methods for determining 3-D atomic structures, such as crystallography, are rarely taught in the undergraduate curriculum, yet are considered to be the norm for 3-D structure determination in a research setting. Although a fully physical understanding of crystallography takes years of practice, practical applications and basic interpretation of small-molecule crystallography can be readily integrated into undergraduate curricula to give students a research-like laboratory experience. Three 1-h crystallography laboratory modules were developed using the free Olex2 software to determine the structure of (dithiolene)2Co(1,3,5-triaza-7-phosphaadamantane)·dichloroethane, while introducing basic crystallography knowledge, crystal evaluation through microscopy, practical structure determination skills, and spatial awareness through 3-D printing. Following implementation in an advanced instrumental analysis class composed of 14 Master’s and undergraduate students, the increase of topical knowledge of small molecule crystallography was 18–30% based on tailored assessment surveys, and student feedback was highly positive. This suggests that students without a prior background in crystallography were able to learn and retain information about small molecule crystallography from these laboratory modules.

A new modulated crystal structure of the ANS complex of the St John's wort Hyp-1 protein with 36 protein molecules in the asymmetric unit of the supercell.

Superstructure modulation, with violation of the strict short-range periodic order of consecutive crystal unit cells, is well known in small-molecule crystallography but is rarely reported for macromolecular crystals. To date, one modulated macromolecular crystal structure has been successfully determined and refined for a pathogenesis-related class 10 protein from Hypericum perforatum (Hyp-1) crystallized as a complex with 8-anilinonaphthalene-1-sulfonate (ANS) [Sliwiak et al. (2015), Acta Cryst. D71, 829-843]. The commensurate modulation in that case was interpreted in a supercell with sevenfold expansion along c. When crystallized in the additional presence of melatonin, the Hyp-1-ANS complex formed crystals with a different pattern of structure modulation, in which the supercell shows a ninefold expansion of c, manifested in the diffraction pattern by a wave of reflection-intensity modulation with crests at l = 9n and l = 9n ± 4. Despite complicated tetartohedral twinning, the structure has been successfully determined and refined to 2.3 Å resolution using a description in a ninefold-expanded supercell, with 36 independent Hyp-1 chains and 156 ANS ligands populating the three internal (95 ligands) and five interstitial (61 ligands) binding sites. The commensurate superstructures and ligand-binding sites of the two crystal structures are compared, with a discussion of the effect of melatonin on the co-crystallization process.

Radiation damage in small-molecule crystallography: fact not fiction.

Traditionally small-molecule crystallographers have not usually observed or recognized significant radiation damage to their samples during diffraction experiments. However, the increased flux densities provided by third-generation synchrotrons have resulted in increasing numbers of observations of this phenomenon. The diversity of types of small-molecule systems means it is not yet possible to propose a general mechanism for their radiation-induced sample decay, however characterization of the effects will permit attempts to understand and mitigate it. Here, systematic experiments are reported on the effects that sample temperature and beam attenuation have on radiation damage progression, allowing qualitative and quantitative assessment of their impact on crystals of a small-molecule test sample. To allow inter-comparison of different measurements, radiation-damage metrics (diffraction-intensity decline, resolution fall-off, scaling B-factor increase) are plotted against the absorbed dose. For ease-of-dose calculations, the software developed for protein crystallography, RADDOSE-3D, has been modified for use in small-molecule crystallography. It is intended that these initial experiments will assist in establishing protocols for small-molecule crystallographers to optimize the diffraction signal from their samples prior to the onset of the deleterious effects of radiation damage.

Semi-Rigid Molecular-Clip-Based Molecular Crystal Gearshift.

A new version of molecular clip, with a semi-rigid symmetrical crab-type architecture and flexible cavity size, has been successfully designed and synthesized via a one-pot Friedel-Crafts alkylation reaction. The X-ray single-crystal diffraction data provide a simple and intuitive explanation, not only for its well-preorganized and regulated conformation but also for its selective and tunable guest-binding capability. For the first time, the newly designed molecular clip was demonstrated to be not only a controllable variable-speed nonporous adsorption material in solution iodine capture, but also capable of on-off switching in volatile iodine capture. The presented new concept of molecular crystal gearshift directly from the molecular clip crystals represents an important advance in the development of synthetic receptor chemistry, which will exert a significant influence on small-molecule crystallography.

Non-crystallographic symmetry in proteins: Jahn-Teller-like and Butterfly-like effects?

Partial symmetry, i.e., the presence of more than one molecule in the asymmetric unit of a crystal, is a relatively rare phenomenon in small-molecule crystallography, but is quite common in protein crystallography, where it is typically known as non-crystallographic symmetry (NCS). Several papers in literature propose molecular determinants such as crystal contacts, thermal factors, or TLS parameters as an explanation for the phenomenon of intrinsic asymmetry among molecules that are in principle equivalent. Nevertheless, are all of the above determinants the cause or are they rather the effect? In the general frame of the NCS often observed in crystals of biomolecules, this paper deals with nickel(II)-substituted human carbonic anhydrase(II) (hCAII) and its SAD structure determination at the nickel edge. The structure revealed two non-equivalent molecules in the asymmetric unit, the presence of a secondary nickel-binding site at the N-terminus of both molecules (which had never been found before in the nickel-substituted enzyme) and two different coordination geometries of the active site nickel (hexa-coordinated in one molecule and mainly penta-coordinated in the other). The above-mentioned standard molecular crystallographic determinants of this asymmetry are analyzed and presented in detail for this particular case. From these considerations, we speculate on the existence of a fundamental, although yet unknown, common cause for the partial symmetry that is so often encountered in X-ray structures of biomolecules.

Connecting Key Concepts with Student Experience: Introducing Small-Molecule Crystallography to Chemistry Undergraduates Using a Flexible Laboratory Module

A strategy for incorporating crystallography laboratory practice into various experimental chemistry courses for undergraduates is described. The flexible approach that relates key concepts to hands-on activities allows students to draw an immediate connection between crystallography theory and their own lab experiences, leading to a deeper understanding of crystallography content and making their brief laboratory visit a memorable experience.

Industrial macromolecular and small-molecule crystallography at the Canadian Light Source

Industrial macromolecular and small-molecule crystallography at the Canadian Light Source