Crystal Structure Determination Research Articles

Improvement of Single-Crystal Structures of Very Heavy Element Compounds by Refining Anomalous Dispersion Parameters.

Refining the anomalous dispersion parameters of the four uranium compounds NaUF5, NaU2F9, Cs2(UO2)TiO4, and Cs2(UO2)Ti2O6 gave insights into the crystallographic model improvement of very heavy atoms. We found that the values for the dispersive and absorptive parts, f' and f″, closely followed the X-ray absorption spectra on their L3, L2, and L1 edges. The obtained values are sensitive to the chemical environment at each crystallographically independent position. An incorrect treatment of the anomalous dispersion correction can lead to a wrong crystallographic model. The above-mentioned, already published structures were improved by this process. General guidelines were given for the crystal structure determination of very heavy compounds. When using Mo Kα radiation with uranium compounds, the proximity of its energy to the uranium L-edges causes a noticeable effect.

The crystal structure of olanzapine form III.

The antipsychotic drug olanzapine is well known for its complex polymorphism. Although widely investigated, the crystal structure of one of its anhydrous polymorphs, form III, is still unknown. Its appearance, always in concomitance with forms II and I, and the impossibility of isolating it from that mixture, have prevented its structure determination so far. The scenario has changed with the emerging field of 3D electron diffraction (3D ED) and its great advantages in the characterization of polyphasic mixtures of nanosized crystals. In this study, we show how the application of 3D ED allows the ab initio structure determination and dynamical refinement of this elusive crystal structure that remained unknown for more than 20 years. Olanzapine form III is monoclinic and shows a similar but shifted packing with respect to form II. It is remarkably different from the lowest-energy structures predicted by the energy-minimization algorithms of crystal structure prediction.

The Curious Case of A31P, a Topology-Switching Mutant of the Repressor of Primer Protein: A Molecular Dynamics Study of Its Folding and Misfolding.

The effect of mutations on protein structures is usually rather localized and minor. Finding a mutation that can single-handedly change the fold and/or topology of a protein structure is a rare exception. The A31P mutant of the homodimeric Repressor of primer (Rop) protein is one such exception: This single mutation ─and as demonstrated by two independent crystal structure determinations─ can convert the canonical (left-handed/all-antiparallel) 4-α-helical bundle of Rop to a new form (right-handed/mixed parallel and antiparallel bundle) displaying a previously unobserved "bisecting U" topology. The main problem with understanding the dramatic effect of this mutation on the folding of Rop is to understand its very existence: Most computational methods appear to agree that the mutation should have had no appreciable effect, with the majority of energy minimization methods and protein structure prediction protocols indicating that this mutation is fully consistent with the native Rop structure, requiring only a local and minor change at the mutation site. Here we use two long (10 μs each) molecular dynamics simulations to compare the stability and dynamics of the native Rop versus a hypothetical structure that is identical with the native Rop but is carrying this single Alanine31 to Proline mutation. Comparative analysis of the two trajectories convincingly shows that, in contrast to the indications from energy minimization ─but in agreement with the experimental data─, this hypothetical native-like A31P structure is unstable, with its turn regions almost completely unfolding, even under the relatively mild 320 K NpT simulations that we have used for this study. We discuss the implication of these findings for the folding of the A31P mutant, especially with respect to the proposed model of a double-funneled energy landscape.

Indium(III) complexes with lapachol: cytotoxic effects against human breast tumor cells and interactions with DNA.

Lapachol (2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione) is a 1,4-naphthoquinone-derived natural product that presents numerous bioactivities and was shown to have cytotoxic effects against several human tumor cells. Indium(III) complexes with a variety of ligands also exhibit antineoplastic activity. Indium(III) complexes [In(lap)Cl2].4H2O (1), [In(lap)2Cl(Et3N)] (2), [In(lap)3]·2H2O (3) [In(lap)(bipy)Cl2] bipy = 2,2'-bipyridine (4) and [In(lap)(phen)Cl2] phen = 1,10-phenanthroline (5) were obtained with 2-hydroxy-3-(3-methylbut-2-en-1-yl)naphthalene-1,4-dione (lapachol). Crystal structure determinations for (4) and (5) revealed that the indium(III) center is coordinated to two O atoms from lapachol, two N atoms from 1,10-phenanthroline or 2,2'-bipyridine, and two chloride anions, in a distorted octahedral geometry. Although both complexes (4) and (5) interacted with CT-DNA in vitro by an intercalative mode, only 5 exhibited cytotoxicity against MCF-7 and MDA-MB breast tumor cells. 1,10-phenanthroline and complex (5) presented cytotoxic effects against MCF-7 and MDA-MB cells, with complex (5) being threefold more active than 1,10-phenanthroline on MCF-7 cells. In addition, complex (5) significantly reduced the formation of MDA-MB-231 colonies in a clonogenicity assay. The foregoing results suggest that further studies on the cytotoxic effects and cellular targets of complex (5) are of utmost relevance.

In situ serial crystallography facilitates 96-well plate structural analysis at low symmetry.

The advent of serial crystallography has rejuvenated and popularized room-temperature X-ray crystal structure determination. Structures determined at physiological temperature reveal protein flexibility and dynamics. In addition, challenging samples (e.g. large complexes, membrane proteins and viruses) form fragile crystals that are often difficult to harvest for cryo-crystallography. Moreover, a typical serial crystallography experiment requires a large number of microcrystals, mainly achievable through batch crystallization. Many medically relevant samples are expressed in mammalian cell lines, producing a meager quantity of protein that is incompatible with batch crystallization. This can limit the scope of serial crystallography approaches. Direct in situ data collection from a 96-well crystallization plate enables not only the identification of the best diffracting crystallization condition but also the possibility for structure determination under ambient conditions. Here, we describe an in situ serial crystallography (iSX) approach, facilitating direct measurement from crystallization plates mounted on a rapidly exchangeable universal plate holder deployed at a microfocus beamline, ID23-2, at the European Synchrotron Radiation Facility. We applied our iSX approach on a challenging project, autotaxin, a therapeutic target expressed in a stable human cell line, to determine the structure in the lowest-symmetry P1 space group at 3.0 Å resolution. Our in situ data collection strategy provided a complete dataset for structure determination while screening various crystallization conditions. Our data analysis reveals that the iSX approach is highly efficient at a microfocus beamline, improving throughput and demonstrating how crystallization plates can be routinely used as an alternative method of presenting samples for serial crystallography experiments at synchrotrons.

Chirality Determination of Nanocrystals by Electron Crystallography.

Chirality is a common phenomenon in nature and plays an important role in the properties of matter. The rational synthesis of chiral compounds and exploration of their applications in various fields require an unambiguous determination of their handedness. However, in many cases, determinations of the chiral crystal structure and chiral morphology have been a challenging task due to the lack of proper characterization methods, especially for nanosized crystals. Therefore, it is crucial to develop novel and efficient characterization methods. Owing to the strong interactions between matter and electrons, electron crystallography has become a powerful tool for structural analysis of nanomaterials. In recent years, methods based on electron crystallography, such as high-resolution electron microscopy imaging and electron diffraction, have been developed to unravel the chirality of nanomaterials. This brings new opportunities to the design, synthesis, and applications of versatile chiral nanomaterials. In this perspective, we summarize the recent methodology developments and ongoing research of electron crystallography for chiral structure and morphology determination of nanocrystals, including inorganic and organic materials, as well as highlight the potential and further improvement of these methods in the future.

Crystal structure determination and Hirshfeld surface analysis of N-acetyl-N-3-meth-oxy-phenyl and N-(2,5-di-meth-oxy-phen-yl)-N-phenyl-sulfonyl derivatives of N-[1-(phenyl-sulfon-yl)-1H-indol-2-yl]methanamine.

Two new [1-(phenyl-sulfon-yl)-1H-indol-2-yl]methanamine derivatives, namely, N-(3-meth-oxy-phen-yl)-N-{[1-(phenyl-sulfon-yl)-1H-indol-2-yl]meth-yl}acetamide, C24H22N2O4S, (I), and N-(2,5-di-meth-oxy-phen-yl)-N-{[1-(phenyl-sulfon-yl)-1H-indol-2-yl]meth-yl}benzene-sulfonamide, C29H26N2O6S2, (II), reveal a nearly orthogonal orientation of their indole ring systems and sulfonyl-bound phenyl rings. The sulfonyl moieties adopt the anti-periplanar conformation. For both compounds, the crystal packing is dominated by C-H⋯O bonding [C⋯O = 3.312 (4)-3.788 (8) Å], with the structure of II exhibiting a larger number, but weaker bonds of this type. Slipped π-π inter-actions of anti-parallel indole systems are specific for I, whereas the structure of II delivers two kinds of C-H⋯π inter-actions at both axial sides of the indole moiety. These findings agree with the results of Hirshfeld surface analysis. The primary contributions to the surface areas are associated with the contacts involving H atoms. Although II manifests a larger fraction of the O⋯H/H⋯O contacts (25.8 versus 22.4%), most of them are relatively distal and agree with the corresponding van der Waals separations.

Multi-physical channels response in a novel layered perovskite: (trans-4-methylcyclohexylammonium)2[CuCl4]

With the continuous development of society, the demand for multi-physical channel responsive materials continues to increase, and it is urgent to develop multi-channel responsive materials with excellent properties. Here, in this work, we reported a novel two-dimensional (2D) organic–inorganic hybrid perovskite, (trans-4-methylcyclohexylammonium)2[CuCl4] (1), with responsive multi-physical channels. 1 experienced a structural phase transition with switchable thermochromism and dielectric response, which has great potential in the application of responsive materials. Under thermal stimulation, crystal 1 displays a reversible color variation between green and yellow. Crystal structure determination reveals that the distortion of inorganic layers plays a predominant role in the thermochromism during the phase transition process. This finding presents a compelling avenue for developing multi-physical channel responsive materials and contributes valuable insights to the exploration of two-dimensional lead-free perovskites for applications in intelligent window technology.

Powder x-ray diffraction analysis with machine learning for organic-semiconductor crystal-structure determination

The crystal structure of organic semiconductors is an important factor that dominates various electronic properties, including charge transport properties. However, compared with the crystal structures of inorganic semiconductors, those of organic semiconductors are difficult to determine by powder x-ray diffraction (PXRD) analysis. Our proposed machine-learning (neural-network) technique can determine the diffraction peaks buried in noise and make deconvolution of the overlapped peaks of organic semiconductors, resulting in crystal-structure determination by the Rietveld analysis. As a demonstration, we apply the method to a few high-mobility organic semiconductors and confirm that the method is potentially useful for analyzing the crystal structure of organic semiconductors. The present method is also expected to be applicable to the determination of complex crystal structures in addition to organic semiconductors.

Electrosynthesis of Unusual Nonfcc Palladium Hydride Nanoparticles.

Intercalation of hydrogen into the palladium atomic layers during the growth of Pd nanoparticles can lead to the synthesis of unique palladium hydride phases. Here, we discover an unusual nonfcc palladium hydride nanoparticle, a structure that is not face-centered cubic (fcc), formed through coreduction of water molecules and Pd ions in solution. Crystal structure determination based on atomic electron tomography points to potential triclinic unit cells, indicating the presence of more than one nonfcc phase, with some of those being a stack of loosened and distorted close-packed layer of atoms. The probability of finding the nonfcc phase in single-crystalline particles varies depending on the number and distribution of contact area with other particles. Roughly half of the isolated and one side-coalesced single-crystal particles exhibit a nonfcc structure, while fcc dominates multiple side-coalesced single crystals as well as polycrystal particles. These observations suggest a coalescence-induced phase transition from a nonfcc to a stable fcc structure, due to the metastable nature of the nonfcc phases. While hydrogen is proven to be a key component for the synthesis of the nonfcc structure, there was limited formation of the unusual phase in a H2 gas bubbling system. Thus, electrochemical pathways can be promising for the in situ creation and study of unique metastable nanomaterials.

Synthesis, crystal structure and photophysical properties of a dinuclear MnII complex with 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline.

A new quinoline derivative, namely, 6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline, C24H23N3 (QP), and its MnII complex aqua-1κO-di-μ-chlorido-1:2κ4 Cl:Cl-di-chlorido-1κCl,2κCl-bis-[6-(di-ethyl-amino)-4-phenyl-2-(pyridin-2-yl)quinoline]-1κ2 N 1,N 2;2κ2 N 1,N 2-dimanganese(II), [Mn2Cl4(C24H23N3)2(H2O)] (MnQP), were synthesized. Their compositions have been determined with ESI-MS, IR, and 1H NMR spectroscopy. The crystal-structure determination of MnQP revealed a dinuclear complex with a central four-membered Mn2Cl2 ring. Both MnII atoms bind to an additional Cl atom and to two N atoms of the QP ligand. One MnII atom expands its coordination sphere with an extra water mol-ecule, resulting in a distorted octa-hedral shape. The second MnII atom shows a distorted trigonal-bipyramidal shape. The UV-vis absorption and emission spectra of the examined compounds were studied. Furthermore, when investigating the aggregation-induced emission (AIE) properties, it was found that the fluorescent color changes from blue to green and eventually becomes yellow as the fraction of water in the THF/water mixture increases from 0% to 99%. In particular, these color and intensity changes are most pronounced at a water fraction of 60%. The crystal structure contains disordered solvent mol-ecules, which could not be modeled. The SQUEEZE procedure [Spek (2015 ▸). Acta Cryst. C71, 9-18] was used to obtain information on the type and qu-antity of solvent mol-ecules, which resulted in 44 electrons in a void volume of 274 Å3, corresponding to approximately 1.7 mol-ecules of ethanol in the unit cell. These ethanol mol-ecules are not considered in the given chemical formula and other crystal data.

Crystal structure and spectroscopic determination of the phase transitions in methylammonium- and formamidinium bismuth iodide perovskites

Understanding of the structural properties of hybrid organic–inorganic perovskites (HOIPs) and their behavior is crucial for their use as photovoltaics and for the design and assembly of solar cells. As part of this work, a detailed study was conducted to further understand bismuth iodide perovskites, with a specific focus on the phase transitions of methylammonium and formamidinium analogs. A detailed analysis of the temperature-dependent IR spectra was also performed in order to analyze the structural changes that occur. The presence of five phases in the methylammonium bismuth iodide (MABiI) and four phases in formamidinium bismuth iodide (FABiI) were determined. An additional confirmation of the reported results was obtained from the differential scanning calorimetry. The ambiguities concerning the crystal structure of FABiI were resolved based on the results by X-ray powder diffraction (XRPD).

Two new coordination polymers of Tl(I) & Hg(II), based on nicotinic acid ligand: synthesis, characterization, crystal structure determination & DFT calculation

Two new coordination polymers of Tl(I) & Hg(II), based on nicotinic acid ligand: synthesis, characterization, crystal structure determination & DFT calculation

GIWAXS experimental methods at the NFPS-BL17B beamline at Shanghai Synchrotron Radiation Facility.

The BL17B beamline at the Shanghai Synchrotron Radiation Facility was first designed as a versatile high-throughput protein crystallography beamline and one of five beamlines affiliated to the National Facility for Protein Science in Shanghai. It was officially opened to users in July 2015. As a bending magnet beamline, BL17B has the advantages of high photon flux, brightness, energy resolution and continuous adjustable energy between 5 and 23 keV. The experimental station excels in crystal screening and structure determination, providing cost-effective routine experimental services to numerous users. Given the interdisciplinary and green energy research demands, BL17B beamline has undergone optimization, expanded its range of experimental methods and enhanced sample environments for a more user-friendly testing mode. Thesemethods include single-crystal X-ray diffraction, powder crystal X-ray diffraction, wide-angle X-ray scattering, grazing-incidence wide-angle X-ray scattering (GIWAXS), and fully scattered atom pair distribution function analysis, covering structure detection from crystalline to amorphous states. This paper primarily presents the performance of the BL17B beamline and the application of the GIWAXS methodology at the beamline in the field of perovskite materials.

Crystal structure via fluctuation scattering.

Crystallography is a quintessential method for determining the atomic structure of crystals. The most common implementation of crystallography uses single crystals that must be of sufficient size, typically tens of micrometres or larger, depending on the complexity of the crystal structure. The emergence of serial data-collection methods in crystallography, particularly for time-resolved experiments, opens up opportunities to develop new routes to structure determination for nanocrystals and ensembles of crystals. Fluctuation X-ray scattering is a correlation-based approach for single-particle imaging from ensembles of identical particles, but has yet to be applied to crystal structure determination. Here, an iterative algorithm is presented that recovers crystal structure-factor intensities from fluctuation X-ray scattering correlations. The capabilities of this algorithm are demonstrated by recovering the structure of three small-molecule crystals and a protein crystal from simulated fluctuation X-ray scattering correlations. This method could facilitate the recovery of structure-factor intensities from crystals in serial crystallography experiments and relax sample requirements for crystallography experiments.

Synthesis, Antibacterial Evaluation, Crystal Structure Determination, Hirshfeld Surface Analysis and Density Functional Theory Analysis of Novel 3-Amino-2-(2-Thienyl)-4(3H)-Quinazolinone

A single crystal of new 2-substitued quinazoline derivative has been successfully synthesized through a simple and novel process based on a two-step reaction involving cyclisation, oxidation and hydrasination. The structure of the newly synthesized product was fully characterized by spectroscopic analysis NMR (1H & 13C), IR and HRMS. This intriguing compound crystalizes crystallises in a monoclinic system with P21/c space group. Notably, the stability of crystal packing was assured via hydrogen bonds, π- stacking and van der Waals interactions. An intermolecular interaction examination of the crystal structure was performed using Hirshfeld surface analysis and two-dimensional fingerprint plots. In addition, the electrostatic surface potential was calculated using density functional theory. In addition, the 3-amino-2-(2-thienyl)-4(3H)-quinazolinone, was applied to selected bacterial strains, and its antibacterial activity was assessed. In addition, a molecular docking study has been realised.

Synthesis and in-depth structure determination of a novel metastable high-pressure CrTe3 phase

This study reports the synthesis and crystal structure determination of a novel CrTe3 phase using various experimental and theoretical methods. The average stoichiometry and local phase separation of this quenched high-pressure phase were characterized by ex situ synchrotron powder X-ray diffraction and total scattering. Several structural models were obtained using simulated annealing, but all suffered from an imperfect Rietveld refinement, especially at higher diffraction angles. Finally, a novel stoichiometrically correct crystal structure model was proposed on the basis of electron diffraction data and refined against powder diffraction data using the Rietveld method. Scanning electron microscopy–energy-dispersive X-ray spectrometry (EDX) measurements verified the targeted 1:3 (Cr:Te) average stoichiometry for the starting compound and for the quenched high-pressure phase within experimental errors. Scanning transmission electron microscopy (STEM)–EDX was used to examine minute variations of the Cr-to-Te ratio at the nanoscale. Precession electron diffraction (PED) experiments were applied for the nanoscale structure analysis of the quenched high-pressure phase. The proposed monoclinic model from PED experiments provided an improved fit to the X-ray patterns, especially after introducing atomic anisotropic displacement parameters and partial occupancy of Cr atoms. Atomic resolution STEM and simulations were conducted to identify variations in the Cr-atom site-occupancy factor. No significant variations were observed experimentally for several zone axes. The magnetic properties of the novel CrTe3 phase were investigated through temperature- and field-dependent magnetization measurements. In order to understand these properties, auxiliary theoretical investigations have been performed by first-principles electronic structure calculations and Monte Carlo simulations. The obtained results allow the observed magnetization behavior to be interpreted as the consequence of competition between the applied magnetic field and the Cr–Cr exchange interactions, leading to a decrease of the magnetization towards T = 0 K typical for antiferromagnetic systems, as well as a field-induced enhanced magnetization around the critical temperature due to the high magnetic susceptibility in this region.

Intramolecular Phenolic H-Atom Abstraction by a N3ArOH Ligand-Supported (μ-η2:η2-Peroxo)dicopper(II) Species Relevant to the Active Site Function of oxy-Tyrosinase.

Synthetic side-on peroxide-bound dicopper(II) (SP) complexes are important for understanding the active site structure/function of many copper-containing enzymes. This work highlights the formation of new {CuII(μ-η2:η2-O22-)CuII} complexes (with electronic absorption and resonance Raman (rR) spectroscopic characterization) using tripodal N3ArOH ligands at -135 °C, which spontaneously participate in intramolecular phenolic H-atom abstraction (HAA). This results in the generation of bis(phenoxyl radical)bis(μ-OH)dicopper(II) intermediates, substantiated by their EPR/UV-vis/rR spectroscopic signatures and crystal structural determination of a diphenoquinone dicopper(I) complex derived from ligand para-C═C coupling. The newly observed chemistry in these ligand-Cu systems is discussed with respect to (a) our Cu-MeAN (tridentate N,N,N',N',N″-pentamethyldipropylenetriamine)-derived model SP species, which was unreactive toward exogenous monophenol addition (J. Am. Chem. Soc. 2012, 134, 8513-8524), emphasizing the impact of intramolecularly tethered ArOH groups, and (b) recent advances in understanding the mechanism of action of the tyrosinase (Ty) enzyme.

A communication hub for phosphoregulation of kinetochore-microtubule attachment

The Mps1 and Aurora B kinases regulate and monitor kinetochore attachment to spindle microtubules during cell division, ultimately ensuring accurate chromosome segregation. In yeast, the critical spindle attachment components are the Ndc80 and Dam1 complexes (Ndc80c and DASH/Dam1c, respectively). Ndc80c is a 600-Å-long heterotetramer that binds microtubules through a globular "head" at one end and centromere-proximal kinetochore components through a globular knob at the other end. Dam1c is a heterodecamer that forms a ring of 16-17 protomers around the shaft of the single kinetochore microtubule in point-centromere yeast. The ring coordinates the approximately eight Ndc80c rods per kinetochore. In published work, we showed that a site on the globular "head" of Ndc80c, including residues from both Ndc80 and Nuf2, binds a bipartite segment in the long C-terminal extension of Dam1. Results reported here show, both by invitro binding experiments and by crystal structure determination, that the same site binds a conserved segment in the long N-terminal extension of Mps1. It also binds, less tightly, a conserved segment in the N-terminal extension of Ipl1 (yeast Aurora B). Together with results from experiments in yeast cells and from biochemical assays reported in two accompanying papers, the structures and graded affinities identify a communication hub for ensuring uniform bipolar attachment and for signaling anaphase onset.

Trifluoromethanesulfonate salt of 5,10,15,20-tetrakis(1-benzylpyridin-1-ium-4-yl)-21H,23H-porphyrin and its CaII complex

The synthesis, crystallization and characterization of a trifluoromethanesulfonate salt of 5,10,15,20-tetrakis(1-benzylpyridin-1-ium-4-yl)-21H,23H-porphyrin, C68H54N8 4+·4CF3SO3 −·4H2O, 1·OTf, are reported in this work. The reaction between 5,10,15,20-tetrakis(pyridin-4-yl)-21H,23H-porphyrin and benzyl bromide in the presence of 0.1 equiv. of Ca(OH)2 in CH3CN under reflux with an N2 atmosphere and subsequent treatment with silver trifluoromethanesulfonate (AgOTf) salt produced a red–brown solution. This reaction mixture was filtered and the solvent was allowed to evaporate at room temperature for 3 d to give 1·OTf. Crystal structure determination by single-crystal X-ray diffraction (SCXD) revealed that 1·OTf crystallizes in the space group P21/c. The asymmetric unit contains half a porphyrin molecule, two trifluoromethanesulfonate anions and two water molecules of crystallization. The macrocycle of tetrapyrrole moieties is planar and unexpectedly it has coordinated CaII ions in occupational disorder. This CaII ion has only 10% occupancy (C72H61.80Ca0.10F12N8O16S4). The pyridinium rings bonded to methylene groups from porphyrin are located in two different arrangements in almost orthogonal positions between the plane formed by the porphyrin and the pyridinium rings. The crystal structure features cation...π interactions between the CaII atom and the π-system of the phenyl ring of neighboring molecules. Both trifluoromethanesulfonate anions are found at the periphery of 1, forming hydrogen bonds with water molecules.