The seventh blind test of crystal structure prediction: structure generation methods.

A seventh blind test of crystal structure prediction was organized by the Cambridge Crystallographic Data Centre featuring seven target systems of varying complexity: a silicon and iodine-containing molecule, a copper coordination complex, a near-rigid molecule, a cocrystal, a polymorphic small agrochemical, a highly flexible polymorphic drug candidate, and a polymorphic morpholine salt. In this first of two parts focusing on structure generation methods, many crystal structure prediction (CSP) methods performed well for the small but flexible agrochemical compound, successfully reproducing the experimentally observed crystal structures, while few groups were successful for the systems of higher complexity. A powder X-ray diffraction (PXRD) assisted exercise demonstrated the use of CSP in successfully determining a crystal structure from a low-quality PXRD pattern.

Bioactivity-driven fungal metabologenomics identifies antiproliferative stemphone analogs and their biosynthetic gene cluster.

Introduction: Fungi biosynthesize chemically diverse secondary metabolites with a wide range of biological activities. Natural product scientists have increasingly turned towards bioinformatics approaches, combining metabolomics and genomics to target secondary metabolites and their biosynthetic machinery. We recently applied an integrated metabologenomics workflow to 110 fungi and identified more than 230 high-confidence linkages between metabolites and their biosynthetic pathways.

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies.

Wheldone is a fungal metabolite isolated from the coculture of and , displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.

A State of Independents: Rationalizing the High ' Crystal Structures of Shikimate Esters.

' is a parameter used to denote the number of symmetry-independent molecules in the asymmetric unit of a crystal structure. High ' (>1) crystal structures are relatively uncommon and are thought to arise through competition between intermolecular interactions of similar strength. As such high ' crystal structures are challenging to predict and new examples are valuable in improving understanding in the field.

High-throughput nanoscale crystallization of dihydropyridine active pharmaceutical ingredients.

Single-crystal X-ray diffraction analysis of small molecule active pharmaceutical ingredients is a key technique in the confirmation of molecular connectivity, including absolute stereochemistry, as well as the solid-state form. However, accessing single crystals suitable for X-ray diffraction analysis of an active pharmaceutical ingredient can be experimentally laborious, especially considering the potential for multiple solid-state forms (solvates, hydrates and polymorphs). In recent years, methods for the exploration of experimental crystallization space of small molecules have undergone a `step-change', resulting in new high-throughput techniques becoming available.

Improving the Conductivity of Amide-Based Small Molecules through Enhanced Molecular Packing and Their Application as Hole Transport Mediators in Perovskite Solar Cells.

Organic-inorganic hybrid halide perovskite solar cells (PSCs) have attracted substantial attention from the photovoltaic research community, with the power conversion efficiency (PCE) already exceeding 26%. Current state-of-the-art devices rely on Spiro-OMeTAD as the hole-transporting material (HTM); however, Spiro-OMeTAD is costly due to its complicated synthesis and expensive product purification, while its low conductivity ultimately limits the achievable device efficiency. In this work, we build upon our recently introduced family of low-cost amide-based small molecules and introduce a molecule (termed TPABT) that results in high conductivity values (∼10 S cm upon addition of standard ionic additives), outperforming our previous amide-based material (EDOT-Amide-TPA, ∼10 S cm) while only costing an estimated $5/g.

Reversible Pressure-Magnetic Modulation in a Tetrathiafulvalene-Based Dyad Piezochromic Dysprosium Single-Molecule Magnet.

The extreme sensitivity of trivalent lanthanide ions to crystal field variations led to the emergence of single-molecule magnetic switching under various stimuli. The use of pressure as an external stimulus instead of classic light irradiation, oxidation or any chemical reactions allows a fine tuning of the magnetic modulation. Here the well-known pure isotopically enriched [ Dy(tta) (L)]⋅C H ( Dy) Single-Molecule Magnet (SMM) (tta =2-2-thenoyltrifluoroacetonate and L=4,5-bis(propylthio)-tetrathiafulvalene-2-(2-pyridyl)benzimidazole-methyl-2-pyridine) was experimentally investigated by single-crystal diffraction and squid magnetometry under high applied pressures.

The structure of a pentachromium(II) extended metal atom chain at 3 K: Cotton's conjecture proven.

We provide definitive experimental proof that the archetypal string-like compound [Cr(tpda)(NCS)] has alternating long and short Cr-Cr separations in the solid state, as conjectured by F. A. Cotton, rather than essentially equally spaced Cr atoms, as initially claimed (Htpda = ,-di(pyridin-2-yl)pyridine-2,6-diamine).

Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355.

A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152.

Differentiable Formation of Chiroptical Lanthanide Heterometallic Ln Ln' (L ) (n=0-4) Tetrahedra with C -Symmetrical Bis(tridentate) Ligands.

Construction of lanthanide heterometallic complex is important for engineering multifunction molecular containers. However, it remains a challenge because of the similar ionic radii of lanthanides. Herein we attempt to prepare chiral lanthanide heterometallic tetrahedra.

The Role of the Fused Ring in Bicyclic Triazolium Organocatalysts: Kinetic, X-ray, and DFT Insights.

Bicyclic triazolium scaffolds are widely employed in -heterocyclic carbene (NHC) organocatalysis. While the incorporation of a fused ring was initially for synthetic utility in accessing chiral, modular triazolyl scaffolds, recent results highlight the potential for impact upon reaction outcome with the underpinning origins unclear. The common first step to all triazolium-catalyzed transformations is C(3)-H deprotonation to form the triazolylidene NHC.

Structural Diversity of Perylenequinones Is Driven by Their Redox Behavior.

Hypocrellins and hypomycins are two subclasses of fungal perylenequinones with unique structural, biological, and photochemical properties. With the growing interest in these naturally occurring photosensitizers, more studies were warranted to better understand the structural relationships between these two subclasses of perylenequinones. In this study, the long-postulated biosynthetic precursor () of class B fungal perylenequinones was isolated and characterized from a -like sp.

Low temperature insights into the crystal and magnetic structure of a neutral radical ferromagnet.

The crystal structure of the radical ferromagnet 1a at 2 K reveals a contraction in the unit cell constant which, at the molecular level, translates into a decrease in slippage of the radical π-stacks and an increase in ferromagnetic exchange interactions along the stacking axis. The results of BS-DFT calculations using long-range corrected functionals are consistent with an overall ferromagnetic topology.

Helicate-to-tetrahedron transformation of chiral lanthanide supramolecular complexes induced by ionic radii effect and linker length.

Controlled formation of desired lanthanide supramolecular complexes is challenging because of the difficulties in predicting coordination geometry, as well as a labile coordination number. Herein, we explore the effect of ionic radii and linker length on supramolecular species formation. A helicate-to-tetrahedron transformation occurred between [LnL1] and [LnL1] (Ln = La, Sm, Eu, Gd, Tb and Lu).

Structural investigations into a new polymorph of FTCNQ: towards enhanced semiconductor properties.

During the course of research into the structure of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (FTCNQ), CFN, an important compound in charge-transfer and organic semiconductor research, a previously unreported polymorph of FTCNQ was grown concomitantly with the known polymorph from a saturated solution of dichloromethane. The structure was elucidated using single-crystal X-ray diffraction and it was found that the new polymorph packs with molecules in parallel layers, in a similar manner to the layered structure of FTCNQ. The structure was analysed using Hirshfeld surface analysis, fingerprint plots and pairwise interaction energies, and compared to existing data.

Minimizing Polymorphic Risk through Cooperative Computational and Experimental Exploration.

We combine state-of-the-art computational crystal structure prediction (CSP) techniques with a wide range of experimental crystallization methods to understand and explore crystal structure in pharmaceuticals and minimize the risk of unanticipated late-appearing polymorphs. Initially, we demonstrate the power of CSP to rationalize the difficulty in obtaining polymorphs of the well-known pharmaceutical isoniazid and show that CSP provides the structure of the recently obtained, but unsolved, Form III of this drug despite there being only a single resolved form for almost 70 years. More dramatically, our blind CSP study predicts a significant risk of polymorphism for the related iproniazid.

Encapsulated Nanodroplet Crystallization of Organic-Soluble Small Molecules.

Single-crystal X-ray diffraction analysis (SCXRD) constitutes a universal approach for the elucidation of molecular structure and the study of crystalline forms. However, the discovery of viable crystallization conditions remains both experimentally challenging and resource intensive in both time and the quantity of analyte(s). We report a robot-assisted, high-throughput method for the crystallization of organic-soluble small molecules in which we employ only micrograms of analyte per experiment.

Trigonal to Pentagonal Bipyramidal Coordination Switching in a Co(II) Single-Ion Magnet.

In molecular magnetism and single-ion magnets in particular, the observation of slow relaxation of the magnetization is intimately linked to the coordination environment of the metal center. Such systems typically have blocking temperatures well below that of liquid nitrogen, and therefore detailed magnetic characterization is usually carried out at very low temperatures. Despite this, there has been little advantage taken of ultralow temperature single-crystal X-ray diffraction techniques that could provide a full understanding of the crystal structure in the same temperature regime where slow magnetic relaxation occurs.

Reducing the background of ultra-low-temperature X-ray diffraction data through new methods and advanced materials.

New methods and advanced materials that significantly reduce the background when collecting single-crystal X-ray diffraction data at ultra-low temperatures using a closed-cycle helium refrigerator are presented here. These include a magnetically controlled internal beamstop and a separate internal collimator that together completely remove the scattering contribution to the background from the beryllium vacuum chamber. Additionally, a new radiation shield made from flexible graphite significantly reduces the background and maintains excellent thermal properties.

Structural and Synthetic Insights into Pyridine Homocouplings Mediated by a β-Diketiminato Magnesium Amide Complex.

The reaction of [( Nacnac)Mg(TMP)] (1) with 4-subtituted pyridines proceeds via sequential regioselective metallation and 1,2-addition to furnish a range of symmetric 4,4'-R -2,2'-bipyridines in good yield, representing a new entry into bipyridine synthesis. Interestingly, the reaction of 1 with 2-OMe-pyridine led to formation of asymmetric bipyridine 6, resulting from the C6-magnesiation of the heterocycle followed by a C-C coupling step by addition to the C2 position of a second, non-metallated molecule, and subsequent elimination of [ NacnacMgOMe] (7). Synthesis combined with spectroscopic and structural analysis help rationalise the underlying processes resulting in the observed reactivity, and elucidate the key role that the sterically encumbered β-diketiminate ligand plays in determining regioselectivity.

Variation of M···H-C Interactions in Square-Planar Complexes of Nickel(II), Palladium(II), and Platinum(II) Probed by Luminescence Spectroscopy and X-ray Diffraction at Variable Pressure.

Luminescence spectra of isoelectronic square-planar d complexes with 3d, 4d, and 5d metal centers show d-d luminescence with an energetic order different from that of the spectrochemical series, indicating that additional structural effects, such as different ligand-metal-ligand angles, are important factors. Variable-pressure luminescence spectra of square-planar nickel(II), palladium(II), and platinum(II) complexes with dimethyldithiocarbamate ({CH}DTC) ligands and their deuterated analogues show unexpected variations of the shifts of their maxima. High-resolution crystal structures and crystal structures at variable pressure for [Pt{(CH)DTC}] indicate that intermolecular M···H-C interactions are at the origin of these different shifts.