Stacking Of Molecules Research Articles

Structure-based discovery of small molecules that disaggregate amyloid fibrils from post-mortem Alzheimer's and Parkinson's brains.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the consequences of neuronal death associated with the aggregation, respectively of proteins tau and alpha-synuclein into amyloid fibrils. Thus disaggregation of these fibrils could be therapeutic approaches to these conditions. The small molecule EGCG, abundant in green tea, has long been known to disaggregate amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain. To understand how EGCG can disaggregate stable fibrils, we have cryogenically trapped an intermediate of brain-extracted tau fibrils on the kinetic pathway to EGCG-induced disaggregation and have determined its cryoEM structure. The structure reveals that EGCG molecules stack in polar clefts between the paired helical protofilaments that pathologically define AD. Treating the EGCG binding position as a pharmacophore, we computationally screened thousands of drug-like compounds for compatibility for the pharmacophore, discovering several that experimentally disaggregate brain-derived tau fibrils in vitro and some that limit alpha-synuclein aggregation in vitro and in C. elegans. This work suggests the potential of structure-based, small-molecule drug discovery for amyloid diseases.

Flexible Optical Waveguides in Heterocyclic Schiff Base Self-Assembled Hydrogen-Bonded Solvates

Flexible fluorescent crystalline materials exhibit both mechanical and optical properties and have received great attention due to their potential applications in flexible optical devices. Simultaneously adjusting the mechanical and optical properties of crystalline materials remains interesting and challenging. In the present work, a guest molecule was introduced via hydrogen-bonded solvation, which achieved excellent mechanical elasticity and higher fluorescence emission than that of the host heterocyclic Schiff base molecule crystal itself. The crystal structure–property relationship and the molecular mechanism of the elasticity were then investigated in detail. It revealed that solvent molecules play a key role in changing both the stacking of fluorescent molecules and the interaction energy framework. In addition, the flexible fluorescent solvate exhibits a good waveguide property. A bent crystal was found to have a larger optical loss coefficient than a straight crystal. Furthermore, the size effect on the optical loss coefficient of the waveguide was discussed in which the optical loss coefficient decreases as the sizes increase. Such a size effect is usually neglected in waveguide material research and should be complemented in the performance evaluation of optical waveguides.

Crystal structure of deracoxib, C17H14F3N3O3S

The crystal structure of deracoxib has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Deracoxib crystallizes in space group Pbca (#61) with a = 9.68338(11), b = 9.50690(5), c = 38.2934(4) Å, V = 3525.25(3) Å3, and Z = 8. The molecules stack in layers parallel to the ab-plane. N–H⋯O hydrogen bonds link the molecules along the b-axis, in chains with the graph set C1,1(4), as well as more-complex patterns. N–H⋯N hydrogen bonds link the layers. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).

A highly ordered 8/1 helical pyramidal column self-organized from the crown conformation of achiral hexa(butyloxy)triphenylene

Liquid crystals of disc-like molecules are known for 45 years. 2,3,6,7,10,11-Hexakis(alkyloxy)triphenylene (HATn) containing n = 4 to 11 carbons in its achiral alkyl groups, represents one of the classic families of disc-like molecules. X-ray analysis suggested that disc-like molecules stack on top of each other at irregular spacing in columns distributed in the melt of their alkyl groups forming discotic or columnar or discotic nematic liquid crystals. Interest in discotic liquid crystals comes mostly from their conducting and photoconducting properties. While writing a recent perspective on the 45th anniversary of discotic liquid crystals we realized that the molecular structures of the 3D crystal and 2D liquid crystal phases of discotic molecules were never determined at the molecular level, in spite of the great interest in their physical properties. Since structure determines function, we decided to perform a detailed investigation of the molecular structure of HATn self-organizations by reconstructing their oriented fiber X-ray diffractograms both in the crystal and liquid crystal states. This communication reports the synthesis, analysis by differential scanning calorimetry of HATn containing n = 4 to 12 carbons in its achiral alkyl groups and the molecular structure of HAT4 in its crystal and liquid crystal states. Unexpectedly, a highly ordered 8/1 helical pyramidal crystalline column assembled from a crown-like conformation of the HAT4 and a non-helical column of the discotic liquid crystal state, the last similar to the original suggested supramolecular structure, were resolved for the first time at the molecular level. These preliminary results raise a lot of fundamental issues in the area of discotic and columnar self-organizations and of related helical columnar self-organizations generated with different building blocks and belonging to different disciplines. A comprehensive mechanistic elucidation of the molecular details of helical and non-helical self-organizations in synthetic complex systems may become as influential in the field of soft condensed matter as that of helical and non-helical self-organizations in the field of molecular biology.

Chiral binol-[4]helicene hybrids: Strong solid-state organic emitters with aggregation-enhanced emission and chiroptical properties

Chiral organic fluorescent materials have attracted broad attention for their application in various chiroptical devices. Helicenes possess special helical structure and unique optical properties, and have been utilized to develop chiral organic fluorescent materials with excellent chiroptical performance. However, the low luminescence efficiency of helicene-based chiral fluorescent materials in solid state limits their practical applications. In this work, chiral organic fluorescent emitters with helicene moiety have been developed from binaphthanol structure. These BINOL [4]helicene compounds display aggregation-enhanced emission properties, and have strong blue emission in solid state with fluorescent quantum yield up to 0.67. The DFT calculation reveals that these compounds have highly twisted molecular structures. Thus, the excellent fluorescent properties in solid state could be aroused by the highly contorted molecular structures, which could limit the π-π stacking of adjacent molecules in solid state. The enantiomers of these compounds show strong Cotton effects in circular dichroism spectra, and the molecules with 4-methoxy phenyl moiety exhibit circularly polarized luminescence properties.

Digital Twins Solve the Mystery of Raman Spectra of Parental and Reduced Graphene Oxides.

Digital Twins concept presents a new trend in virtual material science, common to all computational techniques. Digital twins, virtual devices and intellectual products, presenting the main constituents of the concept, are considered in detail on the example of a complex problem, which concerns an amazing identity of the D-G-doublet Raman spectra of parental and reduced graphene oxides. Digital twins, presenting different aspects of the GO and rGO structure and properties, were virtually synthesized using a spin-density algorithm emerging from the Hartree-Fock approximation. Virtual device presents AM1 version of the semi-empirical unrestricted HF approximation. The equilibrium structure of the twins as well as virtual one-phonon harmonic spectra of IR absorption and Raman scattering constitute a set of intellectual products. It was established that in both cases the D-G doublets owe their origin to the sp3 and sp2 C-C stretchings, respectively. This outwardly similar community reveals different grounds. Thus, multilayer packing of individual rGO molecules in stacks provides the existence of the sp3 D band in addition to sp2 G one. The latter is related to stretchings of the main pool of sp2 C-C bonds, while the sp3 constituent presents out-of-plane stretchings of dynamically stimulated interlayer bonds. In the GO case, the sp3 D component, corresponding to stretchings of the main pool of sp3 C-C bonds, is accompanied by an sp2 G component, which is related to stretchings of the remaining sp2 C-C bonds provided with the spin-influenced prohibition of the 100% oxidative reaction in graphene domain basal plane.

Label-free, rapid and ratiometric detection of tetracyclines via guest stacking-induced emission triggered by MXene-derived nanosensors

Facile, rapid and reliable detection of tetracyclines (TCs) residue in food and environment is of great significance to public safety. This work reports a novel guest stacking-induced emission (GSIE) effect triggered by MXene-derived nanosensors (TiO2/C quantum dots, QDs), which is used for label-free ratiometric fluorescence assays of TCs. The GSIE origin is revealed, which is the π-π stacking and J-aggregate formation of TCs molecules caused by the interaction of guest TCs with functionalized terminal groups of host TiO2/C QDs surface. Molecular planarity leads to the GSIE discrepancy of different TCs. The GSIE-based ratiometric fluorescence method is sensitive to TC with low limit of detection (32 nM) and shows excellent selectivity. The method is response-rapid (30 s) and linearly responsive in the ranges of 0.16–7.5 µM and 7.5–20 µM (R > 0.99), and can accurately detect trace TC in domestic water, honey and milk (recovery: 97.2–103.9 %). Furthermore, a paper microsensor-based point-of-care testing platform was developed for visual quantitative analysis and qualitative recognition of TCs. This is the first report that quantum dots as host sensors trigger the GSIE effect of guest molecules, and it creates a paradigm shift for MXene-based materials in sensing field and broadens the mechanism for TCs detection.

From Biomass to Functional Crystalline Diamond Nanothread: Pressure-Induced Polymerization of 2,5-Furandicarboxylic Acid.

2,5-Furandicarboxylic acid (FDCA) is one of the top-12 value-added chemicals from sugar. Besides the wide application in chemical industry, here we found that solid FDCA polymerized to form an atomic-scale ordered sp3-carbon nanothread (CNTh) upon compression. With the help of perfectly aligned π-π stacked molecules and strong intermolecular hydrogen bonds, crystalline poly-FDCA CNTh with uniform syn-configuration was obtained above 11 GPa, with the crystal structure determined by Rietveld refinement of the X-ray diffraction (XRD). The in situ XRD and theoretical simulation results show that the FDCA experienced continuous [4 + 2] Diels-Alder reactions along the stacking direction at the threshold C···C distance of ∼2.8 Å. Benefiting from the abundant carbonyl groups, the poly-FDCA shows a high specific capacity of 375 mAh g-1 as an anode material of a lithium battery with excellent Coulombic efficiency and rate performance. This is the first time a three-dimensional crystalline CNTh is obtained, and we demonstrated it is the hydrogen bonds that lead to the formation of the crystalline material with a unique configuration. It also provides a new method to move biomass compounds toward advanced functional carbon materials.

Rack-gear structures in columnar liquid crystal phases of trialkoxybenzyl pentafluorobenzoates and their influences on intercolumnar interdigitation and macroscopic morphologies

ABSTRACT In this study, 3,4,5-trialkoxybenzyl pentafluorbenzoates with alkyl chains of various lengths were synthesised, and the phase transition behaviours, liquid crystallinities, and molecular packing structures of their columnar phases were investigated. The results showed that discs comprising two half-discoid molecules stack up to form columns with rack-gear structures, generating columnar liquid crystal phases. From powder and single crystal X-ray diffraction investigation, the mechanism of the self-assembly of molecules into columns and their intercolumnar interdigitation was postulated. Furthermore, it was revealed that the combination of alkyl groups of the benzyl groups was closely related to the type of columnar liquid crystal phases generated and the macroscopic morphologies of the liquid crystal domains.

Cryo-EM of prion strains from the same genotype of host identifies conformational determinants.

Prion strains in a given type of mammalian host are distinguished by differences in clinical presentation, neuropathological lesions, survival time, and characteristics of the infecting prion protein (PrP) assemblies. Near-atomic structures of prions from two host species with different PrP sequences have been determined but comparisons of distinct prion strains of the same amino acid sequence are needed to identify purely conformational determinants of prion strain characteristics. Here we report a 3.2 Å resolution cryogenic electron microscopy-based structure of the 22L prion strain purified from the brains of mice engineered to express only PrP lacking glycophosphatidylinositol anchors [anchorless (a) 22L]. Comparison of this near-atomic structure to our recently determined structure of the aRML strain propagated in the same inbred mouse reveals that these two mouse prion strains have distinct conformational templates for growth via incorporation of PrP molecules of the same sequence. Both a22L and aRML are assembled as stacks of PrP molecules forming parallel in-register intermolecular β-sheets and intervening loops, with single monomers spanning the ordered fibril core. Each monomer shares an N-terminal steric zipper, three major arches, and an overall V-shape, but the details of these and other conformational features differ markedly. Thus, variations in shared conformational motifs within a parallel in-register β-stack fibril architecture provide a structural basis for prion strain differentiation within a single host genotype.

Discotic liquid crystals 45 years later. Dendronized discs and crowns increase liquid crystal complexity to columnar from spheres, cubic Frank-Kasper, liquid quasicrystals and memory-effect induced columnar-bundles

In 1977 Chandrasekhar laboratory reported the first examples of a new class of thermotropic liquid crystals self-organized from planar disc-like molecules substituted with alkyl groups. X-ray analysis demonstrated that these disc-like molecules stack on top of each other at irregular spacing in columns located in the paraffin melt of their alkyl groups. These supramolecular columns self-organize in a hexagonal array defined as the new thermotropic discotic or columnar hexagonal liquid crystal phase. This new thermotropic liquid crystal phase has translational periodicity in two dimensions and liquid-like disorder in the third one, along the column axis. In 2002 Bushby and Lozman dedicated a brief review article to the 25 anniversary of discotic liquid crystals. This review also included a brief discussion of supramolecular discs and columns self-organized from self-assembling dendrons and dendrimers. The current publication is not another review but a brief perspective on new liquid crystal phases self-organized from dendronized rigid planar and conformationally flexible discs as well as from crown-like molecules. Crown-like molecules are the most stable conformation of a transient unstable disc. All dendronized disc-like and crown molecules adopt a crown conformation that self-assemble helical columns and spherical helices. A large diversity of new liquid crystalline phases self-organize from these helical columns and spherical helices. They include helical columnar hexagonal phases from crowns and from supramolecular spheres, Frank-Kasper A15 (known as cubic phase of space group Pm3¯n), σ phase (also known as tetragonal of space group P42/mnm), 12-fold quasi liquid crystals (QLC) and supramolecular orientational memory (SOM) derived complex bundles of supramolecular columnar hexagonal arrays that are not yet completely elucidated. The impact of Chandrasekhar on the discovery of self-assembling dendrons and dendrimers via his biaxial nematic liquid crystal concept will also be discussed. This perspective is dedicated to the 45 anniversary of the discovery of discotic liquid crystals and to the memory of Professor Sivaramakrishna Chandrasekhar, a modest, respectful and great scientist.

Thermal and Structural Characterization of Two Crystalline Polymorphs of Tafamidis Free Acid.

Tafamidis, chemical formula C14H7Cl2NO3, is a drug used to delay disease progression in adults suffering from transthyretin amyloidosis, and is marketed worldwide under different tradenames as a free acid or in the form of its meglumine salt. The free acid (CAS no. 594839-88-0) is reported to crystallize as distinct (polymorphic) crystal forms, the thermal stability and structural features of which remained thus far undisclosed. In this paper, we present-by selectively isolating highly pure batches of Tafamidis Form 1 and Tafamidis Form 4-the full characterization of these solids, in terms of crystal structures (determined using state-of-the-art structural powder diffraction methods) and spectroscopic and thermal properties. Beyond conventional thermogravimetric and calorimetric analyses, variable-temperature X-ray diffraction was employed to measure the highly anisotropic response of these (poly)crystalline materials to thermal stimuli and enabled the determination of the linear and volumetric thermal expansion coefficients and of the related indicatrix. Both crystal phases are monoclinic and contain substantially flat and π-π stacked Tafamidis molecules, arranged as centrosymmetric dimers by strong O-H···O bonds; weaker C-H···N contacts give rise, in both polymorphs, to infinite ribbons, which guarantee the substantial stiffness of the crystals in the direction of their elongation. Complete knowledge of the structural models will foster the usage of full-pattern quantitative phase analyses of Tafamidis in drug and polymorphic mixtures, an important aspect in both the forensic and the industrial sectors.

Organic radicals stabilization above 300 °C in Eu-based coordination polymers for solar steam generation

Organic radicals feature unpaired electrons, and these compounds may have applications in biomedical technology and as materials for solar energy conversion. However, unpaired electrons tend to pair up (to form chemical bonds), making radicals unstable and hampering their applications. Here we report an organic radical system that is stable even at 350 °C, surpassing the upper temperature limit (200 °C) observed for other organic radicals. The system reported herein features a sulfur-rich organic linker that facilitates the formation of the radical centers; on the solid-state level, the molecules are crystallized with Eu(III) ions to form a 3D framework featuring stacks of linker molecules. The stacking is, however, somewhat loose and allows the molecules to wiggle and transform into sulfur-stabilized radicals at higher temperatures. In addition, the resulting solid framework remains crystalline, and it is stable to water and air. Moreover, it is black and features strong broad absorption in the visible and near IR region, thereby enhancing both photothermal conversion and solar-driven water evaporation.

Crystal structure of imepitoin, C13H14ClN3O2

The crystal structure of imepitoin has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Imepitoin crystallizes in space group Pbca (#61) with a = 12.35541(2), b = 28.43308(8), c = 7.340917(7) Å, V = 2578.882(7) Å3, and Z = 8. The roughly planar molecules stack along the c-axis. There are no traditional hydrogen bonds in the structure, but several intramolecular and intermolecular C–H⋯O, C–H⋯N, and C–H⋯Cl hydrogen bonds contribute to the crystal energy. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).

Crystal structure of bis-{4-[(4-methyl-benz-yl)-oxy]-N'-(4-methyl-benzyl-idene)benzohydrazidato}nickel(II).

In the title complex, [Ni(C23H21N2O2)2], the central NiII atom is located on an inversion centre and exhibits a slightly distorted square-planar N2O2 coordination environment. A trans-configuration of the N,O chelating ligands results from the imposed site symmetry of the central NiII atom. In the crystal, individual mol-ecules stack along the a axis through weak π-π stacking inter-actions between the phenyl rings.

Electrospun Lignin-Based Phase-Change Nanofiber Films for Solar Energy Storage

Functional materials for solar energy collection, conversion, and storage need to be developed to address the global energy crisis. In this study, phase-change nanofiber films [PCNFs, sodium lignosulfonate (SLS)/polyvinyl alcohol (PVA)/polyethylene glycol (PEG)], which maintain their shape, were developed for solar-to-thermal energy conversion and storage. The films were constructed by electrospinning with PEG as the phase-change material, SLS/PVA mixture as the supporting matrix, and SLS as the photothermal material. SLS effectively improved the supporting property of the PCNFs owing to sturdy hydrogen bonds and electrostatic entanglement between its macromolecule chains and PVA/PEG, which prevented the leakage and transfer issue for PEG. Moreover, the PCNFs showed excellent solar-to-thermal energy conversion and storage ability, attributed to the π–π stacking of SLS molecules and the phase-change process, respectively. The SLS/PVA/PEG film with a PEG content of 32.43% exhibited a diameter of 465 ± 109 nm and a latent heat of fusion of 42.16 J·g–1, with a phase-change temperature of 45.20 °C. The film showed favorable stability over 50 heating–cooling cycles, thermal stability below 220 °C, good shape stability, and a solar-thermal energy conversion and storage efficiency of 18.03%. This study demonstrates a potential route to improve the utilization of lignin and solar energy and promotes the development of sustainable energy.

Structure-based discovery of small molecules that disaggregate Alzheimer’s disease tissue derived tau fibrils in vitro

Alzheimer’s disease (AD) is the consequence of neuronal death and brain atrophy associated with the aggregation of protein tau into fibrils. Thus disaggregation of tau fibrils could be a therapeutic approach to AD. The small molecule EGCG, abundant in green tea, has long been known to disaggregate tau and other amyloid fibrils, but EGCG has poor drug-like properties, failing to fully penetrate the brain. Here we have cryogenically trapped an intermediate of brain-extracted tau fibrils on the kinetic pathway to EGCG-induced disaggregation and have determined its cryoEM structure. The structure reveals that EGCG molecules stack in polar clefts between the paired helical protofilaments that pathologically define AD. Treating the EGCG binding position as a pharmacophore, we computationally screened thousands of drug-like compounds for compatibility for the pharmacophore, discovering several that experimentally disaggregate brain-derived tau fibrils in vitro. This work suggests the potential of structure-based, small-molecule drug discovery for amyloid diseases.

Hydrothermal synthesis, crystal structure and photoluminescent properties of 2D layered zinc phosphate intercalated with 4,4ˈbiphenyl dicarboxylic acid (ZnPO-BDA)

Herein, we report a new inorganic-organic hybrid, (H3tren)2⸱[Zn3(PO4)4(BDA)]⸱xH2O (ZnPO-BDA) prepared under hydrothermal conditions. This hybrid structure of zinc phosphate layers pillared with 4,4′-biphenyl-dicarboxylic acid (BDA) was characterized by single-crystal X-ray diffraction. The compound, ZnPO-BDA, crystallizes in the monoclinic crystal system (space group C2) with a = 14.9348(3) Å, b = 8.7058(2) Å, c = 17.6455(5) Å, β = 111.6760(10), V = 2132.02(9) Å3, Z = 2. The crystalline host of the 2D zinc phosphate framework was built with vertex linked ZnO4 and PO4 tetrahedra and anchored with tris(2-aminoethyl)amine (H3tren). Biphenyl dicarboxylic acid (BDA) molecules stack between the phosphate framework layers by means of strong hydrogen bonding, resulting in an interlayer distance of 16.4 Å. ZnPO-BDA displayed blue photoluminescence with an emission maximum at 404 nm on photoexcitation at 340 nm.

105 K Wide Room Temperature Spin Transition Memory Due to a Supramolecular Latch Mechanism

Little is known about the mechanisms behind the bistability (memory) of molecular spin transition compounds over broad temperature ranges (>100 K). To address this point, we report on a new discrete FeII neutral complex [FeIIL2]0 (1) based on a novel asymmetric tridentate ligand 2-(5-(3-methoxy-4H-1,2,4-triazol-3-yl)-6-(1H-pyrazol-1-yl))pyridine (L). Due to the asymmetric cone-shaped form, in the lattice, the formed complex molecules stack into a one-dimensional (1D) supramolecular chain. In the case of the rectangular supramolecular arrangement of chains in methanolates 1-A and 1-B (both orthorhombic, Pbcn) differing, respectively, by bent and extended spatial conformations of the 3-methoxy groups (3MeO), a moderate cooperativity is observed. In contrast, the hexagonal-like arrangement of supramolecular chains in polymorph 1-C (monoclinic, P21/c) results in steric coupling of the transforming complex species with the peripheral flipping 3MeO group. The group acts as a supramolecular latch, locking the huge geometric distortion of complex 1 and in turn the trigonal distortion of the central FeII ion in the high-spin state, thereby keeping it from the transition to the low-spin state over a large thermal range. Analysis of the crystal packing of 1-C reveals significantly changing patterns of close intermolecular interactions on going between the phases substantiated by the energy framework analysis. The detected supramolecular mechanism leads to a record-setting robust 105 K wide hysteresis spanning the room temperature region and an atypically large TLIESST relaxation value of 104 K of the photoexcited high-spin state. This work highlights a viable pathway toward a new generation of cleverly designed molecular memory materials.

Modulation of the Fluorination Site on Side-Chain Thiophene Improved Efficiency in All-Small-Molecule Organic Solar Cells.

Fine-tuning the phase-separated morphology is of great importance to achieve efficient all-small-molecule organic solar cells (ASM-OSCs). In this work, a pair of isomers are designed and synthesized, namely, BDT-UF and BDT-DF, in which the fluorine atom in BDT-UF is close to the alkyl chain of side-chain thiophene, while that in BDT-DF is close to the center core. Owing to the noncovalent interaction between fluorine and hydrogen, BDT-DF shows a smaller dihedral angle between the thiophene side chain and the BDT core, which causes better molecular planarity. When mixed with N3, BDT-UF shows better miscibility, higher crystallinity, and more ordered molecule stacking in the blend film. Finally, the device of BDT-DF:N3 gains a power conversion efficiency (PCE) of 14.5%, while that of BDT-UF:N3 shows an increase in Voc, Jsc, and FF and gains a PCE of 15.1%. Our work exhibits a way of adjusting the substitution site of fluorine atoms to improve the PCE of ASM-OSCs.