Helical Assembly Research Articles

Tripodal 1,3,5-benzenetricarboxamide ligand with dipicolinic acid units and its binding with Eu(III) ions

ABSTRACT The synthesis and characterisation of tripodal ligand 1 containing 1,3,5-benzenetricarboxamide core and diethyl 4-(phenylethynyl)pyridine-2,6-dicarboxylate is described. The crystal structure of the intermediate tripodal molecule 7 exhibits an unusual staggered hydrogen-bonded chain motif instead of the anticipated helical assembly. We studied the basic photophysical properties of 1 in solvents of various polarity including CH3OH, CH3CN, DMSO, and CHCl3. The self-assembly experiments between 1 and Eu(CF3SO3)3⋅6H2O confirmed the formation of metal-ligand self-assembly species in the solution of CH3CN. It was also shown that the excitation of the Eu(III)-centred emission in such species occurred through the energy transfer from the ligand acting as an antenna to the metal centre. The binding constant values were evaluated using the nonlinear regression analysis software SPECFIT®, and their values correspond to those previously observed for the assemblies between 2,6-dipicolinic acid derivatives and lanthanide ions.

Numerical Investigation on Transverse Flow of Helical Cruciform Fuel Rod Assembly in a Lead-Bismuth Cooled Fast Reactor

Numerical Investigation on Transverse Flow of Helical Cruciform Fuel Rod Assembly in a Lead-Bismuth Cooled Fast Reactor

Tuneable helices of plasmonic nanoparticles using liquid crystal templates: molecular dynamics investigation of an unusual odd-even effect in liquid crystalline dimers.

Liquid crystalline (LC) dimers formed helical nanofilaments depending on the parity of the alkyl linker, revealing an unusual odd-even effect. Molecular dynamics simulations were used to investigate the observed tendency. Elongation of the linker translates to an increase of the pitch of the helices, which allows achieving tuneable helical assemblies of Au nanoparticles doped to the LC matrix. The impact of the tuneable pitch of helices on the chiral optical properties of composites was investigated with full-wave simulations based on the T-matrix method.

Atomic insight into short helical peptide comprised of consecutive multiple aromatic residues.

The occurrence of sequential multiple aromatic residues in a helical sequence is rare compared to the β-sheet rich structure. Here, using helix promoting α-aminoisobutyric acid (Aib) residues, we unravel atomistic details of the helical secondary structure formation and the super helical assembly of two heptapeptides composed of sequential five and six phenylalanine (Phe) residues.

Mechanical properties of biomimetic ceramic with Bouligand architecture

AbstractBiomimetic Bouligand architecture is constructed in the ceramic to improve its toughness. Firstly, unidirectional carbon fiber‐reinforced ZrB2‐SiC ceramic films are achieved through a vacuum‐assisted filtration method using graphene oxide. Then, ceramic films are helically assembled at a fixed angle of 30° in the graphite die based on the fiber orientation. Finally, the spark plasma sintering method was utilized to densify helical assembly carbon fiber/ceramic films. By constructing Bouligand structure, high fracture toughness (7.4 MPa·m0.5) and work of fracture (∼1055 J/m2) are achieved in ZrB2‐based ceramic. The toughening mechanisms mainly are crack deflection, twisting and branching, carbon fiber pulling out, and bridging.

Target site selection and remodelling by type V CRISPR-transposon systems.

Canonical CRISPR-Cas systems provide adaptive immunity against mobile genetic elements1. However, type I-F, I-B and V-K systems have been adopted by Tn7-like transposons to direct RNA-guided transposon insertion2-7. Type V-K CRISPR-associated transposons rely on the pseudonuclease Cas12k, the transposase TnsB, the AAA+ ATPase TnsC and the zinc-finger protein TniQ7, but the molecular mechanism of RNA-directed DNA transposition has remained elusive. Here we report cryo-electron microscopic structures of a Cas12k-guide RNA-target DNA complex and a DNA-bound, polymeric TnsC filament from theCRISPR-associated transposon system of the photosynthetic cyanobacterium Scytonema hofmanni. The Cas12k complex structure reveals an intricate guide RNA architecture and critical interactions mediating RNA-guided target DNA recognition. TnsC helical filament assembly is ATP-dependent and accompanied by structural remodelling of the bound DNA duplex. In vivo transposition assays corroborate key features of the structures, and biochemical experiments show that TniQ restricts TnsC polymerization, while TnsB interacts directly with TnsC filaments to trigger their disassembly upon ATP hydrolysis. Together, these results suggest that RNA-directed target selection by Cas12k primes TnsCpolymerization and DNAremodelling, generating a recruitment platform for TnsB to catalyse site-specific transposon insertion. Insights from this work will inform thedevelopment of CRISPR-associated transposons as programmable site-specific gene insertion tools.

C-amidation of substituted β 3 oligoamides yields novel supramolecular assembly motif

N-acylated substituted β 3 oligoamides are known to form unique supramolecular nanorods based on a 3-point hydrogen bond self-assembly motif. This motif is an intermolecular extension of the hydrogen bonding network that stabilizes the 14-helix secondary structure unique to β 3 oligoamides. Acetylation of the N-terminus of the molecule provides the necessary third hydrogen bond pair of the motif. Here, the possibility of introducing the third hydrogen bond pair via amidation of the C terminus is investigated. While similar in purpose, this modification introduces a chemically distinct new self-assembly motif, also removing the bulky carboxyl group that does not fold into the 14 helix positioning instead as a side chain. Three substituted β 3 oligoamide variants with the base sequence LIA (where the letters denote β 3 residues with side chains analogous to α amino acids) were compared: N-acylated Ac-β 3[LIA] as a reference, C-amidated β 3[LIA]-CONH2, and β 3[LIA] with free unmodified N and C termini as a negative control. The three variants were dissolved in water to promote self-assembly. The self-assembly was characterised using mid- and far-infrared spectroscopy, small angle x-ray scattering (SAXS) and atomic force microscopy (AFM). IR measurements confirmed that all three samples were in a similar conformation, consistent with pseudo 14-helical secondary structures. Far-infrared spectroscopy measurements of β 3[LIA]-CONH2 showed distinct peaks consistent with highly organised skeletal modes, i.e. regular supramolecular assembly, that was largely absent from the other two oligoamides. Modelling of SAXS data is consistent with elliptical cylinder structures resulting from nanorod bundling for both β 3[LIA]-CONH2 and Ac-β 3[LIA], but not in the unmodified sample. Consistently, AFM imaging showed large nanorod bundling structures in β 3[LIA]-CONH2, varied bundling structures in Ac-β 3[LIA], and only aggregation in β 3[LIA]. Amidation showed much more organised and robust assembly compared to acetylation, providing a new, easy to synthesize self-assembly motif for helical nanorod assembly that is similar but distinct to N-acylation

Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome

NLRP6 is important in host defense by inducing functional outcomes including inflammasome activation and interferon production. Here, we show that NLRP6 undergoes liquid-liquid phase separation (LLPS) upon interaction with double-stranded RNA (dsRNA) invitro and in cells, and an intrinsically disordered poly-lysine sequence (K350-354) of NLRP6 is important for multivalent interactions, phase separation, and inflammasome activation. Nlrp6-deficient or Nlrp6K350-354A mutant mice show reduced inflammasome activation upon mouse hepatitis virus or rotavirus infection, and in steady state stimulated by intestinal microbiota, implicating NLRP6 LLPS in anti-microbial immunity. Recruitment of ASC via helical assembly solidifies NLRP6 condensates, and ASC further recruits and activates caspase-1. Lipoteichoic acid, a known NLRP6 ligand, also promotes NLRP6 LLPS, and DHX15, a helicase in NLRP6-induced interferon signaling, co-forms condensates with NLRP6 and dsRNA. Thus, LLPS of NLRP6 is a common response to ligand stimulation, which serves to direct NLRP6 to distinct functional outcomes depending on the cellular context.

An Accelerated Modular-Orthogonal Ni-Catalyzed Methodology to Symmetric and Nonsymmetric Constitutional Isomeric AB2 to AB9 Dendrons Exhibiting Unprecedented Self-Organizing Principles.

Five libraries of natural and synthetic phenolic acids containing five AB3, ten constitutional isomeric AB2, one AB4, and one AB5 were previously synthesized and reported by our laboratory in 5 to 11 steps. They were employed to construct seven libraries of self-assembling dendrons, by divergent generational, deconstruction, and combined approaches, enabling the discovery of a diversity of supramolecular assemblies including Frank-Kasper phases, soft quasicrystals, and complex helical organizations, some undergoing deracemization in the crystal state. However, higher substitution patterns within a single dendron were not accessible. Here we report three libraries consisting of 30 symmetric and nonsymmetric constitutional isomeric phenolic acids with unprecedented sequenced patterns, including two AB2, three AB3, eight AB4, five AB5, six AB6, three AB7, two AB8, and one AB9 synthesized by accelerated modular-orthogonal Ni-catalyzed borylation and cross-coupling. A single etherification step with 4-(n-dodecyloxy)benzyl chloride transformed all these phenolic acids, of interest also for other applications, into self-assembling dendrons. Despite this synthetic simplicity, they led to a diversity of unprecedented self-organizing principles: lamellar structures of interest for biological membrane mimics, helical columnar assemblies from rigid-solid angle dendrons forming Tobacco Mosaic Virus-like assemblies, columnar organizations from adaptable-solid angle dendrons forming disordered micellar-like nonhelical columns, columns from supramolecular spheres, five body-centered cubic phases displaying supramolecular orientational memory, rarely encountered in previous libraries forming predominantly Frank-Kasper phases, and two Frank-Kasper phases. Lessons from these self-organizing principles, discovered within a single generation of self-assembling dendrons, may help elaborate design principles for complex helical and nonhelical organizations of synthetic and biological matter.

A structural model of a Ras-Raf signalosome.

The protein K-Ras functions as a molecular switch in signaling pathways regulating cell growth. In the human mitogen-activated protein kinase (MAPK) pathway, which is implicated in many cancers, multiple K-Ras proteins are thought to assemble at the cell membrane with Ras effector proteins from the Raf family. Here we propose an atomistic structural model for such an assembly. Our starting point was an asymmetric guanosine triphosphate-mediated K-Ras dimer model, which we generated using unbiased molecular dynamics simulations and verified with mutagenesis experiments. Adding further K-Ras monomers in a head-to-tail fashion led to a compact helical assembly, a model we validated using electron microscopy and cell-based experiments. This assembly stabilizes K-Ras in its active state and presents composite interfaces to facilitate Raf binding. Guided by existing experimental data, we then positioned C-Raf, the downstream kinase MEK1 and accessory proteins (Galectin-3 and 14-3-3σ) on and around the helical assembly. The resulting Ras-Raf signalosome model offers an explanation for a large body of data on MAPK signaling.

Plasmonic Enhancement of Chiroptical Property in Enantiomers Using a Helical Array of Magnetoplasmonic Nanoparticles for Ultrasensitive Chiral Recognition.

Recognition of enantiomeric molecules is essential in pharmaceutical and biomedical applications. In this Article, a novel approach is introduced to monitor chiral molecules via a helical magnetic field (hB), where chiral-inactive magnetoplasmonic nanoparticles (MagPlas NPs, Ag@Fe3O4 core-shell NPs) are assembled into helical nanochain structures to be chiral-active. An in-house generator of hB-induced chiral NP assembly, that is, a plasmonic chirality enhancer (PCE), is newly fabricated to enhance the circular dichroism (CD) signals from chiral plasmonic interaction of the helical nanochain assembly with circularly polarized light, reaching a limit of detection (LOD) of 10-10 M, a 1000-fold enhancement as compared to that of conventional CD spectrometry. These enhancements were successfully observed from enantiomeric molecules, oligomers, polymers, and drugs. Computational simulation studies also proved that total chiroptical properties of helical plasmonic chains could be readily changed by modifying the chiral structure of the analytes. The proposed PCE has the potential to be used as an advanced tool for qualitative and quantitative recognition of chiral materials, enabling further application in pharmaceutical and biomedical sensing and imaging.

Python-based Helix Indexer: A graphical user interface program for finding symmetry of helical assembly through Fourier-Bessel indexing of electron microscopic data.

Many macromolecules form helical assemblies to carry out their functions. Helical reconstruction from electron microscopic images is a powerful approach for solving high-resolution structures of such assemblies. Determination of the symmetry parameters of the helical assemblies is a prerequisite step in helical reconstruction. The most widely used method for deducing the symmetry is through Fourier-Bessel indexing the diffraction pattern of the helical assemblies. This method, however, often leads to incorrect solutions, due to intrinsic ambiguities in indexing helical diffraction patterns. Here, we present Python-based Helix Indexer (PyHI), which provides a graphical user interface (GUI) to guide the users through the process of symmetry determination. Diffraction patterns can be read into the program directly or calculated on the fly from two-dimensional class averages of helical assemblies. PyHI allows deducing the Bessel orders of diffraction peaks by using both the amplitudes and phases of the diffraction data. Based on the Bessel orders of two unit vectors, the Fourier space lattice is constructed with minimal user inputs. The program then uses a refinement algorithm to optimize the Fourier space lattice, and subsequently generate the helical assembly in real space. The program provides both a publication-quality graphic representation of the helical assembly and the symmetry parameters required for subsequent helical reconstruction steps.

Synthesis of coordination polymers based on a 2,2′-dimethoxy-1,1′-biphenyl scaffold and Hg(II), Co(II), or Zn(II)

In this study, 3,3′-di(pyridin-4-yl)-(2,2′-dimethoxy-[1,1′-biphenyl]) (L) was synthetized, structurally characterized by X-ray crystallography and combined with HgCl2, CoCl2, or ZnSiF6 for the formation of three coordination polymers ((HgCl2)2(L), (CoCl2)2(L)2.CHCl3, and Zn(SiF6)(L)2). The crystal structures of synthesis compound indicate the formation of different types of coordination modes, and each adopts a mono (1D) or tri-dimensional (3D) framework by C–H···π interactions. In (CoCl2)2(L)2, the combination of Co(II) with L forms a metallo-macrocycle, while in the other compounds two helical infinite networks were characterized. Compounds (HgCl2)2(L) made of two helical chains with opposite chirality (P and M), and Zn(SiF6)(L)2 exhibits helical tubular assemblies of the L attached to two Zn(SiF6)∞ pillars. This work may pave the way to further study the chemical, structural and physicochemical properties of metal-organic coordination polymers.

Helical Chirality of Supramolecular Columns and Spheres Self‐Organizes Complex Liquid Crystals, Crystals, and Quasicrystals

AbstractHomochiral helical self‐organizations provide some of the most fundamental architectures of biological macromolecules and of their co‐assemblies although they were first discovered and elucidated only during the early 1950. Helical synthetic covalent macromolecules started to be discovered soon after and were followed by supramolecular macromolecules and their co‐assemblies few decades later. This perspective will provide a brief historical development of chiral helical self‐organizations in biology and in supramolecular chemistry. Helical covalent and supramolecular macromolecules self‐organize and co‐organize helical supramolecular columns and spherical helices that can generate complex liquid crystals, crystals including Frank‐Kasper phases, and quasicrystals. The design of new functions based on synthetic helical assemblies will also be discussed. Personal events from the life of scientists contributing to these developments are also briefly mentioned.

Nanoscale Bouligand Multilayers: Giant Circular Dichroism of Helical Assemblies of Plasmonic 1D Nano-Objects.

Chirality is found at all length scales in nature, and chiral metasurfaces have recently attracted attention due to their exceptional optical properties and their potential applications. Most of these metasurfaces are fabricated by top-down methods or bottom-up approaches that cannot be tuned in terms of structure and composition. By combining grazing incidence spraying of plasmonic nanowires and nanorods and Layer-by-Layer assembly, we show that nonchiral 1D nano-objects can be assembled into scalable chiral Bouligand nanostructures whose mesoscale anisotropy is controlled with simple macroscopic tools. Such multilayer helical assemblies of linearly oriented nanowires and nanorods display very high circular dichroism up to 13 000 mdeg and giant dissymmetry factors up to g ≈ 0.30 over the entire visible and near-infrared range. The chiroptical properties of the chiral multilayer stack are successfully modeled using a transfer matrix formalism based on the experimentally determined properties of each individual layer. The proposed approach can be extended to much more elaborate architectures and gives access to template-free and enantiomerically pure nanocomposites whose structure can be finely tuned through simple design principles.

The Role of the 1,2,3-Triazolyl Heterocycle in the Helical Columnar Assembly and Electric Field Response

Here, we have proven the role of the 1,2,3-triazolyl group in the helical assembly and electric field (E-field) response upon comparing liquid crystal analogs 1 and 2 based on 1,2,3-triazolyl and 1,3,4-oxadiazolyl linkers, respectively. An ordered helical column was only observed in 1, driven by the hydrogen-bonding interactions between the adjacent triazolyl nitrogen and hydrogen atoms. X-ray diffraction and energy simulations indicate that the helical column is a 112 helix and the helical axis does not coincide with the center of the molecular long axis. The key for the formation of the helical column is the tilted conformation of 1 originating from the steric repulsion between the triazolyl C-H and C-H of the aromatic core. Analysis of the dynamics in the simple hexagonal columnar phase revealed that the in-plane rotational motion of the triazolyl linker (1) is allowed, while the oxadiazolyl linker of 2 has limited conformational flexibility. A uniform alignment under an E-field only occurs in 1, demonstrating the requirement for conformational flexibility in the polar linker. This alignment enhances the electric conductance of 1 by approximately two-fold.

2D and 3D Structuring of Freestanding Metallic Wires Enabled by Room-Temperature Welding for Soft and Stretchable Electronics.

In this work, a facile and cost-effective approach to assemble metallic wires into two-dimensional (2D) and three-dimensional (3D) freestanding geometries by room-temperature welding is demonstrated. The low melting point of gallium (29.8 °C) enables the welding at room temperature without the aid of high-energy sources required for high-melting-point metals and alloys. The welding enables assembly of solid gallium wires into 2D and 3D geometries that could create freestanding architectures with multiple junctions along any inclined direction. These 2D and 3D freestanding metallic structures are freeze-cast in soft elastomers to obtain stretchable and soft devices: a 2D stretchable resistive and capacitive sensor patterned with parallel metal lines, a 2D stretchable capacitive sensor patterned with an interdigitated metal structure with capacitive changes on stretching in both x- and y-axes, and a 3D compressive sensor by assembly of liquid metal helices, which could sense foot pressure compression. We also developed a facile method to interconnect between soft circuits and external electronics, suppressing stress during mechanical deformation.

CryoEM structure of the Nipah virus nucleocapsid assembly.

Nipah and its close relative Hendra are highly pathogenic zoonotic viruses, storing their ssRNA genome in a helical nucleocapsid assembly formed by the N protein, a major viral immunogen. Here, we report the first cryoEM structure for a Henipavirus RNA-bound nucleocapsid assembly, at 3.5 Å resolution. The helical assembly is stabilised by previously undefined N- and C-terminal segments, contributing to subunit-subunit interactions. RNA is wrapped around the nucleocapsid protein assembly with a periodicity of six nucleotides per protomer, in the "3-bases-in, 3-bases-out" conformation, with protein plasticity enabling non-sequence specific interactions. The structure reveals commonalities in RNA binding pockets and in the conformation of bound RNA, not only with members of the Paramyxoviridae family, but also with the evolutionarily distant Filoviridae Ebola virus. Significant structural differences with other Paramyxoviridae members are also observed, particularly in the position and length of the exposed α-helix, residues 123-139, which may serve as a valuable epitope for surveillance and diagnostics.

STEM Tomography of Au Helical Assemblies.

Composite, helical nanostructures formed using cooperative interactions of liquid crystals and Au nanoparticles were studied using a scanning transmission electron microscopy (STEM) mode. The investigated helical assemblies exhibit long-range hierarchical order across length scales, as a result of the crystallization (freezing) directed growth mechanism of nanoparticle-coated twisted nanoribbons and their ability to form organized bundles. Here, STEM methods were used to reproduce the 3D structure of the Au nanoparticle double helix.

Double-helical assembly of heterodimeric nanoclusters into supercrystals.

DNA has long been used as a template for the construction of helical assemblies of inorganic nanoparticles1-5. For example, gold nanoparticles decorated with DNA (or with peptides) can create helical assemblies6-9. But without such biological ligands, helices are difficult to achieve and their mechanism of formation is challenging to understand10,11. Atomically precise nanoclusters that are protected by ligands such as thiolate12,13 have demonstrated hierarchical structural complexity in their assembly at the interparticle and intraparticle levels, similar to biomolecules and their assemblies14. Furthermore, carrier dynamics can be controlled by engineering the structure of the nanoclusters15. But these nanoclusters usually have isotropic structures16,17 and often assemble into commonly found supercrystals18. Here we report the synthesis of homodimeric and heterodimeric gold nanoclusters and their self-assembly into superstructures. While thehomodimeric nanoclusters form layer-by-layer superstructures, the heterodimeric nanoclusters self-assemble into double- and quadruple-helical superstructures. These complex arrangements are the result of two different motif pairs, one pair per monomer, where each motif bonds with its paired motif on a neighbouring heterodimer. This motif pairing is reminiscent of the paired interactions of nucleobases in DNA helices. Meanwhile, the surrounding ligands on the clusters show doubly or triply paired steric interactions. The helical assembly is driven by van der Waals interactions through particle rotation and conformational matching. Furthermore, the heterodimeric clusters have a carrier lifetime that is roughly 65 times longer than that of the homodimeric clusters. Our findings suggest new approaches for increasing complexity in the structural design and engineering of precision in supercrystals.