High-Speed Atomic Force Microscopy Reveals the Nucleosome Sliding and DNA Unwrapping/Wrapping Dynamics of Tail-less Nucleosomes.

Each nucleosome contains four types of histone proteins, each with a histone tail. These tails are essential for the epigenetic regulation of gene expression through post-translational modifications (PTMs). However, their influence on nucleosome dynamics at the single-molecule level remains undetermined. Here, we employed high-speed atomic force microscopy to visualize nucleosome dynamics in the absence of the N-terminal tail of each histone or all of the N-terminal tails. Loss of all tails stripped 6.7 base pairs of the nucleosome from the histone core, and the DNA entry-exit angle expanded by 18° from that of wild-type nucleosomes. Tail-less nucleosomes, particularly those without H2B and H3 tails, showed a 10-fold increase in dynamics, such as nucleosome sliding and DNA unwrapping/wrapping, within 0.3 s, emphasizing their role in histone-DNA interactions. Our findings illustrate that N-terminal histone tails stabilize the nucleosome structure, suggesting that histone tail PTMs modulate nucleosome dynamics.

Exciplex Formation by Complexation of an Electron-Accepting Guest in an Electron-Donating Pillar[5]arene Host Liquid.

We present a novel system, a liquid-state pillar[5]arene decorated with tri(ethylene oxide) chains, that brings electron-donor and electron-acceptor molecules into proximity for efficient exciplex formation. The electron-accepting guests exhibit a blue-purple emission from a localized excited state upon excitation in common solvents. However, directly dissolving the guests in the electron-donating pillar[5]arene liquid (a bulk system) results in visible green emission from the formed exciplexes. In the bulk system, the guest molecules are always surrounded by excess pillar[5]arene molecules, resulting in the formation of mainly inclusion-type exciplexes. In the bulk system, energy migration occurs between the pillar[5]arene molecules. Excitation of the pillar[5]arenes results in a more intense green exciplex emission than that observed upon direct excitation of the guests. In summary, the pillar[5]arene liquid is a novel system for achieving efficient exciplex formation and energy migration that is different from typical solvent and solid systems.

High-Speed Atomic Force Microscopy Reveals Spontaneous Nucleosome Sliding of H2A.Z at the Subsecond Time Scale.

Nucleosome dynamics, such as nucleosome sliding and DNA unwrapping, are important for gene regulation in eukaryotic chromatin. H2A.Z, a variant of histone H2A that is highly evolutionarily conserved, participates in gene regulation by forming unstable multipositioned nucleosomes in vivo and in vitro. However, the subsecond dynamics of this unstable nucleosome have not been directly visualized under physiological conditions. Here, we used high-speed atomic force microscopy (HS-AFM) to directly visualize the subsecond dynamics of human H2A.Z.1-nucleosomes. HS-AFM videos show nucleosome sliding along 4 nm of DNA within 0.3 s in any direction. This sliding was also visualized in an H2A.Z.1 mutant, in which the C-terminal half was replaced by the corresponding canonical H2A amino acids, indicating that the interaction between the N-terminal region of H2A.Z.1 and the DNA is responsible for nucleosome sliding. These results may reveal the relationship between nucleosome dynamics and gene regulation by histone H2A.Z.

Orientational Control of Circularly Polarized Luminescence from Pyrene Clusters by Using a DNA Scaffold.

We have investigated the chiroptical activities of pyrene clusters incorporated within a DNA duplex. Three pyrene derivatives were prepared on d-threoninol linkers to allow incorporation within a DNA strand. DNA scaffolds containing dimers, tetramers, and hexamers of the pyrene derivatives were prepared. The homodimers of 1- and of 4-pyrenecarboxylic acid, but not 2-pyrenecarboxylic acid, emitted intense circularly polarized luminescence signals. Although increasing the number of pyrene units weakened the signal, insertion of natural base pairs between two dimers enhanced its intensity. Interestingly, circularly polarized luminescence intensities varied non-monotonically depending on the number of intervening base pairs, thus indicating the importance of orientation between pyrene dimers. The results presented here could lead to the development of bright circularly polarized luminescence materials and probes.

Orientational Control of Circularly Polarized Luminescence from Pyrene Clusters by Using a DNA Scaffold.

Invited for the cover of this issue is the group of Hiromu Kashida and Hiroyuki Asanuma at Nagoya University and co-workers. The image depicts the orientation dependence of circularly polarized luminescent. Read the full text of the article at 10.1002/chem.202300182.

Dynamic-to-Static Planar Chirality Conversion in Pillar[5]arenes Regulated by Guest Solvents or Amplified by Crystallization.

Controlling dynamic chirality and memorizing the controlled chirality are important. Chirality memory has mainly been achieved using noncovalent interactions. However, in many cases, the memorized chirality arising from noncovalent interactions is erased by changing the conditions such as the solvent and temperature. In this study, the dynamic planar chirality of pillar[5]arenes was successfully converted into static planar chirality by introducing bulky groups through covalent bonds. Before introducing the bulky groups, pillar[5]arene with stereogenic carbon atoms at both rims existed as a pair of diastereomers, and thus showed planar chiral inversion that was dependent on the chain length of the guest solvent. The pS and pR forms, regulated by guest solvents, were both diastereomerically memorized by introducing bulky groups. Furthermore, the diastereomeric excess was amplified by crystallization of the pillar[5]arene. The subsequent introduction of bulky groups yielded pillar[5]arene with an excellent diastereomeric excess (95 % de).

A Pyrene-Modified Serinol Nucleic Acid Nanostructure Converts the Chirality of Threoninol Nucleic Acids into Circularly Polarized Luminescence Signals.

Herein is reported a circularly polarized luminescent (CPL) probe that can respond to the chirality of nucleic acids. An achiral nanostructure was prepared by the hybridization of symmetric serinol nucleic acid (SNA) containing pyrene-modified residues. When chiral oligomers that were complementary to the SNA were added, they induced helicity into the SNA nanowire. Efficient circular dichroism (CD) signal amplification was observed when pyrene was attached to uracil bases through a rigid alkynyl linker. Both CPL and CD signals were observed; they depended on the chirality of the added acyclic threoninol nucleic acid (aTNA) oligomer. This system can be used to convert the chirality of chiral biomolecules into chiroptical signals.

Thermally Responsive Poly(ethylene oxide)-Based Polyrotaxanes Bearing Hydrogen-Bonding Pillar[5]arene Rings.

Invited for the cover of this issue are Tomoki Ogoshi and co-workers at Kyoto University, Kanazawa University and Tokyo University of Agriculture and Technology. The image depicts musical notation to represent hydrogen bond networks and poly(ethylene oxide) chains. Read the full text of the article at 10.1002/chem.202005099.

Thermally Responsive Poly(ethylene oxide)-Based Polyrotaxanes Bearing Hydrogen-Bonding Pillar[5]arene Rings*.

Poly(ethylene oxide)s (PEOs) are useful polymers with good water solubility, biological compatibility, and commercial availability. PEOs with various end groups were threaded into pillar[5]arene rings in a mixture of water and methanol to afford pseudopolyrotaxanes. Corresponding polyrotaxanes were also constructed by capping COOH-terminated pseudopolyrotaxanes with bulky amines, in which multiple hydrogen bonds involving the pillar[5]arene OH groups were critically important to prevent dethreading. The number of threaded ring components could be rationally controlled in these materials, providing a simple and versatile method to tune the mechanical and thermal properties. Specifically, a polyrotaxane with a high-molecular-weight axle became elastic upon heating above the melting point of PEOs and exhibited temperature-dependent shape memory property because of the topological confinement and crosslinked hydrogen bonds.

Guest Vapor-Induced State Change of Structural Liquid Pillar[6]arene.

State change is a key phenomenon in materials science. We report the first observation of vapor-responsive reversible structural liquid-to-solid and solid-to-structural liquid state changes. We observed that a macrocyclic compound, a pillar[6]arene derivative bearing 12 n-hexyl substituents, is a room temperature structural liquid with unique properties. Formation of a host-guest complex between the pillar[6]arene cavity and the n-hexyl substituent results in a structural liquid with nanoscale structural heterogeneities. The structural liquid solidifies when exposed to competitive cyclohexane guest vapor, whereupon cyclohexane replaces the n-hexyl substituents in the pillar[6]arene cavity and the n-hexyl substituents located outside of the cavity crystallize into distinct nanolayer assemblies. The solid reverts back to the structural liquid when the cyclohexane guest is removed through heating under reduced pressure because of rethreading of the n-hexyl substituents into the cavity. The structural liquid-to-solid and solid-to-structural liquid changes are reversible through the uptake and release of cyclohexane guest vapor.

Stimuli-Responsive Supramolecular Assemblies Constructed from Pillar[ n]arenes.

Supramolecular assemblies are constructed from at least two molecules through various noncovalent bonding modes such as hydrogen bonding, cationic-anionic electrostatic interactions, aromatic interactions, metal-ligand bonding, hydrophobic-hydrophilic interactions, and charge-transfer interactions. Owing to the dynamic and reversible nature of these noncovalent bonds, the assembly and disassembly of these molecules are dynamic and reversible. Molecules self-assemble to form the most conformationally and thermally stable structures through these noncovalent interactions. The formation of these noncovalent interactions is affected by the properties of the environment such as its polarity, temperature, and pressure; thus, the structure of the assembled compounds is determined by the environment. The sizes and shapes of the supramolecular assemblies play an important role in determining their functions. Therefore, controlling their size and shape is important. Introducing stimuli-responsive groups into supramolecular assemblies is a useful way to control their size and shape. Controlling supramolecular structures and motions with external stimuli, i.e., periodic and rotational motions on the molecular scale, structures, and molecular weights at the nano- and micrometer scales, visible shrinking/expansion, and adhesive behavior at a macroscopic scale, is very useful. Macrocyclic host molecules are useful building blocks for the construction of stimuli-responsive supramolecular assemblies because their host ability can be tuned by changing the shape and electron density of the cavity. The size-dependent hosting ability of the cavity is similar to the lock-and-key model in biological systems. Stimuli-responsive supramolecular assemblies have been developed by using macrocyclic compounds such as cyclodextrins, cucurbit[ n]urils, calix[ n]arenes, crown ethers, and related macrocycles. We successfully developed new pillar-shaped macrocyclic hosts in 2008, which were coined pillar[ n]arenes. The unique structural features of pillar[ n]arenes allowed new properties. This year, 2018, marks one decade of research into pillar[ n]arene chemistry, and in that time the properties of pillar[ n]arenes have been widely investigated by various scientists. Thanks to their efforts, the characteristic properties of pillar[ n]arenes that result from their pillar-shaped structures have been elucidated. Their host ability, the chirality of their pillar-shaped structure, and their versatile functionality are unique features of pillar[ n]arenes not seen in other well-known hosts, and these properties are very useful for the creation of new stimuli-responsive supramolecular assemblies. In this Account, we describe photo-, pH- and redox-responsive supramolecular assemblies based on pillar[ n]arenes. First, we discuss molecular-scale stimuli-responsive supramolecular assemblies, i.e., pseudorotaxanes, pseudocatenanes, and supramolecular polymers. We also highlight subnanometer- and micrometer-scale stimuli-responsive supramolecular assembles such as particles and vesicles. Finally, we discuss the macroscopic stimuli-responsive structural changes of surfaces and gels. This Account will provide useful information for researchers working on not only pillar[ n]arene chemistry but also the chemistry of other macrocyclic hosts, and it will inspire new discoveries in the field of supramolecular assemblies and systems containing macrocyclic hosts.

Host-Guest Complexation Using Pillar[5]arene Crystals: Crystal-Structure Dependent Uptake, Release, and Molecular Dynamics of an Alkane Guest.

Host-guest complexation has been mainly investigated in solution, and it is unclear how guest molecules access the assembled structures of host and dynamics of guest molecules in the crystal state. In this study, we studied the uptake, release, and molecular dynamics of n-hexane vapor in the crystal state of pillar[5]arenes bearing different substituents. Pillar[5]arene bearing 10 ethyl groups yielded a crystal structure of herringbone-type 1:1 complexes with n-hexane, whereas pillar[5]arene with 10 allyl groups formed 1:1 complexes featuring a one-dimensional (1D) channel structure. For pillar[5]arene bearing 10 benzyl groups, one molecule of n-hexane was located in the cavity of pillar[5]arene, and another n-hexane molecule was located outside of the cavity between two pillar[5]arenes. The substituent-dependent differences in molecular arrangement influenced the uptake, release, and molecular dynamics of the n-hexane guest. The substituent effects were not observed in host-guest chemistry in solution, and these features are unique for the crystal state host-guest chemistry of pillar[5]arenes.

Applications of Pillar[n]arene-Based Supramolecular Assemblies.

Macrocycles are an important player in supramolecular chemistry. In 2008, a new class of macrocycles, "pillar[n]arenes", were first discovered. Research efforts in the area of pillar[n]arenes have elucidated key properties, such as their shape, reaction mechanism, host-guest properties, and their versatile functionality, which has contributed to the development of pillar[n]arene chemistry and their applications to various fields. This Minireview describes how pillar[n]arene-based supramolecular assemblies can be applied to supramolecular gel formation, reactions, light-harvesting systems, drug-delivery systems, biochemical applications, separation and storage materials, and surface chemistry.

Spacer Length-Independent Shuttling of the Pillar[5]arene Ring in Neutral [2]Rotaxanes.

For a series of neutral [2]rotaxanes consisting of a pillar[5]arene ring and axles possessing two stations separated by flexible spacers of different lengths, the free energies of activation for the ring shuttling between the stations were found to be independent of the spacer length. The constitution of the spacer affects the activation energies: replacement of CH2 groups by repulsive oxygen atoms in the axle increases the barrier. The explanation for the observed length-independence lies in the presence of a barrier for re-forming the stable co-conformation, which makes the ring travel back and forth along the thread in an intermediate state.

Separation of Linear and Branched Alkanes Using Host-Guest Complexation of Cyclic and Branched Alkane Vapors by Crystal State Pillar[6]arene.

Activated crystals of pillar[6]arene produced by removing the solvent upon heating were able to take up branched and cyclic alkane vapors as a consequence of their gate-opening behavior. The uptake of branched and cyclic alkane vapors by the activated crystals of pillar[6]arene induced a crystal transformation to form one-dimensional channel structures. However, the activated crystals of pillar[6]arene hardly took up linear alkane vapors because the cavity size of pillar[6]arene is too large to form stable complexes with linear alkanes. This shape-selective uptake behavior of pillar[6]arene was further utilized for improving the research octane number of an alkane mixture of isooctane and n-heptane: interestingly, the research octane number was dramatically improved from a low research octane number (17 %) to a high research octane number (>99 %) using the activated crystals of pillar[6]arene.

Development of highly-sensitive detection system in 19F NMR for bioactive compounds based on the assembly of paramagnetic complexes with fluorinated cubic silsesquioxanes.

This manuscript reports the detection system with 19F NMR probes for bioactive amine compounds at sub-micro molar concentrations. Water-soluble fluorinated polyhedral oligomeric silsesquioxane (POSS) derivatives were prepared, and the paramagnetic Ni-porphyrin (NiPor) with the fluorinated POSS (F-POSS) was adsorbed in the buffer. By adding the series of amine derivatives to the homogeneous dispersion containing the POSS-NiPor complexes, the changes in the signal intensity were evaluated. It was clearly observed from homogeneous dispersions that the signal intensity of 19F NMR decreased especially in the presence of ethanediamine and hexylamine. From the dynamic light scattering measurements, it was revealed that the assembly of the F-POSS complexes was dramatically induced by the amine compounds when the signal intensity decreased. According to these data, it is proposed that the signal reduction of 19F NMR from the POSS-NiPor complexes could be induced via the strong paramagnetic relaxation enhancement from NiPor in the assembly. Finally, based on the signal reduction by the assembly, we can detect the amine derivatives under 1µM concentration which is similar sensitivity to the conventional fluorescence probes. Our system is valid to monitor the distribution of the bio-active molecules at cellular concentrations.

Development of the optical sensor for discriminating isomers of fatty acids based on emissive network polymers composed of polyhedral oligomeric silsesquioxane.

It was shown that water-soluble network polymers composed of polyhedral oligomeric silsesquioxane (POSS) had hydrophobic spaces inside the network because of strong hydrophobicity of the cubic silica cage. In this study, the water-soluble POSS network polymers connected with triphenylamine derivatives (TPA-POSS) were synthesized, and their functions as a sensor for discriminating the geometric isomers of fatty acids were investigated. Accordingly, in the photoluminescence spectra, different time-courses of intensity and peak wavelengths of the emission bands were detected from the TPA-POSS-containing solution in the presence of cis- or trans-fatty acids during incubation. Furthermore, variable time-dependent changes were obtained by changing coexisting ratios between two geometric isomers. From the mechanistic investigation, it was implied that these changes could be originated from the difference in the degree of interaction between the POSS networks and each fatty acid. Our data could be applicable for constructing a sensing material for generation and proportion of trans-fatty acids in the oil.

Facile design of organic-inorganic hybrid gels for molecular recognition of nucleoside triphosphates.

We report the molecular recognition for nucleoside triphosphates inside the ligand-modified water-soluble organic-inorganic hybrid gels composed of polyhedral oligomeric silsesquioxane (POSS). The series of ligands were designed to make hydrogen bonds with each nucleobase and introduced into the hybrid gels. From the titration experiments, the binding constants between the ligand inside the gels and nucleosides were evaluated. Accordingly, it was found that the ligands inside the gels can form a stable complex only with the target nucleoside triphosphate which has the complementary pattern of the hydrogen bonds (Ka=G-gel/cytidine triphosphate (CTP), 3.5×10(8)M(-1); U-gel/adenosine triphosphate (ATP), 1.6×10(3)M(-1); A-gel/uridine triphosphate (UTP), 1.9×10(7), respectively). With other nucleoside derivatives which have different numbers of phosphate units or different types of nucleobases, the much weaker interaction was detected. These data indicate that the complex formation only with nucleoside triphosphates should occur inside the hybrid gels, and selective recognition of each nucleoside triphosphate can be accomplished.

Supramolecular adhesives to hard surfaces: adhesion between host hydrogels and guest glass substrates through molecular recognition.

Supramolecular materials based on host-guest interactions should exhibit high selectivity and external stimuli-responsiveness. Among various stimuli, redox and photo stimuli are useful for its wide application. An external stimuli-responsive adhesive system between CD host-gels (CD gels) and guest molecules modified glass substrates (guest Sub) is focused. Here, the selective adhesion between host gels and guest substrates where adhesion depends on molecular complementarity is reported. Initially, it is thought that adhesion of a gel material onto a hard material might be difficult unless many guest molecules modified linear polymers immobilize on the surface of hard materials. However, reversible adhesion of the CD gels is observed by dissociating and re-forming inclusion complex in response to redox and photo stimuli.

Acceptor-Induced Fluorescence of Phenolic Polymers Based on Triphenylamine Derivatives.

Conductive polymers facilitate the electrical current flow through the transfer of electrons and holes. They show promise for novel photo-functional materials in photovoltaics. However, substantial electrostatic interactions between electron donors and acceptors induce polymer aggregation, limiting moldability and conductivity. In this study, robust donor polymers with high heat resistance were synthesized by bonding triphenylamine (TPA) derivatives and formaldehyde to phenolic groups. Resulting TPA-based phenolic polymers exhibited flexible structures and fluorescence due to charge transfer with acceptor molecules. Furthermore, TPA-based phenolic polymers' capacity to distinguish acceptor molecule sizes correlated with their molecular weight, reflecting upon donor-acceptor interactions. This novel optical trait in phenolic polymers holds potential for electronic components and conductive materials.