Spontaneous-Spin-Polarized 2D π-d Conjugated Frameworks Towards Enhanced Oxygen Evolution Kinetics.

Alternative strategies to design sustainable-element-based electrocatalysts enhancing oxygen evolution reaction (OER) kinetics are demanded to develop affordable yet high-performance water-electrolyzers for green hydrogen production. Here, it is demonstrated that the spontaneous-spin-polarized 2D π-d conjugated framework comprising abundant elements of nickel and iron with a ratio of Ni:Fe = 1:4 with benzenehexathiol linker (BHT) can improve OER kinetics by its unique electronic property. Among the bimetallic NiFex:y-BHTs with various ratios with Ni:Fe = x:y, the NiFe1:4-BHT exhibits the highest OER activity. The NiFe1:4-BHT shows a specific current density of 140 A g-1 at the overpotential of 350 mV. This performance is one of the best activities among state-of-the-art non-precious OER electrocatalysts and even comparable to that of the platinum-group-metals of RuO2 and IrO2. The density functional theory calculations uncover that introducing Ni into the homometallic Fe-BHT (e.g., Ni:Fe = 0:1) can emerge a spontaneous-spin-polarized state. Thus, this material can achieve improved OER kinetics with spin-polarization which previously required external magnetic fields. This work shows that a rational design of 2D π-d conjugated frameworks can be a powerful strategy to synthesize promising electrocatalysts with abundant elements for a wide spectrum of next-generation energy devices.

Lateral Heterometal Junction Rectifier Fabricated by Sequential Transmetallation of Coordination Nanosheet.

Heterostructures of two-dimensional materials realise novel and enhanced physical phenomena, making them attractive research targets. Compared to inorganic materials, coordination nanosheets have virtually infinite combinations, leading to tunability of physical properties and are promising candidates for heterostructure fabrication. Although stacking of coordination materials into vertical heterostructures is widely reported, reports of lateral coordination material heterostructures are few. Here we show the successful fabrication of a seamless lateral heterojunction showing diode behaviour, by sequential and spatially limited immersion of a new metalladithiolene coordination nanosheet, Zn3 BHT, into aqueous Cu(II) and Fe(II) solutions. Upon immersion, the Zn centres in insulating Zn3 BHT are replaced by Cu or Fe ions, resulting in conductivity. The transmetallation is spatially confined, occurring only within the immersed area. We anticipate that our results will be a starting point towards exploring transmetallation of various two-dimensional materials to produce lateral heterojunctions, by providing a new and facile synthetic route.

Chemically Laminated 2D Bis(terpyridine)metal Polymer Films: Formation Mechanism at the Liquid-Liquid Interface and Redox Rectification.

Invited for the cover of this issue is the group of Hiroshi Nishihara at Tokyo University of Science. The image depicts the moment of the growth of the second layer at the liquid-liquid interface to form a heterolaminated film. Read the full text of the article at 10.1002/chem.202201316.

Chemically Laminated 2D Bis(terpyridine)metal Polymer Films: Formation Mechanism at the Liquid-Liquid Interface and Redox Rectification.

Recent studies on molecular 2D materials with high tunability of structure and function have focused mostly on the discovery of new precursors. Here, we demonstrate a facile one-pot synthesis of laminated 2D coordination polymer films comprising bis(terpyridine)iron and cobalt at a water/dichloromethane interface. Cross-sectional elemental mapping unveiled the stratum-like structure of the film and revealed that the second layer grows to the dichloromethane side below the first layer. Cyclic voltammetry clarified that the bottom layer mediates charge transfer between the top layer and the substrate in a narrow potential region of mixed-valence states. Furthermore, the bilayer film sandwiched by electrodes in a dry condition shows stable rectification character, and the barrier voltage corresponds to the redox potential difference between the two layers. This study introduces a new strategy for polymer design to explore the materials science of molecular 2D materials.

Superior Multielectron-Transferring Energy Storage by π-d Conjugated Frameworks.

Reversible multielectron-transfer materials are of considerable interest because of the potential impact to advance present electrochemical energy storage technology by boosting energy density. To date, a few oxide-based materials can reach an electron-transfer number per metal-cation (eM ) larger than 2 upon a (de)intercalation mechanism. However, these materials suffer from degradation due to irreversible rearrangements of the cation-oxygen bonds, and are based on precious metals, for example, Ir and Ru. Hence, a design of the non-oxide-based reversible multielectron-transfer materials with abundant elements can provide a promising alternative. Herein, it is demonstrated that the bis(diimino)copper framework can show eM  = 3.5 with cation/anion co-redox mechanism together with a dual-ion mechanism. In this study, the role of the cation-anion interactions is unveiled by using an experiment/theory collaboration applied to a series of the model non-oxide abundant electrode systems based on different metal-nitrogen bonds. These models provide designer multielectron-transfer due to the tunable π-d conjugated electronic structures. It is found that the Cu-nitrogen bonds show a unique reversible rearrangement upon Li-intercalation, and this process responds to acquire a significant reversible multielectron-transfer. This work provides new insights into the affordable multielectron-transfer electrodes and uncovers an alternative strategy to advance the electrochemical energy storage reactions.

Heterometallic Benzenehexathiolato Coordination Nanosheets: Periodic Structure Improves Crystallinity and Electrical Conductivity.

Coordination nanosheets are an emerging class of 2D, bottom-up materials having fully π-conjugated, planar, graphite-like structures with high electrical conductivities. Since their discovery, great effort has been devoted to expand the variety of coordination nanosheets; however, in most cases, their low crystallinity in thick films hampers practical device applications. In this study, mixtures of nickel and copper ions are employed to fabricate benzenehexathiolato (BHT)-based coordination nanosheet films, and serendipitously, it is found that this heterometallicity preferentially forms a structural phase with improved film crystallinity. Spectroscopic and scattering measurements provide evidence for a bilayer structure with in-plane periodic arrangement of copper and nickel ions with the NiCu2 BHT formula. Compared with homometallic films, heterometallic films exhibit more crystalline microstructures with larger and more oriented grains, achieving higher electrical conductivities reaching metallic behaviors. Low dependency of Seebeck coefficient on the mixing ratio of nickel and copper ions supports that the large variation in the conductivity data is not caused by change in the intrinsic properties of the films. The findings open new pathways to improve crystallinity and to tune functional properties of 2D coordination nanosheets.

Ultralong π-Conjugated Bis(terpyridine)metal Polymer Wires Covalently Bound to a Carbon Electrode: Fast Redox Conduction and Redox Diode Characteristics.

We developed an efficient and convenient electrochemical method to synthesize π-conjugated redox metal-complex linear polymer wires composed of azobenzene-bridged bis(terpyridine)metal (2-M, M = Fe, Ru) units covalently immobilized on glassy carbon (GC). Polymerization proceeds by electrochemical oxidation of bis(4'-(4-anilino)-2,2':6',2″-terpyridine)metal (1-M) in a water-acetonitrile-HClO4 solution, affording ultralong wires up to 7400 mers (corresponding to ca. 15 µm). Both 2-Fe and 2-Ru undergo reversible redox reactions, and their redox behaviors indicate remarkably fast redox conduction. Anisotropic hetero-metal-complex polymer wires with Fe and Ru centers are constructed via stepwise electropolymerization. The cyclic voltammograms of two hetero-metal-complex polymer wires, GC/[2-Fe]-[2-Ru] (3) and GC/[2-Ru]-[2-Fe] (4), show irreversible redox reactions with opposite electron transfer characteristics, indicating redox diodelike behavior. In short, the present electrochemical method is useful to synthesize polymer wire arrays and to integrate functional molecules on carbon.

Two-Dimensional Bis(dithiolene)iron(II) Self-Powered UV Photodetectors with Ultrahigh Air Stability.

Organometallic two-dimensional (2D) nanosheets with tailorable components have recently fascinated the optoelectronic communities due to their solution-processable nature. However, the poor stability of organic molecules may hinder their practical application in photovoltaic devices. Instead of conventional organometallic 2D nanosheets with low weatherability, an air-stable π-conjugated 2D bis(dithiolene)iron(II) (FeBHT) coordination nanosheet (CONASH) is synthesized via bottom-up liquid/liquid interfacial polymerization using benzenehexathiol (BHT) and iron(II) ammonium sulfate [Fe(NH4)2(SO4)2] as precursors. The uncoordinated thiol groups in FeBHT are easily oxidized, but the Fe(NH4)2(SO4)2 dissociation rate is slow, which facilitates the protection of sulfur groups by iron(II) ions. The density functional theory calculates that the resultant FeBHT network gains the oxygen-repelling function for oxidation suppression. In air, the FeBHT CONASH exhibits self-powered photoresponses with short response times (<40 ms) and a spectral responsivity of 6.57 mA W-1, a specific detectivity of 3.13 × 1011 Jones and an external quantum efficiency of 2.23% under 365 nm illumination. Interestingly, the FeBHT self-powered photodetector reveals extremely high long-term air stability, maintaining over 94% of its initial photocurrent after aging for 60 days without encapsulation. These results open the prospect of using organometallic 2D materials in commercialized optoelectronic fields.

Anti-ORAI1 antibody DS-2741a, a specific CRAC channel blocker, shows ideal therapeutic profiles for allergic disease via suppression of aberrant T-cell and mast cell activation.

ORAI1 constitutes the pore-forming subunit of the calcium release-activated calcium (CRAC) channel, which is responsible for store-operated calcium entry into lymphocytes. It is known that ORAI1 is essential for the activation of T cells and mast cells and is considered to be a potent therapeutic target for autoimmune and allergic diseases. Here, we obtained a new humanized antibody, DS-2741a, that inhibits ORAI1 function. DS-2741a bound to human-ORAI1 with high affinity and without cross-reactivity to rodent Orai1. DS-2741a demonstrated suppression of CRAC-mediated human and mouse T-cell activation and mast cell degranulation in human ORAI1 knock-in mice. Furthermore, DS-2741a ameliorated house dust mite antigen-induced dermatitis in the human ORAI1 knock-in mouse. Taken together, DS-2741a inhibited T-cell and mast cell functions, thus improving skin inflammation in animal models of atopic dermatitis and reinforcing the need for investigation of DS-2741a for the treatment of allergic diseases in a clinical setting.

Redox-active, luminescent coordination nanosheet capsules containing magnetite.

Two-dimensional coordination nanosheets (CONASHs) are grown at the spherical liquid-liquid interface of a dichloromethane droplet in water to form zero-dimensional nano- and micro-capsules using a simple dropping method, a syringe-pump method, and an emulsion method. Reaction of 1,3,5-tris[4-(4'-2,2':6',2″-terpyridyl)phenyl]benzene (1) with Fe(BF4)2 affords electrochromic Fe(tpy)2 CONASH capsules and that of ligand 1 with ZnSO4 does photoluminescent Zn2(µ-O2SO2)2(tpy)2 CONASH capsules. Fe(tpy)2 CONASH capsules containing magnetite particles were produced by the syringe-pump method by adding magnetite to the aqueous phase, with the assembly and dispersion of the magnetite-containing CONASH capsules being easily controlled with a magnet. This indicates that physicochemically functional CONASH capsules are suitable for incorporating other functional materials to develop hybrid systems.

Design, synthesis, and optimization of a series of 2-azaspiro[3.3]heptane derivatives as orally bioavailable fetal hemoglobin inducers.

Pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin (HbF) is a promising approach for the management of ß-thalassemia and sickle cell disease (SCD). We conducted a phenotypic screen in human erythroid progenitor cells to identify molecules that could induce HbF, which resulted in identification of the hit compound 1. Exploration of structure-activity relationships and optimization of ADME properties led to 2-azaspiro[3.3]heptane derivative 18, which is more rigid and has a unique structure. In vivo using cynomolgus monkeys, compound 18 induced a significant dose-dependent increase in globin switching, with developable properties. Moreover, compound 18 showed no genotoxic effects and was much safer than hydroxyurea. These findings could facilitate the development of effective new therapies for the treatment of ß-hemoglobinopathies, including SCD.

Tailoring the Electrochemical Properties of Two-Dimensional Bis(diimino)metal Coordination Frameworks by Introducing Co/Ni Heterometallic Structures.

Bis(diimino)metal coordination frameworks (MDI, M = transition metal), which are a class of metal organic frameworks with two-dimensional anisotropy, high electric conductivity, and redox activity, are attractive platforms for tailoring electrochemical properties by introducing a heterometallic composition. In this study, we synthesized heterometallic CoxNi1-xDI coordination frameworks for electrochemical energy storage applications and investigated their electrochemical properties by experimental and theoretical techniques. Ni atoms were embedded into CoDI, and the crystal structure of CoxNi1-xDI was modified, especially along the interlayer axis, which activated the kinetically impeded redox reactions accompanied by PF6- insertion/extraction. Furthermore, upon charge/discharge with Li+ transport, CoxNi1-xDI with a specific composition exhibited higher specific capacity (248 mAh g-1) than CoDI and NiDI in the potential window of 1.0-3.5 V versus Li+/Li. Density functional theory calculations indicate that the energy levels of the antibonding orbitals around the metals and interlayer spaces are important factors in tailoring the electrochemical properties of CoxNi1-xDI.

Solution-processed organometallic quasi-two-dimensional nanosheets as a hole buffer layer for organic light-emitting devices.

Two-dimensional (2D) vdW materials have been integrated into optoelectronic devices to achieve exceptional functionality. However, the integration of large-area 2D thin films into organic light-emitting devices (OLEDs) remains challenging because of the finite number of inorganic 2D materials and the high-temperature requirements of their deposition process. The construction of 2D organometallic materials holds immense potential because of their solution synthesis and unlimited structural and functional diversity. Here, we report a facile route using an oil-water interfacial coordination reaction between organic ligands and divalent metal ions to synthesize crystalline quasi-2D organometallic bis(dithiolato)nickel (NiDT) nanosheets with a centimeter scale and a tunable thickness. The NiDT nanosheets can be directly integrated into OLEDs for use as a hole buffer layer and a fluorescent mounting medium without the aid of a transfer process. Moreover, OLEDs with NiDT nanosheets show not only comparable efficiency to conventional OLEDs but also prolonged device lifetime by nearly 2 times. These results open up a new dimension to use quasi-2D organometallic nanosheets as functional layers in large-area organic devices.

Design of 2'-O-methyl RNA and DNA double-stranded oligonucleotides: naturally-occurring nucleotide components with strong RNA interference gene expression inhibitory activity.

Double-stranded RNAs consisting of 21-nucleotide passenger and guide strands, known as small interfering RNAs (siRNAs), can be used for the identification of gene functions and the regulation of genes involved in disease for therapeutics. The difficulty with unmodified siRNAs lies in the chemical synthesis of RNA, its degradation by RNase, the immune response derived from natural RNA, and the off-target effects mediated by the passenger strand. In this study, asymmetrical 18 base-paired double-strand oligonucleotides comprised of alternately combined DNAs and 2'-O-methyl RNAs, denoted as MED-siRNA, were evaluated. These modified oligonucleotides showed high RNase resistance, a reduced immune response, a highly efficient cleavage of target mRNA with binding to Argonaute 2 (Ago2) via RNA interference, and the subsequent reduction of target protein expression. These findings suggest the possibility of alternatives to unmodified siRNAs with potential use in therapeutics.

Phenotypic-screening generates active novel fetal globin-inducers that downregulate Bcl11a in a monkey model.

Heritable disorders associated with hemoglobin production are the most common monogenic disorders. These are mainly represented by disorders such as ß-thalassemia and sickle cell disease. Induction of fetal hemoglobin (HbF) has been known to ameliorate the clinical severity of these ß hemoglobinopathies. A high throughput phenotypic screening was used in this study to isolate novel compounds that may enhance the expression of γ-globin, the component of HbF, in human erythroid cell lines and primary erythroid progenitors derived from human CD34+ cells. The effect of lead compounds on epigenetic enzymes and key transcriptional factors was evaluated to identify their mode of action. One hit compound was further evaluated in vivo using monkey models. Among the ~18,000 compounds screened, 18 compounds were selected and tested to determine their ability to induce HbF in human erythroid cell lines and primary erythroid cells. One of these compounds, a 3-phenyl-isoxazole derivative, could potentially induce HbF in monkey bone marrow cells when administered orally. The compound downregulated negative transcriptional regulators of HbF, Bcl11a and LRF without inhibiting the known epigenetic enzymes. These studies demonstrated the advantages associated with phenotype-screening and identified novel fetal globin inducers that may be useful for treating hemoglobinopathies.

Safety assessment of a novel C-type natriuretic peptide derivative and the mechanism of bone- and cartilage-specific toxicity.

ASB20123, a C-type natriuretic peptide/ghrelin chimeric peptide, was designed as a novel peptide and demonstrated full agonistic activity for natriuretic-peptide receptor B and a significantly longer half-life in plasma compared with the native peptide. We researched the toxicological profile of ASB20123, the correlation between the morphological change of the epiphyseal plate and bone and cartilage toxicity, and biomarkers to detect the toxicity. ASB20123 was systemically administered to male and female rats at daily dose levels of 0.5, 1.5, and 5.0 mg/kg/day for 4 weeks. In this study, toxicity was observed as changes related to bone and cartilage tissues, and no other toxicological changes were observed in all animals. Next, ASB20123 was administered to 12-month-old rats with a little epiphyseal plate. The toxic changes related to bone and cartilage tissues were not observed in any animal with a closed epiphyseal plate, indicating that the toxic changes were triggered by the growth-accelerating effect on the bone and cartilage. Furthermore, we searched for the biomarker related to the bone and cartilage toxicity using rats treated with ASB20123 at doses of 0.005, 0.05, 0.5, and 5.0 mg/kg/day for 4 weeks. A close correlation between necrosis/fibrosis in the epiphysis and metaphysis and thickness of the epiphyseal plate in the femur was confirmed in this study. A decrease in the bone mineral density (BMD) of the femur also was associated with the appearance of bone toxicity. These results indicated that the toxicity of ASB20123 was limited to bone- and cartilage-specific changes, and these changes were triggered by an excessive growth accelerating effect. Furthermore, our data suggested that the thickness of the epiphyseal plate and BMD could be reliable biomarkers to predict bone toxicity.

The Accelerating World of Graphdiynes.

Graphdiyne (GDY), a 2D allotrope of graphene, is first synthesized in 2010 and has attracted attention as a new low-dimensional carbon material. This work surveys the literature on GDYs. The history of GDYs is summarized, including their relationship with 2D graphyne carbons and yearly publication trends. GDY is a molecule-based nanosheet woven from a molecular monomer, hexaethynylbenzene; thus, it is synthesized by bottom-up approaches, which allow rich variation via monomer design. The GDY family and the synthetic procedures are also described. Highly developed π-conjugated electronic structures are common important features in GDY and graphene; however, the coexistence of sp and sp2 carbons differentiates GDY from graphene. This difference gives rise to unique physical properties, such as high conductivity and large carrier mobility. Next, the theoretical and experimental studies of these properties are described in detail. A wide variety of applications are proposed for GDYs, including electrocatalysts and energy devices, which exploit the carbon-rich nature, porous framework, and expanded π-electron system of these compounds. Finally, potential uses are discussed.

Interfacial transmetallation synthesis of a platinadithiolene nanosheet as a potential 2D topological insulator.

The construction of two-dimensional metal complex materials is fascinating because of the structural and functional diversity of these materials. Previously, we have reported the synthesis of electroconductive nickelladithiolene (NiDT) and palladadithiolene (PdDT) nanosheets using benzenehexathiol (BHT). Down the group from Ni, Pd to Pt, there is a distinct positive shift in the reduction potential; as a result, it becomes synthetically more challenging to stabilize Pt2+ than to form metallic Pt(0) in the presence of BHT as a reducing agent. Herein, a novel synthetic strategy for the preparation of platinadithiolene nanosheet (PtDT) using a dibutyltin-protected BHT ligand is reported, leading to transmetallation in the presence of dioxygen. Both free-standing stacked sheets and atomic layer sheets were obtained and characterized by microscopic techniques such as AFM, SEM, and TEM. To study the morphology of the sheets and determine their charge neutrality, X-ray photoelectron (XP) and infrared (IR) spectroscopic techniques were used. Powder X-ray diffraction analysis of the multilayer PtDT indicates a half-way slipped hexagonal configuration in the P3[combining macron]1m space group. The band structure of this PtDT exhibits a band gap at the Fermi level, which is different from that of NiDT in the staggered configuration, and a Dirac gap, indicating the possibility of 2D topological insulation at room temperature. PtDT is insulating but chemically activated by oxidation with I2 to increase the conductivity by more than 106 folds up to 0.39 S cm-1. The MDT sheets exhibit electrocatalytic activity for the hydrogen evolution reaction, and the activity order is NiDT < PdDT < PtDT.

ASB20123: A novel C-type natriuretic peptide derivative for treatment of growth failure and dwarfism.

C-type natriuretic peptide (CNP) and its receptor natriuretic peptide receptor B (NPR-B) are physiological potent positive regulators of endochondral bone growth; therefore, the CNP/NPR-B signaling pathway is one of the most promising therapeutic targets for treating growth failure and dwarfism. In this article, we summarized the pharmacological properties of a novel CNP analog peptide ASB20123 as a therapeutic agent for short stature. ASB20123, one of the CNP/ghrelin chimeric peptides, is composed of CNP(1-22) and human ghrelin(12-28, E17D). Compared to CNP(1-22), ASB20123 showed similar agonist activity for NPR-B and improved biokinetics with a longer plasma half-life in rats. In addition, the distribution of ASB20123 to the cartilage was higher than that of CNP(1-22) after single subcutaneous (sc) injection to mice. These results suggested that the C-terminal part of ghrelin, which has clusters of basic amino acid residues and a BX7B motif, might contribute to the retention of ASB20123 in the extracellular matrix of the growth plate. Multiple sc doses of ASB20123 potently stimulated skeletal growth in rats in a dose-dependent manner, and sc infusion was more effective than bolus injection at the same dose. Our data indicated that high plasma levels of ASB20123 would not necessarily be required for bone growth acceleration. Thus, pharmaceutical formulation approaches for sustained-release dosage forms to allow chronic exposure to ASB20123 might be suitable to ensure drug effectiveness and safety.

Expansion of the Graphdiyne Family: A Triphenylene-Cored Analogue.

Graphdiyne (GDY) comprises an important class in functional covalent organic nanosheets based on carbon-carbon bond formation, and recent focus has collected in the expansion of its variations. Here we report on the synthesis of a GDY analogue, TP-GDY, which has triphenylene as the aromatic core. Our liquid/liquid interfacial synthesis for GDY ( J. Am. Chem. Soc. 2017, 139, 3145) was modified for hexaethynyltriphenylene monomer to afford a TP-GDY film with a free-standing morphology, a smooth texture, a domain size of >1 mm, and a thickness of 220 nm. Resultant TP-GDY is characterized by series of microscopies, spectroscopies, and thermogravimetric and gas adsorption analyses.