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.

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.

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.

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.

C-type natriuretic peptide improves growth retardation in a mouse model of cardio-facio-cutaneous syndrome.

Cardio-facio-cutaneous (CFC) syndrome, a genetic disorder caused by germline mutations in BRAF, KRAS, MAP2K1 and MAP2K2, is characterized by growth retardation, heart defects, dysmorphic facial appearance and dermatologic abnormalities. We have previously reported that knock-in mice expressing the CFC syndrome-associated mutation, Braf Q241R, showed growth retardation because of gastrointestinal dysfunction. However, other factors associated with growth retardation, including chondrogenesis and endocrinological profile, have not been examined. Here, we show that 3- and 4-week-old BrafQ241R/+ mice have decreased body weight and length, as well as reduced growth plate width in the proximal tibiae. Furthermore, proliferative and hypertrophic chondrocyte zones of the growth plate were reduced in BrafQ241R/+ mice compared with Braf+/+ mice. Immunohistological analysis revealed that extracellular signal-regulated kinase (ERK) activation was enhanced in hypertrophic chondrocytes in BrafQ241R/+ mice. In accordance with growth retardation and reduced growth plate width, decreased serum levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) were observed in BrafQ241R/+ mice at 3 and 4 weeks of age. Treatment with C-type natriuretic peptide (CNP), a stimulator of endochondral bone growth and a potent inhibitor of the FGFR3-RAF1-MEK/ERK signaling, increased body and tail lengths in Braf+/+ and BrafQ241R/+ mice. In conclusion, ERK activation in chondrocytes and low serum IGF-1/IGFBP-3 levels could be associated with the growth retardation observed in BrafQ241R/+ mice. Our data also suggest that CNP is a potential therapeutic target in CFC syndrome.

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.

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.

The Birth of a Black Rice Gene and Its Local Spread by Introgression.

The origin and spread of novel agronomic traits during crop domestication are complex events in plant evolution. Wild rice (Oryza rufipogon) has red grains due to the accumulation of proanthocyanidins, whereas most cultivated rice (Oryza sativa) varieties have white grains induced by a defective allele in the Rc basic helix-loop-helix (bHLH) gene. Although the events surrounding the origin and spread of black rice traits remain unknown, varieties with black grains due to anthocyanin accumulation are distributed in various locations throughout Asia. Here, we show that the black grain trait originated from ectopic expression of the Kala4 bHLH gene due to rearrangement in the promoter region. Both the Rc and Kala4 genes activate upstream flavonol biosynthesis genes, such as chalcone synthase and dihydroflavonol-4-reductase, and downstream genes, such as leucoanthocyanidin reductase and leucoanthocyanidin dioxygenase, to produce the respective specific pigments. Genome analysis of 21 black rice varieties as well as red- and white-grained landraces demonstrated that black rice arose in tropical japonica and its subsequent spread to the indica subspecies can be attributed to the causal alleles of Kala4. The relatively small size of genomic fragments of tropical japonica origin in some indica varieties indicates that refined introgression must have occurred by natural crossbreeding in the course of evolution of the black trait in rice.

Coordination Nanosheets Based on Terpyridine-Zinc(II) Complexes: As Photoactive Host Materials.

Photoluminescent coordination nanosheets (CONASHs) comprising three-way terpyridine (tpy) ligands and zinc(II) ions are created by allowing the two constitutive components to react with each other at a liquid/liquid interface. Taking advantage of bottom-up CONASHs, or flexibility in organic ligand design and coordination modes, we demonstrate the diversity of the tpy-zinc(II) CONASH in structures and photofunctions. A combination of 1,3,5-tris[4-(4'-2,2':6',2″-terpyridyl)phenyl]benzene (1) and Zn(BF4)2 affords a cationic CONASH featuring the bis(tpy)Zn complex motif (1-Zn), while substitution of the zinc source with ZnSO4 realizes a charge-neutral CONASH with the [Zn2(µ-O2SO2)2(tpy)2] motif [1-Zn2(SO4)2]. The difference stems from the use of noncoordinating (BF4-) or coordinating and bridging (SO42-) anions. The change in the coordination mode alters the luminescence (480 nm blue in 1-Zn; 552 nm yellow in 1-Zn2(SO4)2). The photophysical property also differs in that 1-Zn2(SO4)2 shows solvatoluminochromism, whereas 1-Zn does not. Photoluminescence is also modulated by the tpy ligand structure. 2-Zn contains triarylamine-centered terpyridine ligand 2 and features the bis(tpy)Zn motif; its emission is substantially red-shifted (590 nm orange) compared with that of 1-Zn. CONASHs 1-Zn and 2-Zn possess cationic nanosheet frameworks with counteranions (BF4-), and thereby feature anion exchange capacities. Indeed, anionic xanthene dyes were taken up by these nanosheets, which undergo quasi-quantitative exciton migration from the host CONASH. This series of studies shows tpy-zinc(II) CONASHs as promising potential photofunctional nanomaterials.

Discovery and pharmacological effects of a novel GPR142 antagonist.

GPR142 is a G-protein-coupled receptor (GPCR), whose most potent and efficacious ligand has been reported as being the natural amino acid l-tryptophan. GPR142 is highly expressed in pancreatic ß-cells and immune cells, suggesting the receptor may play a role in the pathogenesis and development of diabetes or inflammatory diseases. In a previous report, we developed GPR142 agonists as insulin secretagogues. In this report, we show the discovery of a selective, potent small-molecule GPR142 antagonist, CLP-3094, and its pharmacological characteristics. These data support targeting this receptor for the treatment of chronic inflammatory diseases.

Photofunctionality in Porphyrin-Hybridized Bis(dipyrrinato)zinc(II) Complex Micro- and Nanosheets.

New bis(dipyrrinato)zinc(II) complex micro- and nanosheets containing zinc(II) porphyrin (N2) are synthesized. A liquid/liquid interface method between dipyrrin porphyrin ligand L2 and zinc acetate produces N2 with a large domain size. N2 can be layered quantitatively onto a flat substrate by a modified Langmuir-Schäfer method. N2 deposited on a SnO2 electrode functions as a photoanode for a photoelectric conversion system. The photoresponse of N2 covers the whole visible wavelength range (400-650 nm), with a maximum quantum efficiency of more than twice that of a bis(dipyrrinato)zinc(II) complex nanosheet without porphyrin.

Coordination Programming of Two-Dimensional Metal Complex Frameworks.

Since the discovery of graphene, two-dimensional materials with atomic thickness have attracted much attention because of their characteristic physical and chemical properties. Recently, coordination nanosheets (CONASHs) came into the world as new series of two-dimensional frameworks, which can show various functions based on metal complexes formed by numerous combinations of metal ions and ligands. This Feature Article provides an overview of recent progress in synthesizing CONASHs and in elucidating their intriguing electrical, sensing, and catalytic properties. We also review recent theoretical studies on the prediction of the unique electronic structures, magnetism, and catalytic ability of materials based on CONASHs. Future prospects for applying CONASHs to novel applications are also discussed.

Effective Method for Micro-Patterning Arene-Terminated Monolayers on a Si(111) Electrode.

Microstructured electrodes are significant to modern electrochemistry. A representative aromatic group, 4-ferrocenylphenyl one, was covalently bound to a micropatterned silicon electrode via the arylation of a hydrogen-terminated silicon(111) surface formed selectively on a Si wafer. Starting from a silicon(100)-on-insulator (SOI) wafer, the aromatic monolayer was attached sequentially by spin-coating a resist, electron beam lithography, Cr/Au deposition, lift-off, anisotropic etching with aqueous KOH solution, and Pd-catalyzed arylation. Cyclic voltammetry (CV) and X-ray photoelectron spectroscopy (XPS) are used to characterize the coupling reaction between 4-ferrocenyl group and silicon substrate, and to confirm performance of the final modified microsized electrode. These data show that this synthetic protocol gives chemically well-defined and robust functionalized monolayers on a silicon semiconducting surface with a small electrode.

π-Conjugated bis(terpyridine)metal complex molecular wires.

Bottom-up approaches have gained significant attention recently for the creation of nano-sized, ordered functional structures and materials. Stepwise coordination techniques, in which ligand molecules and metal sources are reacted alternatively, offer several advantages. Coordination bonds are stable, reversible, and self-assembling, and the resultant metal complex motifs may contain functionalities unique to their own characteristics. This review focuses on metal complex wire systems, specifically the bottom-up fabrication of linear and branched bis(terpyridine)metal complex wires on electrode surfaces. This system possesses distinct and characteristic electronic functionalities, intra-wire redox conduction and excellent long-range electron transport ability. This series of comprehensive studies exploited the customizability of bis(terpyridine)metal complex wires, including examining the influence of building blocks. In addition, simple yet effective electron transfer models were established for redox conduction and long-range electron transport. A fabrication technique for an ultra-long bis(terpyridine)metal complex wire is also described, along with its properties and functionalities.

Effects of Substitution on Solid-State Fluorescence in 9-Aryl-9-methyl-9H-9-silafluorenes.

Aromatic groups were incorporated into 9H-9-silafluorene units at the 9-position (mono-9H-silafluorenes) and 9,9'-positions (di-9H-9-silafluorenes). The aryl substituents showed weak conjugation to the 9H-9-silafluorene for 9-aryl substituted ones 1-7 and a 9,9'-phenylene substituted one (compound 8) and they exhibited similar absorption and emission spectra. The 9H-9-silafluorene 10 containing a 5,5'-(2,2'-bithiophenyl) group showed a significantly red-shifted absorption and fluorescence maxima in the solid-state. Single-crystal X-ray diffraction studies found J-type aggregated structures formed by intermolecular CH-π interactions (ca. 2.6-2.7 Å). Density functional theory (DFT), time-dependent DFT (TD-DFT), and configuration interaction single (CIS) calculations were conducted to explain the observed optical properties.

Electron transport dynamics in redox-molecule-terminated branched oligomer wires on Au(111).

Dendritic bis(terpyridine)iron(II) wires with terminal ferrocene units were synthesized on a Au(111) surface by stepwise coordination using a three-way terpyridine ligand, a ferrocene-modified terpyridine ligand, and Fe(II) ions. Potential-step chronoamperometry, which applied overpotentials to induce the redox of the terminal ferrocene, revealed an unusual electron-transport phenomenon. The current-time profile did not follow an exponential decay that is common for linear molecular wire systems. The nonexponentiality was more prominent in the forward electron-transport direction (from the terminal ferrocene to the gold electrode, oxidation) than in the reverse direction (from the gold electrode to the terminal ferrocenium, reduction). A plateau and a steep fall were observed in the former. We propose a simple electron transport mechanism based on intrawire electron hopping between two adjacent redox-active sites, and the numerical simulation thereof reproduced the series of "asymmetric" potential-step chronoamperometry results for both linear and branched bis(terpyridine)iron(II) wires.

Tyk2 is a therapeutic target for psoriasis-like skin inflammation.

Tyrosine kinase 2 (Tyk2), a member of the Jak kinase family, mediates signals triggered by various cytokines, which are related to the pathogenesis of psoriasis. In this study, we investigated the role of Tyk2 in IL-23-induced psoriasis-like skin inflammation. Tyk2(-/-) mice when injected with IL-23 showed significantly reduced ear skin swelling with epidermal hyperplasia and inflammatory cell infiltration compared with wild-type mice. In addition, Tyk2 deficiency reduced production of pro-inflammatory cytokines and psoriasis-relevant anti-microbial peptides. More noteworthy is that Tyk2 directly regulated IL-22-dependent inflammation and epidermal hyperplasia. Taken together with the inhibition of IL-23-induced inflammation by treatment with neutralizing antibodies against IL-17 or IL-22, Tyk2 participates in both IL-23 and IL-22 signal transduction to mediate psoriasis-like skin inflammation. On the basis of these findings, we demonstrated for the first time that a small-molecule Tyk2 inhibitor significantly inhibited IL-23-induced inflammation and cytokine production in the skin. These observations demonstrate the important role of Tyk2 in experimental skin inflammation and indicate the therapeutic potential of Tyk2 inhibition in human psoriasis.

Medium-chain fatty acid-sensing receptor, GPR84, is a proinflammatory receptor.

G protein-coupled receptor 84 (GPR84) is a putative receptor for medium-chain fatty acids (MCFAs), whose pathophysiological roles have not yet been clarified. Here, we show that GPR84 was activated by MCFAs with the hydroxyl group at the 2- or 3-position more effectively than nonhydroxylated MCFAs. We also identified a surrogate agonist, 6-n-octylaminouracil (6-OAU), for GPR84. These potential ligands and the surrogate agonist, 6-OAU, stimulated [(35)S]GTP binding and accumulated phosphoinositides in a GPR84-dependent manner. The surrogate agonist, 6-OAU, internalized GPR84-EGFP from the cell surface. Both the potential ligands and 6-OAU elicited chemotaxis of human polymorphonuclear leukocytes (PMNs) and macrophages and amplified LPS-stimulated production of the proinflammatory cytokine IL-8 from PMNs and TNFα from macrophages. Furthermore, the intravenous injection of 6-OAU raised the blood CXCL1 level in rats, and the inoculation of 6-OAU into the rat air pouch accumulated PMNs and macrophages in the site. Our results indicate a proinflammatory role of GPR84, suggesting that the receptor may be a novel target to treat chronic low grade inflammation associated-disease.