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The development of efficient and stable electrocatalysts for water oxidation in acidic media is vital for the commercialization of the proton exchange membrane electrolyzers. In this work, we successfully construct Ru–O–Ir atomic interfaces for acidic oxygen evolution reaction (OER). The catalysts achieve overpotentials as low as 167, 300, and 390 mV at 10, 500, and 1500 mA cm −2 in 0.5 M H 2 SO 4 , respectively, with the electrocatalyst showing robust stability for >1000 h of operation at 10 mA cm −2 and negligible degradation after 200,000 cyclic voltammetry cycles. Operando spectroelectrochemical measurements together with theoretical investigations reveal that the OER pathway over the Ru–O–Ir active site is near-optimal, where the bridging oxygen site of Ir–O BRI serves as the proton acceptor to accelerate proton transfer on an adjacent Ru centre, breaking the typical adsorption-dissociation linear scaling relationship on a single Ru site and thus enhancing OER activity. Here, we show that rational design of multiple active sites can break the activity/stability trade-off commonly encountered for OER catalysts, offering good approaches towards high-performance acidic OER catalysts. Efficient and stable electrocatalysts for acidic oxygen evolution are essential for proton exchange membrane electrolyzers. Here, the authors report Ru–O–Ir atomic interfaces that enable bridging oxygen-mediated deprotonation pathways, overcoming the activity/stability trade-off in acidic oxygen evolution.

Designing efficient acidic oxygen evolution catalysts for proton exchange membrane water electrolyzers is challenging due to a trade-off between activity and stability. In this work, we construct high-density microcrystalline grain boundaries (GBs) with V-dopant in RuO 2 matrix (GB-V-RuO 2 ). Our theoretical and experimental results indicate this is a highly active and acid-resistant OER catalyst. Specifically, the GB-V-RuO 2 requires low overpotentials of 159, 222, and 300 mV to reach 10, 100, and 1500 mA cm -2 geo in 0.5 M H 2 SO 4 , respectively. Operando EIS, ATR-SEIRAS FTIR and DEMS measurements reveal the importance of GBs in stabilizing lattice oxygen and thus inhibiting the lattice oxygen mediated OER pathway. As a result, the adsorbate evolution mechanism pathway becomes dominant, even at high current densities. Density functional theory analyses confirm that GBs can stabilize V dopant and that the synergy between them modulates the electronic structure of RuO 2 , thus optimizing the adsorption of OER intermediate species and enhancing electrocatalyst stability. Our work demonstrates a rational strategy for overcoming the traditional activity/stability dilemma, offering good prospects of developing high-performance acidic OER catalysts. Designing efficient and stable acidic oxygen evolution catalysts is challenging. Here, the authors construct high-density grain boundaries in V-doped RuO 2 to tune its electronic structure and boost stability, addressing the activity/stability trade-off in proton exchange membrane water electrolyzers.

AbstractBiaryl scaffolds are prevalent in natural products and drug molecules, and biaryl-containing compounds have been shown to exhibit diverse and interesting biological activities. To date, numerous synthetic methods, particularly direct C–H bond activation, have been developed for the construction of such scaffolds, due to their interesting structural features and biological profiles. We highlight herein recent advances in the construction of biologically important biaryl fragments through direct C–H bond activation and also demonstrate the application of direct C–H arylation in the total synthesis of biaryl-containing natural products and drug molecules.Graphic AbstractSelected biaryl-containing compounds

The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, we report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination, providing an atom- and step-economical synthesis route of two types of fluoroalkyl substituted silanes with exclusive regioselectivity. The anti -Markovnikov addition products (β-fluoroalkyl substituted silanes) are formed with monodentate phosphine ligand. Noteworthy, the bidentate phosphine ligand promote the generation of the more challenging Markovnikov products (α-fluoroalkyl substituted silanes) with tetrasubstituted saturated carbon centers. This protocol features with easy available starting materials and commercially available nickel catalysis, a wide range of substrates and excellent regioselectivity. The structure divergent products undergo a variety of transformations. Comprehensive mechanistic studies including the inverse kinetic isotope effects demonstrate the regioselectivity controlled by ligand structure through α-CF 3 nickel intermediate. DFT calculations reveal a distinctive mechanism involving an open-shell singlet state, which is crucial for generating intricate tetra -substituted Markovnikov products. The fluoroalkyl-containing organic molecules are widely used in drug discovery and material science. Herein, the authors report ligand regulated nickel(0)-catalyzed regiodivergent hydrosilylation of α-(fluoroalkyl)styrenes without defluorination.

Umpolung is an old and important concept in organic chemistry, which significantly expands the chemical space and provides unique structures. While, previous research focused on carbonyls or imine derivatives, the umpolung reactivity of polarized C–C σ-bonds still needs to explore. Herein, we report an umpolung reaction of bicyclo[1.1.0]butanes (BCBs) with electron-deficient alkenes to construct the C(sp 3 )-C(sp 3 ) bond at the electrophilic position of C–C σ-bonds in BCBs without any transition-metal catalysis. Specifically, this transformation relies on the strain-release driven bridging σ-bonds in bicyclo[1.1.0]butanes (BCBs), which are emerged as ene components, providing an efficient and straightforward synthesis route of various functionalized cyclobutenes and conjugated dienes, respectively. The synthetic utilities of this protocol are performed by several transformations. Preliminary mechanistic studies including density functional theory (DFT) calculation support the concerted Alder-ene type process of C–C σ-bond cleavage with hydrogen transfer. This work extends the umpolung reaction to C–C σ-bonds and provides high-value structural motifs. Umpolung reactions typically focus on carbonyls or imine derivatives. Here, the authors report the umpolung reaction of C–C σ-bonds in bicyclo[1.1.0]butanes (BCBs) with electrophilic alkenes, yielding various cyclobutenes or conjugated dienes.

Insights derived from the crystal structures of the extracellular domain of PSKR, the receptor for the plant hormone phytosulfokine (PSK) that affects plant growth and development, reveal that PSK interacts with PSKR and enhances PSKR interaction with its co-receptor SERK allosterically. Mode of action of phytosulfokine The plant hormone phytosulfokine (PSK) affects plant growth and development by binding to PSKR, a leucine-rich repeat receptor kinase. How it recognizes and activates PSKR remains unclear. Jijie Chai and colleagues have determined the crystal structures of the extracellular domain of PSKR in free, PSK-bound and co-receptor-bound forms. The structures and supporting evidence reveal that when PSK interacts with PSKR it enhances the interaction between PSKR and its co-receptor SERK. Intriguingly, PSK is not directly involved in the PSKR–SERK interaction; rather it acts allosterically to stabilize a domain within PSKR that can recruit a SERK. This work could provide a basis for the design of PSKR-specific small molecules. Phytosulfokine (PSK) is a disulfated pentapeptide that has a ubiquitous role in plant growth and development 1 , 2 . PSK is perceived by its receptor PSKR 3 , 4 , a leucine-rich repeat receptor kinase (LRR-RK). The mechanisms underlying the recognition of PSK, the activation of PSKR and the identity of the components downstream of the initial binding remain elusive. Here we report the crystal structures of the extracellular LRR domain of PSKR in free, PSK- and co-receptor-bound forms. The structures reveal that PSK interacts mainly with a β-strand from the island domain of PSKR, forming an anti-β-sheet. The two sulfate moieties of PSK interact directly with PSKR, sensitizing PSKR recognition of PSK. Supported by biochemical, structural and genetic evidence, PSK binding enhances PSKR heterodimerization with the somatic embryogenesis receptor-like kinases (SERKs). However, PSK is not directly involved in PSKR–SERK interaction but stabilizes PSKR island domain for recruitment of a SERK. Our data reveal the structural basis for PSKR recognition of PSK and allosteric activation of PSKR by PSK, opening up new avenues for the design of PSKR-specific small molecules.

Pattern recognition receptors confer plant resistance to pathogen infection by recognizing the conserved pathogen-associated molecular patterns. The cell surface receptor chitin elicitor receptor kinase 1 of Arabidopsis (AtCERK1) directly binds chitin through its lysine motif (LysM)-containing ectodomain (AtCERK1-ECD) to activate immune responses. The crystal structure that we solved of an AtCERK1-ECD complexed with a chitin pentamer reveals that their interaction is primarily mediated by a LysAA and three chitin residues. By acting as a bivalent ligand, a chitin octamer induces AtCERK1-ECD dimerization that is inhibited by shorter chitin oligomers. A mutation attenuating chitin-induced AtCERK1-ECD dimerization or formation of nonproductive AtCERK1 dimer by overexpression of AtCERK1-ECD compromises AtCERK1-mediated signaling in plant cells. Together, our data support the notion that chitin-induced AtCERK1 dimerization is critical for its activation.

Nucleotide-binding and oligomerization domain–like receptor (NLR) proteins oligomerize into multiprotein complexes termed inflammasomes when activated. Their autoinhibition mechanism remains poorly defined. Here, we report the crystal structure of mouse NLRC4 in a closed form. The adenosine diphosphate–mediated interaction between the central nucleotide-binding domain (NBD) and the winged-helix domain (WHD) was critical for stabilizing the closed conformation of NLRC4. The helical domain HD2 repressively contacted a conserved and functionally important α-helix of the NBD. The C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. Disruption of ADP-mediated NBD-WHD or NBD-HD2/NBD-LRR interactions resulted in constitutive activation of NLRC4. Together, our data reveal the NBD-organized cooperative autoinhibition mechanism of NLRC4 and provide insight into its activation.

Brassinosteroids are essential phytohormones that have crucial roles in plant growth and development. Perception of brassinosteroids requires an active complex of BRASSINOSTEROID-INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED KINASE 1 (BAK1). Recognized by the extracellular leucine-rich repeat (LRR) domain of BRI1, brassinosteroids induce a phosphorylation-mediated cascade to regulate gene expression. Here we present the crystal structures of BRI1(LRR) in free and brassinolide-bound forms. BRI1(LRR) exists as a monomer in crystals and solution independent of brassinolide. It comprises a helical solenoid structure that accommodates a separate insertion domain at its concave surface. Sandwiched between them, brassinolide binds to a hydrophobicity-dominating surface groove on BRI1(LRR). Brassinolide recognition by BRI1(LRR) is through an induced-fit mechanism involving stabilization of two interdomain loops that creates a pronounced non-polar surface groove for the hormone binding. Together, our results define the molecular mechanisms by which BRI1 recognizes brassinosteroids and provide insight into brassinosteroid-induced BRI1 activation. Steroid hormone recognition The brassinolides are potent steroid hormones that are central to plant growth and development. They bind to the plasma membrane receptor BRI1, a member of the leucine-rich repeat (LRR) receptor family that also includes the mammalian Toll-like receptors, which are important in innate immunity. Two independent studies now present the crystal structure of BRI1 from Arabidopsis thaliana , both in the free form and in complex with brassinolide. BRI1 is found to adopt a solenoid-like superhelical structure involving 25 leucine-rich repeats. The structure is strikingly different from that of Toll-like receptors and reveals a novel mechanism of steroid recognition. This work suggests synthetic routes to nonsteroidal mimetics of BRI1 that could have a possible use in agriculture.

How FTO targets obesity The fat mass and obesity-associated ( FTO ) gene is associated with increased body weight and obesity risk. FTO protein is a DNA/RNA demethylase, and mice lacking it are abnormally lean. Now the crystal structure of human FTO in complex with the mononucleotide 3-meT has been determined. The structure reveals a novel mechanism by which the protein can discriminate between single- and double-stranded DNA. In addition, biochemical assays show that the C-terminal domain of FTO, previously of unknown function, is required for FTO catalytic activity via interactions with the N-terminal catalytic domain. These results provide a structural basis for understanding FTO substrate specificity, and serve as a foundation for the rational design of FTO inhibitors as potential anti-obesity agents. The fat mass and obesity-associated ( FTO ) gene has been associated with increased body weight. The FTO protein has DNA/RNA demethylase activity. Here, the crystal structure of human FTO in complex with the mononucleotide 3-methylthymidine is presented. The structure provides a basis for understanding the substrate specificity of FTO, and should serve as a foundation for the design of FTO inhibitors. Recent studies 1 , 2 , 3 , 4 , 5 have unequivocally associated the fat mass and obesity-associated ( FTO ) gene with the risk of obesity. In vitro FTO protein is an AlkB-like DNA/RNA demethylase with a strong preference for 3-methylthymidine (3-meT) in single-stranded DNA or 3-methyluracil (3-meU) in single-stranded RNA 6 , 7 , 8 . Here we report the crystal structure of FTO in complex with the mononucleotide 3-meT. FTO comprises an amino-terminal AlkB-like domain and a carboxy-terminal domain with a novel fold. Biochemical assays show that these two domains interact with each other, which is required for FTO catalytic activity. In contrast with the structures of other AlkB members, FTO possesses an extra loop covering one side of the conserved jelly-roll motif. Structural comparison shows that this loop selectively competes with the unmethylated strand of the DNA duplex for binding to FTO, suggesting that it has an important role in FTO selection against double-stranded nucleic acids. The ability of FTO to distinguish 3-meT or 3-meU from other nucleotides is conferred by its hydrogen-bonding interaction with the two carbonyl oxygen atoms in 3-meT or 3-meU. Taken together, these results provide a structural basis for understanding FTO substrate-specificity, and serve as a foundation for the rational design of FTO inhibitors.